When a [[diagnosis]] of human plague is suspected upon [[clinical]] and [[epidemiological]] grounds, appropriate specimens for [[diagnosis]] should be obtained immediately and the patient should be started on specific [[antibiotic|antimicrobial therapy]] prior to a definitive answer from the laboratory.<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref><ref>{{Cite book | last1 = Longo | first1 = Dan L. (Dan Louis) | title = Harrison's principles of internal medici | date = 2012 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-174889-6 | pages = }}</ref> The drugs of choice are [[streptomycin]] or [[gentamicin]], but [[tetracyclines]], [[fluoroquinolones]], and [[chloramphenicol]] are also effective. The regimens should be adjusted depending on the patient's age, medical history, underlying health conditions, and allergies.<ref name=CDC>{{cite web | title = Plague | url = http://www.cdc.gov/plague/healthcare/clinicians.html }}</ref> Upon evidence of [[pneumonia]], suspect plague patients should be placed in isolation and managed under respiratory droplet precautions.<ref name="pmid8789689">{{cite journal| author=Garner JS| title=Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. | journal=Infect Control Hosp Epidemiol | year= 1996 | volume= 17 | issue= 1 | pages= 53-80 | pmid=8789689 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8789689 }} </ref>
When a diagnosis of plague is suspected, appropriate specimens for diagnosis should be obtained immediately and antimicrobial therapy should be started. <ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref><ref>{{Cite book | last1 = Longo | first1 = Dan L. (Dan Louis) | title = Harrison's principles of internal medici | date = 2012 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-174889-6 | pages = }}</ref> The drug of choice is either [[Streptomycin]] or [[Gentamicin]], but [[Tetracyclines]], [[Fluoroquinolones]], and [[Chloramphenicol]] may also be effective. The treatment regimen should be adjusted depending on the patient's age, medical history, underlying health conditions, and allergies.<ref name=CDC>{{cite web | title = Plague | url = http://www.cdc.gov/plague/healthcare/clinicians.html }}</ref> Upon evidence of [[pneumonia]], patients with suspected plague should be placed in isolation and managed under respiratory droplet precautions.<ref name="pmid8789689">{{cite journal| author=Garner JS| title=Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. | journal=Infect Control Hosp Epidemiol | year= 1996 | volume= 17 | issue= 1 | pages= 53-80 | pmid=8789689 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8789689 }} </ref>. Supportive therapy includes aggressive monitoring and management for the possibility of complications such as [[septic shock]], [[multiple organ failure]], [[acute respiratory distress syndrome]], and [[disseminated intravascular coagulopathy]].
==Medical Therapy==
==Medical Therapy==
Shown below is a table summarizing the choices of antibiotics used to treat ''yersina pestis''<ref name=CDC>{{cite web | title = Plague | url = http://www.cdc.gov/plague/healthcare/clinicians.html }}</ref>. Duration of treatment is 10 days, or until 2 days after [[fever]] subsides. Oral therapy may be substituted once the patient demonstrates improvement.<ref name=CDC>{{cite web | title = Plague | url = http://www.cdc.gov/plague/healthcare/clinicians.html }}</ref>
<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font></SMALL><ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref><ref name=CDC>{{cite web | title = Plague | url = http://www.cdc.gov/plague/healthcare/clinicians.html }}</ref>
::* Alternative regimen (3): [[Sulfadiazine]] 2-4 g loading dose {{then}} 1 g PO q4-6h
<font color="#FFF">
::* Alternative regimen (4): [[Doxycycline]] 200 mg/day PO q12-24h
▸ '''Adult Patients'''
::* 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.
</font>
::* Note (2): Other antibiotics have been shown ineffective against plague.
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Streptomycin]] 1 g IM q12h'''''<BR> OR <BR> ▸ '''''[[Gentamicin]] 5 mg/Kg q24h, or 2 mg/kg loading dose followed by 1.7 mg/kg q8h, IM or IV'''''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Doxycycline]] 100 mg IV q12h or 200 mg IV q24h'''''<BR> OR <BR> ▸ '''''[[Ciprofloxacin]] 400 mg IV q12h'''''
|}
|}
|}
====Aminoglycosides====
[[Streptomycin]], the most effective [[antibiotic]] against ''[[Yersinia pestis]]'', is the [[drug]] of choice for treatment of [[plague]], particularly the pneumonic form. Therapeutic effect is expected with '''30 mg/kg/day''' (maximum of 2 g/day) in divided doses given [[intramuscularly]], and continued for a full course of 10 days or until 3 days following temperature normalization.<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref><ref>{{Cite book | last1 = Longo | first1 = Dan L. (Dan Louis) | title = Harrison's principles of internal medici | date = 2012 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-174889-6 | pages = }}</ref><ref name="pmid13139207">{{cite journal| author=SMADEL JE, WOODWARD TE, AMIES CR, GOODNER K| title=Antibiotics in the treatment of bubonic and pneumonic plague in man. | journal=Ann N Y Acad Sci | year= 1952 | volume= 55 | issue= 6 | pages= 1275-84 | pmid=13139207 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13139207 }} </ref><ref name="MeyerQuan1952">{{cite journal|last1=Meyer|first1=K. F.|last2=Quan|first2=S. F.|last3=McCrumb|first3=F. R.|last4=Larson|first4=A.|title=EFFECTIVE TREATMENT OF PLAGUE|journal=Annals of the New York Academy of Sciences|volume=55|issue=6|year=1952|pages=1228–1274|issn=00778923|doi=10.1111/j.1749-6632.1952.tb22687.x}}</ref><ref name="pmid1262715">{{cite journal| author=Butler T, Levin J, Linh NN, Chau DM, Adickman M, Arnold K| title=Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis. | journal=J Infect Dis | year= 1976 | volume= 133 | issue= 5 | pages= 493-9 | pmid=1262715 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1262715 }} </ref>
[[Gentamicin]], found to be effective in animal studies, is also used to treat human plague patients.<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref>
====Chloramphenicol====
[[Chloramphenicol]], a suitable alternative to [[aminoglycosides]] in the treatment of bubonic or septicemic plague, is the drug of choice for patients with a ''[[Yersinia pestis]]'' invasion of tissue spaces where other drugs travel poorly, such as plague [[meningitis]], [[pleuritis]], or [[endophthalmitis]]. Dosage should be '''50 mg/kg/day''' administered in divided doses either parenterally or, if tolerated, orally for 10 days. [[Chloramphenicol]] may be used adjunctively with [[aminoglycosides]].<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref>
====Tetracyclines====
[[Tetracycline]]s, a group of [[bacteriostatic]] antibiotics, are effective in the primary treatment of patients with uncomplicated plague. An oral loading dose of '''15 mg/kg''' tetracycline (maximum of 1g total), should be followed by '''25-50 mg/kg/day''' (maximum of 2 g/day) for 10 days. [[Tetracyclines]] may also be used adjunctively with other [[antibiotics]].<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref>
====Sulfonamides====
Although [[sulfonamides]] have been used extensively in plague treatment and [[prevention]], some studies have demonstrated higher [[mortality]], increased [[complications]], and longer duration of [[fever]] as compared to the use of [[streptomycin]], [[chloramphenicol]] or [[tetracycline]] [[antibiotics]]. [[Sulfadiazine]] is given as a loading dose of '''2-4 g''' followed by a dose of '''1 g every 4-6 hours for a period of 10 days'''. In children, the oral loading dose is '''75 mg/kg''', followed by '''150 mg/kg/day orally in six divided doses'''. The combination drug [[trimethoprim-sulfamethoxazole]] has been used both in the treatment and prevention of plague.<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref>
====Fluoroquinolones====
[[Fluoroquinolones]], such as [[ciprofloxacin]], have been effective against [[Yersinia pestis|Y. pestis]] in both in vitro and animal studies. [[Ciprofloxacin]] is [[bacteriocidal]] and has broad spectrum activity against most [[Gram-negative]] [[aerobic bacteria]], including [[Enterobacteriaceae]] and ''[[Pseudomonas aeruginosa]]'', as well as against many [[Gram-positive bacteria]]. Although it has been used successfully to treat humans with ''[[Francisella tularensis]]'' infection, no studies have been published on its use in treating human plague.<ref name="pmid10635759">{{cite journal| author=| title=Plague manual--epidemiology, distribution, surveillance and control. | journal=Wkly Epidemiol Rec | year= 1999 | volume= 74 | issue= 51-52 | pages= 447 | pmid=10635759 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10635759 }} </ref>
When a diagnosis of plague is suspected, appropriate specimens for diagnosis should be obtained immediately and antimicrobial therapy should be started. [1][2] The drug of choice is either Streptomycin or Gentamicin, but Tetracyclines, Fluoroquinolones, and Chloramphenicol may also be effective. The treatment regimen should be adjusted depending on the patient's age, medical history, underlying health conditions, and allergies.[3] Upon evidence of pneumonia, patients with suspected plague should be placed in isolation and managed under respiratory droplet precautions.[4]. Supportive therapy includes aggressive monitoring and management for the possibility of complications such as septic shock, multiple organ failure, acute respiratory distress syndrome, and disseminated intravascular coagulopathy.
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.
Other cases of antibiotics, such as penicillins, cephalosporins, and macrolides have demonstrated to be ineffective or of variable effect in the treatment of plague and should not be used for this purpose.[1]
Supportive Therapy
Clinicians must prepare for intense supportive management of plague complications, utilizing the latest developments for dealing with Gram-negativesepsis.[7] Aggressive monitoring and management should be instituted for the possibility of:[1]
↑Wheeler, Arthur P.; Bernard, Gordon R. (1999). "Treating Patients with Severe Sepsis". New England Journal of Medicine. 340 (3): 207–214. doi:10.1056/NEJM199901213400307. ISSN0028-4793.