:*1. '''Enterocolitis treatment'''<ref name="pmid11515763">{{cite journal| author=Press N, Fyfe M, Bowie W, Kelly M| title=Clinical and microbiological follow-up of an outbreak of Yersinia pseudotuberculosis serotype Ib. | journal=Scand J Infect Dis | year= 2001 | volume= 33 | issue= 7 | pages= 523-6 | pmid=11515763 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11515763 }} </ref>
::* Preferred regimen: There is also no evidence that early antimicrobial therapy reduces the frequency or severity of chronic sequelae for either Y. enterocolitica or Y. pseudotuberculosis
::* Note: Susceptible to [[Ampicillin]], third generation [[cephalosporins]], [[aminoglycosides]], [[tetracyclines]], and [[chloramphenicol]]<ref>Ryan, K. J., & Ray, C. G. (Eds.). (2004.). Sherris Medical Microbiology: An Introduction to Infectious Disease. (Fourth Edition. ed.). New York.: McGraw-Hill.</ref>
::* Preferred regimen (1): [[Streptomycin]] 2 g/day IM q12h for at least 10 days
:::* Note: Pediatric dose: [[Streptomycin]] 30 mg/kg/day (up to 2 g/day) IM q6-12h for at least 10 days
::* Preferred regimen (2): [[Gentamicin]] 3 mg/kg/day IM or IV q8h for at least 10 days
:::* Note: Pediatric dose: [[Gentamicin]] 6-7.5 mg/kg/day IM or IV q8h for at least 10 days - if neonates/infants use 7.5 mg/kg/day.
::* Alternative regimen (1): [[Chloramphenicol]] 50 mg/kg/day IV or PO q6h for 10 days
::* Alternative regimen (2): [[Tetracycline]] 2 g/day PO qid for 10 days
:::* Note: Pediatric dose: [[Tetracycline]] 15 mg/kg of loading dose {{then}} 25-50 mg/kg/day (up to 2 g/day) PO qid for 10 days
::* Alternative regimen (3): [[Sulfadiazine]] 2-4 g loading dose {{then}} 1 g PO q4-6h
::* Alternative regimen (4): [[Doxycycline]] 200 mg/day PO q12-24h
::* Note (1): Fluoroquinolones have good effect against Y. pestis in both in vitro and animal studies, but no studies have been published on its use in treating human plague.
::* Note (2): Other antibiotics have been shown ineffective against plague.
::* Alternative regimen (2): [[Aztreonam]] {{plus}} [[Vancomycin]]
::* Note (1): monotherapy is preferred since no study has shown superiority for combination therapy.
::* Note (2): add [[Vancomycin]] to the regimen if patient has signs of severe sepsis, hemodynamic instability, pneumonia, positive blood cultures for gram-positive bacteria while awaiting susceptibility results, suspected central venous catheter related infection, skin or soft tissue infection, severe mucositis in patients receiving prophylaxis with a fluoroquinolone lacking acitvity against streptococci and in whom ceftazidime is being used as empiric therapy (addition of gram-positive coverage is recommended in this situation because of the increased risk of Streptococcus viridans infections, which can result in sepsis and the acute respiratory distress syndrome).
::* Note (3): modify the initial regimen if patient is at risk of infection with the following antibiotic-resistant organisms:
:::* MRSA: consider early addition of [[Vancomycin]] {{or}} [[Linezolid]] {{or}} [[Daptomycin]]
:::* VRE: consider early addition of [[Linezolid]] {{or}} [[Daptomycin]]
:::* ESBLs: consider early use of a [[Carbapenem]]
:::* KPCs: consider early use of [[Polymyxin]]-colistin {{or}} [[Tigecycline]]
::* Note (4): the initial regimen should not be changed because of unexplained persistent fever if the patient is stable. However, if an infection is identified, the patient must be treated accordingly.
::* Note (5): if [[Vancomycin]] or other gram-positive coverage was started initially, it may be stopped after two to three days if there is no evidence of a gram-positive infection.
::* Note (6): empiric antifungal coverage should be considered in high-risk neutropenic patients who are expected to have a total duration of neutropenia >7 days and have persistent fever after four to seven days of a broad-spectrum antibacterial regimen and no identified source of fever. Clinically unstable patients with suspected fungal infection should be considered for antifungal therapy even earlier than what is recommended for empiric therapy.Candida spp are the most likely cause of invasive fungal infection in patients who are not receiving prophylaxis. In patients receiving fluconazole prophylaxis, fluconazole-resistant Candida spp and invasive mold infections, particularly Aspergillus spp, are the most likely causes. Recommended antifungal regimen:
:::* [[Caspofungin]] 70 mg IV on day one {{then}} 50 mg IV qd
:::* [[Voriconazole]] 6 mg/kg IV q12h on day one {{then}} 4 mg/kg IV q12h
:::* [[Amphotericin B]] lipid complex 5 mg/kg IV qd
:::* Liposomal [[amphotericin B]] 3 to 5 mg/kg IV qd
* 2. '''Prophylaxis'''
:* 2.1 '''Antifungal prophylaxis'''
:* Indications:
::* Prophylaxis against Candida infections is recommended in patient groups in whom the risk of invasive candidal infections is substantial, such as allogeneic HSCT recipients or those undergoing intensive remission-induction or salvage induction chemotherapy for acute leukemia.
::* Prophylaxis against invasive Aspergillus infections with [[Posaconazole]] should be considered for selected patients >13 years of age who are undergoing intensive chemotherapy for AML/MDS in whom the risk of invasive aspergillosis without prophylaxis is substantial.
::* Prophylaxis against Aspergillus infection in pre- engraftment allogeneic or autologous transplant recipients has not been shown to be efficacious. However, a mold-active agent is recommended in patients with prior invasive aspergillosis, anticipated prolonged neutropenic periods of at least 2 weeks, or a prolonged period of neutropenia immediately prior to HSCT.
:* Recommended drugs:
::* Preferred regimen: [[Fluconazole]]
::* Alternative regimen (1): [[Posaconazole]]
::* Alternative regimen (2): [[Voriconazole]]
::* Alternative regimen (3): [[Caspofungin]]
::* Alternative regimen (4): [[Micafungin]]
:* 2.2 '''Antiviral prophylaxis'''
::* There is usually no indication for the prophylactic use of antiviral drugs in patients with neutropenia. However, if skin or mucous membrane lesions due to herpes simplex or varicella-zoster viruses are present, even if they are not the cause of fever, prophylaxis with [[Acyclovir]] can be considered.
:* Recommended drugs:
::* Preferred regimen: [[Acyclovir]]
:* 2.3 '''Antibacterial prophylxis'''
::* Fluoroquinolone prophylaxis should be considered for high-risk patients with expected durations of prolonged and profound neutropenia (ANC <100 cells/mm3 for >7 days)
:* Recommended drugs:
::* Preferred regimen (1): [[Levofloxacin]]
::* Preferred regimen (2): [[Ciprofloxacin]]
==Sporotrichosis==
{{PBI|Sporotrichosis}}
<ref name="KauffmanBustamante2007">{{cite journal|last1=Kauffman|first1=C. A.|last2=Bustamante|first2=B.|last3=Chapman|first3=S. W.|last4=Pappas|first4=P. G.|title=Clinical Practice Guidelines for the Management of Sporotrichosis: 2007 Update by the Infectious Diseases Society of America|journal=Clinical Infectious Diseases|volume=45|issue=10|year=2007|pages=1255–1265|issn=1058-4838|doi=10.1086/522765}}</ref>
:* '''Lymphocutaneous/cutaneous'''
::* Preferred regimen: [[Itraconazole]] 200mg PO qd
::* Alternative regimen: [[Itraconazole]] 200 mg PO bid {{or}} [[Terbinafine]] 500 mg PO bid {{or}} Saturated solution potassium iodide with increasing doses {{or}} [[Fluconazole]] 400–800 mg PO qd {{or}} local hyperthermia
::* Note (1): Treat for 2–4 weeks after lesions resolved
::* Note (2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) q8h, increasing as tolerated to 40–50 drops q8h
:* '''Osteoarticular'''
::* Preferred regimen: [[Itraconazole]] 200mg PO bid for 12 months
::* Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV {{or}} [[Amphotericin B]] deoxycholate 0.7–1 mg/kg/day IV
::* Note (1): Switch to [[Itraconazole]] after favorable response if AmB used
::* Note (2): Treat for a total of at least 12 months
:* '''Pulmonary'''
::* Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV for severe or life-threatening pulmonary sporotrichosis, then [[Itraconazole]] 200 mg PO bid
::* Preferred regimen(2): [[Itraconazole]] 200 mg PO bid for 12 months for less severe disease
::* Alternative regimen: [[Amphotericin B]] deoxycholate 0.7–1 mg/kg/d IV {{then}} [[Itraconazole]] 200 mg PO bid {{or}} surgical removal
::* Note (1): Treat severe disease with an AmB formulation followed by [[Itraconazole]]
::* Note (2): Treat less severe disease with [[Itraconazole]]
::* Note (3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease
:* '''Meningitis'''
::* Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then [[Itraconazole]] 200 mg PO bid
::* Alternative regimen: [[Amphotericin B]] deoxycholate 0.7–1 mg/kg/d, then [[Itraconazole]] 200 mg PO bid
::* Note (1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
::* Note (2): Treat for a total of at least 12 months.
::* Note (3): May require long-term suppression with [[Itraconazole]].
:* '''Disseminated'''
::* Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then [[Itraconazole]] 200 mg PO bid
::* Alternative regimen: [[Amphotericin B]] deoxycholate 0.7–1 mg/kg/day, then [[Itraconazole]] 200 mg PO bid
::* Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
::* Note(2): Treat for a total of at least 12 months.
::* Note(3): May require long-term suppression with [[Itraconazole]].
:* '''Pregnant women'''
::* Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV {{or}} [[Amphotericin B]] deoxycholate 0.7–1 mg/kg/day IV for severe sporotrichosis
::* Preferred regimen(2): Local hyperthermia for cutaneous disease.
::* Note (1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
::* Note (2): Azoles should be avoided.
:* '''Children'''
::* Preferred regimen:
:::* Mild disease: [[Itraconazole]] 6–10 mg/kg/day PO (400 mg/day maximum)
:::* Severe disease: [[Amphotericin B]] deoxycholate 0.7 mg/kg/day IV followed by [[Itraconazole]] 6–10 mg/kg PO up to a maximum of 400 mg PO daily, as step-down therapy::* Alternative regimen: Saturated solution potassium iodide with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) q8h and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops q8h, whichever is lowest
==MERS==
:*'''Middle East Respiratory Syndrome'''
::* Preferred regimen: supportive care. There is no antiviral recommended for this infection at this moment, even though experimental therapies are at research (IFNs, [[Ribavirin]], [[Lopinavir]], [[Mycophenolic acid]], [[Cyclosporine]], [[Chloroquine]], [[Chlorpromazine]], [[Loperamide]], [[6-mercaptopurine]] and [[6-thioguanine]]). Supportive care include: administer oxygen to patients with severe acute pulmonary infection with signs of respiratory distress, hypoxaemia or shock; use conservative fluids management, avoid administering high-dose systemic glucocorticoids, use non-invasive ventilation, but, if its nor effective, do not delay endotracheal intubation; use lung-protective strategy for intubated patients, recognize sepsis as early as possible and treat it accordingly.<ref>http://apps.who.int/iris/bitstream/10665/178529/1/WHO_MERS_Clinical_15.1_eng.pdf?ua=1</ref>
==Penicilliosis==
:* '''Penicilliosis treatment'''
::*1. '''Mild disease'''
:::* Preferred regimen: [[Itraconazole]] 200 mg PO bid for 8 to 12 weeks without amphotericin B induction therapy<ref name="pmid1339213">{{cite journal| author=Supparatpinyo K, Chiewchanvit S, Hirunsri P, Baosoung V, Uthammachai C, Chaimongkol B et al.| title=An efficacy study of itraconazole in the treatment of Penicillium marneffei infection. | journal=J Med Assoc Thai | year= 1992 | volume= 75 | issue= 12 | pages= 688-91 | pmid=1339213 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1339213 }} </ref>
:::* Alternative regimen: [[Voriconazole]] 400 mg PO bid on day 1 {{then}} 200 mg PO bid for 12 weeks<ref name="pmid17690411">{{cite journal| author=Supparatpinyo K, Schlamm HT| title=Voriconazole as therapy for systemic Penicillium marneffei infections in AIDS patients. | journal=Am J Trop Med Hyg | year= 2007 | volume= 77 | issue= 2 | pages= 350-3 | pmid=17690411 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17690411 }} </ref>
::*2. '''Moderate-severe disease'''
:::* Preferred regimen: Liposomal [[Amphotericin B]] 3-5 mg/kg/day IV qd {{or}} [[Amphotericin B]] lipid complex 5 mg/kg/day IV qd for 2 weeks {{then}} [[Itraconazole]] 200 mg PO bid for 10 weeks<ref name="pmid9831676">{{cite journal| author=Sirisanthana T, Supparatpinyo K| title=Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients. | journal=Int J Infect Dis | year= 1998 | volume= 3 | issue= 1 | pages= 48-53 | pmid=9831676 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9831676 }} </ref>
:::* Alternative regimen: [[Voriconazole]] 6 mg/kg IV q12h on day 1 {{then}} 4 mg/kg q12h for at least 3 days {{then}} [[Voriconazole]] 200 mg PO bid for a total of 12 weeks<ref name="pmid17690411">{{cite journal| author=Supparatpinyo K, Schlamm HT| title=Voriconazole as therapy for systemic Penicillium marneffei infections in AIDS patients. | journal=Am J Trop Med Hyg | year= 2007 | volume= 77 | issue= 2 | pages= 350-3 | pmid=17690411 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17690411 }} </ref>
::*3. '''Maintenance therapy'''<ref name="pmid9845708">{{cite journal| author=Supparatpinyo K, Perriens J, Nelson KE, Sirisanthana T| title=A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 24 | pages= 1739-43 | pmid=9845708 | doi=10.1056/NEJM199812103392403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9845708 }} </ref>
:::* Preferred regimen [[Itraconazole]] 200 mg PO qd
:::* Alternative regimen: [[Voriconazole]] 200 mg PO bid
::* Note: [[Voriconazole]] and [[Itraconazole]] use require serum levels to be monitored to ensure adequate absorption.
==Mucormycosis==
{{PBI|Mucormycosis}}
* '''Mucormycosis'''<ref name="pmid19435437">{{cite journal| author=Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards J, Ibrahim AS| title=Recent advances in the management of mucormycosis: from bench to bedside. | journal=Clin Infect Dis | year= 2009 | volume= 48 | issue= 12 | pages= 1743-51 | pmid=19435437 | doi=10.1086/599105 | pmc=PMC2809216 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19435437 }} </ref>
:* Treatment include surgical debridement of involved tissues, antifungal therapy, use of growth factors to accelerate recovery from neutropenia, provision of granulocyte transfusions with sustained circulating neutrophils until the patient recovers from neutropenia, and discontinuation or reduction in the dose of glucocorticoids, correction of metabolic acidosis and hyperglycemia.
:* Alternative regimen (3): [[Deferasirox]] 20 mg/kg PO qd for 2–4 weeks {{plus}} Lipid [[Amphotericin B]] 5-10 mg/kg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 800 mg/day PO qid or bid
:* Alternative regimen (5): Initial: [[Isavuconazole]] 200 mg PO/IV q8h for 6 doses; maintenance: 200 mg PO/IV qd
:* Note (1): start maintenance dose 12 to 24 hours after the last loading dose.
:* Note (2): For salvage therapy: ([[Posaconazole]] 800 mg/day PO qid or bid {{withorwithout}} Lipid [[Amphotericin B]] 5-10 mg/kg/day IV q24h) {{or}} ([[Deferasirox]] 20 mg/kg PO qd for 2–4 weeks {{plus}} Lipid [[Amphotericin B]] 5-10 mg/kg/day IV q24h) {{or}} Granulocyte transfusions (for persistently neutropenic patients) ∼10ˆ9 cells/kg {{or}} Recombinant cytokines G-CSF 5 μg/kg/day, GM-CSF 100–250 μg/m², or IFN-g at 50 μg/m² for those with body surface area ≥ 0.5 m² and 1.5 μg/kg for those with body surface area <0.5 m²
::* Note (1): Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management<ref name="pmid22819486">{{cite journal| author=Wolz MM, Sciallis GF, Pittelkow MR| title=Human herpesviruses 6, 7, and 8 from a dermatologic perspective. | journal=Mayo Clin Proc | year= 2012 | volume= 87 | issue= 10 | pages= 1004-14 | pmid=22819486 | doi=10.1016/j.mayocp.2012.04.010 | pmc=PMC3538396 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22819486 }}</ref>
::* Note (2): For HIV-positive patients, antiretroviral therapy may be advisable<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
::* Note (3): The most active antiviral compounds against HHV-7 are [[Cidofovir]] and [[Foscarnet]]<ref name="pmid11747000">{{cite journal| author=De Clercq E, Naesens L, De Bolle L, Schols D, Zhang Y, Neyts J|title=Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8. | journal=Rev Med Virol | year= 2001 | volume= 11 | issue= 6 | pages= 381-95 | pmid=11747000 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11747000 }} </ref><ref name="pmid22819486">{{cite journal| author=Wolz MM, Sciallis GF, Pittelkow MR| title=Human herpesviruses 6, 7, and 8 from a dermatologic perspective. | journal=Mayo Clin Proc | year= 2012 | volume= 87 | issue= 10 | pages= 1004-14 | pmid=22819486 | doi=10.1016/j.mayocp.2012.04.010 | pmc=PMC3538396 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22819486 }} </ref>
==Hepatitis E==
{{PBI|Hepatitis E virus}}
* '''Hepatitis E treatment'''<ref>{{citeweb|title=Hepatitis E virus|url=http://www.who.int/mediacentre/factsheets/fs280/en/}}</ref>
:* Preferred regimen: supportive therapy. There is no specific treatment available.
::* Note (1): Hepatitis E is usually self-limiting, hospitalization is generally not required.
::* Note (2): Hospitalization is required for people with fulminant hepatitis and should also be considered for symptomatic pregnant women.
==Enterovirus D68==
{{PBI|Enterovirus D68}}
:* '''Enterovirus treatment'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
:::* Preferred regimen: supportive therapy
:::* Note: A new drug [[Pleconaril]] designed to affect Rhinovirus is being suggested to be effective against Enterovirus D68 but further investigation is required<ref name="pmid25554786">{{cite journal| author=Liu Y, Sheng J, Fokine A, Meng G, Shin WH, Long F et al.| title=Structure and inhibition of EV-D68, a virus that causes respiratory illness in children. | journal=Science | year= 2015 | volume= 347 | issue= 6217 | pages= 71-4 | pmid=25554786 | doi=10.1126/science.1261962 | pmc=PMC4307789 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25554786 }} </ref>
==Adenovirus==
{{PBI|Adenovirus}}
:* '''Adenovirus'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
::* 1. '''In severe cases of pneumonia or post hematopoietic stem cell transplantation'''
:::* Preferred regimen (1): [[Cidofovir]] 5 mg/kg/week IV for 2 weeks, then every 2 weeks {{and}} [[Probenecid]] 1.25 g/M<sup>2</sup> PO given 3 hours before [[Cidofovir]] and 3 & 9 hours after each infusion
:::* Preferred regimen (2): [[Cidofovir]] 1 mg/kg IV 3 times per week
:::* Note: [[Ganciclovir]], [[Foscarnet]] and [[Ribavirin]] are not recommended for use on adenovirus infection.<ref name="pmid24982316">{{cite journal| author=Lion T| title=Adenovirus infections in immunocompetent and immunocompromised patients. | journal=Clin Microbiol Rev | year= 2014 | volume= 27 | issue= 3 | pages= 441-62 | pmid=24982316 | doi=10.1128/CMR.00116-13 | pmc=PMC4135893 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24982316 }} </ref>
::* 2. '''For hemorrhagic cystitis'''
:::* Preferred regimen: [[Cidofovir]] (5 mg/kg in 100 mL saline instilled into bladder) intravesical<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
::* 3. '''Pink eye (viral conjunctivitis)'''
:::* Preferred regimen: No specific treatment available. If symptomatic, cold artificial tears may help.
::* 4.'''Bronchitis'''
:::* Preferred regimen: No specific therapy recommended, treatment is symptomatic.
==SARS==
{{PBI|SARS}}
* '''Severe acute respiratory distress syndrome- coronavirus'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref><ref name="pmid16968120">{{cite journal| author=Stockman LJ, Bellamy R, Garner P| title=SARS: systematic review of treatment effects. | journal=PLoS Med | year= 2006 | volume= 3 | issue= 9 | pages= e343 | pmid=16968120 | doi=10.1371/journal.pmed.0030343 | pmc=PMC1564166 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16968120 }} </ref><ref name="pmid15766649">{{cite journal| author=Groneberg DA, Poutanen SM, Low DE, Lode H, Welte T, Zabel P| title=Treatment and vaccines for severe acute respiratory syndrome. | journal=Lancet Infect Dis | year= 2005 | volume= 5 | issue= 3 | pages= 147-55 | pmid=15766649 | doi=10.1016/S1473-3099(05)01307-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15766649 }} </ref>
:* Preferred regimen: supportive therapy
:* Note: New therapies were studied for SARS during the last outbreaks which concluded:
::* [[Ribavirin]] ineffective and probably harmful due to haemolytic anaemia
::* [[Lopinavir]] {{plus}} [[Ritonavir]] is still controversial and need further investigation
::* Interferon has no benefit and its studies are inconclusive
::* [[Corticosteroids]] increases risk of fungal infections, some studies showed a higher incidence of psychosis, diabetes, avascular necrosis and osteoporosis
::* Inhaled [[Nitric oxide]] potent mediator of airway inflammation, its has improved oxygenation in some studies
----
==CMV==
{{PBI|Cytomegalovirus}}
:* '''Cytomegalovirus treatment'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
::*1. '''Immunocompetent patients'''
:::*1.1 '''Mononucleosis syndrome'''
::::* Preferred regimen: supportive therapy
:::*1.2 '''CMV in pregnancy'''
::::* Preferred regimen: Hyperimmune 200 IU/kg of maternal weight as single-dose during pregnancy
::*2. '''Immunocompromised patients'''
:::*2.1 '''Retinitis'''
::::* Preferred regimen (1): [[Ganciclovir]] intraocular implant {{plus}} [[Valganciclovir]] 900 mg PO bid for 14-21 days {{then}} [[Valganciclovir]] 900mg PO qq for maintenance therapy - for immediate sight-threatening lesions
::::* Preferred regimen (2): [[Valganciclovir]] 900 mg PO bid for 14-21 days {{then}} [[Valganciclovir]] 900 mg PO qq for maintenance therapy - for peripheral lesions
::::* Alternative regimen (1): [[Foscarnet]] 60 mg/kg IV q8h {{or}} [[Foscarnet]] 90 mg/kg IV q12h for 14-21 days {{then}} [[Foscarnet]] 90-120 mg/kg IV q24h
::::* Alternative regimen (2): [[Cidofovir]] 5 mg/kg IV for 2 weeks {{then}} [[Cidofovir]] 5 mg/kg IV every other week - each dose should be admnistered with IV saline hydration and probenecid
::::* Alternative regimen (3): [[Ganciclovir]] 5 mg/kg IV q12h for 14-21 days {{then}} [[Valganciclovir]] 900 mg PO bid
::::* Alternative regimen (4): [[Fomivirsen]] intravitreal injection - for relapses
::::* Note: keep a maintenance dose of [[Valganciclovir]] 900 mg PO qd until CD4 >100/mm³
:::* 2.2 '''Transplant patients'''
::::* Preferred regimen: [[Valganciclovir]] 900 mg PO bid {{or}} [[Ganciclovir]] 5 mg/kg IV q12h for at least 2-3 weeek
::::* Note: Use [[Valganciclovir]] 900 mg PO qd for 1-3 months if high dose of immunosuppression.
:::* 2.3 '''Colitis, esophagitis, gastritis'''
::::* Preferred regimen: [[Ganciclovir]] 5 mg/kg/dose IV q12h for 3-6 weeks weeks for induction. There is no agreement on the use of maintenance.
::::* Alternative regimen: [[Cidofovir]] 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
::::* Note: Switch to oral [[Valganciclovir]] when PO tolerated & when symptoms not severe enough to interfere with absorption.
:::* 2.4 '''Pneumonia'''
::::* Preferred regimen: [[Valganciclovir]] 900 mg PO bid for 14–21 days, then 900 mg PO qd for maintenance therapy
::::* Alternative regimen for retinitis: [[Ganciclovir]] 5 mg/kg IV q12h for 14–21 days, then [[Valganciclovir]] 900 mg PO qd
::::* Note: In bone marrow transplant patients, combine therapy with CMV immune globulin.
:::* 2.5 '''Encephalitis, ventriculitis'''
::::* Note: Treatment not defined, but should be considered the same as retinitis. Disease may develop while taking [[Ganciclovir]] as suppressive therapy.
:::* 2.6 '''Lumbosacral polyradiculopathy'''
::::* Preferred regimen: [[Ganciclovir]], as with retinitis
::::* Alternative regimen: [[Foscarnet]] 40 mg/kg IV q12h another option
::::* Alternative regimen: [[Cidofovir]] 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
::::* Note (1): Switch to [[Valganciclovir]] when possible.
::::* Note (2): Suppression continued until CD4 remains >100/mm³ for 6 months.
:::*2.7 '''Peri/postnatal severe CMV infection in very low birth weight infants'''
::::* Preferred regimen: [[Ganciclovir]] 6 mg/kg/dose IV q12h for 3 weeks<ref name="pmid25243446">{{cite journal| author=Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT et al.| title=Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. | journal=JAMA Pediatr | year= 2014 | volume= 168 | issue= 11 | pages= 1054-62 | pmid=25243446 | doi=10.1001/jamapediatrics.2014.1360 | pmc=PMC4392178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25243446 }} </ref>
::* Preferred regimen: supportive therapy. There is no specific antiviral drug available for Ebola thus far. For information of investigational therapies including Favipiravir, Brincidofovir, ZMapp, TKM-Ebola, AVI-6002, and BCX4430, see [[Ebola future or investigational therapies|here]].
:::*Isolate patient
:::*Provide intravenous fluids (IV) (patients need large volumes in some cases) and maintain electrolytes at normal levels
:::*Maintain oxygen saturation and blood pressure
:::*Administer blood products if coagulopathy or bleeding, antiemetics if vomiting , antipyretics if fever, analgesics, anti-motility if severe diarrhea, total parenteral nutrition if patient has poor oral intake and dialysis if there's renal failure
:::*Treat other infections if they occur. Provide adequate Gram-negative coverage and gram-positive if the patient has any catheter or hospital-acquired pneumonia.
:::*If there's respiratory failure, invasive mechanical ventilation may be the best option to offer respiratory support
::* Note (1): Recovery from Ebola depends on good supportive care and the patient’s immune response.
::* Note (2): While there is no proven treatment available for Ebola virus disease, human convalescent whole blood has been used as an empirical treatment with promising results in a small group of EVD cases.<ref>[http://apps.who.int/iris/bitstream/10665/135591/1/WHO_HIS_SDS_2014.8_eng.pdf interim]</ref><ref name="pmid9988160">{{cite journal| author=Mupapa K, Massamba M, Kibadi K, Kuvula K, Bwaka A, Kipasa M et al.| title=Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue= | pages= S18-23 | pmid=9988160 | doi=10.1086/514298 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988160 }} </ref>
::* Note (3): People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola.
::* Note (4): Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems.
==Marburg==
{{PBI|Marburg virus}}
:*Marburg virus treatment
::* Preferred regimen: supportive therapy including maintenance of blood volume and electrolyte balance, as well as analgesics and standard nursing care<ref>http://www.cfsph.iastate.edu/Factsheets/pdfs/viral_hemorrhagic_fever_filovirus.pdf</ref><ref>http://www.cdc.gov/vhf/marburg/treatment/index.html</ref>
::* Preferred regimen: Supportive therapy, there is no specific treatment for hantavirus cardiopulmonary syndrome
::* Note (1): ICU management should include careful assessment, monitoring and adjustment of volume status and cardiac function, including inotropic and vasopressor support if needed
::* Note (2): Fluids should be administered carefully due to the potential for capillary leakage
::* Note (3): Supplemental oxygen should be administered if patients become hypoxic
::* Note (4): Equipment and materials for intubation and mechanical ventilation should be readily available since onset of respiratory failure may be precipitous
::* Note (5): Extracorporeal membrane oxygenation was used with survival rates of 50% in some studies in patients with cardiac index output <2.5L/min/m²<ref name="pmid9468181">{{cite journal| author=Crowley MR, Katz RW, Kessler R, Simpson SQ, Levy H, Hallin GW et al.| title=Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation. | journal=Crit Care Med | year= 1998 | volume= 26 | issue= 2 | pages= 409-14 | pmid=9468181 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9468181 }} </ref>
==Streptococcus pyogenes==
{{PBI|Streptococcus pyogenes}}
*1. '''Streptococcus pyogenes tonsilitis'''<ref name="pmid8215292">{{cite journal| author=Betriu C, Sanchez A, Gomez M, Cruceyra A, Picazo JJ| title=Antibiotic susceptibility of group A streptococci: a 6-year follow-up study. | journal=Antimicrob Agents Chemother | year= 1993 | volume= 37 | issue= 8 | pages= 1717-9 | pmid=8215292 | doi= | pmc=PMC188051 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8215292 }} </ref>
:* Preferred regimen (1): [[Penicillin V]] 250 mg PO bid or tid (for children) 250 mg PO qid or 500 mg PO bid (for adults) for 10 days<ref name="pmid19246689">{{cite journal| author=Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST et al.| title=Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. | journal=Circulation | year= 2009 | volume= 119 | issue= 11 | pages= 1541-51 | pmid=19246689 | doi=10.1161/CIRCULATIONAHA.109.191959 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19246689 }} </ref>
:* Preferred regimen (2): [[Benzathine penicillin G]] if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose<ref name="pmid23091044">{{cite journal| author=Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G et al.| title=Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2012 | volume= 55 | issue= 10 | pages= 1279-82 | pmid=23091044 | doi=10.1093/cid/cis847 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23091044 }} </ref>
:* Alternative regimen (1): [[Amoxicillin]] 50 mg/kg/day PO qd for 10 days {{or}} 25 mg/kg/day PO bid for 10 days. Its oral suspension is more tolerable to children and it is better absorbed by the GI tract<ref name="pmid12739920">{{cite journal| author=Curtin-Wirt C, Casey JR, Murray PC, Cleary CT, Hoeger WJ, Marsocci SM et al.| title=Efficacy of penicillin vs. amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis. | journal=Clin Pediatr (Phila) | year= 2003 | volume= 42 | issue= 3 | pages= 219-25 | pmid=12739920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12739920 }} </ref>
:* Alternative regimen (2): first generation [[Cephalosporins]] are acceptable for treating recurrent group A streptococcus infection but not as first-line therapy<ref name="pmid15805383">{{cite journal| author=Pichichero ME| title=A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. | journal=Pediatrics | year= 2005 | volume= 115 | issue= 4 | pages= 1048-57 | pmid=15805383 | doi=10.1542/peds.2004-1276 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15805383 }} </ref><ref name="pmid23091044">{{cite journal| author=Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G et al.| title=Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2012 | volume= 55 | issue= 10 | pages= 1279-82 | pmid=23091044 | doi=10.1093/cid/cis847 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23091044 }} </ref>
:* Alternative regimen (3): [[Clarithromycin]] 250 mg PO bid for 10 days {{or}} [[Azithromycin]] 12 mg/kg maximum 500 mg PO on day 1 {{then}} 6 mg/kg maximum 250 mg PO qd on days 2 through 5 {{or}} [[Erythromycin]] 20 mg/kg/day PO or 40 mg/kg/day (ethylsuccinate) PO bid for 10 days.
:* Alternative regimen (4): [[Clindamycin]] for penicillin-intolerant patients with erythromycin-resistant strains.
:* Note: Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies<ref name="pmid14837911">{{cite journal| author=WANNAMAKER LW, RAMMELKAMP CH, DENNY FW, BRINK WR, HOUSER HB, HAHN EO et al.| title=Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin. | journal=Am J Med | year= 1951 | volume= 10 | issue= 6 | pages= 673-95 | pmid=14837911 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14837911 }} </ref>
*2. '''Recurrent Streptococcus pyogenes tonsilitis'''<ref name="pmid12087516">{{cite journal| author=Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL, Schwartz RH, Infectious Diseases Society of America| title=Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2002 | volume= 35 | issue= 2 | pages= 113-25 | pmid=12087516 | doi=10.1086/340949 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12087516 }} </ref>
:* Preferred regimen (1): [[Clindamycin]] 20-30 mg/kg/day PO tid (for children), 600 mg/day bid, tid or qid (for adults) for 10 days
:* Preferred regimen (2): [[Amoxicillin-clavulanic acid]] 40 mg/kg/day PO tid (for children), 500 mg bid (for adults) for 10 days
:* Alternative regimen: [[Benzathine penicillin G]] if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose {{withorwithout}} [[Rifampin]] 20 mg/kg/day PO bid for 4 days
*3. '''Secondary prophylaxis for rheumatic fever'''<ref name="pmid23091044">{{cite journal| author=Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G et al.| title=Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2012 | volume= 55 | issue= 10 | pages= 1279-82 | pmid=23091044 | doi=10.1093/cid/cis847 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23091044 }} </ref>
:* Preferred regimen (1): [[Benzathine penicillin G]] if <27kg: 600,000 U, if >27kg 1,200,000 U IM every 4 weeks
:* Alternative regimen (1): [[Penicillin V]] potassium 250 mg PO bid
:* Alternative regimen (2): [[Sulfadiazine]] if <27kg 0.5 g PO qd, if >27kg 1 g PO qd
:*Duration of treatment: if residual cardiac disease, keep treatment until 40 patient is 40 years old or for 10 years (whichever is longer); if there's no residual cardiac disease keep treatment for 10 years or until age 21 years (whichever is longer); if there's rheumatic fever without carditis keep it for 5 years or until age 21 years (whichever is longer).
:* Note: For patients allergic to penicillin and sulfadiazine, consider a macrolide or azalide antibiotic
*4. '''Streptococcus pyogenes bacteremia'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
:* Preferred regimen: [[Penicillin G]] 4 million units IV q4h {{and}} [[Clindamycin]] 900 mg IV q8h for at least 14 days
:* [[Penicillin]] is added to the regimen to cover any other group A streptococcus which might be resistant to [[Clindamycin]].
:* Alternative regimen (1): [[Erythromycin]]
:* Alternative regimen (2): [[Azithromycin]]
:* Alternative regimen (3): [[Clarithromycin]]
:* Alternative regimen (4): any other β-lactam<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
:* Note (1): Macrolide resistance is increasing.
:* Note (2): Consider using intravenous immune globulin in patients with invasive infection and signs of shock. Immunoglobulin-G IV 1 g/kg day 1, then 0.5 g/kg days 2 & 3.
:* Note (3): If shock, administer massive IV fluids (10-20 L/day), [[Albumin]] if <2 g/dL, debridement of necrotic tissue.
*5. '''Streptococcus pyogenes celulitis'''
:* Preferred regimen: treat as Streptococcus pyogenes bacteremia
*6 '''Epiglottitis in childern'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen (1): [[Cefotaxime]] 50 mg/kg IV q8h
:* Preferred regimen (2): [[Ceftriaxone]] 50 mg/kg IV q24h
:* Alternative regimen (1): [[Amoxicillin]]-SB 100–200 mg/kg qd q6h
:* Alternative regimen (2): [[Trimethoprim-Sulfamethoxazole]] 8–12 mg/kg bid
:* Note: Have tracheostomy set “at bedside.” Chloro is effective, but potentially less toxic alternative agents available.
*7 '''Burn wound sepsis'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: [[Vancomycin]] 1 gm IV q12h {{and}} ([[Amikacin]] 10 mg/kg IV loading dose then 7.5 mg/kg IV q12h) {{and}} [ [[Piperacillin]] 4 g IV q4h (give ½ q24h dose of [[Piperacillin]] into subeschar tissues with surgical eschar removal within 12 hours]. Can use [[Piperacillin]]-[[Tazobactam]] if [[Piperacillin]] not available.
*8. '''Soft tissue'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Note: For necrotizing fasciitis, surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.
*9. '''Muscle'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Note: For myositis-debirdement is recommended.
*10.''' Eye'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:*10.1 '''Keratitis '''
::*10.1.1 '''Acute bacterial keratitis'''
:::* Preferred regimen: [[Moxifloxacin]] eye gtts. 1 gtt tid for 7 days
:::*Alternative therapy: [[Gatifloxacin]] eye gtts. 1-2 gtts q2h while awake for 2 days, then q4h for 3-7 days.
:::* Note: Prefer [[Moxifloxacin]] due to enhanced lipophilicity and penetration into aqueous humor (1 gtt = 1 drop).
::*10.1.2 '''Keratitis due to dry cornea, diabetes, immunosuppression'''
:::* Preferred regimen: [[Cefazolin]] (50 mg/mL) {{and}} ([[Gentamicin]] {{or}} [[Tobramycin]] (14 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction)
:::*Alternative therapy: [[Vancomycin]] (50 mg/mL) {{and}} [[Ceftazidime]] (50 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction.
:::* Note: Specific therapy guided by results of alginate swab culture and sensitivity. [[Ciprofloxacin]] 0.3% found clinically equivalent to [[Cefazolin]]{{and}} [[Tobramycin]]; only concern was efficacy of [[Ciprofloxacin]] vs S. pneumoniae
:*10.2 '''Dacryocystitis (lacrimal sac)'''
::* Preferred regimen: [[Moxifloxacin]] 1 gtt tid for 7 days {{or}} [[Cefazolin]] (50 mg/mL) (1 gtt = 1 drop)
*11.''' Suppurative phlebitis'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: [[Vancomycin]] 15 mg/kg IV q12h (normal weight)
:* Alternative regimen: [[Daptomycin]] 6 mg/kg IV q12h
:* Note: Retrospective study for suppurative phlebitis recommends 2-3 weeks IV therapy and 2 weeks PO therapy.
*12. ''' Infected prosthetic joint'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: [[Penicillin G]] 2 million units IV q4h {{or}} [[Ceftriaxone]] 2 g IV q24h for 4 weeks
:* Note: Debridement & prosthesis retention with intravenous antibiotics.
*13. ''' “Hot” tender parotid swelling'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: [[Nafcillin]] {{or}} [[Oxacillin]] 2 g IV q4h
:* Note: Predisposing factors are stone(s) in Stensen’s duct, dehydration. Therapy depends on ID of specific etiologic organism.
*14. '''Diabetic foot ulcer (ulcer with <2 cm of superficial inflammation)'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: ([[Trimethoprim-Sulfamethoxazole]] 800/160 mg 1-2 tabs PO bid {{or}} [[Minocycline]] 100 mg PO bid) {{and}} ([[Penicillin VK]] 500 mg PO qid {{or}} selected [[Cephalosporins]] 2nd, 3rd generation - cefprozil 500 mg PO bid {{or}} cefuroxime axetil 500 mg PO bid {{or}} cefdinir 300 mg PO bid or 600 mg PO qd {{or}} cefpodoxime 200 mg PO bid {{or}} [[Fluoroquinolones]] Levofloxacin 750 mg PO qd).
*15. ''' Recurrent cellulitis, chronic lymphedema prophylaxis'''<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: [[Clindamycin]] 150 mg PO qd {{or}} [[Trimethoprim]]-[[Sulfamethoxazole]] 800/160 mg 1 tablet PO qd {{or}} “stand-by therapy” immediate treatment with [[Penicillin V]] {{or}} [[Amoxicillin]] 500-750 mg PO bd at onset of symptoms.
==Staphylococcus epidermidis==
{{PBI|Staphylococcus epidermidis}}
*Staphylococcus epidermidis<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
::* Preferred regimen (1): [[Oxacillin]] 1-2 g IV q4h
::* Preferred regimen (2): [[Nafcillin]] 1-2 g IV q4h
::* Preferred regimen (3): [[Cephalothin]]
::* Alternative regimen: [[Rifampin]] 600 mg/day PO qd {{plus}} [[Sulfamethoxazole]] and [[Trimethoprim]] {{or}} [[Fluoroquinolones]] {{and}} [[Daptomycin]] 600 mg PO/IV q12h<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
::* Note: 75% of the S. epidermidis are methicillin-resistant.
::* Preferred regimen: [[Vancomycin]] 1 g IV q12h {{withorwithout}} [[Rifampin]] 600 mg/day PO qd
:* Note: For deep-seated infections consider adding [[Gentamicin]] {{and}}/{{or}} [[Rifampin]] 600 mg/day PO qd to the regimen<ref name="pmid15956145">{{cite journal| author=Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME et al.| title=Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. | journal=Circulation | year= 2005 | volume= 111 | issue= 23 | pages= e394-434 | pmid=15956145 | doi=10.1161/CIRCULATIONAHA.105.165564 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15956145 }} </ref>
:*3. '''Prosthetic device infections'''
::* Preferred regimen: [[Oxacillin]] 1-2 g IV q4h {{or}} [[Vancomycin]] 1 g IV q12h {{plus}} [[Rifampin]] 600 mg/day PO qd {{and}} [[Gentamicin]] 3 mg/kg/day IV/IM q8-24h is appropriate<ref name="pmid15956145">{{cite journal| author=Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME et al.| title=Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. | journal=Circulation | year= 2005 | volume= 111 | issue= 23 | pages= e394-434 | pmid=15956145 | doi=10.1161/CIRCULATIONAHA.105.165564 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15956145 }} </ref>
:* Note: Duration depends on site of infection and severity.
==Actinomycosis==
{{PBI|Actinomycosis}}
*'''Actinomyces species including A. israeli'''<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
:* Preferred regimen: [[Penicillin]] 3-4 million units IV q4h for 2-6 weeks {{then}} [[Penicillin V]] 2-4 g/day PO qid for 6-12 months
:* Alternative regimen (1): [[Erythromycin]] 500-1000 mg IV q6h {{or}} 500 mg PO qid
:* Alternative regimen (2): [[Tetracyclin]] 500 mg PO qid
:* Alternative regimen (3): [[Doxycycline]] 100 mg IV q12h {{or}} 100 mg PO bid
:* Alternative regimen (4): [[Clindamycin]] 900 mg IV q8h {{or}} 300-450 mg PO qd
:* Alternative regimen (5): [[Minocycline]] 100 mg IV q12h {{or}} 100 mg PO bid
==Sparganosis==
{{PBI|Sparganosis}}
:* '''Sparganosis (Spirometra mansonoides) treatment''' <ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
::* Preferred treatment: Surgical resection or ethanol injection of subcutaneous masses
::* Note: [[Praziquantel]] 75 mg/kg/day PO qd for 3 days is controversial. It's been innefective in some cases, but has had some results in patients when surgical therapy wasn't an option.<ref name="pmid21359068">{{cite journal| author=Lee JH, Kim GH, Kim SM, Lee SY, Lee WY, Bae JW et al.| title=A case of sparganosis that presented as a recurrent pericardial effusion. | journal=Korean Circ J | year= 2011 | volume= 41 | issue= 1 | pages= 38-42 | pmid=21359068 | doi=10.4070/kcj.2011.41.1.38 | pmc=PMC3040402 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21359068 }} </ref>
:::* Preferred regimen: [[Diethylcarbamazine]] 6 mg/day PO qd for 12 days (single dose if patient will continue to live in endemic area or is younger than 9 years old) {{withorwithout}} [[Albendazole]] 400 mg PO qd
:::* Alternative regimen: [[Doxycycline]] 200 mg/day for 4 weeks {{withorwithout}} [[Ivermectin]] 150 μg/kg single dose (do not administer [[Ivermectin]] if there's a risk of serious adverse effects in areas where L loa is coendemic)
:::* Note: Do not administer [[Diethylcarbamazine]] where onchocerciasis is endemic due to the risk of causing severe local inflammation in patients with ocular microfilariae.
:::* Preferred regimen: [[Doxycycline]] 150 μg/kg single dose
:::* Preferred regimen: ([[Doxycyclin]] 100 mg PO qd for 6 weeks {{or}} 200 mg PO qd for 4 weeks) {{then}} [[Ivermectin]] after 4-6 months 150 μg/kg single dose; {{or}} [[Doxycyclin]] 200 mg PO qd for 6 weeks {{then}} [[Ivermectin]] after 4-6 months 150 μg/kg single dose
:* 1.1 '''Echinococcus granulosus (hydatid disease) treatment'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
::* Preferred regimen: [[Albendazole]] ≥60 kg 400 mg PO bid or <60 kg 10-15 mg/kg/day PO bid with meals for 3-6 months
::* Alternative regimen: [[Mebendazole]] 40-50mg/kg/day PO tid for 3-6 months
::* Note: Percutaneous aspiration-injection-reaspiration (PAIR). Puncture & needle aspirate cyst content. Instill hypertonic saline (15–30%) or absolute alcohol, wait 20–30 min, then re-aspirate with final irrigation. Administer [[Albendazole]] at least 4 hours before PAIR.
::* Note: If surgery is needed, make sure to administer [[Albendazole]] for at least a week before the surgery, and to keep the medication for at least 4 weeks after the procedure.
:* 1.2 '''Echinococcus multilocularis (alveolar cyst disease) treatment'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref>
::* Preferred regimen: [[Albendazole]] ≥60 kg 400 mg PO bid or <60 kg 15 mg/kg/day PO bid with meals for at least 2 years. Long-term follow up needed to evaluate progression of the lesions.
::: Note: Wide surgical resection only reliable treatment; technique evolving.
==Parvovirus B19==
{{PBI|Parvovirus B19}}
:* Parvovirus B19<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref><ref name="pmid14762186">{{cite journal| author=Young NS, Brown KE| title=Parvovirus B19. | journal=N Engl J Med | year= 2004 | volume= 350 | issue= 6 | pages= 586-97 | pmid=14762186 | doi=10.1056/NEJMra030840 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14762186 }} </ref>
::* 1. '''Erythema infectiosum'''
:::* Supportive therapy: Symptomatic treatment only
:::* Preferred regimen: transfusion and IVIG (there are different IVIG regimens such as 400 mg/kg of commercial IVIG for 5 or 10 days or 1000 mg/kg for 3 days both with good results). Relapses have been treated with maintenance IVIG at doses of 0.4 grams/kg/day every four weeks.<ref name="pmid2173460">{{cite journal| author=Frickhofen N, Abkowitz JL, Safford M, Berry JM, Antunez-de-Mayolo J, Astrow A et al.| title=Persistent B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anemia in AIDS. | journal=Ann Intern Med | year= 1990 | volume= 113 | issue= 12 | pages= 926-33 | pmid=2173460 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2173460 }} </ref>
::* 6.'''Chronic infection without anemia'''
:::* Preferred regimen: IVIG is controversial. Further studies needed.
==JC virus==
{{PBI|JC virus}}
:* '''Progressive Multifocal Leukoencephalopathy (PML) caused by JC Virus ( John Cunningham virus) infections'''<ref>{{citeweb|title=JCvirus|url=https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf}}</ref>
::* There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV.
::* Initiate anti retroviral therapy (ART) immediately in ART-naive patients, and optimize ART in patients who develop Progressive Multifocal Leukoencephalopathy in phase of HIV viremia on ART .
::* [[Corticosteroids]] may be used for Progressive Multifocal Leukoencephalopathy- immune reconstitution inflammatory syndrome (IRIS) characterized by contrast enhancement, edema or mass effect, and with clinical deterioration
==RSV==
{{PBI|Respiratory Syncytial Virus}}
:* Preferred regimen: Supportive therapy
::* Hydration and supplemental oxygen.
::* Routine use of [[Ribavirin]] not recommended. [[Ribavirin]] therapy associated with small increases in O2 saturation.
::* No consistent decrease in need for mechanical ventilation or ICU stays. High cost, aerosol administration and potential toxicity<ref name="pmid19736258">{{cite journal| author=Committee on Infectious Diseases| title=From the American Academy of Pediatrics: Policy statements--Modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. | journal=Pediatrics | year= 2009 | volume= 124 | issue= 6 | pages= 1694-701 | pmid=19736258 | doi=10.1542/peds.2009-2345 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19736258 }} </ref>
::* Note (1): Its is FDA-approved for RSV infection in children, but not for RSV infection in adults. Dose: [[Ribavirin]] 20mg/dl 6 g inhaled continuosly for 12-18h.
::* Note (2): Respiratory Syncytial Virus major cause of morbidity in neonates/infants.
:* Prevention of Respiratory syncytial virus
::* 1. In children <24 months old with chronic lung disease of prematurity (formerly broncho-pulmonary dysplasia) requiring supplemental oxygen or
::* 2. In premature infants (<32 wks gestation) and <6 months old at start of Respiratory syncytial virus season or
::* 3. In children with selected congenital heart diseases.
:::* Preferred regimen for prevention of Respiratory syncytial virus: [[Palivizumab]] (Synagis) 15 mg per kg IM q month Nov.-April<ref name="pmid19736258">{{cite journal| author=Committee on Infectious Diseases| title=From the American Academy of Pediatrics: Policy statements--Modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. | journal=Pediatrics | year= 2009 | volume= 124 | issue= 6 | pages= 1694-701 | pmid=19736258 | doi=10.1542/peds.2009-2345 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19736258 }} </ref>
::::* Note: Significant reduction in Respiratory syncytial virus hospitalization among children with congenital heart disease<ref name="pmid17727335">{{cite journal| author=Feltes TF, Sondheimer HM| title=Palivizumab and the prevention of respiratory syncytial virus illness in pediatric patients with congenital heart disease. | journal=Expert Opin Biol Ther | year= 2007 | volume= 7 | issue= 9 | pages= 1471-80 | pmid=17727335 | doi=10.1517/14712598.7.9.1471 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17727335 }} </ref>
==Rhinovirus==
{{PBI|Rhinovirus}}
*'''Rhinovirus treatment (commom cold)'''
:* '''Supportive therapy'''
::* Preferred regimen: An association of antihistamines and decongestants (such as brompheniramine and sustained-release pseudoephedrine) can be used to treat acute cough.
::* Alternative regimen: [[Naproxen]] - no dose established yet, maximum 1g/day<ref name="pmid16428695">{{cite journal| author=Pratter MR| title=Cough and the common cold: ACCP evidence-based clinical practice guidelines. | journal=Chest | year= 2006 | volume= 129 | issue= 1 Suppl | pages= 72S-74S | pmid=16428695 | doi=10.1378/chest.129.1_suppl.72S | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16428695 }} </ref>
:* '''Treatment of diarrhea caused by rotavirus '''
::* Preferred regimen: Suportive therapy. No specific antiviral available.
:::* Rehydration with oral rehydration salts (ORS) solution.
:::* Rehydration with intravenous fluids in case of severe dehydration or shock.
==Clostridium==
{{PBI|Clostridium botulinum}}
*'''1. Antibiotics'''
:* Antibiotics are not recommended in gastrointestinal botulism due to the risk of worsening of neurological symptoms caused by the lysis of the bacteria. For wound botulism antibiotics are indicated with surgical treatment as followed:
::* Preferred regimen: [[Metronidazole]] 500 mg IV q8h
::* Alternative regimen: [[Penicillin G]] 3 million units IV q4h
*'''2. Antitoxin''' <ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:* Preferred regimen: Trivalent antitoxin (A 7,500 IU, B 5,000 IU, and E 5,000 IU) 1 vial diluted 1:10, IV infusion over 30 min
:* Alternative regimen: Equine antitoxin
*'''3. General Therapy'''
:* Preferred regimen: Mechanical ventilation; IV hydration; tube feedings
{{PBI|Clostridium perfringens}}
:* Clostridium perfringens <ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
:*'''Gas gangrene'''
:::* Preferred regimen: [[Penicillin G]] 3-4 million units IV q4h {{and}} ([[Clindamycin]] 900 mg IV q8h {{or}} [[Tetracycline]] 500 mg IV q6h)<ref name="pmid5109333">{{cite journal| author=Altemeier WA, Fullen WD| title=Prevention and treatment of gas gangrene. | journal=JAMA | year= 1971 | volume= 217 | issue= 6 | pages= 806-13 | pmid=5109333 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5109333 }} </ref>
{{PBI|Clostridium tetani}}
:*1. '''General measures''' <ref name=World Health Organization>{{cite web | title = Current recommendations for treatment of tetanus during humanitarian emergencies| url =http://www.who.int/diseasecontrol_emergencies/publications/who_hse_gar_dce_2010.2/en/ }}</ref>
::* Preferred regimen: Patients should be placed in a quiet shaded area and protected from tactile and auditory stimulation as much as possible; All wounds should be cleaned and debrided as indicated
:*2. '''Immunotherapy'''
::* Preferred regimen: Human TIG 500 units IV/IM as soon as possible {{and}} Age-appropriate TT-containing vaccine, 0.5 cc IM at a separate site
::* Note: patients without a history of primary TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later
::* Preferred regimen: [[Diazepam]] 5 mg IV {{or}} [[Lorazepam]] 2 mg IV titrating to achieve spasm control without excessive sedation and hypoventilation
::* Alternative regimen (1): [[Magnesium]] sulphate 5 g (or 75mg/kg) IV loading dose, then 2–3 g per hour until spasm control is achieved {{withorwithout}} [[Benzodiazepines]]
::* Note: Monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased
::* Alternative regimen (3): [[Barbiturates]] 100–150 mg q1-4h by any route
::* Alternative regimen (4): [[Chlorpromazine]] 50–150 mg IM q4–8h
::*Pediatric regimen: [[Lorazepam]] 0.1–0.2 mg/kg IV q2–6h, titrating upward as needed; [[Barbiturates]] 6–10 mg/kg in children by any route; [[Chlorpromazine]] 4–12 mg IM every q4–8h
::* Note: As for [[Benzodiazepines]], large amounts may be required (up to 600 mg/day); Oral preparations could be used but must be accompanied by careful monitoring to avoid respiratory depression or arrest
::* Note: Drugs used to control spasm and provide sedation can result in respiratory depression. If spasm, including laryngeal spasm, is impeding or threatening adequate ventilation, mechanical ventilation is recommended when possible. Early tracheostomy is preferred as endotracheal tubes can provoke spasm and exacerbate airway compromise.
{{PBI|Clostridium difficile}}
:* 1. '''Pseudomembranous colitis - mild to moderate'''<ref name="pmid25626036">{{cite journal| author=Bagdasarian N, Rao K, Malani PN| title=Diagnosis and treatment of Clostridium difficile in adults: a systematic review. | journal=JAMA | year= 2015 | volume= 313 | issue= 4 | pages= 398-408 | pmid=25626036 | doi=10.1001/jama.2014.17103 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25626036 }} </ref>
::* Preferred regimen:[[Metronidazole]] 500 mg PO tid for 10-14 days
::* Alternative regimen: [[Vancomycin]] 125 mg PO qid for 10-14 days
::* Note: If significant risk of recurrence: [[Vancomycin]] 125 mg PO qid for 10-14 days {{or}} [[Fidaxomicin]] 200 mg PO bid for 10 days
:* 2. '''Pseudomembranous colitis - severe'''<ref name="pmid25626036">{{cite journal| author=Bagdasarian N, Rao K, Malani PN| title=Diagnosis and treatment of Clostridium difficile in adults: a systematic review. | journal=JAMA | year= 2015 | volume= 313 | issue= 4 | pages= 398-408 | pmid=25626036 | doi=10.1001/jama.2014.17103 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25626036 }} </ref>
::* Preferred regimen: [[Vancomycin]] 125 mg PO qid for 10-14 days
::* Note: If significant risk of recurrence: [[Vancomycin]] 125 mg PO qid for 10-14 days {{or}} [[Fidaxomicin]] 200 mg PO bid for 10 days
:*3 . '''Pseudomembranous colitis - severe, complicated'''<ref name="pmid25626036">{{cite journal| author=Bagdasarian N, Rao K, Malani PN| title=Diagnosis and treatment of Clostridium difficile in adults: a systematic review. | journal=JAMA | year= 2015 | volume= 313 | issue= 4 | pages= 398-408 | pmid=25626036 | doi=10.1001/jama.2014.17103 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25626036 }} </ref>
::* Preferred regimen: [[Vancomycin]] 125-500 mg PO qid for 10-14 days {{and}} [[Vancomycin]] 500 mg diluted in 500 ml of saline as enema per rectum q6h {{and}} [[Metronidazole]] 500 mg IV q8h
::* Note: Consider urgent surgical consult
:* 4. '''Recurrent pseudomembranous colitis'''<ref name="pmid25626036">{{cite journal| author=Bagdasarian N, Rao K, Malani PN| title=Diagnosis and treatment of Clostridium difficile in adults: a systematic review. | journal=JAMA | year= 2015 | volume= 313 | issue= 4 | pages= 398-408 | pmid=25626036 | doi=10.1001/jama.2014.17103 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25626036 }} </ref>
::*First recurrence treatment
:::* Preferred regimen: same as first episode or [Fidaxomicin]] 200 mg PO bid for 10 days
::*Second or more recurrence treatment
:::* Preferred regimen: [[Vancomycin]] 125 mg PO qid for 14 days {{then}} [[Vancomycin]] 125 mg PO tid for 7 days {{then}} [[Vancomycin]] 125 mg PO bid for 7 days {{then}} [[Vancomycin]] 125 mg PO qd for 7 days {{then}} [[Vancomycin]] 125 mg PO q48h for 7 days {{then}} [[Vancomycin]] 125 mg PO q72h for 7 days {{or}} [[Fidaxomicin]] 200 mg PO bid for 10 days
:::* Note: Consider expert consult for fecal microbiota transplantation
==Plasmodium==
{{PBI|Plasmodium}}
* 1. '''Plasmodium falciparum'''<ref>{{cite web | title = Guidelines for the treatment of malaria. Third edition April 2015 | url = http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf?ua=1&ua=1 }}</ref>
:* 1.1 '''Treatment of uncomplicated P. falciparum malaria'''
::* 1.1.1 Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)
:::* Preferred regimen (1): [[Artemether]] 5–24 mg/kg/day PO bid {{and}} [[Lumefantrine]] 29–144 mg/kg/day PO bid for 3 days.
:::* Note: The first two doses should, ideally, be given 8 h apart.
::::* Dosage regimen based on Body weight (kg)
::::* Body weight (kg)-5 to < 15- [[Artemether]] 20 mg PO bid {{and}} [[Lumefantrine]] 120 mg PO bid for 3 days
::::* Body weight (kg)-15 to < 25- [[Artemether]] 40 mg PO bid {{and}} [[Lumefantrine]] 240 mg PO bid for 3 days
::::* Body weight (kg)-25 to < 35- [[Artemether]] 60 mg PO bid {{and}} [[Lumefantrine]] 360 mg PO bid for 3 days
::::* Body weight (kg) ≥ 35- [[Artemether]] 80 mg PO bid {{and}} [[Lumefantrine]] 480 mg PO bid for 3 days
:::* Preferred regimen (2): [[Artesunate]] 2–10 mg/kg/day PO qd {{and}} [[Amodiaquine]] 7.5–15 mg/kg/day PO qd for 3 days
:::* Note: A total therapeutic dose range of 6–30 mg/kg/day artesunate and 22.5–45 mg/kg/day per dose amodiaquine is recommended.
::::* Dosage regimen based on Body weight (kg)
::::* Body weight (kg)-4.5 to < 9- [[Artesunate]] 25 mg PO qd {{and}} [[Amodiaquine]] 67.5 mg PO qd for 3 days
::::* Body weight (kg)-9 to < 18 - [[Artesunate]] 50 mg PO qd {{and}} [[Amodiaquine]] 135 mg PO qd for 3 days
::::* Body weight (kg)-18 to < 36- [[Artesunate]] 100 mg PO qd {{and}} [[Amodiaquine]] 270 mg PO qd for 3 days
::::* Body weight (kg) ≥ 36 - [[Artesunate]] 200 mg PO qd {{and}} [[Amodiaquine]] 540 mg PO qd for 3 days
:::* Preferred regimen (3): [[Artesunate]] 2–10 mg/kg/day PO qd {{and}} [[Mefloquine]] 2–10 mg/kg/day PO qd for 3 days
::::* Dosage regimen based on Body weight (kg)
::::* Body weight (kg)-5 to < 9- [[Artesunate]] 25 mg PO qd {{and}} [[Mefloquine]] 55 mg PO qd for 3 days
::::* Body weight (kg)-9to < 18- [[Artesunate]] 50 mg PO qd {{and}} [[Mefloquine]] 110 mg PO qd for 3 days
::::* Body weight (kg)-18 to < 36- [[Artesunate]] 100 mg PO qd {{and}} [[Mefloquine]] 220 mg PO qd for 3 days
::::* Body weight (kg)- ≥ 36 - [[Artesunate]] 200 mg PO qd {{and}} [[Mefloquine]] 440 mg PO qd for 3 days
:::* Preferred regimen (4): [[Artesunate]] 2–10 mg/kg/day PO qd for 3 days {{and}} [[Sulfadoxine]]-[[Pyrimethamine]] 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1
::::* Dosage regimen based on Body weight (kg)
::::* Body weight (kg)-5 to < 10- [[Artesunate]] 25 mg PO qd for 3 days {{and}} [[Sulfadoxine]]-[[Pyrimethamine]] 250/12 mg PO given as a single dose on day 1
::::* Body weight (kg)-10 to < 25- [[Artesunate]] 50 mg PO qd for 3 days {{and}} [[Sulfadoxine]]-[[Pyrimethamine]] 500/25 mg PO given as a single dose on day 1
::::* Body weight (kg)-25 to < 50- [[Artesunate]] 100 mg PO qd for 3 days {{and}} [[Sulfadoxine]]-[[Pyrimethamine]] 1000/50 mg PO given as a single dose on day 1
::::* Body weight (kg)- ≥50- [[Artesunate]] 200 mg PO qd for 3 days {{and}} [[Sulfadoxine]]-[[Pyrimethamine]] 1500/75 mg PO given as a single dose on day 1
:::* Preferred regimen (5): [[Dihydroartemisinin]] 2–10 mg/kg/day PO qd {{and}} [[Piperaquine]]16–27 mg/kg/day PO qd for 3 days
::::* Dosage regimen based on Body weight (kg)
::::* Body weight (kg)-5 to < 8- [[Dihydroartemisinin]] 20 mg PO qd {{and}} [[Piperaquine]] 160 mg PO qd for 3 days
::::* Body weight (kg)-8 to < 11- [[Dihydroartemisinin]] 30 mg PO qd {{and}} [[Piperaquine]] 240 mg PO qd for 3 days
::::* Body weight (kg)-11 to < 17 - [[Dihydroartemisinin]] 40 mg PO qd {{and}} [[Piperaquine]] 320 mg PO qd for 3 days
::::* Body weight (kg)-17 to < 25- [[Dihydroartemisinin]] 60 mg PO qd {{and}} [[Piperaquine]] 480 mg PO qd for 3 days
::::* Body weight (kg)-25 to < 36- [[Dihydroartemisinin]] 80 mg PO qd {{and}} [[Piperaquine]] 640 mg PO qd for 3 days
::::* Body weight (kg)-36 to < 60- [[Dihydroartemisinin]] 120 mg PO qd {{and}} [[Piperaquine]] 960 mg PO qd for 3 days
::::* Body weight (kg)-60 < 80 - [[Dihydroartemisinin]] 160 mg PO qd {{and}} [[Piperaquine]] 1280 mg PO qd for 3 days
::::* Body weight (kg)- >80- Dose of [[Dihydroartemisinin]] 200 mg PO qd {{and}} [[Piperaquine]] 1600 mg PO qd for 3 days
::* 1.1.2 '''Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) '''
::::* Preferred regimen: Single dose of 0.25 mg/kg [[Primaquine]] with ACT
:* 1.2 '''Recurrent Falciparum Malaria'''
::* 1.2.1 '''Failure within 28 days '''
:::* Note:The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens (with artesunate or quinine both of which should be co-administered with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.
::* 1.2.2 '''Failure after 28 days'''
:::* Note: all presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.
:* 1.3 '''Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) '''
::* Note: Single dose of 0.25 mg/kg bw [[Primaquine]] with ACT
:* 1.4 '''Treating uncomplicated P. falciparum malaria in special risk groups'''
::* 1.4.1 '''Pregnancy '''
:::* First trimester of pregnancy : [[Quinine]] {{and}} [[Clindamycin]] 10mg/kg/day PO bid for 7 days
:::* Second and third trimesters : [[Mefloquine]] is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
:::* Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
:::* Note (2): Primaquine and tetracyclines should not be used in pregnancy.
::*1.4.2 '''Infants less than 5kg body weight''' : with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
::*1.4.3 '''Patients co-infected with HIV''': should avoid [[Artesunate]] + SP if they are also receiving [[Co-trimoxazole]], and avoid [[Artesunate]] {{and}} [[Amodiaquine]] if they are also receiving efavirenz or zidovudine.
::*1.4.4 '''Large and Obese adults''': For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
::*1.4.5 '''Patients co-infected with TB''': Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate
::*1.4.6 '''Non-immune travellers''' : Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
::*1.4.7 '''Uncomplicated hyperparasitaemia''': People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.
* 2. '''Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae or P. knowlesi'''
:* 2.1 '''Blood Stage infection'''
::* 2.1.1. '''Uncomplicated malaria caused by P. vivax'''
:::* 2.1.1.1 '''In areas with chloroquine-sensitive P. vivax'''
::::* Preferred regimen: [[Chloroquine]] total dose of 25 mg/kg PO. [[Chloroquine]] is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day.
:::* 2.1.1.2 '''In areas with chloroquine-resistant P. vivax'''
::::* Note: ACTs containing [[Piperaquine]], [[Mefloquine]] {{or}} [[Lumefantrine]] are the recommended treatment, although [[Artesunate]] + [[Amodiaquine]] may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, [[Dihydroartemisinin]] + [[Piperaquine]] provided a longer prophylactic effect than ACTs with shorter half-lives ([[Artemether]] + [[Lumefantrine]], [[Artesunate]] + [[Amodiaquine]]), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.
::* 2.1.2 '''Uncomplicated malaria caused by P. ovale, P. malariae or P. knowlesi malaria'''
:::* Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to chloroquine. In only one study, conducted in Indonesia, was resistance to chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or [[Chloroquine]], as for vivax malaria.
::* 2.1.3 '''Mixed malaria infections '''
:::* Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.
:* 2.2 '''Liver stages (hypnozoites) of P. vivax and P. ovale'''
::* Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.]
::* 2.2.1 '''Primaquine for preventive relapse'''
:::* Preferred regimen: [[Primaquine]] 0.25–0.5 mg/kg/day PO qd for 14 days
::* 2.2.2 '''Primaquine and glucose-6-phosphate dehydrogenase deficiency'''
:::* Preferred regimen: [[Primaquine]] 0.75 mg base/kg/day PO once a week for 8 weeks.
:::* Note: The decision to give or withhold [[Primaquine]] should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.
::*2.2.3 '''Prevention of relapse in pregnant or lacating women and infants'''
:::* Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient).
*3. '''Treatment of severe malaria'''
:* 3.1 Treatment of severe falciparum infection with Artesunate
::* 3.1.1 Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women):-
:::* Preferred regimen: [[Artesunate]] IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose [[Primaquine]] in areas of low transmission).
::* 3.1.2 Young children weighing < 20 kg
:::* Preferred regimen: [[Artesunate]] 3 mg/kg per dose IV/IM q24h
:::* Alternatives regimen: use [[Artemether]] in preference to quinine for treating children and adults with severe malaria
:* 3.2.'''Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)'''
::*3.2.1 Adults and children
:::* Preferred regimen: [[Artesunate]] IM qd
:::* Alternative regimen: [[Artemether]] IM {{or}} [[Quinine]] IM
::*3.2.2 Children < 6 years
:::* Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of [[Artesunate]], and refer immediately to an appropriate facility for further care.
:::* Note: Do not use rectal artesunate in older children and adults.
:*3.3 '''Pregancy'''
::* Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.
:*3.4 '''Treatment of severe P. Vivax infection'''
::* Note: parenteral artesunate, treatment can be completed with a full treatment course of oral ACT or chloroquine (in countries where chloroquine is the treatment of choice). A full course of radical treatment with primaquine should be given after recovery.
:*3.5 '''Additional aspects of management in severe malaria'''
::* '''Fluid therapy''': It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
::* '''Blood Transfusion ''':In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin, 7 g/100 mL) is recommended.
::* '''Exchange blood transfusion''': Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.
==Bartonella==
{{PBI|Bartonella}}<ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
:*1. Bartonella quintana
::*'''1.1 Acute or chronic infections without endocarditis'''
:::* Preferred regimen: [[Doxycycline]] 200 mg PO qd or 100 mg bid for 4 weeks {{plus}} [[Gentamicin]] 3 mg/kg IV q24h for the first 2 weeks<ref name="pmid12821469">{{cite journal| author=Foucault C, Raoult D, Brouqui P| title=Randomized open trial of gentamicin and doxycycline for eradication of Bartonella quintana from blood in patients with chronic bacteremia. | journal=Antimicrob Agents Chemother | year= 2003 | volume= 47 | issue= 7 | pages= 2204-7 | pmid=12821469 | doi= | pmc=PMC161867 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12821469 }} </ref>
::*'''1.2 Endocarditis'''
:::* Preferred regimen: [[Gentamicin]] 3 mg/kg/day IV q8h for 14 days {{and}} [[Ceftriaxone]] 2 g/day IV for 6 weeks {{withorwithout}} [[Doxycycline]] 100 mg PO bid for 6 weeks<ref name="pmid15956145">{{cite journal| author=Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME et al.| title=Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. | journal=Circulation | year= 2005 | volume= 111 | issue= 23 | pages= e394-434 | pmid=15956145 | doi=10.1161/CIRCULATIONAHA.105.165564 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15956145 }} </ref>
:*2. Bartonella elizabethae
::*'''2.2 Endocarditis'''
:::* Preferred regimen: [[Gentamicin]] 3 mg/kg/day IV q8h for 14 days {{and}} [[Ceftriaxone]] 2 g/day IV for 6 weeks {{withorwithout}} [[Doxycycline]] 100 mg PO bid for 6 weeks<ref name="pmid15956145">{{cite journal| author=Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME et al.| title=Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. | journal=Circulation | year= 2005 | volume= 111 | issue= 23 | pages= e394-434 | pmid=15956145 | doi=10.1161/CIRCULATIONAHA.105.165564 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15956145 }} </ref>
:*3. Bartonella bacilliformis
::*'''3.1 Oroya fever'''
:::* Preferred regimen: [[Ciprofloxacin]] 500 mg PO bid for 14 days
:::* Note: if severe disease, associate [[Ceftriaxone]] 1 g IV q24h for 14 days
::*'''3.2 Verruga peruana'''<ref>Bradley JS, Jackson MA, Committee on Infectious Diseases, American Academy of Pediatrics. The use of systemic and topical fluoroquinolones. Pediatrics 2011; 128:e1034.</ref>
:::* Preferred regimen: [[Azithromycin]] 500 mg PO qd for 7 days
:::* Alternative regimen (1): [[Rifampin]] 600 mg PO qd for 14-21 days
:::* Alternative regimen (2): [[Ciprofloxacin]] 500 mg bid for 7-10 days
:*4. Bartonella hansealae
::*4.1 '''Cat scratch disease'''
:::*If extensive adenopathy<ref name="pmid15155180">{{cite journal| author=Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D| title=Recommendations for treatment of human infections caused by Bartonella species. | journal=Antimicrob Agents Chemother | year= 2004 | volume= 48 | issue= 6 | pages= 1921-33 | pmid=15155180 | doi=10.1128/AAC.48.6.1921-1933.2004 | pmc=PMC415619 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15155180 }} </ref>
::::* Preferred regimen: [[Azithromycin]] 500 mg PO at day 1 {{then}} 250 mg PO for 4 days for patients weighting less than 45kg, 1 g PO at day 1 {{then}} 500 mg PO for 4 days for patients weighting more than 45 kg
:::* Alternative regimen (1): [[Clarithromycin]] 500 mg PO bid
:::* Alternative regimen (3): [[Ciprofloxacin]] 500 mg PO bid for patients >17 years of age for 7-10 days
:::* Alternative regimen (4): [[Trimethoprim-sulfamethoxazole]] one double strength tablet bid for 7-10 days
:::* Note: Pediatric dose: trimethoprim 8 mg/kg per day, sulfamethoxazole 40 mg/kg per day bid for 7-10 days
::*4.2 '''Endocarditis'''
:::* Preferred regimen: [[Gentamicin]] 3 mg/kg/day IV q8h for 14 days {{and}} [[Ceftriaxone]] 2 g/day IV for 6 weeks {{withorwithout}} [[Doxycycline]] 100 mg PO bid for 6 weeks
::*4.3 '''Retinitis'''
:::* Preferred regimen: [[Doxycycline]] 100 mg bid {{and}} [[Rifampin]] 300 mg bid PO for 4-6 weeks
:::* Preferred regimen (1): [[Erythromycin]] 500 mg PO qid for 4 months at least
:::* Preferred regimen (2): [[Doxycycline]] 100 mg PO bid for 4 months at least
==Blastomycosis==
{{PBI|Blastomycosis}}
*[[Blastomycosis]]<ref name="pmid18462107">{{cite journal| author=Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG et al.| title=Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 12 | pages= 1801-12 | pmid=18462107 | doi=10.1086/588300 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18462107 }} </ref>
:* '''1. Mild to moderate pulmonary blastomycosis'''
::* Preferred regimen: [[Itraconazole]] 200 mg PO qd or bid for 6–12 months
::* Note: Oral [[Itraconazole]], 200 mg tid PO for 3 days and {{then}} 200 mg PO qd or bid for 6–12 months
:* '''2. Moderately severe to severe pulmonary blastomycosis'''
::* Preferred regimen (1): Lipid [[Amphotericin B]] 3–5 mg/kg IV q24h for 1–2 weeks {{and}} [[Itraconazole]] 200 mg PO bid for 6–12 months
::* Preferred regimen (2): [[Amphotericin B]] deoxycholate 0.7–1 mg/kg IV q24h for 1–2 weeks {{and}} [[Itraconazole]] 200 mg PO bid for 6–12 months
::* Note: Oral [[Itraconazole]], 200 mg tid PO for 3 days {{then}} 200 mg PO bid, for a total of 6–12 months
:* '''3. Mild to moderate disseminated blastomycosis'''
::* Preferred regimen: [[Itraconazole]] 200 mg PO qd or bid for 6–12 months
::* Note (1): Treat osteoarticular disease for 12 months
::* Note (2): Oral [[Itraconazole]], 200 mg PO tid for 3 days {{then}} 200 mg PO bid, for 6–12 months
:* '''4. Moderately severe to severe disseminated blastomycosis'''
::* Preferred regimen (1): Lipid [[Amphotericin B]] 3–5 mg/kg IV q24h, for 1–2 weeks {{and}} [[Itraconazole]] 200 mg PO bid for 6–12 months
::* Preferred regimen (2): [[Amphotericin B]] deoxycholate 0.7–1 mg/kg IV q24h, for 1–2 weeks {{and}} [[Itraconazole]] 200 mg PO bid for 6–12 months
::* Note: oral [[Itraconazole]], 200 mg PO tid for 3 days {{then}} 200 mg PO bid, for 6–12 months
:* '''5. CNS disease'''
::* Preferred regimen: Lipid [[Amphotericin B]] 5 mg/kg IV q24h for 4–6 weeks {{and}} an oral azole for at least 1 year
::* Note (1): Step-down therapy can be with [[Fluconazole]], 800 mg/day PO qd or bid {{or}} [[Itraconazole]], 200 mg bid or tid {{or}} voriconazole, 200–400 mg bid.
::* Note (2): Longer treatment may be required for immunosuppressed patients.
:* '''6. Immunosuppressed patients'''
::* Preferred regimen (1): Lipid [[Amphotericin B]] 3–5 mg/kg IV q24h, for 1–2 weeks, {{and}} [[Itraconazole]], 200 mg PO bid for 12 months
::* Preferred regimen (2): [[Amphotericin B]] deoxycholate, 0.7–1 mg/kg IV q24h, for 1–2 weeks, {{and}} [[Itraconazole]], 200 mg PO bid for 12 months
::* Note (1): Oral [[Itraconazole]], 200 mg PO tid for 3 days {{then}} 200 mg PO bid, for 12 months
::* Note (2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.
:* '''7. Pregnant women'''
::* Preferred regimen: Lipid [[Amphotericin B]] 3–5 mg/kg IV q24h
::* Note (1): Azoles should be avoided because of possible teratogenicity
::* Note (2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg IV q24h
:* '''8. Children with mild to moderate disease'''
::* Preferred regimen: [[Itraconazole]] 10 mg/kg PO qd for 6–12 months
::* Note: Maximum dose 400 mg/day
:* '''9. Children with moderately severe to severe disease'''
::* Preferred regimen (1): Amphotericin B deoxycholate 0.7–1 mg/kg IV q24h for 1–2 weeks {{and}} [[Itraconazole]] 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
::* Preferred regimen (2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg IV q24h for 1–2 weeks {{and}} [[Itraconazole]] 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
::* Note: Children tolerate Amphotericin B deoxycholate better than adults do.
:* Preferred regimen: [[Itraconazole]] 200-400 mg PO q24h {{or}} 400 mg pulse therapy once daily for 1 week monthly for 6-12 months
:* Note: Pulse therapy reduces cost but it is questionable if it produces resistance to the drug.
:* Alternative regimen (1): [[Terbinafine]] 500-1000 mg PO qd for 6-12 months
:* Alternative regimen (2): [[Posaconazole]] 800 mg PO qd for 6-12 months
:* Alternative regimen (3): [[5-fluorocytosine]] 100-150 mg/kg/day PO qd for 6-12 months
:* Note: This disease has a low cure ratio and high relapse ratio. Physical treatment is needed to achieve better results:
::*Cryosurgery with liquid nitrogen - most used physical therapy, it's used in localized lesions and it has a very good treatment response, probably achieved by immune mechanisms since fungi are eliminated from lesions as late as 1-2 weeks after the therapy.
::*Thermotherapy - used in conjunction with systemic therapy, was developed by Japanese authors and consists in placing "pocket warmers" in the lesions for 24h/day for some months, as the fungi is sensible to heat.
::*Laser vaporization - studied in Germany as an alternative therapy, reported to successfully treat relapsing lesions.
==Hepatitis C==
{{PBI|Hepatitis C virus}}
'''Chronic Hepatitis C'''
*'''1. Treatment regimens for chronic hepatitis C virus genotype 1'''<ref> {{Cite web | title = INITIAL TREATMENT OF HCV INFECTION
::* Preferred regimen (1): [[Ledipasvir]] 90 mg PO qd {{and}} [[Sofosbuvir]] 400 mg PO qd for 12 weeks
::* Preferred regimen (2): [[Paritaprevir]] 150 mg PO qd {{and}} [[Ritonavir]] 100 mg PO qd {{and}} [[Ombitasvir]] 25 mg PO qd {{and}} Dasabuvir 250 mg PO bid {{and}} weight-based [[Ribavirin]] PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) {{or}} 24 weeks (cirrhosis)
::* Preferred regimen (3): [[Sofosbuvir]] 400 mg PO qd {{and}} [[Simeprevir]] 150 mg PO qd {{withorwithout}} weight-based [[Ribavirin]] PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
::* Note: these regimens are recommended for treatment-naive patients with HCV genotype 1a infection.
:*'''1.2. Treatment regimens for genotype 1b''':
::* Preferred regimen (1): [[Ledipasvir]] 90 mg PO qd {{and}} [[Sofosbuvir]] 400 mg PO qd for 12 weeks
::* Preferred regimen (2): [[Paritaprevir]] PO 150 mg qd {{and}} [[Ritonavir]] 100 mg PO qd {{and}} Ombitasvir 25 mg PO qd {{and}} Dasabuvir 250 mg PO bid for 12 weeks. The addition of weight-based [[Ribavirin]] PO qd (1000 mg [<75kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis
::* Preferred regimen (3): [[Sofosbuvir]] 400 mg PO qd {{and}} [[Simeprevir]] 150 mg PO qd for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
::* Note: these regimens are recommended for treatment-naive patients with HCV genotype 1b infection.
*'''2. Treatment regimens for chronic hepatitis C virus genotype 2'''<ref> {{Cite web | title = INITIAL TREATMENT OF HCV INFECTION
:* Preferred regimen: [[Sofosbuvir]] 400 mg PO qd and weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd for 24 weeks
:* Alternative regimen: [[Sofosbuvir]] 400 mg and weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd {{and}} weekly [[PEG-IFN]] for 12 weeks is an acceptable regimen for IFN-eligible, treatment-naive patients with HCV genotype 3 infection.
:* Note: These regimens are recommended for treatment-naive patients with HCV genotype 3 infection.
*'''4. Treatment regimens for chronic hepatitis C virus genotype 4'''
:* Preferred regimen (1): [[Ledipasvir 90 mg]] PO qd {{and}} [[Sofosbuvir]] 400 mg PO qd for 12 weeks
:* Preferred regimen (2): [[Paritaprevir 150 mg]] PO qd {{and}} [[Ritonavir]] 100 mg PO qd {{and}} Ombitasvir 25 mg PO qd {{and}} weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
:* Preferred regimen (3): [[Sofosbuvir]] 400 mg PO qd {{and}} weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks
:* Alternative regimen (1): [[Sofosbuvir]] 400 mg PO qd {{and}} weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) {{and}} weekly PEG-IFN for 12 weeks
:* Alternative regimen (2): [[Sofosbuvir]] 400 mg PO qd {{and}} [[Simeprevir]] 150 mg PO qd {{withorwithout}} weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
:* Note: These regimens are accpetable for treatment-naive patients with HCV genotype 3 infection.
*'''5. Treatment regimens for chronic hepatitis C virus genotype 5'''<ref> {{Cite web | title = INITIAL TREATMENT OF HCV INFECTION
:* Preferred regimen: [[Sofosbuvir]] 400 mg PO qd {{and}} weight-based [[Ribavirin]] PO qd(1000 mg [<75 kg] to 1200 mg [>75 kg]) {{and}} weekly [[PEG-IFN]] for 12 weeks is recommended for treatment-naive patients with HCV genotype 5 infection.
:* Alternative regimen: Weekly [[PEG-IFN]] {{and}} weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 48 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 5 infection.
*'''6. Treatment regimens for chronic hepatitis C virus genotype 6'''<ref> {{Cite web | title = INITIAL TREATMENT OF HCV INFECTION
:* Preferred regimen: [[Ledipasvir]] 90 mg PO qd {{and}} [[Sofosbuvir]] PO qd 400 mg for 12 weeks is recommended for treatment-naive patients with HCV genotype 6 infection.
:* Alternative regimen: [[Sofosbuvir]] 400 mg PO qd {{and}} weight-based [[Ribavirin]] PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) {{and}} weekly PEG-IFN for 12 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 6 infection.
==Toxocariasis==
{{PBI|Toxocariasis}}
:*'''1.1.Visceral toxocariasis'''<ref>{{Cite web | title = Parasites - Toxocariasis| url = http://www.cdc.gov/parasites/toxocariasis/health_professionals/index.html}}</ref>
::* Preferred regimen: [[Albendazole]] 400 mg PO bid for five days (both adult and pediatric dosage)
::* Alternative regimen: [[Mebendazole]] 100-200 mg PO bid for five days (both adult and pediatric dosage)
::* Note: Treatment is indicated for moderate-severe cases. Patients with mild symptoms of toxocariasis may not require anthelminthic therapy as symptoms are limited.
:*'''1.2.Ocular toxocariasis'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
::* Preferred regimen: [[Prednisone]] 0.5-1 mg/kg/day PO q24h {{and}} [[Albendazole]] 400 mg PO bid for 2 to 4 weeks (pediatric dose: 400 mg PO qd)<ref name="pmid11436948">{{cite journal| author=Barisani-Asenbauer T, Maca SM, Hauff W, Kaminski SL, Domanovits H, Theyer I et al.| title=Treatment of ocular toxocariasis with albendazole. | journal=J Ocul Pharmacol Ther | year= 2001 | volume= 17 | issue= 3 | pages= 287-94 | pmid=11436948 | doi=10.1089/108076801750295317 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11436948 }} </ref>
:::* Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 48 weeks
:::* Preferred regimen (2): [[Tenofovir]] (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
::::*If creatinine clearance 30–49 give 300 mg q48 hrs
::::*If creatinine clearance 10–29 give 300 mg q72-96 hrs
::::*If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
::::*If creatinine clearance <10 without dialysis there is no recommendation
::::* Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
:::* Preferred regimen (3): [[Entecavir]] (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior [[Lamivudine]] treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
::::*If creatinine clearance 30–49 give 0.25 mg PO qd {{or}} 0.5 mg PO q48 hr for patients with no prior [[Lamivudine]] treatment, and 0.5 mg PO qd {{or}} 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
::::*If creatinine clearance 10–29 give 0.15 mg PO qd {{or}} 0.5 mg PO q 72 hr for patients with no prior [[Lamivudine]] treatment, and 0.3 mg PO qd {{or}} 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
::::*If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd {{or}} 0.5 mg PO q7 days for patients with no prior [[Lamivudine]] treatment, and 0.1 mg PO qd {{or}} 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
::::* Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
:::* Alternative regimen (1): [[Interferon alpha]] (IFNα) 5 MU daily or 10 MU thrice weekly SC for 16 weeks
:::* Alternative regimen (2): [[Lamivudine]] (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 100 mg PO qd
::::*If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
::::*If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
::::*If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
::::*If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
::::*The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
::::* Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
:::* Alternative regimen (3): [[Adefovir]] (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 10 mg PO daily
::::*If creatinine clearance 30–49 give 10 mg PO every other day
::::*If creatinine clearance 10–19 10 mg PO every third day
::::*If hemodialysis patients give 10 mg PO every week following dialysis
::::* Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
:::* Alternative regimen (4): [[Telbivudine]] (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 600 mg PO once daily
::::*If creatinine clearance 30–49 600 give mg PO once every 48 hours
::::*If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
::::*If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
:::* Note (1): duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
:::* Note (2): Observe for 3-6 months and treat if no spontaneous HBeAg loss.
:::* Note (3): Consider liver biopsy prior to treatment if compensated.
:::* Note (4): Immediate treatment if icteric or clinical decompensation.
:::* Note (5): [[Interferon alpha]] (IFNα)/ pegylated interferon-alpha (peg-IFNα), [[Lamivudine]] (LAM), [[Adefovir]] (ADV), [[Entecavir]] (ETV), tenofovir disoproxil fumarate (TDF) or [[telbivudine]] (LdT) may be used as initial therapy.
:::* Note (6): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
:::* Note (7): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
:::* Note (8): End-point of treatment – Seroconversion from HBeAg to anti-HBe.
:::* Note (9): [[Interferon alpha]] (IFNα) non-responders / contraindications to IFNα change to [[Tenofovir]] (TDF)/[[Entecavir]] (ETV).
::*'''1.3. Children with elevated ALT greater than 2 times normal'''<ref name="pmid19714720">{{cite journal| author=Lok AS, McMahon BJ| title=Chronic hepatitis B: update 2009. | journal=Hepatology | year= 2009 | volume= 50 | issue= 3 | pages= 661-2 | pmid=19714720 | doi=10.1002/hep.23190 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19714720 }} </ref>
:::* Preferred regimen(1): [[Interferon alpha]] (IFNα) 6 MU/m2 SC thrice weekly with a maximum of 10 MU
:::* Preferred regimen(2): [[Lamivudine]] (LAM) 3 mg/kg/d PO with a maximum of 100 mg/d.
::*'''2.1. HBV DNA >2,000 IU/mL and elevated ALT >2 times normal'''
:::* Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 1 year
:::* Preferred regimen (2): [[Tenofovir]] (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
::::*If creatinine clearance 30–49 give 300 mg q48 hrs
::::*If creatinine clearance 10–29 give 300 mg q72-96 hrs
::::*If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
::::*If creatinine clearance <10 without dialysis there is no recommendation
::::* Note: duration of treatment is more than 1 year
:::* Preferred regimen (3): [[Entecavir]] (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior [[Lamivudine]] treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine
::::*If creatinine clearance 30–49 give 0.25 mg PO qd {{or}} 0.5 mg PO q48 hr for patients with no prior [[Lamivudine]] treatment, and 0.5 mg PO qd {{or}} 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine
::::*If creatinine clearance 10–29 give 0.15 mg PO qd {{or}} 0.5 mg PO q 72 hr for patients with no prior [[Lamivudine]] treatment, and 0.3 mg PO qd {{or}} 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine
::::*If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd {{or}} 0.5 mg PO q7 days for patients with no prior [[Lamivudine]] treatment, and 0.1 mg PO qd {{or}} 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
::::* Note: duration of treatment is more than 1 year
:::* Alternative regimen (1): [[Interferon alpha]] (IFNα) 5 MU daily or 10 MU thrice weekly SC for 1 year
:::* Alternative regimen (2): [[Lamivudine]] (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 100 mg PO qd
::::*If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
::::*If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
::::*If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
::::*If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
::::*The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
::::* Note: duration of treatment is more than 1 year
:::* Alternative regimen (3): [[Adefovir]] (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 10 mg PO daily
::::*If creatinine clearance 30–49 give 10 mg PO every other day
::::*If creatinine clearance 10–19 10 mg PO every third day
::::*If hemodialysis patients give 10 mg PO every week following dialysis
::::* Note: duration of treatment is more than 1 year
:::* Alternative regimen (4): [[Telbivudine]] (LdT)Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 600 mg PO once daily
::::*If creatinine clearance 30–49 600 give mg PO once every 48 hours
::::*If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
::::*If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
:::* Note (1): duration of treatment is more than 1 year
:::* Note (2): [[Interferon alpha]] (IFNα)/ pegylated interferon-alpha (peg-IFNα), [[Lamivudine]] (LAM), [[Adefovir]] (ADV), [[Entecavir]] (ETV), tenofovir disoproxil fumarate (TDF) or [[telbivudine]] (LdT) may be used as initial therapy.
:::* Note (3): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
:::* Note (4): [[Lamivudine]] (LAM) and [[Telbivudine]] (LdT) not preferred due to high rate of drug resistance.
:::* Note (5): End-point of treatment – not defined
:::* Note (6): [[Interferon alpha]] (IFNα) non-responders / contraindications to IFNα change to [[Tenofovir]] (TDF)/[[Entecavir]] (ETV).
::*'''5.1. Compensated Cirrhosis and HBV DNA >2,000'''
:::* Preferred regimen (1): [[Entecavir]] (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior [[Lamivudine]] treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
::::*If creatinine clearance 30–49 give 0.25 mg PO qd {{or}} 0.5 mg PO q48 hr for patients with no prior [[Lamivudine]] treatment, and 0.5 mg PO qd {{or}} 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
::::*If creatinine clearance 10–29 give 0.15 mg PO qd {{or}} 0.5 mg PO q 72 hr for patients with no prior [[Lamivudine]] treatment, and 0.3 mg PO qd {{or}} 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
::::*If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd {{or}} 0.5 mg PO q7 days for patients with no prior [[Lamivudine]] treatment, and 0.1 mg PO qd {{or}} 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
:::* Preferred regimen (2): [[Tenofovir]] (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
::::*If creatinine clearance 30–49 give 300 mg q48 hrs
::::*If creatinine clearance 10–29 give 300 mg q72-96 hrs
::::*If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
::::*If creatinine clearance <10 without dialysis there is no recommendation
:::* Alternative regimen (1): [[Lamivudine]] (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 100 mg PO qd
::::*If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
::::*If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
::::*If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
::::*If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
::::*The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
:::* Alternative regimen (2): [[Adefovir]] (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 10 mg PO daily
::::*If creatinine clearance 30–49 give 10 mg PO every other day
::::*If creatinine clearance 10–19 give 10 mg PO every third day
::::*If hemodialysis patients give 10 mg PO every week following dialysis
:::* Alternative regimen (3): [[Telbivudine]] (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 600 mg PO once daily
::::*If creatinine clearance 30–49 600 give mg PO once every 48 hours
::::*If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
::::*If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
:::* Note (1): LAM and LdT not preferred due to high rate of drug resistance.
:::* Note (2): ADV not preferred due to weak antiviral activity and high risk of resistance after 1st year.
:::* Note (3): These patients should receive long-term treatment. However, treatment may be stopped in HBeAg-positive patients if they have confirmed HBeAg seroconversion and have completed at least 6 months of consolidation therapy and in HBeAg-negative patients if they have confirmed HBsAg clearance.
::*'''5.2. Compensated Cirrhosis and HBV DNA <2,000'''
:::*Consider treatment if ALT elevated.
::*'''5.3. Decompensated Cirrhosis'''
:::* Preferred regimen (1): [[Tenofovir]] (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
::::*If creatinine clearance 30–49 give 300 mg q48 hrs
::::*If creatinine clearance 10–29 give 300 mg q72-96 hrs
::::*If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
::::*If creatinine clearance <10 without dialysis there is no recommendation
:::* Preferred regimen (2): [[Entecavir]] (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
::::*If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior [[Lamivudine]] treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
::::*If creatinine clearance 30–49 give 0.25 mg PO qd {{or}} 0.5 mg PO q48 hr for patients with no prior [[Lamivudine]] treatment, and 0.5 mg PO qd {{or}} 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
::::*If creatinine clearance 10–29 give 0.15 mg PO qd {{or}} 0.5 mg PO q 72 hr for patients with no prior [[Lamivudine]] treatment, and 0.3 mg PO qd {{or}} 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
::::*If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd {{or}} 0.5 mg PO q7 days for patients with no prior [[Lamivudine]] treatment, and 0.1 mg PO qd {{or}} 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
::* Preferred regimen: [[Praziquantel]] 40 mg/kg per day PO in qd or bid for one day
::* Alternative regimen (1): [[Oxamniquine]] 20 mg/kg PO single dose<ref>National Center for Biotechnology Information. PubChem Compound Database; CID=4612, https://pubchem.ncbi.nlm.nih.gov/compound/4612 (accessed July 16, 2015).</ref><ref>BINA, J. C. and PRATA, A.. Tratamento da esquistossomose com oxamniquine (xarope) em crianças. Rev. Soc. Bras. Med. Trop.[online]. 1975, vol.9, n.4 [cited 2015-07-16], pp. 175-178 . Available from: <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86821975000400002&lng=en&nrm=iso>. ISSN 0037-8682. http://dx.doi.org/10.1590/S0037-86821975000400002.</ref>
::* Alternative regimen (2): [[Artemisinin]] no dose is established yet<ref name="pmid24698483">{{cite journal| author=Colley DG, Bustinduy AL, Secor WE, King CH| title=Human schistosomiasis. | journal=Lancet | year= 2014 | volume= 383 | issue= 9936 | pages= 2253-64 | pmid=24698483 | doi=10.1016/S0140-6736(13)61949-2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24698483 }} </ref>
::* Alternative regimen (3): [[Mefloquine]] 250 mg PO single dose
::* Note: There is no benefit in associating the alternative therapies to Praziquantel.
::* Note: Praziquantel is not effective against larval/egg stages of the disease.<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref>
::* Note: Praziquantel should be used after 4-6 weeks of exposure, because it cannot kill the larvae stages of the Schistosoma. Praziquantel should be used after acute schistosomiasis syndrome symptoms have resolved always together with corticosteroids, only when ova are detected in stool or urine samples.<ref name="pmid19292640">{{cite journal| author=Jauréguiberry S, Paris L, Caumes E| title=Difficulties in the diagnosis and treatment of acute schistosomiasis. | journal=Clin Infect Dis | year= 2009 | volume= 48 | issue= 8 | pages= 1163-4; author reply 1164-5 | pmid=19292640 | doi=10.1086/597497 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19292640 }} </ref>
:*'''4. Neuroschistosomiasis'''
::* Preferred regimen: prednisone 1-2 mg/kg
::* Note: Praziquantel should only be introduced after a few days of the initiation of corticosteroid therapy, due to the risk of increasing the inflammatory response.
==Clonorchis sinensis==
{{PBI|Clonorchis sinensis}}
:* Preferred regimen: [[Praziquantel]] 75 mg/kg/day PO tid for 2 days<ref>{{Cite web | title =Clonorchis | url = http://www.cdc.gov/parasites/clonorchis/health_professionals/index.html}}</ref>
:* Alternative regimen (1): [[Albendazole]] 10 mg/kg/day PO qd for 7 days<ref>{{Cite web | title =Clonorchis | url = http://www.cdc.gov/parasites/clonorchis/health_professionals/index.html}}</ref>
:* Alternative regimen (2): [[Tribendimidine]] 400 mg PO single dose<ref name="pmid23223597">{{cite journal| author=Qian MB, Yap P, Yang YC, Liang H, Jiang ZH, Li W et al.| title=Efficacy and safety of tribendimidine against Clonorchis sinensis. | journal=Clin Infect Dis | year= 2013 | volume= 56 | issue= 7 | pages= e76-82 | pmid=23223597 | doi=10.1093/cid/cis1011 | pmc=PMC3588115 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23223597 }} </ref>
:* Note: This regimen is still under investigation, but it appears to be as effective as [[Praziquantel]].
:* Note: Urgent biliary decompression might be required for patients with acute cholangitis.
==Dicrocoelium dendriticum==
{{PBI|Dicrocoelium dendriticum}}
:* Preferred regimen: [[Praziquantel]] 25 mg/kg PO tid for 2 days<ref>{{Cite web | title =Dicrocoeliasis| url =http://www.cdc.gov/dpdx/dicrocoeliasis/tx.html }}</ref>
::* Note: [[Praziquantel]] is not approved for treatment of children less than 4 years old<ref>{{Cite web | title =Dicrocoeliasis| url =http://www.cdc.gov/dpdx/dicrocoeliasis/tx.html }}</ref>
:* Alternative regimen (1): [[Myrrh]] (commiphora molmol) 12 mg/kg/day PO for 6 days<ref name="pmid17418062">{{cite journal| author=Rana SS, Bhasin DK, Nanda M, Singh K| title=Parasitic infestations of the biliary tract. | journal=Curr Gastroenterol Rep | year= 2007 | volume= 9 | issue= 2 | pages= 156-64 | pmid=17418062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17418062 }} </ref>
:* Alternative regimen (2): [[Triclabendazole]] 10 mg/kg PO single dose<ref name="pmid17418062">{{cite journal| author=Rana SS, Bhasin DK, Nanda M, Singh K| title=Parasitic infestations of the biliary tract. | journal=Curr Gastroenterol Rep | year= 2007 | volume= 9 | issue= 2 | pages= 156-64 | pmid=17418062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17418062 }} </ref>
==Fasciola hepatica==
{{PBI|Fasciola hepatica}}
:* Preferred regimen: [[Triclabendazole]] 10 mg/kg PO one dose<ref>{{Cite web | title =Parasites - Fascioliasis| url = http://www.cdc.gov/parasites/fasciola/health_professionals/}}</ref>
:* Note: Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy.
:* Alternative regimen: [[Nitazoxanide]] 500 mg PO bid for 7 days
==Paragonimus westermani==
{{PBI|Paragonimus westermani}}
:* Preferred regimen (1): [[Praziquantel]] 25 mg/kg PO tid for 3 days<ref>{{Cite web | title =Parasites - Paragonimiasis| url =http://www.cdc.gov/parasites/paragonimus/health_professionals/index.html }}</ref>
:* Preferred regimen (2): [[Triclabendazole]] 10 mg/kg PO qd or bid
:* Alternative regimen (1): [[Bithinol]] 30-50 mg/kg PO on alternate days for 10-15 doses
:* Alternative regimen (2): [[Niclosamide]] 2 mg/kg PO single dose
==Gnasthostoma spinigerum==
{{PBI|Gnathostoma spinigerum}}
:*'''Eosinophilic Meningitis'''
:** Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.<ref name="pmid19123863">{{cite journal| author=Ramirez-Avila L, Slome S, Schuster FL, Gavali S, Schantz PM, Sejvar J et al.| title=Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species. | journal=Clin Infect Dis | year= 2009 | volume= 48 | issue= 3 | pages= 322-7 | pmid=19123863 | doi=10.1086/595852 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19123863 }} </ref>
:*'''Cutaneous disease:'''
::* Preferred regimen: [[Albendazole]] 400 mg bid for 21 days {{or}} [[Ivermectin]] 200 mcg/kg qd for 2 days<ref>{{Cite web | title =Gnathostomiasis| url =http://www.cdc.gov/dpdx/gnathostomiasis/tx.html }}</ref>
::* Alternative regimen: [[Albendazole]] 400 mg qd for 21 days {{or}} [[Ivermectin]] 200 mcg/kg qd single dose<ref>{{Cite web | title =Gnathostomiasis| url =http://www.cdc.gov/dpdx/gnathostomiasis/tx.html }}</ref>
==Ancylostoma braziliense==
{{PBI|Ancylostoma braziliense}}
::* Preferred regimen<ref>{{Cite web | title = Parasites - Zoonotic Hookworm | url = http://www.cdc.gov/parasites/zoonotichookworm/health_professionals/index.html}}</ref>
:::* Adult: [[Albendazole]] 400 mg PO qd for 3 to 7 days
:::* Pediatric: [[Albendazole]] > 2 years 400 mg PO qd for 3 days
:::* Note: This drug is contraindicated in children younger than 2 years age
::* Alternative regimen<ref>{{Cite web | title = Parasites - Zoonotic Hookworm | url = http://www.cdc.gov/parasites/zoonotichookworm/health_professionals/index.html}}</ref>
:::* Adult: [[Ivermectin]] 200 mcg/kg PO qd for one or two days
:::* Pediatric: [[Ivermectin]] >15 kg give 200 mcg/kg single dose
==Angiostrongylus cantonensis==
{{PBI|Angiostrongylus cantonensis}}
:*Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60 mg qd for 2 weeks) and analgesics.<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
:* Note: [[Albendazole]] and [[Mebendazole]] are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.<ref name="pmid19706911">{{cite journal| author=Chotmongkol V, Kittimongkolma S, Niwattayakul K, Intapan PM, Thavornpitak Y| title=Comparison of prednisolone plus albendazole with prednisolone alone for treatment of patients with eosinophilic meningitis. | journal=Am J Trop Med Hyg | year= 2009 | volume= 81 | issue= 3 | pages= 443-5 | pmid=19706911 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19706911 }} </ref>
==Ascaris lumbricoides==
{{PBI|Ascaris lumbricoides}}
::* Preferred regimen: [[Albendazole]] 400 mg PO qd {{or}} [[Mebendazole]] 500 mg PO qd or 100 mg bid for 3 days<ref>{{Cite web | title = Parasites - Ascariasis| url = http://www.cdc.gov/parasites/ascariasis/health_professionals/}}</ref>
:::* Note: [[Albendazole]] dose for children of 1-2 years is 200 mg instead of 400 mg.
::* Alternative regimen (1): [[Ivermectin]] 150 to 200 µg/kg PO single dose<ref>{{Cite web | title = Parasites - Ascariasis| url = http://www.cdc.gov/parasites/ascariasis/health_professionals/}}</ref>
::* Alternative regimen (2): [[Nitazoxanide]] 500 mg bid for 3 days <ref name="pmid9580117">{{cite journal| author=Romero Cabello R, Guerrero LR, Muñóz García MR, Geyne Cruz A| title=Nitazoxanide for the treatment of intestinal protozoan and helminthic infections in Mexico. | journal=Trans R Soc Trop Med Hyg | year= 1997 | volume= 91 | issue= 6 | pages= 701-3 | pmid=9580117 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9580117 }} </ref>
::* Alternative regimen (3): [[Levamisole]] 150 mg PO single dose
::* Alternative regimen (4): [[Pyrantel]] Pamoate 11 mg/kg single dose PO - maximum 1.0 g<ref name="pmid8863040">{{cite journal| author=Khuroo MS| title=Ascariasis. | journal=Gastroenterol Clin North Am | year= 1996 | volume= 25 | issue= 3 | pages= 553-77 | pmid=8863040 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8863040 }} </ref>
::* Alternative regimen (5): [[Piperazine citrate]] 75 mg/kg qd for 2 days - maximum 3.5 g<ref name="pmid8863040">{{cite journal| author=Khuroo MS| title=Ascariasis. | journal=Gastroenterol Clin North Am | year= 1996 | volume= 25 | issue= 3 | pages= 553-77 | pmid=8863040 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8863040 }} </ref>
==Capillaria philippinensis==
{{PBI|Capillaria philippinensis}}
::* '''1. Intestinal capillariasis'''<ref>{{Cite journal| issn = 0893-8512| volume = 5| issue = 2| pages = 120–129| last = Cross| first = J. H.| title = Intestinal capillariasis| journal = Clinical Microbiology Reviews| date = 1992-04| pmid = 1576584| pmc = PMC358231}}</ref><ref>{{Cite journal| doi = 10.4269/ajtmh.2012.11-0321| issn = 1476-1645| volume = 86| issue = 1| pages = 126–133| last1 = Attia| first1 = Rasha A. H.| last2 = Tolba| first2 = Mohammed E. M.| last3 = Yones| first3 = Doaa A.| last4 = Bakir| first4 = Hanaa Y.| last5 = Eldeek| first5 = Hanan E. M.| last6 = Kamel| first6 = Shereef| title = Capillaria philippinensis in Upper Egypt: has it become endemic?| journal = The American Journal of Tropical Medicine and Hygiene| date = 2012-01| pmid = 22232463| pmc = PMC3247121}}</ref><ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref>
:::* Preferred regimen: [[Albendazole]] 400 mg/day PO for 10-30 days
:::* Alternative regimen: [[Mebendazole]] 200 mg PO bid for 20-30 days
==Enterobius vermicularis==
{{PBI|Enterobius vermicularis}}
::* Preferred regimen (1): [[Albendazole]] 400 mg PO single dose - repeat in 2 weeks<ref name="pmid3130234">{{cite journal| author=Wang BR, Wang HC, Li LW, Zhang XL, Yue JQ, Wang GX et al.| title=Comparative efficacy of thienpydin, pyrantel pamoate, mebendazole and albendazole in treating ascariasis and enterobiasis. | journal=Chin Med J (Engl) | year= 1987 | volume= 100 | issue= 11 | pages= 928-30 | pmid=3130234 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3130234 }} </ref>
::* Preferred regimen (2): [[Mebendazole]] 100 mg PO single dose - repeat in 2 weeks
::* Alternative regimen (1): [[Ivermectin]] 200 µg/kg PO single dose - repeat in 10 days<ref name="pmid15344847">{{cite journal| author=Heukelbach J, Wilcke T, Winter B, Sales de Oliveira FA, Sabóia Moura RC, Harms G et al.| title=Efficacy of ivermectin in a patient population concomitantly infected with intestinal helminths and ectoparasites. | journal=Arzneimittelforschung | year= 2004 | volume= 54 | issue= 7 | pages= 416-21 | pmid=15344847 | doi=10.1055/s-0031-1296993 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15344847 }} </ref>
::* Alternative regimen (2): [[Pyrantel pamoate]] 11 mg/kg up to 1.0 g PO single dose - repeat in 2 weeks<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
==Necator americanus==
{{PBI|Necator americanus}}
::* Preferred regimen: [[Albendazole]] 400 mg PO single dose<ref name="pmid18430913">{{cite journal| author=Keiser J, Utzinger J| title=Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. | journal=JAMA | year= 2008 | volume= 299 | issue= 16 | pages= 1937-48 | pmid=18430913 | doi=10.1001/jama.299.16.1937 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18430913 }} </ref>
::* Alternative regimen (1): [[Mebendazole]] 100 mg PO bid or 500 mg daily for 3 days
::* Alternative regimen (2): [[Pyrantel pamoate]] 11 mg/kg PO qd (maximum 1 g/day) for 3 days<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
==Ancylostoma duodenale==
{{PBI|Ancylostoma duodenale}}
::* Preferred regimen: [[Albendazole]] 400 mg PO single dose<ref name="pmid18430913">{{cite journal| author=Keiser J, Utzinger J| title=Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. | journal=JAMA | year= 2008 | volume= 299 | issue= 16 | pages= 1937-48 | pmid=18430913 | doi=10.1001/jama.299.16.1937 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18430913 }} </ref>
::* Alternative regimen (1): [[Mebendazole]] 100 mg PO bid or 500 mg daily for 3 days
::* Alternative regimen (2): [[Pyrantel pamoate]] 11 mg/kg PO qd (maximum 1 g/day) for 3 days<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
==Strongyloides stercoralis==
{{PBI|Strongyloides stercoralis}}
::* Preferred regimen: [[Ivermectin]] 200 mcg/kg/day PO qd for 2 days or two doses 2 weeks apart from each other<ref>{{Cite web | title = WGO Practice Guideline Management of Strongyloidiasis| url = http://www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/15_management_strongyloidiasis_en.pdf}}</ref>
::* Alternative regimen: [[Albendazole]] 400 mg PO bid for 3-7 days<ref name="pmid8483992">{{cite journal| author=Archibald LK, Beeching NJ, Gill GV, Bailey JW, Bell DR| title=Albendazole is effective treatment for chronic strongyloidiasis. | journal=Q J Med | year= 1993 | volume= 86 | issue= 3 | pages= 191-5 | pmid=8483992 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8483992 }} </ref>
==Trichuris trichiura==
{{PBI|Trichuris trichiura}}
::* Preferred regimen: [[Albendazole]] 400 mg PO qd for 3 days
::* Alternatie regimen (1): [[Mebendazole]] 100 mg PO bid for 3 days
::* Alternative regimen (2): [[Ivermectin]] 200 mcg/kg/day PO qd for 3 days<ref>{{Cite web | title = Parasites - Trichuriasis| url = http://www.cdc.gov/parasites/whipworm/health_professionals/index.html#tx}}</ref>
==Entamoeba histolytica==
:* '''1. Amebic Liver Abscess'''<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
::* Preferred regimen: ([[Metronidazole]] 750 mg PO tid for 10 days {{or}} [[Tinidazole]] 2 g PO qd for 5 days) {{and}} ([[Paromomycin]] 30 mg/kg/day PO tid for 5-10 days {{or}} [[Diloxanide furoate]] 500 mg PO tid for 10 days)
::* Alternative regimen (1): [[Nitazoxanide]] 500 mg bid for 10 days {{and}} ([[Paromomycin]] 30 mg/kg/day PO tid for 5-10 days {{or}} [[Diloxanide furoate]] 500 mg PO tid for 10 days)
::* Alternative regimen (2): [[Tinidazole]] 2 g PO qd for 5 days {{and}} ([[Paromomycin]] 30 mg/kg/day PO tid for 5-10 days {{or}} [[Diloxanide furoate]] 500 mg PO tid for 10 days)
::* Alternative regimen (2): [[Tinidazole]] 2 g PO qd for 5 days
:* '''2. Amebic Colitis'''<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
::* Preferred regimen: [[Metronidazole]] 500-750 mg PO tid for 7-10 days. Pediatric dose: 35-50 mg/kg per day tid {{and}} ([[Paromomycin]] 30 mg/kg/day PO tid for 5-10 days {{or}} [[Diloxanide furoate]] 500 mg PO tid for 10 days)
::* Alternative regimen: [[Tinidazole]] 2 g PO qd for 5 days {{and}} ([[Paromomycin]] 30 mg/kg/day PO tid for 5-10 days {{or}} [[Diloxanide furoate]] 500 mg PO tid for 10 days)
:* '''3. Asymptomatic Intestinal Colonization'''<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
::* Preferred regimen: [[Paromomycin]] 30 mg/kg/day PO tid for 5-10 days
::* Alternative regimen (1): [[Diloxanide furoate]] 500 mg PO tid for 10 days
::* Alternative regimen (2): [[Diiodohydroxyquin]] 650 mg PO tid for 20 days for adults and 30 to 40 mg/kg per day tid for 20 days for children
==Paracoccidiodomycosis==
:* Preferred regimen (1): <ref name="pmid16906260">{{cite journal| author=Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP, Colombo AL, Moretti ML| title=[Guidelines in paracoccidioidomycosis]. | journal=Rev Soc Bras Med Trop | year= 2006 | volume= 39 | issue= 3 | pages= 297-310 | pmid=16906260 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16906260 }} </ref>
::* Adults: [[Itraconazole]] 200 mg/day PO
::* Children: [[Itraconazole]] (<30/kg and >5 yr) 5-10 mg/kg/day PO
::* Note: Treatment duration based on organ involvement:
:::*Mild involvement: 6-9 months
:::*Moderate involvement: 12-18 months
:* Preferred regimen (2): <ref name="pmid16906260">{{cite journal| author=Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP, Colombo AL, Moretti ML| title=[Guidelines in paracoccidioidomycosis]. | journal=Rev Soc Bras Med Trop | year= 2006 | volume= 39 | issue= 3 | pages= 297-310 | pmid=16906260 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16906260 }} </ref>
::* Note (1): Treatment duration based on organ involvement:
:::* Minor involvement: 12 months
:::* Moderate involvement: 18-24 months
::* Note (2): Preferred treatment in children due to larger experience.
::* Note (3): Preferred in IV formulation in severe forms of the disease - 2 ampules IV q8h until patient condition improves so that oral medication can be given.
:* Preferred regimen (3): [[Amphotericin B]] deoxycholate 1 mg/kg/day IV until patient improves and can be treated by the oral route.<ref name="pmid16906260">{{cite journal| author=Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP, Colombo AL, Moretti ML| title=[Guidelines in paracoccidioidomycosis]. | journal=Rev Soc Bras Med Trop | year= 2006 | volume= 39 | issue= 3 | pages= 297-310 | pmid=16906260 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16906260 }} </ref>
::* Note: Preferred in severe forms of the disease.<ref name="pmid16906260">{{cite journal| author=Shikanai-Yasuda MA, Telles Filho Fde Q, Mendes RP, Colombo AL, Moretti ML| title=[Guidelines in paracoccidioidomycosis]. | journal=Rev Soc Bras Med Trop | year= 2006 | volume= 39 | issue= 3 | pages= 297-310 | pmid=16906260 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16906260 }} </ref>
:* Alternative regimen (4): [[Ketoconazole]] 200-400 mg/day PO for 9-12 months<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
:* Alternative regimen (5): [[Voriconazole]] initial dose 400 mg PO/IV q12h for one day, then 200 mg q12h for 6 months<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
::* Note: Diminish the dose to 50% if weight is <40 kg.
==Aspergillosis==
{{PBI|Aspergillosis}}<ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
* '''1. Invasive pulmonary aspergillosis'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
* '''2. Invasive sinus aspergillosis'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
* '''3. Tracheobronchial aspergillosis'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
* '''5. Aspergillosis of the CNS'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Note: There are drug interactions with anticonvulsant therapy.
* '''6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.
* '''7. Aspergillus osteomyelitis and septic arthritis'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Note: Surgical resection of devitalized bone and cartilage is important for curative intent.
* '''8. Aspergillus infections of the eye (endophthalmitis and keratitis)'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.
* '''9. Cutaneous aspergillosis'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Note: Surgical resection is indicated when feasible.
* '''10. Aspergillus peritonitis'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
* '''11. Prophylaxis against invasive aspergillosis'''
:* Preferred regimen: [[Posaconazole]] PO 200 mg tid
:* Alternative regimen: (1) [[Itraconazole]] 200 mg IV q12h for 2 days then 200 mg IV q24h {{or}} [[Itraconazole]] PO 200mg bid
:* Alternative regimen: (2) [[Micafungin]] 50 mg/day PO qd
* '''12. Aspergilloma'''
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen: [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Preferred regimen: [[Voriconazole]] 6 mg/kg IV q12h single dose, {{then}} 4 mg/kg IV q12h or PO 200 mg q12h
:* Alternative regimen (1): Liposomal [[Amphotericin B]] (L-AMB) 3–5 mg/kg/day IV q24h
:* Alternative regimen (2): [[Amphotericin B]] lipid complex (ABLC) 5 mg/ kg/day IV q24h
:* Alternative regimen (3): [[Caspofungin]] 70 mg IV single dose {{then}} 50 mg/day IV q24h
:* Alternative regimen (4): [[Posaconazole]] 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
:* Alternative regimen (5): [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (6): [[Micafungin]] 100–150 mg/day PO qd<ref name="pmid24445340">{{cite journal| author=Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G| title=Invasive fungal infections in the ICU: how to approach, how to treat. | journal=Molecules | year= 2014 | volume= 19 | issue= 1 | pages= 1085-119 | pmid=24445340 | doi=10.3390/molecules19011085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24445340 }} </ref><ref name="pmid18177225">{{cite journal| author=Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA et al.| title=Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2008 | volume= 46 | issue= 3 | pages= 327-60 | pmid=18177225 | doi=10.1086/525258 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18177225 }} </ref>
:* Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
:* Preferred regimen: [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Alternative regimen (1): [[Voriconazole]] PO 200 mg bid
:* Alternative regimen (2): [[Posaconazole]] PO 400 mg bid
:* Note: Corticosteroids are a cornerstone of the therapy.
*'''15. Allergic aspergillus sinusitis'''
:* Preferred regimen: None or [[Itraconazole]] dosage depends upon formulation - 600 mg/day PO for 3 days, {{then}} 400 mg/day PO {{or}} 200 mg q12h IV for 2 days, {{then}} 200 mg IV q24h
:* Note: Few data available for other agents.
*'''16. Relative indications for surgical treatment of invasive aspergillosis'''
:*Pulmonary lesion in proximity to great vessels or pericardium;
:*Pericardial infection;
:*Invasion of chest wall from contiguous pulmonary lesion;
:*Aspergillus empyema;
:*Persistent hemoptysis from a single cavitary lesion;
:*Infection of skin and soft tissues;
:*Infected vascular catheters and prosthetic devices;
:*Endocarditis;
:*Osteomyelitis;
:*Sinusitis;
:*Cerebral lesions.
== Yellow Fever Virus ==
:* '''1. Yellow fever'''<ref>{{cite web | title = District guidelines for yellow fever surveillance | url = http://www.who.int/csr/resources/publications/yellowfev/whoepigen9809.pdf?ua=1 }}</ref><ref> name="pmid3547569">{{cite journal| author=Monath TP| title=Yellow fever: a medically neglected disease. Report on a seminar. | journal=Rev Infect Dis | year= 1987 | volume= 9 | issue= 1 | pages= 165-75 |pmid=3547569 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3547569 }} </ref>
:*'''1.1. Summary'''
::* Yellow fever was one of the most lethal diseases before the development of the vaccine. It is a major health concern for unvaccinated travellers to tropical regions in South America and Africa. It is transmitted by mosquitoes (Aedes aegypti) bites in a cycle which involve these mosquitoes biting also monkeys and human beings, which act as hosts for the virus. The yellow fever virus is a member of the Flaviviridae family, which comprises about 70 viruses, most of which are arthropod-borne.
:*'''1.2. Epidemiology'''
::*Up to 5000 cases are reported annually in Africa and 300 annually in South America, although it is believed that numbers are underestimated. In Africa the human population is seasonally exposed in and around villages and small cities so the highest risk of disease are children without naturally acquired immunity. In South America the virus is transmitted in poorly populated forested areas and it occurs mainly with workers and farmers in the borders of the forested areas.
:*'''1.3. Clinical Manifestations'''
::* Yellow fever can present itself in three forms: subclinical infection, nonspecific abortive febrile disease and fatal hemorrhagic fever. The incubation time for the disease is 3-6 days. After this period, the onset of fever, myalgia, lower back pain, irritability, nausea, malaise, headache, fotofobia and dizziness is oftenly abrupt. These findings are not specific to Yellow Fever and can be found in any acute infection. During this period the patient can be a source of virus for mosquitoes.
::*On physical examination the liver can be enlarged with tenderness, Faget sign (slow pulse rate despite high fever) can be found. Skin might appear flushed with reddening of conjunctivae and gums. Between 48-72h after onset and before the jaundice, hepatic enzymes starts to rise. Laboratory studies may show leukopenia with relative neutropenia. This is called period of infection and may last for several days and may be {{then}} a remission period which last about 48h, with the disappearance of the fever and the symptoms. Patients with the abortive form of the disease recover at this stage.
::*After the third to sixth day of the onset of the symptoms the patient may present return of the fever, vomiting, renal failure (oliguria), jaundice, epigastric pain and hemorrhagic diathesis. The viremia terminates during this stage and the antibodies appear in the blood. The patient may evolve with multiorgan failure during this phase. Also in this stage, AST concentrations might exceed ALT, probably due to myocardial and skeletal muscle damage. Serum creatinine and bilirubin levels also rise at this stage. Hemorrhagic manifestations may include petechiae, ecchymoses, epistaxis, melena, metrorrhagia, haematemesis. Laboratory studies may show thrombocytopenia, reduced fibrinogen levels, presence of fibrin split products, reduced factors II, V, VII, VIII, IX and X, which suggest a multifactorial cause for the bleeding with a consumption coagulopathy. Myocardial disfunction may be demonstrated by abnormalities in the ST-T segment in the electrocardiogram. Encephalitis is very rare.
::*20-50% of the patients with the hepatorenal disease die after 7-10 days of the onset.
:*'''1.4. Diagnosis'''
::* Diagnosis can be made by serology, detection of viral genome by polymerase chain reaction, immunohistochemistry on postmortem tissues, viral isolation or histopathology. No commercial test is available and diagnostic capabilities are restricted to selected laboratories only. Serologic diagnosis is made by dosing IgM antibodies with ELISA. The virus might be isolated by inoculating it in mice, cell cultures or mosquitoes. PCR is generally used to detect viral genome in clinical samples that were negative by virus isolation or other method.
:*'''1.5. Treatment'''
::* Preferred regimen: No specific treatment is available for yellow fever. In the toxic phase, supportive treatment includes therapies for treating dehydration and fever. Ribavirin has failed in several studies in the monkey model.
:::* Note: An international seminar held by WHO in 1984 recommended maintenance of nutrition, prevention of hypoglycemia, maintenance of the blood pressure with fluids and vasoactive drugs, prevention of bleeding with fresh-frozen plasma, dialysis if renal failure, correction of metabolic acidosis, administration of cimetidine IV to avoid gastric bleeding and oxygen if needed.
:*'''1.6. Prevention'''
::* The Yellow fever 17D is highly effective, safe, attenuated vaccine that has been used for over 60 years. It should be taken my travellers who are going to endemic areas of the disease. Revaccination is needed after 10 years from the first dose. The side effects of the vaccines are rare but they include yellow fever associated viscerotropic disease and neurotropic disease. Immunization is contraindicated during pregnancy and in patients with immunodeficiency due to cancers, HIV/AIDS, or treatment with immunosuppressive agents.
==Chikungunya Fever==
::'''Chikungunya Fever''' <ref name="pmid25806915">{{cite journal| author=Weaver SC, Lecuit M| title=Chikungunya virus and the global spread of a mosquito-borne disease. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 13 | pages= 1231-9 | pmid=25806915 | doi=10.1056/NEJMra1406035 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25806915 }} </ref>
::* Preferred regimen: no specific therapeutics agents are available and there are no licensed vaccines to prevent Chikungunya Fever.
:::* Note: Anti inflammatory drugs can be used to control joint swelling and arthritis.
==Rabies==
:*'''Rabies'''
::* Preferred regimen: no specific therapeutics agents are available once the disease is established.
:::* Note: There are vaccines and immune globulins available for postexposure prophylaxis:
::::* Postexposure Prophylaxis for non immunized individuals: Wound cleansing, human rabies immune globulin - administer full dose infiltrated around any wound. Administer any remaining volume IM at other site anatomically distant from the wound. Administer vaccine 1,0ml, IM at deltoid area one each on days 0, 3, 7 and 14.
::::* Postexposure Prophylaxis for immunized individuals: Wound cleansing, do not administer human rabies immune globulin. Administer vaccine 1,0ml, IM at deltoid area one each on days 0 and 3.
==Cryptococcus==
{{PBI|Cryptococcus}}
:* 1. '''Cryptococcus neoformans'''
::* 1.1 '''Cryptococcus neoformans meningitis in HIV infected patients'''<ref name="pmid20047480">{{cite journal| author=Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ et al.| title=Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. | journal=Clin Infect Dis | year= 2010 | volume= 50 | issue= 3 | pages= 291-322 | pmid=20047480 | doi=10.1086/649858 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20047480 }} </ref>
:::* Preferred regimen for induction and consolidation: ([[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV q24h {{or}} [[Liposomal AmB]] 3-4 mg/kg IV q24h {{or}} [[Amphotericin B]] lipid complex 5 mg/kg IV q24h) {{and}} [[Flucytosine]] 100 mg/kg/day PO/IV q6h for at least 2 weeks {{then}} [[Fluconazole]] 400 mg (6 mg/kg) PO qd for at least 8 weeks
:::* Alternative regimen for induction and consolidation (1): [[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV q24h {{or}} [[Liposomal AmB]] 3-4 mg/kg IV q24h {{or}} AmB lipid complex 5 mg/kg IV q24h for 4-6 weeks
:::* Alternative regimen for induction and consolidation (2): [[Amphotericin B]] deoxycholate 0.7 mg/kg IV q24h {{and}} [[Fluconazole]] 800 mg PO qd for 2 weeks, {{then}} [[Fluconazole]] 800 mg PO qd for at least 8 weeks
:::* Alternative regimen for induction and consolidation (3): [[Fluconazole]] 800-1200 mg PO qd {{and}} [[Flucytosine]] 100 mg/kg/day PO qid for 6 weeks
:::* Alternative regimen for induction and consolidation (4): [[Fluconazole]] PO 800-2000 mg qd for 10-12 weeks
:::* Preferred regimen for maintenance and prophylactic therapy: Initiate HAART 2-10 weeks after commencing initial antifungal therapy {{and}} [[Fluconazole]] 200 mg PO qd
:::* Alternative regimen for maintenance and prophylactic therapy: [[Itraconazole]] 200 mg PO bid - monitor drug-level (trough concentration must be higher than 0.5 μg/ml) {{or}} [[Amphotericin B]] deoxycholate 1 mg/kg per week IV (should be used in azole-intolerant patients)
:::* Note (1): Consider discontinuing supressive therapy if CD4 count is higher than 100 cells/uL {{and}} undetectable {{or}} very low HIV RNA level for more than 3 months. Consider reinstitution of maintenance therapy if CD4 count <100 cels/uL.
:::* Note (2): Do not use [[acetazolamide]] {{or}} [[mannitol]] {{or}} [[corticosteroids]] to treat increased intracranial pressure, instead it should be used lombar puncture in the absence of focal neurologic signs or impaired mentation (which, if present, patient must be submitted to CT or MRI scan first).
::'''1.2. Cerebral cryptococcomas'''
:::* Preferred regimen for induction and consolidation: ([[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV q24h {{or}} [[Liposomal AmB]] 3-4 mg/kg IV q24h {{or}} [[Amphotericin B]] lipid complex 5 mg/kg IV q24h) {{and}} [[Flucytosine]] 100 mg/kg/day PO/IV q6h for at least 2 weeks {{then}} [[Fluconazole]] 400 mg (6 mg/kg) PO qd for at least 8 weeks
:::* Note: Consider surgery if lesions are larger than 3 cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS.
::'''1.3. Cryptococcus neoformans meningitis in HIV negative patients'''
:::* Preferred regimen: [[Amphotericin B deoxycholate]] 0.7-1.0 mg/kg IV q24h {{and}} [[Flucytosine]] 100 mg/kg/day PO or IV q6h for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) {{then}} [[Fluconazole]] 400 mg PO qd for 8 weeks.
:::* Note (1): If there's toxicity to [[Amphotericin B]] deoxycholate, consider changing to [[Liposomal AmB]] or [[Amphotericin B]] lipid complex in the second 2 weeks.
:::* Note (2): After induction and consolidation therapy, start [[Fluconazole]] 200 mg (3 mg/kg) PO qd for 6-12 months.
:::* Note (3): If [[Flucytosine]] is not given, consider lengthening the induction therapy for at least 2 weeks.
:::*Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
::::* Preferred regimen: [[Fluconazole]] 400 mg PO qd for 6-12 months
:::*Severe pneumonia or disseminated disease or CNS infection:
::::* Preferred regimen: treat like CNS cryptococcosis.
:::* Note (1): In HIV- infected patients, treatment should be stopped after 1 year if CD4 count is >100 and a cryptococcal antigen titer is <1:512 and not increasing.
:::* Note (2): Consider [[corticosteroid]] if ARDS is present in a context which it might be attributed to IRIS.
:::*Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
::::* Preferred regimen: [[Fluconazole]] 400 mg PO qd for 6-12 months
::::* Alternative regimen: if [[Fluconazole]] is unavailable or contraindicated, [[Itraconazole]] 200 mg PO bid, [[Voriconazole]] 200 mg PO bid, and [[Posaconazole]] 400 mg PO bid
:::*If there's severe pneumonia, disseminated disease or CNS infection:
::::* Preferred regimen: treat like CNS cryptococcosis for 6-12 months.
:::*Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer >1:512):
::::* Preferred regimen: treat like CNS infection.
:::*If infection occurs at a single site and no immunosupressive risk factors
::::* Preferred regimen: [[Fluconazole]] 400 mg PO qd for 6-12 months
::'''1.7. Cryptococcosis in Children'''
::::* Preferred regimen for induction and consolidation: [[Amphotericin B]] deoxycholate 1.0 mg/kg qd IV {{and}} [[Flucytosine]] 100 mg/kg PO or IV q6h for 2 weeks {{then}} [[Fluconazole]] 10-12 mg/kg PO qd for 8 weeks
::::* Alternative regimen: patients with renal dysfunction: change [[Amphotericin B]] deoxycholate by [[Liposomal AmB]] 5 mg/kg IV q24h or [[Amphotericin B]] lipid complex (ABLC) 5 mg/kg IV q24h
::::* Preferred regimen for maintenance: Fluconazole 6 mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized.
:::*Cryptococcal pneumonia:
::::* Preferred regimen [[Fluconazole]] 6-12 mg/kg PO qd for 6-12 months
::'''1.8. Cryptococcosis in Pregnant Women'''
:::* Preferred regimen for induction and consolidation: [[Amphotericin B]] deoxycholate 0.7-1.0 mg/kg IV q24h. Start [[Fluconazole]] after delivery. Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy.
:::* Note (1): Consider using lipid formulations for patients with renal dysfunction - [[Liposomal AmB]] 3-4 mg/kg IV q24h {{or}} [[Amphotericin B]] lipid complex (ABLC) 5 mg/kg IV q24h.
:::* Note (2): Consider using [[Flucytosine]] in relationship to benefit risk basis, since it is a Category C drug for pregnancy.
:::* Note (3): If pulmonary cryptococcosis: perform close follow-up and administer fluconazole after delivery.
:'''2. Cryptococcus gatti'''
::*Disseminated cryptococcosis or CNS disease:
:::* Preferred regimen: treatment is the same as C. neoformans
::*Pulmonary disease: single and small cryptococcoma:
:::* Preferred regimen: [[Fluconazole]] 400 mg per day PO for 6-18 months
::*Pulmonary disease: Very large or multiple cryptococcomas:
:::* Preferred regimen: administer [[Flucytosine]] {{and}} [[AmB deocycholate]] for 4-6 weeks, {{then}} [[Fluconazole]] for 6-18 months
:::* Note: Surgery should be considered if there is compression of vital structures {{or}} failure to reduce the size of the cryptococcoma after 4 weeks of therapy
==Dermatophytosis==
:* Dermatophytosis<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
::::* Preferred regimen: Larger lesions: [[terbinafine]] 250 mg/day PO for 2 weeks; [[itraconazole]] 200 mg/day PO for 1 week, [[fluconazole]] 250 mg PO weekly for 2-4 weeks
:::* Note (1): If "Dry type": Oral: [[terbinafine]] 250 mg/day PO for 2-4 weeks, [[itraconazole]] 400 mg/day PO for 1 week per month (repeat if necessary), [[fluconazole]] 200 mg PO weekly for 4-8 weeks
::*'''4. Tinea Capitis'''
:::* Preferred regimen: [[Griseofulvin]] 10-20 mg/kg/day PO qd for at least 6 weeks (Preferred for children).
:::* Alternative regimens: [[Terbinafine]] 62.5 mg/day if <20kg; 125 mg/day if 20-40kg; 250 mg/day if >40kg PO qd for 8 weeks {{or}} [[Itraconazole]] 4-6 mg/kg/day (maximum 400 mg) PO for 4-6 weeks
::::* Note: [[Nistatin]] is not effective in the treatment of dermatophytosis.
::*'''5. Tinea Barbae'''
::::* Preferred regimen: [[Terbinafine]] 250 mg/day PO qd for 4 weeks
::::* Alternative regimen: [[Itraconazole]] 200 mg/day PO qd for 2 weeks
::*'''6. Tinea Incognito'''
::::* Preferred regimen: Stop topical [[steroids]] and treat with topical 1% [[terbinafine]] cream for 6 weeks
::*'''7. Tinea Manuum'''
::::* Preferred regimen: topical or systemic [[terbinafine]] 250 mg/day PO qd por 2-4 weeks
::*'''8.Tinea Versicolor'''
::::* Preferred regimen: [[Itraconazole]] 200 mg PO qd for a week
::::* Alternative regimen: [[Ketoconazole]] 200 mg PO qd for 4 weeks
::*'''9. Majocchi's Granuloma'''
::::* Preferred regimen: [[Terbinafine]] 250 mg/day PO for 2-4 weeks or [[Itraconazole]] 200 mg PO bid for 1 week, per month for 2 months
::::* Preferred regimen: [[Terbinafine]] 250 mg/day PO for 6 weeks {{or}} [[Itraconazole]] 200 mg PO bid for one week per month for 2 months (European guidelines)
:::*10.2 Toenails
::::* Preferred regimen: Toenails [[Terbinafine]] 250 mg/day PO for 12 weeks {{or}} [[Itraconazole]] 200 mg/day PO for 12 weeks (U.S. guidelines) {{or}} [[Itraconazole]] 200 mg PO bid for one week per month for 3 months (European guidelines)
:::* Note: There is no evidence that combining systemic and topic treatments has any benefit to the patient.
| Antibiotic prophylaxis has been proved beneficial in the following patients: reconstruction of abdominal aorta, procedures on the leg that involve a groin incision, any vascular procedure that inserts prosthesis/foreign body, lower extremity amputation for ischemia, cardiac surgery, permanent pacemakers, heart transplant. The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses. Some experts recommend an additional dose when patients are removed from bypass during open-heart surgery.
|-
|
|
| [[Cefuroxime]]
| 1.5 g IV
| Some experts recommend an additional dose when patients are removed from bypass during open-heart surgery.
|-
|
|
| [[Vancomycin]]
| 1 g IV
| [[Vancomycin]] is preferable in hospitals with high frequency of MRSA, high risk patients, those colonized with MRSA or for pen-allergic patients. [[Clindamycin]] 900 mg IV is another alternative for pen-allergic or vanco-allergic patients. [[Vancomycin]] can be used in hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with [[Diphenhydramine]] (Benadryl, and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of [[Vancomycin]] to patients weighing more than 751<g, up to a maximum of 1.5 g, with a slower infusion rate (90 minutes for 1.5 g). For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside ([[Gentamicin]], [[Tobramycin]] or [[Amikacin]]), [[Aztreonam]] or a fluoroquinolone.
|-
|
|
| [[Mupirocine]]
|
| Consider intranasal [[Mupirocine]] evening before, day of surgery and bid for 5 days post-op in patients with positive nasal culture for S. aureus. [[Mupirocine]] resistance has been encountered.
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses. PEG placement: high-risk is marked obesity, obstruction, reduced gastric acid or reduced motility.
| High-risk only: [[Cefazolin]], [[Cefoxitin]] or [[Cefotetan]]
| 1-2 g IV
| High risk: age >70, acute cholecystitis, non-functioning gallbladder, obstructive jaundice or common duct stones. With cholangitis, treat as infection, not prophylaxis. The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses. Low-risk, laparoscopic: no prophylaxis.
|-
|
|
| {{or}} [[Ampicillin/Sulbactam]]
| 3 g IV
|
|-
| Endoscopic retrograde cholangiopancreatography
|
| [[Ciprofloxacin]]
| 500 - 750 mg PO {{or}} 400 mg IV 2 hours before procedure
| Only needed if there is obstruction. Greatest benefit of prophylaxis occurs when complete drainage cannot be achieved.
| In addition to mechanical bowel preparation, 1 g of [[Neomycin]] {{plus}} 1 g of [[Erythromycin]] at 1 PM, 2 PM and 11 PM or 2 g of [[Neomycin]] {{plus}} 2 g of [[Metronidazole]] at 7 PM and 11 PM the day before an 8 AM operation.
|-
|
|
| Parenteral: [[Cefoxitin]] or [[Cefotetan]]
| 1-2 g IV
|
|-
|
|
| {{or}} [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{plus}} [[Metronidazole]]
| 0.5 g IV
|
|-
|
|
| [[Ampicillin/Sulbactam]]
| 3 g IV
|
|-
|
|
| [[Ertapenem]]
| 1 g IV
| [[Ertapenem]] can be used if there is beta-lactam allergy. Other regimens include: [[Clindamycin]] 900 mg IV {{plus}} [[Gentamycin]] 5mg/kg {{or}} [[Aztreonam]] 2 g IV {{or}} [[Ciprofloxacin]] 400 mg IV.
|-
| Appendectomy, non-perforated
| Same as for colorectal
| [[Cefoxitin]] {{or}} [[Cefotetan]]
| 1-2 g IV
| For patients allergic to penicillins and cephalosporins, [[Clindamycin]] {{or}} [[Vancomycin]] with either [[Gentamicin]], [[Ciprofloxacin]], [[Levofloxacin]] or [[Aztreonam]] is a reasonable alternative. Fluoroquinolones should not be used for prophylaxis in cesarean section.
|-
|
|
| {{or}} [[Cefazolin]]
| 1-2 g IV
|
|-
|
|
| {{plus}} [[Metronidazole]]
| 0.5 g IV
|
|-
| colspan=5 |Genitourinary
|-
| Cystoscopy alone
| Enteric gram-negative bacilli, enterococci
| High-risk only: [[Ciprofloxacin]]
| 500 mg PO {{or}} 400 mg IV
| Due to increasing resistance of E. coli to fluoroquinolones and [[Ampicillin/Sulbactam]], local sensitivity profiles should be reviewed prior to use. AUA recommends prophylaxis for those with several potentially adverse host factors (e.g. advanced age, immunocompromised state, anatomic abnormalities, etc.).
|-
|
|
| {{or}} [[Trimethoprim-Sulfamethoxazole]]
| 1 DS tablet
|
|-
| Cystoscopy with manipulation or upper tract instrumentation
| Enteric gram-negative bacilli, enterococci
| [[Ciprofloxacin]]
| 500 mg PO {{or}} 400 mg IV
| Due to increasing resistance of E. coli to fluoroquinolones and [[Ampicillin/Sulbactam]], local sensitivity profiles should be reviewed prior to use.
|-
|
|
| {{or}} [[Trimethoprim-Sulfamethoxazole]]
| 1 DS tablet
| Viable alternative in populations with low rates of resistance.
|-
| Transrectal prostate biopsy
| Enteric gram-negative bacilli, enterococci
| [[Ciprofloxacin]]
| 500 mg PO 12 hours before biopsy and 12 hours after first dose.
|
|-
| Open or laparoscopic surgery
| Enteric gram-negative bacilli, enterococci
| [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
| colspan=5 |Gynecologic and Obstetric
|-
| Vaginal, abdominal or laparoscopic hysterectomy
| Enteric gram-negative bacilli, anaerobes, Gp B strep, enterococci
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses. For patients allergic to penicillins and cephalosporins, [[Clindamycin]] {{or}} [[Vancomycin]] with either [[Gentamicin]], [[Ciprofloxacin]], [[Levofloxacin]] or [[Aztreonam]] is a reasonable alternative. Fluoroquinolones should not be used for prophylaxis in cesarean section. Due to increasing resistance of E. coli to fluoroquinolones and [[Ampicillin/Sulbactam]], local sensitivity profiles should be reviewed prior to use.
|-
|
|
| {{or}} [[Ampicillin/Sulbactam]]
| 3 g IV
| For patients allergic to penicillins and cephalosporins, [[Clindamycin]] {{or}} [[Vancomycin]] with either [[Gentamicin]], [[Ciprofloxacin]], [[Levofloxacin]] or [[Aztreonam]] is a reasonable alternative. Fluoroquinolones should not be used for prophylaxis in cesarean section. Due to increasing resistance of E. coli to fluoroquinolones and [[Ampicillin/Sulbactam]], local sensitivity profiles should be reviewed prior to use.
|-
| Cesarean section
| Same as for hysterectomy
| [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses. For patients allergic to penicillins and cephalosporins, [[Clindamycin]] {{or}} [[Vancomycin]] with either [[Gentamicin]], [[Ciprofloxacin]], [[Levofloxacin]] or [[Aztreonam]] is a reasonable alternative. Fluoroquinolones should not be used for prophylaxis in cesarean section. Due to increasing resistance of E. coli to fluoroquinolones and [[Ampicillin/Sulbactam]], local sensitivity profiles should be reviewed prior to use.
|-
|
|
| [[Clindamycin]]
| 900 mg IV
| Use as alternative method to [[Cefazolin]] and associated with [[Gentamicin]] 5 mg/kg IV {{or}} [[Tobramycin]] 5 mg/kg IV single dose.
|-
| Abortion, surgical
| Same as for hysterectomy
| [[Doxycycline]]
| 300 mg PO
| Divided into 100 mg before the procedure and 200 mg after.
|-
| colspan=5 |Head and Neck Surgery
|-
| Incisions through oral or pharyngeal mucosa
| Anaerobes, enteric gram-negative bacilli, S. aureus
| [[Clindamycin]]
| 600 mg - 900 mg IV
| Clean, uncontaminated head and neck surgery does not require prophylaxis. If using [[Clindamycin]], consider associating [[Gentamicin]] 5 mg/kg IV single dose.
|-
|
|
| {{or}} [[Cefazolin]]
| 2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{plus}} [[Metronidazole]]
| 0.5 g IV
|
|-
|
|
| {{or}} [[Ampicillin/Sulbactam]]
| 3 g IV
|
|-
| colspan=5 | Neurosurgery
|-
|
| S. aureus, S. epidermidis
| [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{or}} [[Vancomycin]]
| 1 g IV
| [[Vancomycin]] can be used in hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with [[Diphenhydramine]] (Benadryl, and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of [[Vancomycin]] to patients weighing more than 751<g, up to a maximum of 1.5 g, with a slower infusion rate (90 minutes for 1.5 g). For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside ([[Gentamicin]], [[Tobramycin]] or [[Amikacin]]), [[Aztreonam]] or a fluoroquinolone.
|-
|
|
| [[Clindamycin]]
| 900 mg IV
| [[Clindamycin]] can be used in clean, contaminated surgeries (cross sinuses, or naso/oropharynx). British recommend [[Amoxicilin-clavulanate]] 1.2 g IV {{or}} [[Cefuroxime]] 1.5 g IV {{plus}} [[Metronidazole]] 0.5 mg g IV.
|-
| colspan=5 | Ophthalmic
|-
|
| S. aureus, S. epidermidis, streptococci, enteric gram-negative bacilli, Pseudomonas spp.
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{or}} [[Vancomycin]]
| 1 g IV
| [[Vancomycin]] can be used in hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with [[Diphenhydramine]] (Benadryl, and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of [[Vancomycin]] to patients weighing more than 751<g, up to a maximum of 1.5 g, with a slower infusion rate (90 minutes for 1.5 g). For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside ([[Gentamicin]], [[Tobramycin]] or [[Amikacin]]), [[Aztreonam]] or a fluoroquinolone. If a tourniquet is to be used in the procedure, the entire dose of antibiotic must be infused prior to its inflation. For patients weighing >90 kg use [[Vancomycin]] 1.5 g IV as single dose {{or}} [[Clindamycin]] 900 mg IV.
|-
| Open reduction of closed fracture with internal fixation
| S. aureus, S. epidermidis
| [[Ceftriaxone]]
| 2 g IV single dose
|
|-
| colspan=5 | Thoracic (non-cardiac)
|-
|
| S. aureus, S. epidermidis, enteric gram-negative bacilli, streptococci
| [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{or}} [[Vancomycin]]
| 1 g IV
| [[Vancomycin]] can be used in hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with [[Diphenhydramine]] (Benadryl, and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of [[Vancomycin]] to patients weighing more than 751<g, up to a maximum of 1.5 g, with a slower infusion rate (90 minutes for 1.5 g). For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside ([[Gentamicin]], [[Tobramycin]] or [[Amikacin]]), [[Aztreonam]] or a fluoroquinolone.
|-
|
|
| {{or}} [[Ampicillin/Sulbactam]]
| 3 g IV
| Due to increasing resistance of E. coli to fluoroquinolones and [[Ampicillin/Sulbactam]], local sensitivity profiles should be reviewed prior to use.
|-
| colspan=5 | Vascular
|-
| Arterial surgery involving· a prosthesis, the abdominal aorta, or a groin incision
| S. aureus, S. epidermidis, enteric gram-negative bacilli
| [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{or}} [[Vancomycin]]
| 1 g IV
| [[Vancomycin]] can be used in hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with [[Diphenhydramine]] (Benadryl, and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of [[Vancomycin]] to patients weighing more than 751<g, up to a maximum of 1.5 g, with a slower infusion rate (90 minutes for 1.5 g). For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside ([[Gentamicin]], [[Tobramycin]] or [[Amikacin]]), [[Aztreonam]] or a fluoroquinolone.
|-
| Lower extremity amputation for ischemia
| S. aureus, S. epidermidis, enteric gram-negative bacilli, clostridia
| [[Cefazolin]]
| 1-2 g IV
| The recommended dose of [[Cefazolin]] is 1 g for patients who weigh <80 kg and 2 g for those ~80 kg. Morbidly obese patients may need higher doses.
|-
|
|
| {{or}} [[Vancomycin]]
| 1 g IV
| [[Vancomycin]] can be used in hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with [[Diphenhydramine]] (Benadryl, and others) and further slowing of the infusion rate may be helpful. Some experts would give 15 mg/kg of [[Vancomycin]] to patients weighing more than 751<g, up to a maximum of 1.5 g, with a slower infusion rate (90 minutes for 1.5 g). For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside ([[Gentamicin]], [[Tobramycin]] or [[Amikacin]]), [[Aztreonam]] or a fluoroquinolone.
|}
Revision as of 05:00, 13 September 2020
Emergency Medicine Chapters - Internal Medicine Related
Below is shown a compendium of information summarizing the diagnosis of gastroesophageal reflux disease (GERD) according the the American Journal of Gastroenterology guidelines.[4]
Preoperatively for non-erosive disease, refractory GERD symptoms or GERD diagnosis in question
Correlate symptoms with reflux, document abnormal acid exposure or reflux frequency
Treatment
Shown below is an algorithm summarizing the treatment of refractory GERD according the the American Journal of Gastroenterology guidelines.[4]
Lifestyle modifications are indicated for all patients and include:
Dietary changes (reduce ingestion of chocolate, caffeine, alcohol, acidic and/or spicy foods - low degree of evidence, but there are reports of improvements with elimination);
Weight loss for overweight patients or patients that have had recent weight gain;
Head of bed elevation and avoidance of meals 2–3 h before bedtime if nocturnal symptoms.[4]
Do not request manometry or ambulatory reflux monitoring routinely.
References
↑"Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management". National Institute for Health and Care Excellence: Clinical Guidelines. 2019. PMID31935049.
Rare vasculitis mostly seen in young Asians males who are smokers. Causes inflammation and thrombosis of the arteries of the legs, feet, forearms, and hands.
Conventional angiography - multilevel occlusions and segmental narrowing of the lower extremity arteries with extensive collateral flow showing a corkscrew or “tree root” appearance
Rare vasculitis mostly seen on Asian and South American women. Stenosis of the abdominal aorta and iliac arteries are present in 17% of the patients and may cause claudication.
1 in 1200 cases of claudication, most common in men, 20-50 years without risk factors for atherosclerosis. It is caused by repetitive trauma, which causes the formation of a mucin-containing cystic structure in the wall of the popliteal artery.
Motor weakness is the most important symptom, which may be accompanied by pain. It starts soon after standing up, and may be relieved by sitting or bending (lumbar spine flexion)
May present with absent or reduced peripheral pulses, and audible bruits but some patients may not present with these symptoms. A low ankle-brachial pressure index (<0.9) is suggestive of the disease but if normal it does not exclude it. An exercise ankle-brachial pressure index can be done on patients that doesn't present with these signs.
Other clinical features include: decreased skin temperature, shiny, hairless skin over the lower extremities, pallor on elevation of the extremity, dystrophic toenails, and rubor when the limb is dependent.
Caused by compression of the nerve root by other structure, such as an herniated disc. The pain usually radiates down the back of the leg and is described as sharp lancinating pain. It may be relieved by adjusting the position of the back (leaning forward).
Pain starts when the patient undergoes weight bearing and is worsened by activity. The pain is continuous and intensified by weight bearing, with inflammatory signs such as tenderness, swelling, and hyperthermia.
Shown below is an algorithm summarizing the diagnosis of claudication due to peripheral arterial disease according the the British Medical Journal guidelines.
Evaluate affected limb - check for color and trophic changes, early ulcerations, skin temperature, capillary refill time, pulses at the groin and popliteal fossa, and the pedal pulses.
If peripheral arterial disease is suspected:
Screening test: ankle-brachial index (systolic blood pressure of the dorsalis pedis, posterior tibialis, or fibularis artery is obtained with a handheld Doppler and divided by the higher of the two brachial pressures) - if <0.9 confirms peripheral arterial disease.
Secondary prevention for coronary arterial disease: start aspirin 75mg daily and statins
Control cardiovascular risk factors (hyperglycemia, obesity, dyslipidemia, smoking)
Advise the patient to exercise for 30 minutes twice daily to increase pain-free walking and total walking distance by stimulating collateral blood flow)
Antiplatelet drugs with either aspirin or clopidogrel alone is recommended to reduce myocardial infarction, stroke, and vascular death in patients with symptomatic PAD.[3]
In patients with claudication, supervised exercise programs increases functional status and reduce leg symptoms.[3]
Patients with diabetes mellitus should be oriented to perform self-foot examination and healthy foot behaviors. Quick diagnosis and treatment of foot infections can prevent amputation.[3]
Don'ts
Symptomatic treatment of the claudication and leg pain must not overshadow the reduction of cardiovascular risk, as these patients have a significantly increased risk of death.
When treating peripheral arterial disease, always attempt reducing symptoms with less invasive treatment options such as exercising, do not immediately refer patients to more invasive treatment options;
Don't forget to address other causes of claudication if the patient is presenting it at a younger age, or if the treatment doesn't improve the symptoms.
Do not perform invasive or non-invasive anatomic assessments for asymptomatic patients.[3]
In patients not at increased risk of peripheral arterial disease, and without history of physical examination findings suggestive of PAD, the ankle-brachial index is not recommended.[3]
Anticoagulation should not be used to reduce the risk of cardiovascular ischemic events in patients with PAD.[3]
Pentoxifylline is not effective for treatment of claudication.[3]
COVID-19-associated multisystem inflammatory syndrome (also known as PIMS-TS - pediatric inflammatory multisystem syndrome temporally with SARS-CoV2 infection or MIS-C - multisystem inflammatory syndrome in children) is an uncommon clinical entity caused by SARS-CoV2 and seen mostly on children. It presents with: fever > 3 days and elevated markers of inflammation and 2 of the following 5 criteria: rash or conjunctivitis; hypotension or shock; myocardial dysfunction, pericarditis, valvulitis or coronary abnormalities; evidence of coagulopathy and/or acute gastrointestinal problems along with evidence of COVID-19. It seems to be a severe form of COVID-19 in children presenting with symptoms that can be challenging to differentiate from other pediatric infectious diseases such as toxic shock syndrome and Kawasaki disease. The pathophysiology of this form of SARS-CoV2 infection remains unknown.
Cases of children with such symptoms were quickly identified in the New York City area, which was then the most heavily affected city in the U.S. by the COVID-19 pandemic;[1]
In 22 May, an article from the Journal of Pediatric Infectious Diseases Society addressed some of the similarities and differences of this new entity with Kawasaki's disease, noting that the demographics affected was significantly different, as it was not seen in Asia despite the pandemic also affecting such countries, but it was affecting mostly children of African ethnicity. The author also differentiated some of the laboratory findings, resembling the macrophage activation syndrome and not Kawasaki's disease.[1]
Classification of Disease Severity of COVID-19-associated multisystem inflammatory syndrome
There is no established system for the classification of COVID-19-associated multisystem inflammatory syndrome.
Pathophysiology
The exact pathophysiological mechanism of COVID-19-associated multisystem inflammatory syndrome is unclear.
Since there is a lag time between COVID-19-associated multisystem inflammatory syndrome appearance and COVID-19 infection (median time: 25 days) it is suspected to be a post-infectious phenomenon related to IgG antibody-mediated enhancement of disease. There are two arguments that support this theory: the presence of IgGantibodies against SARS-CoV2 and the presence of the lag time between COVID-19 symptoms and COVID-19-associated multisystem inflammatory syndrome.
There is, however, another theory that states that it is still an acuteviral presentation of the disease due to the fact that children presenting with such symptoms undergone exploratory laparotomy which found mesenteric adenitis, supporting GI infection. SARS-CoV2 is also known to easily infect enterocytes. Another interesting point to consider is that the worsening of illness has not been seen in patients with COVID-19 who are treated with convalescent plasma, which could have occurred if it was an antibody-mediated enhancement.[2]
There is another hypothesis for the cytokine storm seen on children with COVID-19-associated multisystem inflammatory syndrome is originated from the known ability of coronaviruses to block type I and type III interferon responses, delaying the cytokine storm in patients that could not control the viral replication on earlier phases of the disease.[2]
PCR tests for SARS-CoV-2 were positive in the minority of cases (26%), while the IgGantibody was positive in most patients (87%)[3] and it remains as the preferred laboratory test for differentiating such diseases;
The first cases of COVID-19-associated multisystem inflammatory syndrome presented with: unrelenting fever (38–40°C), conjunctivitis, cutaneous rash, peripheral edema, extremity pain and remarkable gastrointestinal symptoms. Most didn't have any respiratory symptoms, and all progressed to warm vasoplegic shock, refractory to volume resuscitation demanding vasopressors for hemodynamic support.
SerumIL-6 level was elevated in most patients. IL-2R, IL-18, and CXCL 9 levels were elevated in all patients of a cohort and mildly increased IFN-γ and IL-8 levels in some.
TNF-α, IL-1b, IL-2, IL-4, IL-5, and IL-13 levels remained normal in one in a series of cases from New York City.
Summary of laboratory parameters of a COVID-19-associated multisystem inflammatory syndrome cohort compared with the historic cohorts of Kawasaki Disease, Kawasaki Disease Shock Syndrome and Toxic Shock Syndrome[3]
Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes. According to recent evidence, it is suggested that children with MIS-C had antibodies against COVID-19 suggesting children had COVID-19 infection in the past. This syndrome appears to be similar in presentation to Kawasaki disease, hence also called Kawasaki -like a disease. It also shares features with staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes.
Classification of Disease Severity of MIS-C
Mild Disease
Children with MIS-C fall under this category who-
require minimal to no respiratory support.
minimal to no organ injury
normotensive
Do not meet the criteria for ICU admission.
Severe Disease
Children with MIS-C fall under this category who-[1]
have significant oxygen requirements (HFNC, BiPAP, mechanical ventilation).
have a mild-severe organ injury and ventricular dysfunction.
have a vasoactive requirement.
meet the criteria for ICU admissions
Pathophysiology
The excat pathophysiological mechanism of MIS-C is unclear. Since there is a lag time between MIS-C appearance and COVID-19 infection it is suspected to be causing by antibody dependent enhancement.
Another hypothesis is that since coronavirus block type1 and type III interferons, it results in delayed cytokine response in children with initially high viral load or whose immune response is unable to control infections causing MIS-C. Therefore, IFN responses result in viral clearance when the viral load is low resulting in mild infection. However, when the viral load is high and /or immune system is not able to clear the virus, the cytokine storm result in multisystem inflammatory syndrome in children (MIS-C).[2]
It is also suspected that since MIS-C presents predominantly with gastrointestinal manifestations, it replicates predominantly in the gastrointestinal tract.[2]
Differentiating Any Disease from other disease
It should be differentiated from following diseases
Bacterial sepsis
Staphylococcal and streptococcal toxic shock syndrome
Kawasaki disease.
More information about the differential diagnosis could be found here.
Epidemiology and Demographics
According to a recent study among the 186 children with MIS-C, the rate of hospitalization was 12% between March 16 and April 15 and 88% between April 16 and May 20.
80% of the children were admitted to the intensive care unit and 20% of the children required mechanical ventilation.
4% of the children required extracorporeal membrane oxygenation.[3]
The mortality rate among 186 children with MIS-C was 2%.[3]
Age
Among the 186 children with MIS-C distribution of age group was[3]
<1yr-7%
1-4yr-28%
5-9yr-25%
10-14yr-24%
15-20yr-16%.
Gender
Among the 186 children with MIS-C
Comorbidities
Children with MIS-C had following underlying comorbidities.[3]
Clinically diagnosed Obesity-8%
BMI-Based Obesity-29%
Cardiovascular diasease-3%
Respiratory disease-18%
Autoimmune disease or immunocompromising condition-5%
Organ System Involved
71% of children had involvement of at least four organ systems.[3]
The most common organ system involved in MIS-C children among a total of 186 children were.[3]
Gastrointestinal(92%)
Cardiovascular(80%)
Hematologic(76%)
Mucocutaneous(74%)
Pulmonary(70%)
Historical perspective
External links
Classification
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Tuberous sclerosis complex (TSC), is a rare autosomal dominant congenital disorder that affects multiple organ systems and is characterized by an abnormal growth of ectodermal and mesodermal cells that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs, and skin. [4]
The disease presents with a myriad of symptoms, having been described by multiple doctors throughtout the 19th century and called by many different names, but it is now called tuberous sclerosis complex, and the relationship between benign brain tumors and the symptoms of the disease was first described by Désiré-Magloire Bourneville in 1880. [6]
Historical Perspective
Tuberous Sclerosis was described as a specific disease in the 19th century, being initially referred to adenoma sebaceum, epiloia, Pringle's disease or Bourneville's disease. Rayer, a French dermatologist, was the one to first describe the disease and the fibrovascular papules that characterize it, making illustrations of it. He described two cases of tuberous sclerosis in patients who had the nasolabial papular eruption with telangiectasias at the base. In 1850 the first written report of tuberous sclerosis appeared in "Vitiligoidea", published by Addison and Gull. It was not recognized as a distinct disease but was classified as "vitiligoidea tuberosa". In 1862, von Recklinghausen reported a tumor of the heart found in a newborn during autopsy, and by that he is credited to be the first that described the microscopic appearance of tuberous sclerosis. Bourneville in 1880, a French neurologist, described the case of a girl who presented at the age of 3 with facial eruption and died at 15 years of age due to epilepsy, which complicated with pneumonia and inanition. He found brain and kidney tumors on the autopsy which were correctly believed to be the cause of her seizures and mental retardation. In 1911, E. B. Sherlock, superintendent of Belmont Asylum of Idiots, London, coined the word "epiloia" that indicated a clinical triad of epilepsy, low intelligence and adenoma sebaceum.[6]
In 2002, treatment with rapamycin was found to be effective at shrinking tumours in animals. This has led to human trials of rapamycin as a drug to treat several of the tumors associated with TSC.[7]
Classification
There is no established system for the classification of tuberous sclerosis.
Pathophysiology
Patients with tuberous sclerosis have loss-of-function germline mutations in both alleles of the following tumor suppressor genes: TSC1 or TSC2. One third of the mutations is inherited, two thirds are de novo mutations. The mutations causes the loss of one allele, but as long as the second one remains intact, the cell won't present any metabolic change. When there is a second TSC1 or TSC2 mutation, which typically occurs in multiple cells over a person's lifetime, then the disease starts to manifest (fitting the "two-hit" tumor-suppressor gene model, with the germline mutation inactivating one gene and then a somatic event inactivating the remaining other one). TSC1 codes for a protein called hamartin, and TSC2 codes for a protein called tuberin. They belong to a protein complex that inhibits the mammalian target of rapamycin (mTOR) complex 1 via RAS homologue enriched in brain (RHEB) which regulates cell growth. In a normal patient, RHEB activates mTORC1 when bound to GTP, but in TSC there is a hyperactivarion of RHEB and consequently of mTORC1. mTOR regulates cellular proliferation, autophagy, growth and protein and lipid synthesis and it enhances protein translation when activated, reprograming the cell metabolism, which increases cell proliferation but also may make it vulnerable to death in nutrient-restricted media.
Besides the TSC-RHEB-mTORC1 pathway, there is evidence of alternate pathways also having a role in the disease that are mTORC1 independent, but they are currently under investigation.[8][4]
Causes
Loss of function mutation of the genes TSC1 and TSC2 which are responsible for the production of hamartin and tuberin. These proteins regulate the cell cycle. Damage to this pathway leads to a very variable presentation of benign tumors in multiple systems.
TSC1 and TSC2 are both tumor suppressor genes that function according to Knudson's "two hit" hypothesis. That is, a second random mutation must occur before a tumor can develop. This explains why, despite its high penetrance, TSC has wide expressivity.[4]
Differentiating Tuberous Sclerosis from other Diseases
Tuberous sclerosis must be differentiated from other diseases that cause myxoma or other benign tumors and/or seizures, such as Sturge Weber, hypomelanosis of Ito, Birt-Hogg-Dube syndrome, multiple endocrine neoplasia and various seizures disorders.[9]
Epidemiology and Demographics
Tuberous sclerosis complex affects about 1 in 6,000 people, occurring in all races and ethnic groups, and in both genders. Prior to the invention of CT scanning to identify the nodules and tubers in the brain, the prevalence was thought to be much lower and the disease associated with those people diagnosed clinically with learning disability, seizures, and facial angiofibroma. Whilst still regarded as a rare disease, TSC is common when compared to many other genetic diseases, with at least 1 million individuals worldwide.[10][11]
Risk Factors
There are no established environmental risk factors for tuberous sclerosis. One third of the cases are familial, so family history can be a risk factor for the disease.[4]
Screening
As it is a rare disease, screening is not recommended.
Natural History, Complications, and Prognosis
Skin
Symptoms develop in almost all patients with TSC and include ungual fibromas, facial angiofibromas (may demand treatment and may worsen with UV exposure), shagreen patches (oval-shaped lesions, generally skin-colored but can be sometimes pigmented, may be crinkled or smooth), focal hypopigmented macules (ash-leaf spots), dental enamel pits (present in 100% of the patients), oral fibromas, retinal astrocytic hamartomas (tumors of the retinal nerve), retinal achromic patches (light or dark spots on the eye).[4]
Renal
TSC leads to the formation of renal angiomyolipomas (present in 60-80% of the TSC patients), benign tumors composed of abnormal vessels, smooth-muscle cells and fat cells which may cause hematuria. These tumors can be detectable in early childhood by MRI, CT or ultrasound. Although benign, in TSC they are commonly multiple and bilateral. Angiomyolipomas larger than 4 cm are at risk for potentially catastrophic hemorrhage either spontaneously or with minimal trauma. Patients may also develop epithelial cysts, polycystic kidney disease (as 2-3% of the patients carries a deletion that affects both TSC2 gene and one of the genes that lead to autosomal dominant polycystic kidney disease) and renal-cell carcinomas that may be diagnosed at a younger age (mean 28 years).[12][4] Patients ≥18 years may have higher rates of chronic kidney disease, hematuria, kidney failure, embolization (EMB), and partial and complete nephrectomy compared to patients <18 years.[13]
Pulmonary
Lymphangiomyomatosis affects mostly women and is a proliferation of smooth-muscle cells that may result in cystic changes in the lungs. Recent genetic analysis has shown that the proliferative bronchiolar smooth muscle in TSC-related lymphangioleiomyomatosis is monoclonal metastasis from a coexisting renal angiomyolipoma. Cases of TSC-related lymphangioleiomyomatosis recurring following lung transplant have been reported.[14] Diagnosed mostly during early adulthood, may cause pneumothorax. Multifocal micronodular pneumocyte hyperplasia can occur in both men and women and are mostly asymptomatic.[12][4]
In 2020 a paper showed that epilepsy remission by appropriate treatment in early life can possibly prevent autism and intellectual disability.[15]
Neurologic
These manifestations are one of the major causes of morbidity in patients with TSC. TSC may cause epilepsy, which is the most common neurological presentation occurring in 70-80% of patients and may complicate with infantile spasms, a severe form of epileptic syndrome. If epilepsy presents with an early onset t is associated with cognitive disabilities, which are also very prevalent in such patients. Neuropsychiatric disorders are present in two-thirds of the patients and anxiety is one of the most common presentations. Autism is one possible manifestation and is especially associated with cerebral cortical tubers. It consists of neurologic tissue that grows in a different pattern, losing the normal six-layered cortical structure, with dysmorphic neurons, large astrocytes and giant cells. Some patients may also present with subependymal giant cell astrocytomas, which may cause obstructive hydrocephalus. Risk of such benign tumors decreases after age of 20.[12][4]
Cardiovascular
Rhabdomyomas may be present, being intramural or intracavitary in its distribution along the myocardium. May be detected in utero on fetuses and is associated with cardiac failure. Often disappear spontaneously in later life.[4] 80% of children under two-years-old with TSC have at least one rhabdomyoma, and about 90% of those will have several.[16]
Diagnosis
Tuberous sclerosis complex is diagnosed if a set of diagnostic criteria are met. These criteria include major and minor features. If a case meets the clinical diagnostic criteria, then it is performed a genetic molecular testing which is seem mostly as corroborative. Most of the patients seek medical assistance due to their dermatologic lesions or seizures but for making this diagnosis an evaluation that assesses all the clinical features of the tuberous sclerosis complex is necessary, as these manifestations have variable penetrance.[12] The latest diagnostic criteria was developed by the 2012 International Tuberous Sclerosis Complex Consensus Conference, and it is showed at the table below:
Diagnostic Criteria for Tuberous Sclerosis Complex[17]
TSC can be first diagnosed at any stage of life. Prenatal diagnosis is possible by chance if heart tumours are discovered during routine ultrasound. In infancy, white patches on the skin may be noticed, or the child may present with epilepsy, particularly infantile spasms, or developmental delay may lead to neurological tests. In childhood, behavioural problems and autism spectrum disorder may also lead to a clinical investigation and a diagnosis. During adolescence it is usually that skin problems appear while in adulthood, kidney and lung problems may become evident. An individual may also be diagnosed at any time as a result of genetic testing of family members of another affected person.[18]
History and Symptoms
The most common symptoms of tuberous sclerosis are due to the growth of the already disclosed benign tumors. Tumors in the CSN may cause epilepsy, autism and children may also present with cognitive disabilities. Tumors in the kidneys may compromise renal function and metastasize to the lungs, which in most cases is asymptomatic. Tumors in the heart may compromise heart function, but they tend to spontaneously disappear later in life.
Physical Examination
Physical examination of patients with tuberous sclerosis is a very rich one due to the different skin lesions that the disease can cause and it is usually remarkable for dental enamel pits (present in 100% of the patients)[4],hypomelanotic macules, shagreen patches, and forehead plaques.[19]
Laboratory Findings
There are no typical diagnostic laboratory findings associated with tuberous sclerosis. Patients may present with elevated BUN or creatinine if their renal angiomyolipomas compromise renal function or if they also present with autosomal dominant polycystic kidney disease.
Electrocardiogram
There are no ECG findings associated with tuberous sclerosis.
X-ray
There are no typical x-ray findings associated with tuberous sclerosis, but patients may present with pneumothorax and/or chylous pleural effusions due if they develop lymphangioleiomyomatosis.
Echocardiography or Ultrasound
Echocardiography/ultrasound may be helpful raising the suspicion of tuberous sclerosis. Echocardiographs can detect cardiac rhabdomyomas, present in more than 80% of the children with TSC. Ultrasound can detect hepatic angiomyolipomas, renal angiomyolipomas (present in 55-75% of patients) and renal cysts (present in 18-55% of the patients).[20]
CT scan
CT scan may be helpful in the diagnosis of tuberous sclerosis. It can diagnose cortical or subependymal tubers and white matter abnormalities, subependymal hamartomas, subependymal giant cell astrocytomas, renal angiomyolipomas, renal cysts, renal cell carcinoma (associated with tuberous sclerosis), retroperitoneal lymphangiomyomatosis, gastrointestinal polyps, pancreatic neuroendocrine tumors, lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia and cardiac rhabdomyomas.[20]
MRI
MRI may be helpful in the diagnosis of tuberous sclerosis as it can find the same abnormalities found on CT scan which are described above, some of them with much more detail, but it is especially useful for evaluating white matter changes seen in the disease.[20]
Other Imaging Findings
There are no other imaging findings associated with tuberous sclerosis.
Other Diagnostic Studies
Genetic testing may be helpful in the diagnosis of tuberous sclerosis but some patients may not have detectable genetic mutations on the test and still have the disease. It is considered to be a corroborative test.
Treatment
Tuberous sclerosis complex affects multiple organ systems so a multidisciplinary team of medical professionals is required.
Screening of complications:
In suspected or newly diagnosed TSC, the following tests and procedures are recommended by 2012 International Tuberous Sclerosis Complex Consensus Conference.[21]
A magnetic resonance imaging (MRI) of the brain to identify tubers, subependymal nodules (SEN) and sub-ependymal giant cell astrocytomas (SEGA).
Children undergo a baseline electroencephalograph (EEG) and family educated to identify seizures if/when they occur.
Assess children for behavioural issues, autism spectrum disorder, psychiatric disorders, developmental delay, and neuropsychological problems.
Scan the abdomen for tumours in various organs, but most importantly angiomyolipomata in the kidneys. MRI is superior to CT or ultrasound. Take blood pressure and test renal function.
Examine the skin under a Wood's lamp (hypomelanotic macules), the fingers and toes (ungual fibroma), the face (angiofibromas), and the mouth (dental pits and gingival fibromas).
Use a fundoscope to spot retinal hamartomas or achromic patches.
Treatment:
The various symptoms and complications from TSC may appear throughout life, requiring continued surveillance and adjustment to treatments. The following ongoing tests and procedures are recommended by 2012 International Tuberous Sclerosis Complex Consensus Conference:[21]
In children and adults younger than 25 years, a magnetic resonance imaging (MRI) of the brain is performed every one to three years to monitor for subependymal giant cell astrocytoma (SEGA). If a SEGA is large, growing or interfering with ventricles, the MRI is performed more frequently. After 25 years, if there are no SEGAs then periodic scans may no longer be required. A SEGA causing acute symptoms are removed with surgery, otherwise either surgery or drug treatment with an mTOR inhibitor may be indicated.
Repeat screening for TSC-associated neuropsychiatric disorders (TAND) at least annually. Sudden behavioural changes may indicate a new physical problem (for example with the kidneys, epilepsy or a SEGA).
Routine EEG determined by clinical need.
Infantile spasms are best treated with vigabatrin and adrenocorticotropic hormone used as a second-line therapy. Other seizure types have no TSC-specific recommendation, though epilepsy in TSC is typically difficult to treat (medically refractory).
Repeat MRI of abdomen every one to three years throughout life. Check renal (kidney) function annually. Should angiomyolipoma bleed, this is best treated with embolisation and then corticosteroids. Removal of the kidney (nephrectomy) is strongly to be avoided. An asymptomatic angiomyolipoma that is growing larger than 3cm is best treated with an mTOR inhibitor drug. Other renal complications spotted by imaging include polycystic kidney disease and renal cell carcinoma.
Repeat chest HRCT in adult women every five to 10 years. Evidence of lymphangioleiomyomatosis (LAM) indicates more frequent testing. An mTOR inhibitor drug can help, though a lung transplant may be required.
A 12-lead ECG should be performed every three to five years.
The mTOR inhibitor everolimus was approved in the US for treatment of TSC-related tumors in the brain (subependymal giant cell astrocytoma) in 2010 and in the kidneys (renal angiomyolipoma) in 2012.[22][23] Everolimus also showed evidence of effectiveness at treating epilepsy in some people with TSC.[24][25] In 2017, the European Commission approved everolimus for treatment of refractory partial-onset seizures associated with TSC.[26]
Neurosurgical intervention may reduce the severity and frequency of seizures in TSC patients.[27][28]Embolization and other surgical interventions can be used to treat renal angiomyolipoma with acute hemorrhage. Surgical treatments for symptoms of lymphangioleiomyomatosis (LAM) in adult TSC patients include pleurodesis to prevent pneumothorax and lung transplantation in the case of irreversible lung failure.[21]
Other treatments that have been used to treat TSC manifestations and symptoms include a ketogenic diet for intractable epilepsy and pulmonary rehabilitation for LAM.[29] Facial angiofibromas can be reduced with laser treatment and the effectiveness of mTOR inhibitor topical treatment is being investigated. Laser therapy is painful, requires anaesthesia, and has risks of scarring and dyspigmentation.[30]
↑Song, Xue, et al. "Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma." Current medical research and opinion 33.7 (2017): 1277-1282.
↑Henske EP (December 2003). "Metastasis of benign tumor cells in tuberous sclerosis complex". Genes, Chromosomes & Cancer. 38 (4): 376–81. doi:10.1002/gcc.10252. PMID 14566858.
↑Gupta, Ajay, et al. "Epilepsy and neurodevelopmental comorbidities in tuberous sclerosis complex: a natural history study." Pediatric Neurology (2020).
↑Hinton RB, Prakash A, Romp RL, Krueger DA, Knilans TK (November 2014). "Cardiovascular manifestations of tuberous sclerosis complex and summary of the revised diagnostic criteria and surveillance and management recommendations from the International Tuberous Sclerosis Consensus Group". Journal of the American Heart Association. 3 (6): e001493. doi:10.1161/JAHA.114.001493. PMC 4338742. PMID 25424575.
↑Curatolo P, ed. (2003). "Diagnostic Criteria". Tuberous Sclerosis Complex: From Basic Science to Clinical Phenotypes. International review of child neurology. London: Mac Keith Press. ISBN978-1-898683-39-1. OCLC53124670.
↑ 20.020.120.2Radiopaedia - tuberous sclerosis - available at: https://radiopaedia.org/articles/tuberous-sclerosis accessed at 06/15/2020
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An aortic aneurysm is a dilation of the aorta in which the aortic diameter is ≥ 3.0 cm if abdominal[1] or >4 cm if thoracic[2], usually representing an underlying weakness in the wall of the aorta at that location. While the stretched vessel may occasionally cause discomfort, a greater concern is the risk of rupture which causes severe pain, massive internal hemorrhage which are often fatal. Aneurysms often are a source of blood clots (emboli) stemming from the most common etiology of atherosclerosis.
Classification
There are 2 types of aortic aneurysms: thoracic and abdominal. These can be further classified according to the respective part of the vessel that's been affected:
Suprarenal - not as common, often more difficult to repair surgically due to the presence of many aortic branches;
Infrarenal - often more easily surgically repaired and more common;
Pararenal - aortic aneurysm is infrarenal but affects renal arteries;
Juxtarenal - infrarenal aortic aneurysm that affects the aorta just below the renal arteries.
Aortic aneurysms may also be classified according to Crawford classification into 5 subtypes/groups:
Type 1: from the origin of left subclavian artery in descending thoracic aorta to the supra-renal abdominal aorta.
Type 2: from the left subclavian to the aorto-iliac bifurcation.
Type 3: from distal thoracic aorta to the aorto-iliac bifurcation
Type 4: limited to abdominal aorta below the diaphragm
Type 5: from distal thoracic aorta to celiac and superior mesenteric origins, but not the renal arteries.[3]
Historical Perspective
Aortic aneurysm was first recorded by Antyllus, a Greek surgeon, in the second century AD. In the Renaissaince era, in 1555, Vesalius first diagnosed an abdominal aortic aneurysm. The first publication on the pathology with case studies was published by Lancisi in 1728. Finally, in 1817, Astley Cooper was the first surgeon to ligate the abdominal aorta to treat a ruptured iliac aneurysm. In 1888, Rudoff Matas came up with the concept of endoaneurysmorrhaphy.[4]
Pathophysiology
The aortic aneurysms are a multifactorial disease associated with genetic and environmental risk factors. Marfan's syndrome and Ehlers-Danlos syndrome are associated with the disease, but there are also rarer syndromes like the Loeys-Dietz syndrome that are associated as well. Even in patients that do not have genetic syndromes, it has been observed that genetics can also play a role on aortic aneurysms' development. There has been evidence of genetic heterogeneity as there has already been documented in intracranial aneurysms.[5] The genetic alterations associated with these genetic syndromes are the following:
Genetic diseases associated with aortic aneurysms [6]
These genetic diseases mostly affect either the synthesis of extracellular matrix protein or damage the smooth muscle cells both important component's of the aortic wall. Injury to any of these components lead to weakening of the aortic wall and dilation - resulting in aneurysm formation.
The aorta is the largest vessel of the body, but it is not homogenous. Its upper segment is composed by a larger proportion of elastin in comparison to collagen, therefore being more distensible. The lower segment has a larger proportion of collagen, therefore it is less distensible. It is also where most of the atherosclerotic plaques of the aorta are located.[1] Historically it was thought that abdominal and thoracic aortic aneurysms were caused by the same etiology: atherosclerotic degeneration of the aortic wall, but recently it has been theorized that they are indeed different diseases.[1]
When neural crest vascular smooth muscle cells are treated with TGF-β they demonstrate increased collagen production, while mesodermal vascular smooth muscle cell did not.[10] Not coincidently, mutations of the TGF-β receptor can cause thoracic aortic aneurysm but do not cause abdominal aortic ones.
The thoracic and abdominal aorta are very structurally different. While they both have three layers: intimal, medial and adventitia, the media of the thoracic aorta is comprised of approximately 60 units divided into vascular and avascular regions. The abdominal aorta consists of about 30 units and is entirely avascular, being dependent on trans-intimal diffusion of nutrients for its smooth muscle cells to survive.[11] It is believed that both differences explain why the abdominal aorta is more likely to form aneurysms.
Thoracic aortic aneurysms: The aneurysms tend to grow slowly and most of them will never rupture. As they grow, however, their symptoms become more evident and present with mass effects over surrounding structures and pain. They may present with thoracic symptoms: interscapular or central pain, ripping chest pain and dyspnea. Atypical presentations include hoarseness, dizziness and dysphagia, due to esophageal compression.[13] Aneurysm rupture lead to massive internal bleeding, hypovolemic shock and it is usually fatal.
Abdominal aortic aneurysms: as the thoracic aneurysms, they begin asymptomatic but may cause symptoms as they grow and compress surrounding structures.[14]Even though they usually remain asymptomatic, when they rupture they present with an ensuing mortality of 85 to 90%., and symptomatic patients require urgent surgical repair.[15]
When symptomatic, abdominal aortic aneurysms present with:
Pain: in the chest, abdomen, lower back, or flanks. It may radiate to the groin, buttocks, or legs. The pain characteristics vary and may be deep, aching, gnawing, or throbbing It may also last for hours or days, not affected by movement. Occasionally, certain positions can be more comfortable and alleviate the symptoms;
Pulsating abdominal mass;
Ischemia: "cold foot" or a black or blue painful toe. This is usually the presentation when an aneurysm forms a blood cloth and it releases emboli to the lower extremities;
If ruptured, the abdominal aortic aneurysm can present with sharp abdominal pain, often radiating to the back, discoloration of the skin and mucosa, tachycardia and low blood pressure due to hypovolemic shock.
Differentiating Aortic Aneurysm from other Diseases
These conditions can be easily differentiated using abdominal or thoracic imaging.
Epidemiology and Demographics
In the United States alone 15,000 people die yearly due to aortic aneurysms and it is the 13th leading cause of death. 1-2% of the population may have aortic aneurysms and prevalence rises up to 10% in older age groups. The disease varies according to where it takes place. In the thorax, the aortic arch is the less affected segment (10%) and the most common is the ascending aorta (50%). Regarding abdominal aneurysms, the infrarenal segment aortic aneurysms are three times more prevalent than the aortic aneurysms and dissections.[5]
Regarding other factors as age, abdominal aortic aneurysms usually present 10 years later than thoracic aortic aneurysms. Both lesions are more present in men, but the proportion is much higher regarding abdominal aortic aneurysms (6:1 male:female ratio) in comparison to thoracic ones.[5]
Abdominal aortic aneurysms also affect patients differently regarding race, as they are more prevalent among whites than blacks, asians and hispanics. It also seems to be declining in prevalence as evidenced by a Swedish study that found out a 2% prevalence of abdominal aortic aneurysms in comparison to earlier studies which reported 4-8%, probably due to risk-factor modification. [18]
Risk Factors
Many risk factors are common between both forms of aortic aneurysms, but some are specific for each presentation:
Even though the majority of the aortic aneurysms remain asymptomatic for years, their natural history is dissection or rupture.[3] According to Laplace's law, as the aneurysms grow larger they have a higher rate of expansion. Due to that, the frequency of monitoring changes with the diameter of the abdominal aortic aneurysm, being every 3 years for aneurysms with a 3-3.4cm diameter, yearly for diameters of 3.5-4.4cm, and every 6 months for larger than 4.5cm.[18] For the thoracic one, up to 80% of the aneurysms will eventually rupture, and patients present with a 10-20% five-year survival rate if they remain untreated.[3] Risk of rupture doubles every 1cm in growth over the 5cm diameter in descending thoracic aorta.[20]
Besides rupturing and dissection of the aorta, aortic aneurysms can also present with systemic embolization and aortic regurgitation (if the thoracic aortic aneurysm is located in the ascending aorta). The altered blood flow in the aneurysm can also lead to the formation of blood cloths and embolization. [21]
Beta-blockers may help in reducing the rate of expansion of the aortic aneurysm, reducing shear stress - studies have been mostly on Marfan patients and they found a low compliance with propranolol due to a significant effect on quality of life[23];
Tetracyclines inhibit the MMPendopeptidases, and has been used in conditions in which MMP are overexpressed such as rheumatoid arthritis. There are studies in humans showing that doxycycline reduced the rate of expansion of aortic aneurysms. Roxithromycin, a macrolide has been also show to reduce the expansion of the aortic aneurysms.
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers promotes vascular hypertrophy, cell proliferation and production of extracellular matrix. It also activates the NADH/NADPH oxidase system, both stimulating and inhibiting MMPs and degradation of extracellular matrix. There is a controversy of which class is more effective, and ongoing trials are being run to further clarify these questions.[23]
There are no established guidelines for this matter, treatment is still controversial and should be individualized.[24][25]
Surgery
Decision to perform elective surgery to prevent aneurysm rupture is complicated as there must be an appropriate patient selection and timing for repair of the aneurysm which demands selecting patients at the greatest risk of aneurysm rupture. Once rupture occurs, mortality is extremely high. Fatality rates of emergency surgical repair is 50% if the patient manages to reach the hospital, in comparison to 1-5% fatality rate in elective surgical repair.[26]
According to the 2005 AHA/ACC guidelines - it is recommended surgical repair of abdominal aortic aneurysms:
5.5 cm in diameter or greater in asymptomatic patients;
Increase by 0.5 cm or greater in diameter in 6 months;
Symptomatic aneurysms.
Endovascular repair may be performed with better short-term morbidity and mortality rates but with failed long-term benefits over surgical repair. Endovascular is preferred in high-risk patients while surgical repair is generally indicated for low/average-risk patients.[26]
In thoracic aortic aneurysms, surgery is indicated in Marfan's syndrome when the aortic diameter reaches 5.0cm, or the rate of increase of the aortic root diameter approaches 1.0 cm per year, or progressive and severe aortic regurgitation. If family history is positive for aortic aneurysms, aggressive therapy may be indicated in individuals with Marfan and Loeys Dietz syndrome. Surgery consists in replacing the affected portion of the aorta. [25]
Prevention
Smoking cessation is an important measure to prevent aortic aneurysm progression and rupture, as is control of the other cardiovascular risks, such as hypertension, sedentarism and dyslipidemia.[17]
↑ 1.01.11.21.3Kuivaniemi, Helena, et al. "Understanding the pathogenesis of abdominal aortic aneurysms." Expert review of cardiovascular therapy 13.9 (2015): 975-987.
↑ 3.03.13.2Frederick, John R., and Y. Joseph Woo. "Thoracoabdominal aortic aneurysm." Annals of cardiothoracic surgery 1.3 (2012): 277.
↑Livesay, James J., Gregory N. Messner, and William K. Vaughn. "Milestones in treatment of aortic aneurysm: Denton A. Cooley, MD, and the Texas Heart Institute." Texas Heart Institute Journal 32.2 (2005): 130.
↑ 5.05.15.2Kuivaniemi, Helena, Chris D. Platsoucas, and M. David Tilson III. "Aortic aneurysms: an immune disease with a strong genetic component." Circulation 117.2 (2008): 242-252.
↑Ruddy JM, Jones JA, Ikonomidis JS. Pathophysiology of thoracic aortic aneurysm (TAA): is it not one uniform aorta? Role of embryologic origin. Progress in cardiovascular diseases. 2013;56(1):68–73.
↑Steed MM, Tyagi SC. Mechanisms of cardiovascular remodeling in hyperhomocysteinemia. Antioxidants & redox signaling. 2011;15(7):1927–1943.
↑Bruemmer D, Daugherty A, Lu H, Rateri DL. Relevance of angiotensin II-induced aortic pathologies in mice to human aortic aneurysms. Ann N Y Acad Sci. 2011;1245:7–10.
↑Gadson PF, Jr, Dalton ML, Patterson E, et al. Differential response of mesoderm- and neural crest-derived smooth muscle to TGF-beta1: regulation of c-myb and alpha1 (I) procollagen genes. Experimental cell research. 1997;230(2):169–180.
↑Wolinsky H, Glagov S. Comparison of abdominal and thoracic aortic medial structure in mammals. Deviation of man from the usual pattern. Circulation research. 1969;25(6):677–686.
↑Ailawadi G, Eliason JL, Upchurch GR Jr. Current concepts in the pathogenesis of abdominal aortic aneurysm. J Vasc Surg 2003;38:584-8.
↑Hiller, H. G., and N. R. F. Lagattolla. "Thoracic aortic aneurysm presenting with dysphagia: a fatal delay in diagnosis." Thoracic surgical science 4 (2007).
↑Radiopaedia - Abdominal Aortic Aneurysms https://radiopaedia.org/articles/abdominal-aortic-aneurysm?lang=us
Accessed at 06/08/2020
↑ 23.023.123.2Danyi, Peter, John A. Elefteriades, and Ion S. Jovin. "Medical therapy of thoracic aortic aneurysms: are we there yet?." Circulation 124.13 (2011): 1469-1476.
↑Yoshimura, Koichi, et al. "Current status and perspectives on pharmacologic therapy for abdominal aortic aneurysm." Current drug targets 19.11 (2018): 1265-1275.
↑ 25.025.1Clift, Paul F., and Elena Cervi. "A review of thoracic aortic aneurysm disease." Echo Research and Practice 7.1 (2020): R1-R10.
↑ 26.026.1Aggarwal, Sourabh, et al. "Abdominal aortic aneurysm: A comprehensive review." Experimental & Clinical Cardiology 16.1 (2011): 11.
Short QT syndrome is a rare autosomal dominant inherited disease of the electrical conduction system of the heart. It is defined by short QT intervals (≤ 360 ms) that increases an individual propensity to atrial and ventricular tachyarrhythmias.[1] It occurs due to gain-of-function mutations in genes encoding for cardiac potassium channels KCNH2, KCNQ1 and KCNJ2. The shortened QT interval does not significantly change with heart rate, and there are tall and peaked T waves in the right precordium. It is associated with an increased risk of atrial fibrillation, syncope and sudden death.
Historical Perspective
The syndrome was first described by Dr. Prebe Bjerregaard MD, DMSc in 1999, who wrote the first clinical report of three members of one family who presented with persistently short QT interval.[2][3]
Classification
Short QT syndrome type 1 (SQT1): This variant is due to a gain-of-function mutation of the rapid component of the delayed rectifier potassium current HERG (KCNH2) channel(IKr)[4]. The variant is a result of missense mutations which increase IKr. It is associated with sudden death and sudden infant death syndrome.
Short QT syndrome type 2 (SQT2): Caused by a mutation in the KCNQ1 gene[5]. In the first patient, a g919c substitution in the KCNQ1 gene encoding for the K+ channel KvLQT1 was identified. The mutation led to a gain of function in in the KvLQT1 (I(Ks)) channel. This variant is associated with ventricular fibrillation.
Short QT syndrome type 3 (SQT3): This variant results from a G514A substitution in the KCNJ2 gene ( a change from aspartic acid to asparagine at position 172 (D172N))[6]. This causes a defect in the gene coding for the inwardly rectifying Kir2.1 (I(K1)) channel. The ECG shows asymmetrical T waves. These patients have an increased risk for re-entry arrhythmias.
Short QT syndrome type 4 (SQT4): A loss of function mutation in the CACNA1C gene alters the encoding for the α1- and β2b-subunits of the L-type calcium channel. The phenotype is similar to Brugada syndrome combined with a short QT interval. There is an increased risk of sudden cardiac death.
Short QT syndrome type 5 (SQT5): A loss of function mutation in the CACNB2B gene alters the encoding for the α1- and β2b-subunits of the L-type calcium channel. The phenotype is similar to Brugada syndrome combined with a short QT interval. There is an increased risk of sudden cardiac death.
Short QT syndrome type 6 (SQT6): A loss of function mutation in the CACNAD2D1 coding for the Cavα2δ-1 subunit of the L-type calcium channel. [7]
Pathophysiology
Short QT syndrome types 1-3 are due to increased activity of outward potassium currents in phase 2 and 3 of the cardiac action potential due to mutations in potassium channels. This causes a shortening of the plateau phase of the action potential (phase 2), causing a shortening of the overall action potential, leading to an overall shortening of refractory periods and the QT interval. In the families afflicted by short QT syndrome, two different missensemutations have been described in the human ether-a-go-go gene (HERG). These mutations result in expression of the same amino acid change in the cardiac IKr ion channel. This mutated IKr has increased activity compared to the normal ion channel, and would theoretically explain the above hypothesis. Short QT syndrome types 4 and 5 and 6 are due to mutations in the calcium channel and consequent reduction in L-type Ca-channel current.[8]
Genetics
In the families afflicted by short QT syndrome, mutations have been described in three genes, KvLQT1, the human ether-a-go-go gene (HERG), and KCNJ2. Mutations in the KCNH2, KCNJ2, and KCNQ1 genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an autosomal dominant pattern of inheritance.
Due to the autosomal dominant inheritance pattern, individuals may have family members with a history of unexplained or sudden death at a young age (even in infancy), palpitations, or atrial fibrillation. The penetrance of symptoms is high in affected family members. It is also interesting to note that while mutations involving potassium channel genes associated with the long QT syndrome are loss-of-function mutations, the mutations that cause short QT syndrome are gain-of-function mutations.[9]
The calcium channels' dysfunction are mostly due to CACNA1C and CACNB2b genes mutation which caused Brugada-like ECG changes with short QT interval. Lastly, a novel mutation of the CACNA2D1 gene was reported in a 17-year-old female who presented with short QT interval and ventricular fibrillation.[9]
Causes
The causes of shortening of the QT interval can be divided into primary causes (Short QT syndrome types 1-5) and secondary causes such as drugs and electrolyte disturbances.
Differentiating Short QT Syndrome from other Disorders
Short QT may have secondary causes that must be ruled out, since the short QT syndrome is by definition a primary, congenital disease of the heart. Such causes include: hyperkalemia, hypercalcemia, acidosis, hyperthermia - caused by the use of drugs like digitalis, effect of acetylcholine or catecholamine and activation of Katp or Kach current.[1] Only after ruling out such causes is that the diagnosis of short QT syndrome may be made.
Epidemiology and Demographics
European studies have estimated a prevalence of 0.02% to 0.1% among adults. A paper from 2015 which tried to assess the prevalence among pediatric population in the U.S. estimated a prevalence of 0.05% at this population.[10]Sudden cardiac arrest has a peak incidence between the second and fourth decades of life, which might indicate an association with testosterone levels in males.[9]
Natural History, Complications, Prognosis
The disease can have clinical manifestations from the first year of life until as late as 80 years old, and most cases are symptomatic.[9] Its most frequent symptoms include cardiac arrest (which was the first symptom in 28% of the patients), followed by palpitations, and syncope. Patients may also present with atrial fibrillation and ventricular extrasystoles. They remain at high risk for sudden death during their lifetime and may present with a strong family history for this occurence.[9]Sudden cardiac death presents with two high-risk peaks, one in the first year of life, and another one from 20 to 40 years old.[11] Even though familial association is present in the majority of patients, the yields for genetic tests is low.[9]
Screening
Since the disease is so rare, no screening for the general population is advised. Individuals with short QT interval detected on the ECG must first rule out other causes. Genetic screening is performed if a patient presents with: sudden cardiac arrest, history of polymorphic ventricular tachycardia or ventricular fibrillation without a known cause, history of unexplained syncope, young individuals with atrial fibrillation, family members diagnosed with short QT syndrome, family members who died from sudden cardiac arrest.[12]
Diagnosis
The first step for diagnosing short QT syndrome is ruling out secondary causes, such as the ones cited above.[1] Once them are ruled out, there are two suggested diagnostic approaches in the medical literature: one proposed by GOLLOB, and another one proposed by PRIORI:
- Scoring type of diagnostic criteria, as proposed by the Arrhythmia Research Laboratory at the University of Ottawa Heart Institute from Drs. Michael H Gollob and Jason D Roberts.[13]
Diagnostic Criteria for Short QT Syndrome from UoO Heart Institute
1st or 2nd degree relative with sudden death = 1 point
Sudden infant death syndrome = 1 point
Genotype
Genotype positive = 2 points
Mutation of undetermined significance in a culprit gene = 1 point
The points are summed and interpreted as follows:
> or equal to 4 points: High-probability of SQTS
3 Points: Intermediate probability of SQTS
2 points or less: Low probability of SQTS
- Diagnostic criteria suggested by PRIORI, 2015 for the European Society of Cardiology:
QTc <340ms or QTc <360ms and one or more of the following:
Confirmed pathogenic mutation;
Family history of SQTS;
Family history of sudden death at 40 years of age;
Survival from a VT/VF episode at the absence of heart diseases.[14]
Electrocardiogam
Duration of the QT Interval
Tall peaked T wave and short QT in the right precordial lead V2
While the QT interval is generally short, the QT interval alone cannot be used to distinguish the patient with short QT syndrome from a normal patient (similar to long QT syndrome).[15] In general though, if the QTc is < 330 msec in a male, and <340 msec in a female, then short QT syndrome can be diagnosed even in the absence of symptoms as these QT intervals are much shorter than in the rest of the population. On the other hand, if the QTc is moderately shortened to < 360 msec in a male or < 370 msec in a female, the short QT syndrome should only be diagnosed in the presence of symptoms or a family history according to the guidelines above. [14][13]
The short QT interval does not vary significantly with the heart rate. Normally the QT will become longer at slow heart rates and this does not occur among patients with short QT syndrome. The Bazett formula may overcorrect (i.e. shorten) the QT interval in the patient with bradycardia, and it is therefore important to use treadmill testing to increase the heart rate and confirm the absence of QT interval variation.[17]
Other ECG findings:
There is a high prevalence of early depolarization patterns on SQTS.[8]
QRS complex is followed by T wave without any ST segment.[9]
Prominent U wave separated by isoelectric T-U segment.[9]
Prolongation of the QT interval at slower heart rates is suppressed, remaining below the lower limit.[9]
Depressed PQ segment commonly observed in the inferior and anterior leads.[9]
In a very limited number of patients it has been observed that early repolarization (which is present in 65% of patients with SQTS) and a longer T wave peak to T wave end period is associated with the occurrence of arrhythmic events.[18]
Among patients with SQTS, the atrial and ventricular refractory periods are shortened (ranging from 120 to 180 ms). Ventricular fibrillation can be induced on programmed stimulation in 90% of patients with short QT syndrome. Despite the high rate of VF inducibility, the risk of sudden death in an individual patient is difficult to predict given the genetic and clinical heterogeneity of short QT syndrome and the limited number of patients with short follow-up to date. The limitations of electrophysiologic testing are highlighted by a study of Giustetto et al in which the sensitivity of electrophysiologic testing in relation to the clinical occurrence of ventricular fibrillation was only 50% (3 of 6 cases)[19]. Importantly, lack of inducibility does not exclude a future episode of ventricular fibrillation[20]. Thus, the role of electrophysiologic testing in risk stratification of the patient with SQTS is not clear at present.
Genetic Testing
Because new genetic variants of SQTS are still being identified, a negative genetic test for existing variants does not exclude the presence of SQTS. A negative genetic test for existing variants could mean that a patient with a short QT interval does not have a heretofore unidentified variant of SQTS.
However, among family members of an affected patient, genetic testing may identify the syndrome in an asymptomatic patient, and may also rule out the presence of the syndrome in asymptomatic patients.
Mutations in the KCNH2, KCNJ2, and KCNQ1 genes cause short QT syndrome. These genes provide instructions for making proteins that act as channels across the cell membrane. These channels transport positively charged atoms (ions) of potassium into and out of cells. In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. Mutations in the KCNH2, KCNJ2, or KCNQ1 gene increase the activity of the channels, which changes the flow of potassium ions between cells. This disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of short QT syndrome. Short QT syndrome appears to have an autosomal dominant pattern of inheritance.
Centers Performing Genetic Testing for Short QT Syndrome
An implantable cardioverter-defibrillator (ICD) is indicated in symptomatic patients who have either survived a sudden cardiac arrest and/or have had documented episodes of spontaneous sustained ventricular tachyarrhythmias with or without syncope. There's a problem with ICD in such patients though, because the tall and peaked T wave can be interpreted as a short R-R interval provoking inappropriate shock.[9]
Generally accepted criteria for implantation of an AICD also include:
Inducibility on electrophysiologic testing;
Positive genetic test, although a negative result does not exclude the presence of a previously unreported mutation or the occurrence of a future arrhythmic event.
The efficacy of pharmacotherapy in preventing ventricular fibrillation has only been studies in patients with SQT1. Given the limited number of patients studied, and the limited duration of follow-up, pharmacotherapy as primary or secondary preventive therapy for patients with SQT1 cannot be recommended at this time. AICD implantation remains the mainstay of therapy in these patients. Pharmacotherapy may play an adjunctive role in reducing the risk of events in patients with an AICD as described below in the indications section.
Patients with Short QT Syndrome 1 (SQT1) have a mutation in KCNH2 (HERG). Class IC and III antiarrhythmic drugs do not produce any significant QT interval prolongation [22][23] . Flecainide has not been shown to consistently reduce the inducibility of ventricular fibrillation.[24] Although it does not prolong the QT interval in SQT1 patients, propafenone reduces the risk of recurrent atrial fibrillation in SQT1 patients.[25]
Quinidine in contrast may be effective in patients with SQT1 in so far as it blocks both potassium channels (IKr, IKs, Ito, IKATP and IK1) and the inward sodium and calcium channels. In four out of four patients, Quinidine prolonged the QT interval from 263 +/- 12 msec to 362 +/-25 msec, most likely due to its effects on prolonging the action potential and by virtue of its action on the IK channels. Although Quinidine was successful in preventing the inducibility of ventricular fibrillation in 4 out of 4 patients, it is unclear if the prolongation of the QT interval by quinidine would reduce the risk of sudden cardiac death. It also prolonged the ST interval and T wave durations, restored the heart rate dependent variability in the QT interval and decreased depolarization dispersion in patients with SQT1.
There is a report which states that disopyramide was also effectively used in two patients with SQT-1, increasing their QT interval and ventricular refractory period while also abbreviating the Tpeak-Tend interval.
As atrial fibrillation is also very commonly found on those patients propafenone has also been successfully used to prevent its paroxysms, without having any effect on QT interval.[9]
Although pharmacotherapy can be used to suppress the occurrence of atrial fibrillation in patients with SQT1, AICD implantation is the mainstay of therapy, and pharmacotherapy to prevent sudden death should is only indicated if AICD implantation is not possible.
Indications for Pharmacologic Therapy
The following are indications for pharmacologic therapy of SQTS[26]:
In patients with appropriate AICD discharges to reduce the frequency of discharges;
In patients with atrial fibrillation to reduce the frequency of symptomatic episodes.
References
↑ 1.01.11.2Patel, Chinmay, Gan-Xin Yan, and Charles Antzelevitch. "Short QT syndrome: from bench to bedside." Circulation: Arrhythmia and Electrophysiology 3.4 (2010): 401-408. Available at https://doi.org/10.1161/CIRCEP.109.921056
↑Templin, Christian, et al. "Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6)." European heart journal 32.9 (2011): 1077-1088.
↑ 8.08.1Ossama K. Abou Hassan, MD (10/05/2016). "Short QT Syndrome". American College of Cardiology. Check date values in: |date= (help)
↑ 9.009.019.029.039.049.059.069.079.089.099.109.119.12Rudic, Boris, Rainer Schimpf, and Martin Borggrefe. "Short QT syndrome–review of diagnosis and treatment." Arrhythmia & electrophysiology review 3.2 (2014): 76.
↑Guerrier, Karine, et al. "Short QT interval prevalence and clinical outcomes in a pediatric population." Circulation: Arrhythmia and Electrophysiology 8.6 (2015): 1460-1464.
↑Campuzano, Oscar, et al. "Recent advances in short QT syndrome." Frontiers in cardiovascular medicine 5 (2018): 149.
↑ 13.013.1Gollob M, Redpath C, Roberts J. (2011). "The Short QT syndrome: Proposed Diagnostic Criteria". J Am Coll Cardiol. 57 (7): 802–812. doi:10.1016/j.jacc.2010.09.048. PMID21310316.CS1 maint: Multiple names: authors list (link)
↑ 14.014.1Priori, Silvia Giuliana, and Carina Blomström-Lundqvist. "2015 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death summarized by co-chairs." European heart journal 36.41 (2015): 2757-2759.
↑Viskin S. The QT interval: Too long, too short or just right. Heart Rhythm 2009; 6: 711–715.
↑Antzelevitch C, Pollevick GD, Cordeiro JM et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST- segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007: 115: 442-449.
↑Moreno-Reviriego S, Merino JL.Short QT Syndrome. An article from the E-Journal of the ESC Council for Cardiology Practice. Vol9 N°2, 17 Sep 2010 [1]
