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__NOTOC__
Hospitalized patients
{| class="wikitable"
!Infection
!
!Organisms
!First DOC
!Alternative
!
|-
| rowspan="2" |'''Osteomyelitis'''
|Presumed hematogenous source or contiguous without vascular insufficiency
|''S. aureus''
|Vancomycin
|Vanc
|
* If ''S. aureus'' is methicillin-susceptible then cefazolin 2 g IV q8h or nafcillin 2 g IV q4h are the antibiotics of choice.
 
* Obtain bone biopsy to determine microbiologic cause prior to initiation of antimicrobial therapy if blood cultures are negative and patient clinically stable.
|-
|With vascular insufficiency or diabetes mellitus (e.g. severe diabetic foot ulcer)
|''S. aureus'' 
Enterobacteriaceae
 
Anaerobes
|'''Vancomycin'''
PLUS ONE OF:
 
'''Piperacillin/Tazobactam''' 4.5 g IV q6-8h
 
OR
 
'''Ertapenem''' 1 g IV daily
|For '''severe''' PCN allergy:
'''Vancomycin'''
 
PLUS ONE OF:


==Overview==
'''Ciprofloxacin'''400 mg IV q12h


==Historical Perspective==
OR
*Transplacental transmission from an asymptomatic infected mother was first described in 1906.<ref name="urlGuidelines for the Prevention and Control of Congenital Syphilis">{{cite web |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00026330.htm |title=Guidelines for the Prevention and Control of Congenital Syphilis |format= |work= |accessdate=}}</ref>


==Classification==
'''Levofloxacin''' 750 mg IV daily
Congenital Syphilis is classified based on the timing of appearance of signs and symptoms into:<ref name="pmid23919053">{{cite journal| author=Balaji G, Kalaivani S| title=Observance of Kassowitz law-late congenital syphilis: Palatal perforation and saddle nose deformity as presenting features. | journal=Indian J Sex Transm Dis | year= 2013 | volume= 34 | issue= 1 | pages= 35-7 | pmid=23919053 | doi=10.4103/0253-7184.112869 | pmc=3730472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23919053  }} </ref>
*'''Early congenital Syphilis:'''If the signs and symptoms are identified in children aged less than 2 years. It is usally diagnosed in new born or in the first few weeks after birth.<ref name="pmid25079189">{{cite journal| author=Cavagnaro S M F, Pereira R T, Pérez P C, Vargas Del V F, Sandoval C C| title=[Early congenital syphilis: a case report]. | journal=Rev Chil Pediatr | year= 2014 | volume= 85 | issue= 1 | pages= 86-93 | pmid=25079189 | doi=10.4067/S0370-41062014000100012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25079189  }} </ref>
*'''Late congenital Syphilis:''' If the signs and symptoms of the disease are identified in children aged more than 2 years. The signs are usually non-specific and more than half the children are asymptomatic. They can present with interstitial keratitis, eighth nerve deafness or clutton's joints.
*'''Stigmata:''' These are the scars resulting from early or late congenital syphilis. The features of stigmata in early congenital syphilis include saddle nose deformity, Hutchinson's teeth, rhagades, choriod scarring and onychia. Stigmata secondary to late congenital syphilis include perforation of the palate, corneal opacities, optic atrophy and periosteal changes of tibia.


==Pathophysiology==
OR


===Pathogenesis===
'''Aztreonam''' 2 g IV q8h
*Transmission to the fetus is transplacental, it can also occur during delivery in the presence of maternal genital lesions.<ref name="pmid11438902">{{cite journal| author=Wicher V, Wicher K| title=Pathogenesis of maternal-fetal syphilis revisited. | journal=Clin Infect Dis | year= 2001 | volume= 33 | issue= 3 | pages= 354-63 | pmid=11438902 | doi=10.1086/321904 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11438902  }} </ref>
*The risk of transmission to the fetus is dependent on the stage of the maternal disease(dependent on the spirochete concentration in the blood stream) and the duration of exposure to the fetus in utero.<ref name="pmid15356936">{{cite journal| author=Berman SM| title=Maternal syphilis: pathophysiology and treatment. | journal=Bull World Health Organ | year= 2004 | volume= 82 | issue= 6 | pages= 433-8 | pmid=15356936 | doi= | pmc=2622860 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15356936  }} </ref>
*The risk of vertical transmission of syphilis from an infected untreated mother decreases as maternal disease duration progresses: transmission risk of 70–100% for primary syphilis and 40% for early latent syphilis to 10% for late latent disease. The variation in the percentages with the duration of infection is because the concentration of spirochetes in the blood stream decrease with the duration of maternal syphilis infection.<ref name="pmid10858706">{{cite journal |vauthors=Genç M, Ledger WJ |title=Syphilis in pregnancy |journal=Sex Transm Infect |volume=76 |issue=2 |pages=73–9 |year=2000 |pmid=10858706 |pmc=1758294 |doi= |url=}}</ref>
*Kassowitz's law describes the an inverse relationship of interval between the disease and pregnancy. Longer the interval between infection and pregnancy more benign is the outcome.<ref name="pmid23919053">{{cite journal| author=Balaji G, Kalaivani S| title=Observance of Kassowitz law-late congenital syphilis: Palatal perforation and saddle nose deformity as presenting features. | journal=Indian J Sex Transm Dis | year= 2013 | volume= 34 | issue= 1 | pages= 35-7 | pmid=23919053 | doi=10.4103/0253-7184.112869 | pmc=3730472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23919053  }} </ref>
*Transmission of infection typically takes place between the 16th and 28th week of pregnancy, however the transmission can be as early as the first trimester of pregnancy.<ref name="pmid56895">{{cite journal |vauthors=Harter C, Benirschke K |title=Fetal syphilis in the first trimester |journal=Am. J. Obstet. Gynecol. |volume=124 |issue=7 |pages=705–11 |year=1976 |pmid=56895 |doi= |url=}}</ref>


===Genetics===
ALL WITH OR WITHOUT:
===Gross Pathology===


===Microscopic Pathology===
'''Metronidazole'''500 mg IV q8h (if patient critically ill)
*Skin lesion on microscopy are characterized by perivascular infiltration by lymphocytes, plasma cells and histiocytes, with endarteritis and extensive fibrosis.
|
* Other organisms are possible, esp. with hardware microbiologic diagnosis and ID consultation recommended


==Risk Factors==
* Obtain bone biopsy to determine microbiologic cause prior to initiation of antimicrobial therapy if patient clinically stable
Risk factors for congenital syphilis include all the risk factors which predispose a pregnant woman to have syphilis infection:<ref name="pmid2356911">{{cite journal| author=Rolfs RT, Goldberg M, Sharrar RG| title=Risk factors for syphilis: cocaine use and prostitution. | journal=Am J Public Health | year= 1990 | volume= 80 | issue= 7 | pages= 853-7 | pmid=2356911 | doi= | pmc=1404975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2356911  }} </ref><ref name="pmid17675391">{{cite journal| author=Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM et al.| title=Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China. | journal=Sex Transm Infect | year= 2007 | volume= 83 | issue= 6 | pages= 476-80 | pmid=17675391 | doi=10.1136/sti.2007.026187 | pmc=2598725 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17675391  }} </ref><ref name="pmid15247352">{{cite journal| author=Hook EW, Peeling RW| title=Syphilis control--a continuing challenge. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 2 | pages= 122-4 | pmid=15247352 | doi=10.1056/NEJMp048126 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15247352  }} </ref><ref name="pmid16205297">{{cite journal| author=Buchacz K, Greenberg A, Onorato I, Janssen R| title=Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention. | journal=Sex Transm Dis | year= 2005 | volume= 32 | issue= 10 Suppl | pages= S73-9 | pmid=16205297 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16205297  }} </ref><ref name="pmid25514173">{{cite journal| author=Solomon MM, Mayer KH| title=Evolution of the syphilis epidemic among men who have sex with men. | journal=Sex Health | year= 2015 | volume= 12 | issue= 2 | pages= 96-102 | pmid=25514173 | doi=10.1071/SH14173 | pmc=4470884 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25514173  }} </ref><ref name="pmid24927712">{{cite journal| author=Hakre S, Arteaga GB, Núñez AE, Arambu N, Aumakhan B, Liu M et al.| title=Prevalence of HIV, syphilis, and other sexually transmitted infections among MSM from three cities in Panama. | journal=J Urban Health | year= 2014 | volume= 91 | issue= 4 | pages= 793-808 | pmid=24927712 | doi=10.1007/s11524-014-9885-4 | pmc=4134449 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24927712  }} </ref><ref name="newell">Newell, J., et al. "A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour." Genitourinary medicine 69.6 (1993): 421-426.</ref>
*Inadequate antenatal care
*Multiple sexual partners
*Prostitution
*Illicit drug use
*Unprotected sex
*Residence in highly prevalent areas
*[[Human Immunodeficiency Virus (HIV)|HIV]] infection
*Presence of other [[STI]]<nowiki/>s
*Previous history of STIs
*Intravenous drug use
*Health care professionals who are predisposed to occupational risk
*Low socioeconomic status


==Screening==
* Once stable, switch to oral antibiotics based on susceptibility results.
Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women and screening is a key component to decrease the incidence of congenital syphilis. The recommendations for screening are as follows:
{| border="1"
|-
|-
!
|'''Septic Arthritis'''
!'''Screening Recommendations'''
|
|''S. aureus''
''Streptococci spp.''
 
''N. gonorrhoeae''
 
''Enterobacteriaceae (rarely)''
|'''Vancomycin'''
PLUS
 
'''Ceftriaxone'''1 g IV daily
|For '''severe''' PCN allergy:
'''Vancomycin'''
 
PLUS ONE OF:
 
'''Ciprofloxacin''' 400 mg IV q12h
 
OR
 
'''Levofloxacin''' 500 mg IV daily
 
OR
 
'''Aztreonam''' g IV q8h if gonococcus is strongly suspected
|Gram stain recommended to guide therapy.
Narrow coverage to microbiologically confirmed pathogens.
|}
{| class="wikitable"
|-
|-
!'''Timing of Screening'''
|'''Brain abscess'''
|Test all pregnant women at the first prenatal visit.                                                                                                               
|Streptococci (anaerobic or aerobic)
''Bacteroides spp''
 
''Prevotella'' spp
 
Enterobacteriacea
|'''Ceftriaxone'''
2 g IV q12h
 
PLUS
 
'''Metronidazole''' 500 mg PO/IV q8h
 
WITH OR WITHOUT*:
 
'''Vancomycin'''
|'''Aztreonam'''
2 g IV q8h
 
PLUS
 
'''Vancomycin'''
 
PLUS
 
'''Metronidazole''' 500 mg PO/IV q8h
|Consider expanded Gram-positive coverage if patient at risk for drug-resistant streptococci or MRSA
|-
|-
!'''Screening Tests'''
|'''Meningitis'''
|
Community-onset
*Nontreponemal tests commonly used for initial screening include:
|''S. pneumoniae''
**Venereal Disease Research Laboratory (VDRL)
 
**Rapid Plasma Reagin (RPR)
''Neisseria meningitidis''
*Confirmatory tests include:
**Fluorescent treponemal antibody absorbed (FTA-ABS)
**Treponema pallidum particle agglutination (TPPA)
|-
!'''High Risk Population'''
|
*Most organizations recommend testing high-risk women again during the third trimester and at delivery.<br>Groups at increased risk include:
**Uninsured women
**Women living in poverty
**Sex workers
**Illicit drug users
**Those diagnosed with other sexually transmitted diseases (STDs)
**Other women living in communities with high syphilis morbidity
|}


==Epidemiology, Demographics==
''Listeria'' (especially in immuno-compromised, elderly patients, and alcoholics)
===Incidence===
|'''ceftriaxone'''
*It is estimated that every year 2 million pregnant women are infected with syphilis every year.
2 g IV q12h
*In 2005, WHO reported that 460,000 abortions or still birth and 270,000 cases of congenital syphilis every year can be attributed to maternal syphilis.
*The incidence of congenital syphilis in United States in the year 2014 is 11.6 cases per 100,000 live births. The incidence of congenital syphilis has increased when compared to the numbers from 2008 to 2012 and the change is attributed to the increase in the number of women with primary and secondary syphilis.


===Race===
PLUS
*Congenital syphilis is ten times and three times more prevalent in black population compared to whites and Hispanics respectively.


==Natural History, Complications and Prognosis==
'''Vancomycin'''
===Natural History===
*Syphilis is a sexually transmitted disease and is prevalent in high risk population. Women with syphilis infection can transmit the infection to the fetus in utero resulting in a wide spectrum of outcomes. The risk of transmission is higher in pregnant women who do not undergo regular antenatal screening or in women who are untreated or adequately treated during the period of gestation. The risk of transmission to the fetus is dependent on the stage of syphilis infection in the mother (primary, secondary, tertiary or latent), duration of maternal infection and the exposure to fetus in utero. The transmission of infection typically occurs during the second trimester but early transmission also occurs. Syphilis can complicate the outcome of pregnancy and is dependent on the severity of infection in the fetus, severe infection has adverse outcomes in the new born.<ref name="pmid6340889">{{cite journal| author=Charles D| title=Syphilis. | journal=Clin Obstet Gynecol | year= 1983 | volume= 26 | issue= 1 | pages= 125-37 | pmid=6340889 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6340889  }} </ref>


===Complications===
WITH OR WITHOUT* one of:
*Severe infection in the fetus can result in spontaneous abortion, stillbirth, non-immune hydrops, intrauterine growth restriction, and perinatal death, and serious sequelae in liveborn infected children.
===Prognosis===
*Adequate treatment of infected mother during the period of gestation can prevent the transmission of disease significantly and *Treatment of the mother with one dose of pencillin is proven to improve outcomes in the fetus.<ref name="pmid12232835">{{cite journal |vauthors=Watson-Jones D, Gumodoka B, Weiss H, Changalucha J, Todd J, Mugeye K, Buvé A, Kanga Z, Ndeki L, Rusizoka M, Ross D, Marealle J, Balira R, Mabey D, Hayes R |title=Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes |journal=J. Infect. Dis. |volume=186 |issue=7 |pages=948–57 |year=2002 |pmid=12232835 |doi=10.1086/342951 |url=}}</ref>
*In newborns and infants with congenital syphilis treatment with penicillin has a good prognosis with normal development.


==Diagosis==
'''TMP/SMX''' 15 mg/kg/day (in divided doses)


===History and Symptoms===
OR
Early syphilis: It is diagnosed at birth or in the first few weeks of life. A combination of maternal risk factors and symptoms in the baby are essential to suspect congenital syphilis. The most common symptoms in the new born include:
*Skin rash occurs in 70% of affected cases
*Yellowish discoloration of the skin
*Abdominal distension
*Generalized edema
*Irritability
*Low birth weight
*Failure to thrive
*Fever
*Difficulty breathing
Late Syphilis: It is diagnosed in children aged greater than 2 years. The symptoms are non specific.


===Physical Examination===
'<nowiki/>'''''Ampicillin'''''' 2 g IV q4h
The physical examination findings suggestive of congenital syphilis include:<ref name="EwingRoberts1985">{{cite journal|last1=Ewing|first1=C I|last2=Roberts|first2=C|last3=Davidson|first3=D C|last4=Arya|first4=O P|title=Early congenital syphilis still occurs.|journal=Archives of Disease in Childhood|volume=60|issue=12|year=1985|pages=1128–1133|issn=0003-9888|doi=10.1136/adc.60.12.1128}}</ref>
|For '''severe''' PCN allergy:
*Vesiculobullous or maculopapular rash occurring on the palms and soles is present in 70% of the children with congenital syphilis. Other patterns of rash such as vesiculobullous lesions, condylomata lata lesions, annular lesions, and erythema multiforme-like targetoid lesions are present in affected infants.<ref name="FerreiraCorreia2016">{{cite journal|last1=Ferreira|first1=Sara Tavares|last2=Correia|first2=Cátia|last3=Marçal|first3=Monica|last4=Tuna|first4=Madalena Lopo|title=Skin rash: a manifestation of early congenital syphilis|journal=BMJ Case Reports|year=2016|pages=bcr2016216148|issn=1757-790X|doi=10.1136/bcr-2016-216148}}</ref>
'''Vancomycin'''
*Low birth weight with signs of prematurity
*Nonimmune hydrops : It is characteristic of congenital syphilis and the features of non-immune hydrops include ascites, pericardial effusion, pleural effusion and skin edema, however Rh incompatability should be ruled out as a cause of hydrops.<ref name="pmid8822333">{{cite journal| author=Barron SD, Pass RF| title=Infectious causes of hydrops fetalis. | journal=Semin Perinatol | year= 1995 | volume= 19 | issue= 6 | pages= 493-501 | pmid=8822333 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8822333  }} </ref>
*Jaundice
*Hepatosplenomegaly
*Rhinitis
*Pseudoparalysis of an extremities


===Laboratory Findings===
PLUS
====Prenatal Diagnosis====
*Detection of IgM antibodies aganist T.pallidum in the blood collected by chordocentesis.<ref name="pmid1923218">{{cite journal |vauthors=Wendel GD, Sánchez PJ, Peters MT, Harstad TW, Potter LL, Norgard MV |title=Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies complicated by congenital syphilis |journal=Obstet Gynecol |volume=78 |issue=5 Pt 2 |pages=890–5 |year=1991 |pmid=1923218 |doi= |url=}}</ref>
*PCR of the amniotic fluid to detect the T. pallidum DNA.<ref name="MullerEwert2006">{{cite journal|last1=Muller|first1=M|last2=Ewert|first2=I|last3=Hansmann|first3=F|last4=Tiemann|first4=C|last5=Hagedorn|first5=H J|last6=Solbach|first6=W|last7=Roider|first7=J|last8=Nolle|first8=B|last9=Laqua|first9=H|last10=Hoerauf|first10=H|title=Detection of Treponema pallidum in the vitreous by PCR|journal=British Journal of Ophthalmology|volume=91|issue=5|year=2006|pages=592–595|issn=0007-1161|doi=10.1136/bjo.2006.110288}}</ref>
*Antenatal ultrasound is commonly done and the findings suggestive of congenital syphilis include: hydrops fetalis characterised by scalp oedema, placental thickening, serous cavity effusion, and polyhydramnios. Other additional findings inlcude hepatosplenomegaly, placentomegaly, non-continuous gastrointestinal obstruction and dilatation of the small bowel.<ref name="pmid9565220">{{cite journal |vauthors=Levine Z, Sherer DM, Jacobs A, Rotenberg O |title=Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening |journal=Am J Perinatol |volume=15 |issue=4 |pages=233–6 |year=1998 |pmid=9565220 |doi=10.1055/s-2007-993933 |url=}}</ref><ref name="Russell1974">{{cite journal|last1=Russell|first1=Peter|title=Placental Abnormalities of Congenital Syphilis|journal=American Journal of Diseases of Children|volume=128|issue=2|year=1974|pages=160|issn=0002-922X|doi=10.1001/archpedi.1974.02110270034007}}</ref><ref name="pmid7927729">{{cite journal |vauthors=Riley BS, Oppenheimer-Marks N, Radolf JD, Norgard MV |title=Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells |journal=Infect. Immun. |volume=62 |issue=10 |pages=4622–5 |year=1994 |pmid=7927729 |pmc=303152 |doi= |url=}}</ref>


====Postnatal Diagnosis====
'''Aztreonam'''2 g IV q6h-q8h
*Examination of the placenta or umbilical cord using a silver  stain demonstrates spirochetes or a T. pallidum PCR test can be done.
*Darkfield microscopic examination or PCR testing of suspicious lesions or body fluids (e.g., bullous rash and nasal discharge) helps confirm the diagnosis.
*The use of serological tests to identify the infection in infants less than 15months of age born to infected mothers is not performed as passive transfer of IgG antibodies to the fetus occurs during the pregnancy.
*Other laboratory findings in the new born include:<ref name="pmid11384701">{{cite journal |vauthors=Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD |title=Fetal syphilis: clinical and laboratory characteristics |journal=Obstet Gynecol |volume=97 |issue=6 |pages=947–53 |year=2001 |pmid=11384701 |doi= |url=}}</ref>
*Elevated liver enzymes
*Leucocytosis
*Coombs negative haemolytic anaemia
*Thrombocytopenia
*Hypoalbuminemia
*Hyperbilirubinemia


===Imaging Studies===
WITH OR WITHOUT*:
====X-Ray====
*Skeletal survey is done in a still born, typical osseous lesions are demonstrated in congenital syphilis.
====Ultrasound====
Antenatal sonographic features include:<ref name="radiop2"> https://radiopaedia.org/articles/in-utero-syphilis-infection. Accessed on September 28th, 2016. </ref><ref name="pmid21844732">{{cite journal| author=Reyna-Figueroa J, Esparza-Aguilar M, Hernández-Hernández Ldel C, Fernández-Canton S, Richardson-Lopez Collada VL| title=Congenital syphilis, a reemergent disease in Mexico: its epidemiology during the last 2 decades. | journal=Sex Transm Dis | year= 2011 | volume= 38 | issue= 9 | pages= 798-801 | pmid=21844732 | doi=10.1097/OLQ.0b013e31821898ca | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21844732  }} </ref>
*Fetal [[hepatosplenomegaly]]
* Placentomegaly
* Fetal [[ascites]]<br>
In severe cases findings include:
*Fetal [[hydrops]]
*Bent fetal long bones


====Doppler Studies====
'''TMP/SMX''' (if ''Listeria'') 15 mg/kg/day (in divided doses)
Doppler ultrasound of the uterine and umbilical arteries show increases in the mean systolic to diastolic ratios in mothers infected with syphilis indicating an increased resistance to perfusion of the placenta secondary to vasculitis, placental villitis and obliterative arteritis caused by syphilis.<ref name="Genc2000">{{cite journal|last1=Genc|first1=M.|title=Syphilis in pregnancy|journal=Sexually Transmitted Infections|volume=76|issue=2|year=2000|pages=73–79|issn=13684973|doi=10.1136/sti.76.2.73}}</ref>
|
* Therapy should be guided by Gram stain.


==Treatment==
* If bacterial meningitis suspected'','' dexamethasone 10 mg PO/IV q6h x 4 days given before or with initial dose of antibiotics. 


===Medical Therapy===
* Coverage for ''Listeria'' with TMP/SMX or ampicillin should be added for patients who are <2 or >50 years of age or immunocompromised.
====Management during the period of gestation====
{| border="1"
|-
|-
!
|'''Meningitis'''
!'''CDC Recommendations for management of pregnant woman with Syphilis infection'''
Post-neurosurgical or device associated
|''S. aureus''
Coagulase negative
 
Staphylococci
 
Gram negative rods
|'''Cefepime'''
PLUS
 
'<nowiki/>'''''Vancomycin'''''' 
|For '''severe''' PCN allergy:
'''Aztreonam''' 2 g IV q6h-q8h
 
PLUS
 
'''Vancomycin'''
|
|}
{| class="wikitable"
|-
|-
!'''Approach during the Prenatal Period'''
|'''Native Valve'''
|''S. aureus''
''Streptococci spp.''
 
''Enterococcus spp.''
 
Occasional gram negative rods
 
HACEK < 5%
|'''Vancomycin'''
WITH or WITHOUT*
 
'''Ceftriaxone'''
 
2 g IV daily
|For '''severe''' PCN allergy:
'''Vancomycin'''
 
WITH or WITHOUT*
 
'''Ciprofloxacin'''ID-R: VASF 400 mg IV q12h
|
|
*All women should be screened [[Syphilis laboratory tests#Serology|serologically]] for syphilis early in pregnancy.<ref name=syphilis>https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/syphilis-infection-in-pregnancy-screening Accessed on september 27,2016</ref><ref name=cdc2015>http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016</ref>
* Narrow coverage to microbiologically confirmed pathogens
*Most states mandate screening at the first prenatal visit for all women;<ref name="pmid11384701">Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11384701 Fetal syphilis: clinical and laboratory characteristics.] ''Obstet Gynecol'' 97 (6):947-53. PMID: [http://pubmed.gov/11384701 11384701]</ref> antepartum screening by [[Syphilis laboratory findings#Nontreponemal test|nontreponemal antibody testing]] is typical, but in some settings, [[Syphilis laboratory findings#Treponemal test|treponemal antibody testing]] is being used.
 
*Pregnant women with reactive treponemal screening tests should have confirmatory testing with nontreponemal tests with titers to monitor treatment response.
* Addition of Gram-negative coverage should be considered if the patient has a sub-acute presentation.
*In populations in which use of prenatal care is not optimal, [[Rapid plasma reagent|RPR test]] screening and treatment (if the RPR test is reactive) should be performed at the time that pregnancy is confirmed.
*For communities and populations in which the prevalence of syphilis is high and for patients at high risk, serologic testing should be performed twice during the third trimester (ideally at 28-32 weeks' gestation) and at delivery.
*Any woman who delivers a stillborn infant after 20 weeks' gestation should be tested for syphilis.
*No infant should leave the hospital without the maternal serologic status having been determined at least once during pregnancy.
*Quantitative maternal nontreponemal titer, especially if >1:8, might be a marker of early infection and bacteremia. However, risk for fetal infection is still significant in pregnant women with late latent syphilis and low titers.
*Seropositive pregnant women should be considered infected unless an adequate treatment history is documented clearly in the medical records and sequential serologic antibody titers have declined.
*Serofast low antibody titers might not require treatment; however, persistent higher titer antibody tests might indicate reinfection, and treatment might be required.
|-
|-
!'''Recommended Regimen for Treatment'''
|'''Prosthetic Valve'''
|''S. aureus''
''S. epidermidis''
|'''Vancomycin'''
PLUS
 
'''Rifampin'''300 mg PO q8h
 
PLUS
 
'''Gentamicin''' 1 mg/kg/dose IV q8h for initial two weeks only
 
Single daily dose of gentamicin is not recommended
|
|Rifampin has numerous clinically significant drug interactions.  Medication lists should be reviewed for potential drug-drug interactions with rifampin.
|}
{| class="wikitable"
|'''Spontaneous Bacterial Peritonitis (SBP)'''
|''E. coli''
''Klebsiella spp.''
 
'<nowiki/>'''Streptococci. spp''.'''''
|'''Ceftriaxone''' 1 g IV daily x 5 days
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Aztreonam''' 2 g IV q8h
|
|
*Pregnant women should be treated with the [[penicillin]] regimen appropriate for their stage of infection.<ref name="urlSexually Transmitted Diseases Treatment Guidelines, 2010">{{cite web|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm |title=Sexually Transmitted Diseases Treatment Guidelines, 2010 |format= |work= |accessdate=2012-12-19}}</ref>
* [[Penicillin]] is effective for preventing maternal transmission to the fetus and for treating fetal infection.<ref name="pmid9916946">Alexander JM, Sheffield JS, Sanchez PJ, Mayfield J, Wendel GD (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9916946 Efficacy of treatment for syphilis in pregnancy.] ''Obstet Gynecol'' 93 (1):5-8. PMID: [http://pubmed.gov/9916946 9916946]</ref> Evidence is insufficient to determine optimal, recommended penicillin regimens.<ref name="pmid11686978">Walker GJ (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11686978 Antibiotics for syphilis diagnosed during pregnancy.] ''Cochrane Database Syst Rev''  (3):CD001143. [http://dx.doi.org/10.1002/14651858.CD001143 DOI:10.1002/14651858.CD001143] PMID: [http://pubmed.gov/11686978 11686978]</ref>
|-
|-
!'''Additional Considerations'''
|'''Secondary Peritonitis'''
'''Mild-Moderate''' intra-abdominal abscess
|''E. coli''
''Klebsiella'' 
 
''B. fragilis''
 
''Streptococci spp''
 
''S. aureus''
|'''Ertapenem''' 1g IV daily
OR
 
'''Piperacillin/tazobactam''' 3.375 g IV q6h - 4.5g IV q6h
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Aztreonam''' 2 g IV q8h
 
PLUS
 
'''Metronidazole'''500 mg IV q8h
|
|
*Some evidence suggests that additional therapy can be beneficial for pregnant women in some settings (e.g., a second dose of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin]] 2.4 million units IM administered 1 week after the initial dose for women who have [[Syphilis pathophysiology#Primary syphilis|primary]], [[Syphilis pathophysiology#Secondary syphilis|secondary]], or [[Syphilis pathophysiology#Latent syphilis|early latent syphilis]]).<ref name="pmid12353207">Wendel GD, Sheffield JS, Hollier LM, Hill JB, Ramsey PS, Sánchez PJ (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12353207 Treatment of syphilis in pregnancy and prevention of congenital syphilis.] ''Clin Infect Dis'' 35 (Suppl 2):S200-9. [http://dx.doi.org/10.1086/342108 DOI:10.1086/342108] PMID: [http://pubmed.gov/12353207 12353207]</ref>
*When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for [[congenital syphilis]], but this evaluation should not delay therapy.
*Sonographic signs of fetal or placental syphilis (i.e., [[hepatomegaly]], [[ascites]], [[hydrops]], [[anemia|fetal anemia]], or a thickened placenta) indicate a greater risk for fetal treatment failure;<ref name="pmid11384701">Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11384701 Fetal syphilis: clinical and laboratory characteristics.] ''Obstet Gynecol'' 97 (6):947-53. PMID: [http://pubmed.gov/11384701 11384701]</ref> such cases should be managed in consultation with obstetric specialists. Evidence is insufficient to recommend specific regimens for these situations.
*Women treated for syphilis during the second half of pregnancy are at risk for [[premature labor]] and/or [[fetal distress]] if the treatment precipitates the [[Jarisch-Herxheimer reaction]].<ref name="pmid2304710">Klein VR, Cox SM, Mitchell MD, Wendel GD (1990) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=2304710 The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy.] ''Obstet Gynecol'' 75 (3 Pt 1):375-80. PMID: [http://pubmed.gov/2304710 2304710]</ref> These women should be advised to seek obstetric attention after treatment if they notice any fever, contractions, or decrease in fetal movements.
*[[Stillbirth]] is a rare complication of treatment, but concern for this complication should not delay necessary treatment.
*Pregnant women taking treatment for late latent syphilis should not miss any dose, else she must repeat the whole course of therapy.<ref name="pmid8355931">{{cite journal| author=Nathan L, Bawdon RE, Sidawi JE, Stettler RW, McIntire DM, Wendel GD| title=Penicillin levels following the administration of benzathine penicillin G in pregnancy. | journal=Obstet Gynecol | year= 1993 | volume= 82 | issue= 3 | pages= 338-42 | pmid=8355931 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8355931  }} </ref>
*All patients who have syphilis should be offered testing for HIV infection.
|-
|-
!'''In patients with Penicillin Allergy'''
|'''Secondary Peritonitis'''
'''Severe''' (major peritoneal soilage, large or multiple abscesses, patient hemodynamically unstable)
|''E. coli'' 
''Klebsiella''
 
''B. fragilis'' 
 
''P. aeruginosa''
 
''Enterococcus spp.''
 
''Streptococcus spp''
 
''S. aureus''
|'''Vancomycin'''
PLUS
 
'''Piperacillin/tazobactam''' 4.5 g IV q6h
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Aztreonam''' 2 g IV q8h
 
PLUS
 
'''Metronidazole'''500 mg IV q8h
|For hemodynamically unstable health-care associated infection, consider meropenem.
|-
|''Clostridium difficile''-associated diarrhea
|''Clostridium difficile''
|Initial episode, mild to moderate disease
(WBC ≤15K and SCr less than 1.5 times premorbid level)
 
'''Vancomycin''' 125mg PO q6h x 10-14 days.  If unable to obtain at discharge, can complete course with '''Metronidazole'''500mg po q8h
 
Initial episode, severe disease
 
(WBC >15k and/or 50% increase in SCr)
 
'''Vancomycin''' 125mg PO q6h x 10-14 days.
 
Initial episode, severe disease with complications
 
(Severe disease with hypotension, shock, ilios, and/or megacolon)
 
'''Vancomycin''' 500mg PO/NG q6h x 10-14 days
 
PLUS
 
'''Metronidazole''' 500 mg IV q8h x 10-14 days
 
WITH OR WITHOUT
 
'''Vancomycin''' PR Rectal vancomycin should be considered in patients with ileus. It is given as 500 mg in 100 mL of 0.9% NaCl and instilled q6h (retain each dose for 1h)
* First recurrence
Same therapy as initial episode, stratified by illness severity
* First recurrence, special population (hematologic malignancy with >30 days expected neutropenia, recent HSCT, recent treatment for GVHD, solid organ transplant <3 months)
'''Fidaxomicin'''ID-R: UCSF SFGH  VASF 200mg PO BID x10 days
* Second recurrence
'''Vancomycin''' with tapered or pulsed regimen
 
PLUS
 
Consult ID, GI
 
PLUS
 
Evaluate for fecal microbiota transplant
|
* IV metronidazole alone is not indicated for treatment of ''C. difficile'' diarrhea.
 
* IV metronidazole should only be used in combination with PO vancomycin in the ICU.
 
* Recurrence in 5-30% of patients after first episode and 33-60% after second episode.
 
* ID CONSULT recommended in patients with severe disease with complications or multiply recurrent disease, and for consideration of rectal vancomycin administration.
|
|
*For treatment of syphilis during pregnancy, no proven alternatives to [[penicillin]] exist.
|}
*Pregnant women who have a history of [[Syphilis medical therapy#Pencillin allergy|penicillin allergy]] should be desensitized and treated with [[penicillin]].
{| class="wikitable"
*Oral step-wise penicillin dose challenge or [[Syphilis medical therapy#Pencillin allergy: Penicillin skin test|skin testing]] may be helpful in identifying women at risk for acute allergic reactions.
|'<nowiki/>'''''Endometritis'''''' 
*[[Tetracycline]] and [[doxycycline]] usually are not used during pregnancy. [[Erythromycin]] and [[azithromycin]] should not be used, because neither reliably cures maternal infection or treats an infected fetus.<ref name="pmid11686978">Walker GJ (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11686978 Antibiotics for syphilis diagnosed during pregnancy.] ''Cochrane Database Syst Rev'' (3):CD001143. [http://dx.doi.org/10.1002/14651858.CD001143 DOI:10.1002/14651858.CD001143] PMID: [http://pubmed.gov/11686978 11686978]</ref> Data are insufficient to recommend [[ceftriaxone]] for treatment of maternal infection and prevention of [[congenital syphilis]].
|''Bacteroides''
|-
''Prevotella bivia''
!'''Pregnant Woman with HIV Infection'''
 
Group B & Astreptococci
 
Enterobacteriaceae
 
''M. hominis''
|'''''1st line:'''''
'''Cefoxitin''' 2 g IV q6h 
 
'''''2nd line:'''''
 
'''Ertapenem''' 1 g IV daily
 
'''''3rd line:'''''
 
'''Ampicillin/sulbactam''' 3 g IV q6h
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Gentamicin'''
 
PLUS
 
'''Metronidazole''' 500 mg IV q12h
|
|
*Placental inflammation from congenital infection might increase the risk for perinatal transmission of HIV.  
* If test for chlamydia is positive add azithromycin or doxycycline.
*All HIV-infected women should be evaluated for syphilis and receive treatment as recommended.  
 
*Data are insufficient to recommend a specific regimen for HIV-infected pregnant women.
* Continue antibiotics until afebrile for 24-48 hours.
|-
 
!'''Follow Up'''
* If still febrile > 48 hours and on cefoxitin or clindamycin/gentamicin postpartum, switch to ertapenem.
 
* Wait 48 hours on an antibiotic regimen before considering regimen failed.
|}
{| class="wikitable"
|'''Peritonsillar abscess,''' deep neck infections
|Group A streptococci
Anaerobes
 
''S. aureus''
|'''Ampicillin/sulbactam''' 3 g IV q6h
WITH OR WITHOUT*
 
'''Vancomycin''' 
 
Alternatively:
 
'''Ertapenem''' 1 g IV daily
 
WITH OR WITHOUT*
 
'''Vancomycin''' 
 
Alternatively:
 
'''Metronidazole''' 500 mg IV/PO q8h
 
PLUS
 
'''Ceftriaxone'''1 g IV q24h
 
WITH OR WITHOUT*
 
'''Vancomycin'''
|For severe PCN allergy:
'''Clindamycin'''ID-R: VASF 600 – 900 mg IV q8h
 
PLUS
 
'''Ciprofloxacin'''ID-R: VASF 400 mg IV q12h
 
OR
 
'''Levofloxacin'''ID-R: VASF 500 mg IV daily
|Often polymicrobial
* Combinations of piperacillin/tazobactam, ampicillin/sulbactam, or ertapenem PLUS metronidazole should not be used.
 
* Consider vancomycin use for patients at high risk for MRSA
|}
{| class="wikitable"
|'''Line-related bacteremia''' 
|''S. epidermidis''
''S. aureus''
 
''Enterococci spp.''
 
Gram-negative rods*
 
''Yeast**''
|'''Vancomycin'''
WITH OR WITHOUT* one of:
 
'''Piperacillin/tazobactam'''
 
ID-R: SFGH
 
4.5 g IV q6h
 
OR
 
'<nowiki/>''Cefepime'''I'<nowiki/>''''' 2 g IV q8h
|For severe PCN allergy:
'''Vancomycin'''
 
WITH OR WITHOUT* one of:
 
'''Aztreonam''' ID-R: SFGH 2 g q8h
|
|
*Coordinated prenatal care and treatment are vital.
* Remove the offending intravascular device immediately, if possible.
*Serologic titers should be repeated at 28-32 weeks' gestation and at delivery as recommended for the disease stage. Providers should ensure that the clinical and antibody responses are appropriate for the patient's stage of disease, although most women will deliver before their serologic response to treatment can be assessed definitively.  
 
*Inadequate maternal treatment is likely if delivery occurs within 30 days of therapy, if clinical signs of infection are present at delivery, or if the maternal antibody titer at delivery is fourfold higher than the pretreatment titer.
* Consider Gram-negative coverage for immunocompromised patients or those with prolonged hospitalization, recent antibiotic exposure or sepsis.
*Serologic titers can be checked monthly in women at high risk for reinfection or in geographic areas in which the prevalence of syphilis is high. <ref name="urlSexually Transmitted Diseases Treatment Guidelines, 2010">{{cite web|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm |title=Sexually Transmitted Diseases Treatment Guidelines, 2010 |format= |work= |accessdate=2012-12-19}}</ref>
|}
|}
{| class="wikitable"
| rowspan="2" |'''Community-Acquired Pneumonia''' 
|'''Immunocompetent patient''' – Medical Ward
|''S. pneumoniae''
''Mycoplasma pneumoniae''
''Chlamydia pneumoniae''
''H. influenzae''
''Legionella pneumophilia''
''Klebsiella pneumoniae''
''(alcoholics)''
|No Recent antibiotic therapy:*
'''Ceftriaxone''' 1 g IV daily
PLUS
'<nowiki/>'''''Doxycycline''''''100 mg PO/IV q12h
|For severe PCN allergy:
'''Levofloxacin''' 750 mg PO/IV daily
OR
'''Moxifloxacin'''ID-R: SFGH 400 mg PO/IV daily
|
* If patient has had recent antibiotic therapy, antibiotics from a different class should be selected (i.e. recent use of a fluoroquinolone should dictate selection of a non-fluoroquinolone regimen, and vice versa).


====Management of a Neonate or an Infant with Congenital Syphilis====
* Consider influenza testing and treatment with oseltamivir.
The diagnosis of congenital syphilis can be difficult, as maternal nontreponemal and treponemal IgG antibodies can be transferred through the placenta to the fetus, complicating the interpretation of reactive serologic tests for syphilis in neonates. Therefore, treatment decisions frequently must be made on the basis of:
*Identification of syphilis in the mother
*Adequacy of maternal treatment
*Presence of clinical, laboratory, or radiographic evidence of syphilis in the neonate
*Comparison of maternal (at delivery) and neonatal nontreponemal serologic titers using the same test, preferably conducted by the same laboratory.
====Evaluation and Approach====
*All neonates born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test (RPR or VDRL) performed on the neonate's serum, because umbilical cord blood can become contaminated with maternal blood and yield a false-positive result, and Wharton's jelly within the umbilical cord can yield a false-negative result.
*Conducting a treponemal test (i.e., TP-PA, FTA-ABS, EIA, or CIA) on neonatal serum is not recommended because it is difficult to interpret.
*Any neonate at risk for congenital syphilis should receive a full evaluation and testing for HIV infection.
*The following scenarios describe the congenital syphilis evaluation and treatment of neonates born to women who have reactive serologic tests for syphilis during pregnancy. Maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the neonate for congenital syphilis in most scenarios, except when congenital syphilis is proven or highly probable.
{| border="1"
|-
|-
!
|'''Community-Acquired Pneumonia'''
!'''CDC Recommendations for management of neonates with Congenital Syphilis'''
'''Immunocompetent patient''' – ICU
|''S. pneumoniae''
''Mycoplasma pneumoniae''
 
''Chlamydia pneumoniae''
 
''H. influenzae''
 
''Legionella pneumophilia''
 
''Klebsiella pneumoniae''
 
(alcoholics)
 
''S. aureus''
|'''Ceftriaxone''' 1 g IV daily
PLUS
 
'''Azithromycin''' 500 mg IV daily
 
WITH OR WITHOUT*:
 
'''Vancomycin'''
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS one of:
 
'''Levofloxacin''' 750 mg IV daily
 
OR
 
'''Moxifloxacin''' 400 mg IV daily
|
* MRSA risk factors: prior influenza, presence cavitary disease, empyema.
 
* Consider influenza testing and treatment with oseltamivir.
 
* If no microbiologic confirmation of MRSA then discontinue vancomycin.
 
* See HCAP for risk factors for infection with ''Pseudomonas aeruginosa.''
|-
|-
!'''Clinical senario 1'''
|'''Healthcare –associated pneumonia (HCAP):'''
acquired in long-term care facility where antimicrobials used or ''Pseudomonas'' risk factors (see Comments)
|''S.aureus''
''S.pneumoniae''
 
''H.influenzae'' 
 
Antibiotic sensitive enteric gram negative bacilli:
 
''E. coli''
 
''Enterobacter aerogenes''
 
''Klebsiella pneumoniae''
 
''Proteus mirabilis''
 
''Serratia marcesans''
 
''P. aeruginosa (''if risk factors present)
|Hemodynamically stable & no ''Pseudomonas'' risk factors
'''Vancomycin'''
 
PLUS one of:
 
'''Ertapenem''' 1 g IV daily
 
WITH OR WITHOUT one of*:
 
'''Doxycycline''' 100 mg IV/PO BID
 
OR
 
'''Levofloxacin''' 750 mg IV/PO daily
 
Hemodynamically unstable or ''Pseudomonas'' risk factors
 
'''Vancomycin'''
 
PLUS one of:
 
'''Piperacillin/tazobactam'''ID-R: SFGH 4.5 g IV q6h
 
OR
 
'''Cefepime'''ID-R: SFGH VASF 2 g IV q8h-q12h
 
WITH OR WITHOUT*:
 
'''Azithromycin''' 500 mg IV daily
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS one of:
 
'''Aztreonam'''ID-R: SFGH 2 g IV q8h
 
WITH OR WITHOUT one of*:
 
'''Doxycycline''' 100 mg IV/PO BID
 
OR
 
'''Azithromycin''' 500 mg IV daily
|
|
*Infants with proven or highly probable disease and with any one of the following :
**An abnormal physical examination that is consistent with congenital syphilis '''or'''
**A serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer '''or'''
**A positive darkfield test of body fluid(s).
'''Recommended Evaluation'''
*CSF analysis for VDRL, cell count, and protein
*Complete blood count (CBC) and differential and platelet count
*Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver-function tests, neuroimaging, ophthalmologic examination, and auditory brain stem response)
'''Preferred regimen 1:''' [[Aqueous crystalline penicillin G]] 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days<br>
'''Preferred regimen 2:''' [[Procaine penicillin G]] 50,000 U/kg/dose IM q24h for 10 days<br>
<small>Note: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., [[ampicillin]]). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with ''T. pallidum'' and treatment for syphilis must be considered when evaluating and treating the infant <small>
|-
!'''Clinical senario 2'''
|
|
*Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer '''and''' with one of the following:
* ''Pseudomonas'' risk factors include: structural lung disease, repeated exacerbations of severe COPD leading to frequent steroid and/or antibiotic use, recent mechanical ventilation, recent prior exposure to broad-spectrum antibiotics
**Mother was not treated or inadequately treated, or has no documentation of having received treatment '''or'''
 
**Mother was treated with [[erythromycin]] or another non-penicillin regimen '''or'''
* Avoid using levofloxacin if the patient has recently been treated with a fluoroquinolone.
**Mother received treatment less than 4 weeks before delivery.
 
'''Recommended Evaluation'''
* For patients admitted from the community with HCAP and not treated with levofloxacin, consider  adding atypical coverage with doxycycline (floor patients) or azithromycin (ICU patients).
*CSF analysis for VDRL, cell count, and protein**
*CBC, differential, and platelet count
*Long-bone radiographs
'''Preferred regimen 1:''' [[Aqueous crystalline penicillin G]] 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days<br>
'''Preferred regimen 2:''' [[Procaine penicillin G]] 50,000 U/kg/dose IM q24h for 10 days<br>
'''Preferred regimen 3:''' [[Benzathine penicillin G]] 50,000 U/kg/dose IM single dose<br>
<small>Note: If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered<br>
Before using the single-dose benzathine penicillin G regimen, the complete evaluation (i.e., CSF examination, long-bone radiographs, and CBC with platelets) must be normal, and follow-up must be certain. If any part of the infant's evaluation is abnormal or not performed, if the CSF analysis is uninterpretable because of contamination with blood, or if follow-up is uncertain, a 10-day course of penicillin G is required. If the neonate's nontreponemal test is nonreactive and the provider determines that the mother's risk of untreated syphilis is low, treatment of the neonate with a single IM dose of benzathine penicillin G 50,000 units/kg for possible incubating syphilis can be considered without an evaluation.<br>
Neonates born to mothers with untreated early syphilis at the time of delivery are at increased risk for congenital syphilis, and the 10-day course of penicillin G may be considered even if the complete evaluation is normal and follow-up is certain.<small>
|-
|-
!'''Clinical senario 3'''
| rowspan="2" |'''Hospital-acquired pneumonia''' 
|'''EARLY ONSET'''
including ventilator-associated or less than 5 days of hospitalization, no risk factors for drug-resistant organisms*
|''S. aureus''
''S.pneumoniae''
 
''H.influenzae'' 
 
Antibiotic sensitive enteric gram negative bacilli:
 
''E. coli''
 
''Enterobacter aerogenes''
 
''Klebsiella pneumoniae''
 
''Proteus mirabilis''
 
''Serratia marcesans''
|'''Vancomycin'''
PLUS one of
 
'''Levofloxacin''' 750 mg IV daily
 
OR
 
'''Ertapenem''' 1 g IV daily 
|
|
*Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer '''and'''
*Mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery '''and'''
*Mother has no evidence of reinfection or relapse.
'''Recommended Evaluation''''
*No evaluation recommended
'''Preferred regimen:''' [[Benzathine penicillin G]] 50,000 U/kg/dose IM single dose
|-
!'''Clinical senario 4'''
|
|
*Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer '''and'''
* Risk factors include recent antibiotic exposure (within 30 days).
*Mother's treatment was adequate before pregnancy '''and'''
 
*Mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4)
* Consider influenza testing and treatment with oseltamivir when influenza is known to be circulating.
'''Recommended evaluation'''
*No evaluation recommended
*No treatment is required
*[[Benzathine penicillin G]] 50,000 U/kg IM single dose might be considered, particularly if follow-up is uncertain
|-
|-
!'''Follow up'''
|'''LATE ONSET'''
including ventilator-associated OR ≥ 5 days of hospitalization or risk factors for resistant organisms*
|''E. coli''
''Enterobacter aerogenes''
 
''P. aeruginosa''
 
''Klebsiella pneumoniae''
 
'<nowiki/>'''S. aureus'''' 
|'''Vancomycin'''
PLUS one of:
 
'''Piperacillin/tazobactam''' 4.5 g IV q6h  
 
OR
 
'''Cefepime''' 2 g IV q8-12h
 
''Alternatively'':
 
'''Vancomycin'''
 
PLUS
 
'''Meropenem''' 1-2 g IV q8h**
|For severe PCN allergy:
'''Vancomycin'''2
 
PLUS
 
'''Aztreonam''' 2 g IV q8h
 
WITH OR WITHOUT***:
 
'''Tobramycin'''
|**Consider use in patients with current or recent use (< 7 days) of piperacillin/tazobactam or cefepime and in patients with recent infection with multidrug resistant gram-negative bacteria.
<nowiki>***</nowiki>Weigh risks and benefits of adding aminoglycoside for critical illness, immunocompromise, or history of infection or colonization with drug-resistant Gram-negative rods.
|}
{| class="wikitable"
|'<nowiki/>'''''Septic Shock''''''
Community onest, no recent healthcare exposure
|Enterobacteriaceae
''S. aureus''
 
''Streptococci spp.''
|'''Vancomycin'''
PLUS one of:
 
'''Piperacillin/'''
 
'''Tazobactam'''ID-R: SFGH 4.5 g IV q8h
 
OR
 
'<nowiki/>'''''Ertapenem'''''' 1 g IV daily
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Metronidazole''' 500 mg IV/PO q8h
 
PLUS one of
 
'''Aztreonam'''ID-R: SFGH 2 g IV q8h
 
OR
 
'''Tobramycin'''
|
|
*All neonates with reactive nontreponemal tests should receive careful follow-up examinations and serologic testing (i.e., a nontreponemal test) every 2–3 months until the test becomes nonreactive.
*In the neonate who was not treated because congenital syphilis was considered less likely or unlikely, nontreponemal antibody titers should decline by age 3 months and be nonreactive by age 6 months, indicating that the reactive test result was caused by passive transfer of maternal IgG antibody.
*At 6 months, if the nontreponemal test is nonreactive, no further evaluation or treatment is needed; if the nontreponemal test is still reactive, the infant is likely to be infected and should be treated.
*Treated neonates that exhibit persistent nontreponemal test titers by 6–12 months should be re-evaluated through CSF examination and managed in consultation with an expert. Retreatment with a 10-day course of a penicillin G regimen may be indicated.
*Neonates with a negative nontreponemal test at birth and whose mothers were seroreactive at delivery should be retested at 3 months to rule out serologically negative incubating congenital syphilis at the time of birth.
*Neonates whose initial CSF evaluations are abnormal should undergo a repeat lumbar puncture approximately every 6 months until the results are normal
<small>Note: Treponemal tests should not be used to evaluate treatment response because the results are qualitative and passive transfer of maternal IgG treponemal antibody might persist for at least 15 months<br>
A reactive CSF Venereal Disease Research Laboratory (VDRL) test or abnormal CSF indices that persist and cannot be attributed to other ongoing illness requires retreatment for possible neurosyphilis and should be managed in consultation with an expert.<small>
|-
|-
!'''Penicillin Allergy'''
|'''Healthcare-associated and/or previous antibiotic therapy'''
|
|Enterobacteriaceae
*Infants and children who require treatment for congenital syphilis but who have a history of penicillin allergy or develop an allergic reaction presumed secondary to penicillin should be desensitized and then treated with penicillin.
''S. aureus''
* Data are insufficient regarding the use of other antimicrobial agents (e.g., ceftriaxone) for congenital syphilis in infants and children.
 
''Streptococci spp.''
 
''P. aeruginosa''
|'''Vancomycin'''
PLUS
 
'''Piperacillin/'''
 
'''Tazobactam''' 4.5 g IV q6h
 
OR
 
'''Cefepime''' 2 g IV q8h
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Metronidazole''' 500 mg IV q8h
 
AND
 
'''Aztreonam''' 2 g IV q8h
 
WITH OR WITHOUT:
 
'''Tobramycin'''
|''For patients with neutropenia, organ transplant, severe hepatic failure, or current/recent (<7 days) piperacillin/tazobactam or cefepime:''
'''Vancomycin'''
 
''Plus''
 
'''Meropenem''' 1-2 g IV q8h
|}
|}
{| class="wikitable"
|'<nowiki/>'''''Abscess''''''
|'<nowiki/>'''S.aureus''''
|Vancomycin
|Empirical Gram-negative and/or anaerobic coverage is not routinely indicated.
Incision and drainage is primary therapy for abscesses. After incision and drainage and once patient is stable, switch to oral antibiotics based on culture and susceptibility results.
|-
|'<nowiki/>'''''Cellulitis''''''
|Group A streptococci
Other beta-hemolytic streptococci
''S.aureus''
|'''Vancomycin'''
''Alternatively:''
'''Cefazolin''' 1 g IV q8h if patient is stable and cellulitis is not associated with an abscess or other purulent focus of infection
|Empirical Gram-negative and/or anaerobic coverage is not routinely indicated.
|-
|'''Necrotizing fasciitis or suspected deep tissue extension'''
|Group A streptococci
''S. aureus''
Anaerobes
Gram-negative rods
|'''Vancomycin'''
PLUS ONE OF:
'''Piperacillin/tazobactam''' 4.5 g IV q6-8h
OR
'''Ertapenem''' 1 g IV daily
ALL WITH:
'''Clindamycin'''600 – 900 mg IV q8h 
Alternatively if infection is health-care associated:
'''Vancomycin'''
PLUS


'''Meropenem'''1-2 g IV q8h


PLUS


{| border="1"
'''Clindamycin'''600-900 mg IV q8h
|For severe PCN allergy:
'''Vancomycin'''
 
PLUS
 
'''Aztreonam'''ID-R: SFGH 2 g IV q8h
 
PLUS
 
'''Clindamycin''' ID-R: VASF 600-900 mg IV q8h
 
Clindamycin added for anti-toxin properties. Limited data support use for infections caused by Group A streptococci and ''Clostridium perfringens.'' Discontinue clindamycin once adequate surgical debridement is achieved.  
|}
{| class="wikitable"
|'''Asymptomatic bacteriuria'''
|Enterobacteriaceae
''Enterococcus''species
|No treatment required
|Exceptions: pregnant women, patients having traumatic urologic procedures, recent kidney transplant .
|-
|-
!
|'''Catheter-associated candiduria'''
!'''CDC Recommendations for management of Infants and Children with Congenital Syphilis'''
|'''''Candida'' species'''
|No treatment required
|Pyuria alone is not an indication for treatment.
|-
|-
!'''Congenital Syphilis in infants and children'''
|'''Community-acquired Pyelonephritis''' 
|
|Enterobacteriaceae ''(E. coli)''
*Infants and children aged ≥1 month who are identified as having reactive serologic tests for syphilis should be examined thoroughly and have maternal serology and records reviewed to assess whether they have congenital or acquired syphilis.
|'''Ceftriaxone'''
*Any infant or child at risk for congenital syphilis should receive a full evaluation and testing for HIV infection
1 g IV q24h
'''Recommended Evaluation'''
 
*CSF analysis for VDRL, cell count, and protein
OR
*CBC, differential, and platelet count
 
*Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver function tests, abdominal ultrasound, ophthalmologic examination, neuroimaging, and auditory brain-stem response)
'''Cefazolin''' 1g IV q8h (VASF only)
 
OR
 
'''Ertapenem''' 1g IV daily
|For '''severe''' PCN allergy:
'''Vancomycin'''
 
PLUS ONE OF EITHER:
 
'''Gentamicin'''
 
OR
 
'''Aztreonam''' ID-R: SFGH
 
2 g IV q8h


'''Preferred regimen:''' [[Aqueous crystalline penicillin G]] 50,000 U/kg q4–6h for 10 days<br>
 '''Duration of therapy 7-14 days based on clinical response.'''
*If the infant or child has no clinical manifestations of congenital syphilis and the evaluation (including the CSF examination) is normal, treatment with up to 3 weekly doses of benzathine penicillin G, 50,000 U/kg IM can be considered. A single dose of benzathine penicillin G 50,000 units/kg IM up to the adult dose of 2.4 million units in a single dose can be considered after the 10-day course of IV aqueous penicillin to provide more comparable duration of treatment in those who have no clinical manifestations and normal CSF. All of the above treatment regimens also would be adequate for children who might have other treponemal infections.
|-
|-
!'''Follow Up'''
|'''Healthcare-associated UTI'''
|
|Enterobacteriaceae ''(e.g. E. coli)''
*Careful follow-up examinations and serologic testing (i.e., a nontreponemal test) of infants and children treated for congenital syphilis after the neonatal period (30 days of age) should be performed every 3 months until the test becomes nonreactive or the titer has decreased fourfold.
''P. aeruginosa'' (less common)
*If the titers increase at any point for more than 2 weeks or do not decrease fourfold after 12–18 months, the infant or child should be evaluated (e.g., through CSF examination), treated with a 10-day course of parenteral penicillin G, and managed in consultation with an expert.
|'''Ceftriaxone'''
* Treponemal tests should not be used to evaluate treatment response, because the results are qualitative and persist after treatment; further, passive transfer of maternal IgG treponemal antibody might persist for at least 15 months after delivery.
1 g IV q24h
*Infants or children whose initial CSF evaluations are abnormal should undergo a repeat lumbar puncture approximately every 6 months until the results are normal. After 2 years of follow-up, a reactive CSF VDRL test or abnormal CSF indices that persists and cannot be attributed to other ongoing illness requires retreatment for possible neurosyphilis and should be managed in consultation with an expert.
 
|-
OR
!'''Penicillin Allergy'''
 
|
'''Ertapenem''' 1g IV daily
*Infants and children who require treatment for congenital syphilis but who have a history of penicillin allergy or develop an allergic reaction presumed secondary to penicillin should be desensitized and treated with penicillin
 
|}
OR
 
'''Piperacillin/tazobactam'''ID-R: SFGH 4.5g IV q8h
|For '''severe''' PCN allergy:
ONE OF:Criteria: signs and symptoms compatible with a UTI, no other identified source of infection, & ≥ 1000 cfu of ≥ 1 bacterial species on urine culture
 
'''Gentamicin'''
 
OR
 
'''Aztreonam''' ID-R: SFGH
 
2 g IV q8h
 
BOTH WITH OR WITHOUT:
 
'''Vancomycin'''


==Prevention==
* Pyuria alone is not an indication for treatment.


===Primary Prevention===
* A negative urinalysis suggests an alternative source of infection.
Primary prevention of syphilis in women of reproductive age and  men who have sex with women and prevention of mother to infant transmission in infected individuals plays a important role in decreasing incidence of congenital syphilis.Effective measures for the primary prevention of congenital syphilis include reducing the risk of mother having syphilis infection and also screening during the antenatal period:<ref name="pmid19805553">{{cite journal |author=Stamm LV |title=Global challenge of atibiotic-resistant Treponema pallidum |journal=[[Antimicrobial Agents and Chemotherapy]] |volume=54 |issue=2 |pages=583–9 |year=2010 |month=February |pmid=19805553 |pmc=2812177 |doi=10.1128/AAC.01095-09 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=19805553 |accessdate=2012-02-21}}</ref><ref name="pmid24135571">{{cite journal |vauthors=Cameron CE, Lukehart SA |title=Current status of syphilis vaccine development: need, challenges, prospects |journal=Vaccine |volume=32 |issue=14 |pages=1602–9 |year=2014 |pmid=24135571 |pmc=3951677 |doi=10.1016/j.vaccine.2013.09.053 |url=}}</ref><ref name=CDCsyphilis>http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 27, 2016</ref>
*Routine screening in pregnant females, individuals with high risk behaviours, and those residing in highly prevalent areas.
*Abstinence from intimate physical contact with an infected person.
*Consistent use of latex condoms.
*Limiting no of sexual partners.
*Avoid sharing sex toys.
*Practising safe sex.


===Secondary Prevention===
* Remove catheter if possible.
*Frequent screening, treatment and follow up in pregnant females diagnosed with syphilis.<ref name="pmid28146163">{{cite journal| author=Feliz MC, Prizybicien AR, Rossoni AM, Tahnus T, Pereira AM, Rodrigues C| title=Adherence to the follow-up of the newborn exposed to syphilis and factors associated with loss to follow-up. | journal=Rev Bras Epidemiol | year= 2016 | volume= 19 | issue= 4 | pages= 727-739 | pmid=28146163 | doi=10.1590/1980-5497201600040004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28146163  }} </ref><ref name="pmid26474815">{{cite journal| author=Wallace HE, Broomhall HM, Isitt CE, Miall LS, Wilson JD| title=Serological follow-up of infants born to mothers with positive syphilis serology - real-world experiences. | journal=Int J STD AIDS | year= 2016 | volume= 27 | issue= 13 | pages= 1213-1217 | pmid=26474815 | doi=10.1177/0956462415612394 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26474815  }} </ref>
*New born screening, early diagnosis and treatment.


==References==
* Switch to oral therapy when susceptibilities known and patient stable.
{{reflist|2}}


{{WH}}
* 7 days of therapy is recommend if patient has prompt resolution of symptoms
{{WS}}
|}

Latest revision as of 19:45, 29 June 2017

Hospitalized patients

Infection Organisms First DOC Alternative
Osteomyelitis Presumed hematogenous source or contiguous without vascular insufficiency S. aureus Vancomycin Vanc
  • If S. aureus is methicillin-susceptible then cefazolin 2 g IV q8h or nafcillin 2 g IV q4h are the antibiotics of choice.
  • Obtain bone biopsy to determine microbiologic cause prior to initiation of antimicrobial therapy if blood cultures are negative and patient clinically stable.
With vascular insufficiency or diabetes mellitus (e.g. severe diabetic foot ulcer) S. aureus 

Enterobacteriaceae

Anaerobes

Vancomycin

PLUS ONE OF:

Piperacillin/Tazobactam 4.5 g IV q6-8h

OR

Ertapenem 1 g IV daily

For severe PCN allergy:

Vancomycin

PLUS ONE OF:

Ciprofloxacin400 mg IV q12h

OR

Levofloxacin 750 mg IV daily

OR

Aztreonam 2 g IV q8h

ALL WITH OR WITHOUT:

Metronidazole500 mg IV q8h (if patient critically ill)

  • Other organisms are possible, esp. with hardware microbiologic diagnosis and ID consultation recommended
  • Obtain bone biopsy to determine microbiologic cause prior to initiation of antimicrobial therapy if patient clinically stable
  • Once stable, switch to oral antibiotics based on susceptibility results.
Septic Arthritis S. aureus

Streptococci spp.

N. gonorrhoeae

Enterobacteriaceae (rarely)

Vancomycin

PLUS

Ceftriaxone1 g IV daily

For severe PCN allergy:

Vancomycin

PLUS ONE OF:

Ciprofloxacin 400 mg IV q12h

OR

Levofloxacin 500 mg IV daily

OR

Aztreonam g IV q8h if gonococcus is strongly suspected

Gram stain recommended to guide therapy.

Narrow coverage to microbiologically confirmed pathogens.

Brain abscess Streptococci (anaerobic or aerobic)

Bacteroides spp

Prevotella spp

Enterobacteriacea

Ceftriaxone

2 g IV q12h

PLUS

Metronidazole 500 mg PO/IV q8h

WITH OR WITHOUT*:

Vancomycin

Aztreonam

2 g IV q8h

PLUS

Vancomycin

PLUS

Metronidazole 500 mg PO/IV q8h

Consider expanded Gram-positive coverage if patient at risk for drug-resistant streptococci or MRSA
Meningitis

Community-onset

S. pneumoniae

Neisseria meningitidis

Listeria (especially in immuno-compromised, elderly patients, and alcoholics)

ceftriaxone

2 g IV q12h

PLUS

Vancomycin

WITH OR WITHOUT* one of:

TMP/SMX 15 mg/kg/day (in divided doses)

OR

'Ampicillin' 2 g IV q4h

For severe PCN allergy:

Vancomycin

PLUS

Aztreonam2 g IV q6h-q8h

WITH OR WITHOUT*:

TMP/SMX (if Listeria) 15 mg/kg/day (in divided doses)

  • Therapy should be guided by Gram stain.
  • If bacterial meningitis suspected, dexamethasone 10 mg PO/IV q6h x 4 days given before or with initial dose of antibiotics. 
  • Coverage for Listeria with TMP/SMX or ampicillin should be added for patients who are <2 or >50 years of age or immunocompromised.
Meningitis

Post-neurosurgical or device associated

S. aureus

Coagulase negative

Staphylococci

Gram negative rods

Cefepime

PLUS

'Vancomycin' 

For severe PCN allergy:

Aztreonam 2 g IV q6h-q8h

PLUS

Vancomycin

Native Valve S. aureus

Streptococci spp.

Enterococcus spp.

Occasional gram negative rods

HACEK < 5%

Vancomycin

WITH or WITHOUT*

Ceftriaxone

2 g IV daily

For severe PCN allergy:

Vancomycin

WITH or WITHOUT*

CiprofloxacinID-R: VASF 400 mg IV q12h

  • Narrow coverage to microbiologically confirmed pathogens
  • Addition of Gram-negative coverage should be considered if the patient has a sub-acute presentation.
Prosthetic Valve S. aureus

S. epidermidis

Vancomycin

PLUS

Rifampin300 mg PO q8h

PLUS

Gentamicin 1 mg/kg/dose IV q8h for initial two weeks only

Single daily dose of gentamicin is not recommended

Rifampin has numerous clinically significant drug interactions.  Medication lists should be reviewed for potential drug-drug interactions with rifampin.
Spontaneous Bacterial Peritonitis (SBP) E. coli

Klebsiella spp.

'Streptococci. spp.

Ceftriaxone 1 g IV daily x 5 days For severe PCN allergy:

Vancomycin

PLUS

Aztreonam 2 g IV q8h

Secondary Peritonitis

Mild-Moderate intra-abdominal abscess

E. coli

Klebsiella 

B. fragilis

Streptococci spp

S. aureus

Ertapenem 1g IV daily

OR

Piperacillin/tazobactam 3.375 g IV q6h - 4.5g IV q6h

For severe PCN allergy:

Vancomycin

PLUS

Aztreonam 2 g IV q8h

PLUS

Metronidazole500 mg IV q8h

Secondary Peritonitis

Severe (major peritoneal soilage, large or multiple abscesses, patient hemodynamically unstable)

E. coli 

Klebsiella

B. fragilis 

P. aeruginosa

Enterococcus spp.

Streptococcus spp

S. aureus

Vancomycin

PLUS

Piperacillin/tazobactam 4.5 g IV q6h

For severe PCN allergy:

Vancomycin

PLUS

Aztreonam 2 g IV q8h

PLUS

Metronidazole500 mg IV q8h

For hemodynamically unstable health-care associated infection, consider meropenem.
Clostridium difficile-associated diarrhea Clostridium difficile Initial episode, mild to moderate disease

(WBC ≤15K and SCr less than 1.5 times premorbid level)

Vancomycin 125mg PO q6h x 10-14 days.  If unable to obtain at discharge, can complete course with Metronidazole500mg po q8h

Initial episode, severe disease

(WBC >15k and/or 50% increase in SCr)

Vancomycin 125mg PO q6h x 10-14 days.

Initial episode, severe disease with complications

(Severe disease with hypotension, shock, ilios, and/or megacolon)

Vancomycin 500mg PO/NG q6h x 10-14 days

PLUS

Metronidazole 500 mg IV q8h x 10-14 days

WITH OR WITHOUT

Vancomycin PR Rectal vancomycin should be considered in patients with ileus. It is given as 500 mg in 100 mL of 0.9% NaCl and instilled q6h (retain each dose for 1h)

  • First recurrence

Same therapy as initial episode, stratified by illness severity

  • First recurrence, special population (hematologic malignancy with >30 days expected neutropenia, recent HSCT, recent treatment for GVHD, solid organ transplant <3 months)

FidaxomicinID-R: UCSF SFGH  VASF 200mg PO BID x10 days

  • Second recurrence

Vancomycin with tapered or pulsed regimen

PLUS

Consult ID, GI

PLUS

Evaluate for fecal microbiota transplant

  • IV metronidazole alone is not indicated for treatment of C. difficile diarrhea.
  • IV metronidazole should only be used in combination with PO vancomycin in the ICU.
  • Recurrence in 5-30% of patients after first episode and 33-60% after second episode.
  • ID CONSULT recommended in patients with severe disease with complications or multiply recurrent disease, and for consideration of rectal vancomycin administration.
'Endometritis'  Bacteroides

Prevotella bivia

Group B & Astreptococci

Enterobacteriaceae

M. hominis

1st line:

Cefoxitin 2 g IV q6h 

2nd line:

Ertapenem 1 g IV daily

3rd line:

Ampicillin/sulbactam 3 g IV q6h

For severe PCN allergy:

Vancomycin

PLUS

Gentamicin

PLUS

Metronidazole 500 mg IV q12h

  • If test for chlamydia is positive add azithromycin or doxycycline.
  • Continue antibiotics until afebrile for 24-48 hours.
  • If still febrile > 48 hours and on cefoxitin or clindamycin/gentamicin postpartum, switch to ertapenem.
  • Wait 48 hours on an antibiotic regimen before considering regimen failed.
Peritonsillar abscess, deep neck infections Group A streptococci

Anaerobes

S. aureus

Ampicillin/sulbactam 3 g IV q6h

WITH OR WITHOUT*

Vancomycin 

Alternatively:

Ertapenem 1 g IV daily

WITH OR WITHOUT*

Vancomycin 

Alternatively:

Metronidazole 500 mg IV/PO q8h

PLUS

Ceftriaxone1 g IV q24h

WITH OR WITHOUT*

Vancomycin

For severe PCN allergy:

ClindamycinID-R: VASF 600 – 900 mg IV q8h

PLUS

CiprofloxacinID-R: VASF 400 mg IV q12h

OR

LevofloxacinID-R: VASF 500 mg IV daily

Often polymicrobial
  • Combinations of piperacillin/tazobactam, ampicillin/sulbactam, or ertapenem PLUS metronidazole should not be used.
  • Consider vancomycin use for patients at high risk for MRSA
Line-related bacteremia  S. epidermidis

S. aureus

Enterococci spp.

Gram-negative rods*

Yeast**

Vancomycin

WITH OR WITHOUT* one of:

Piperacillin/tazobactam

ID-R: SFGH

4.5 g IV q6h

OR

'CefepimeI' 2 g IV q8h

For severe PCN allergy:

Vancomycin

WITH OR WITHOUT* one of:

Aztreonam ID-R: SFGH 2 g q8h

  • Remove the offending intravascular device immediately, if possible.
  • Consider Gram-negative coverage for immunocompromised patients or those with prolonged hospitalization, recent antibiotic exposure or sepsis.
Community-Acquired Pneumonia  Immunocompetent patient – Medical Ward S. pneumoniae

Mycoplasma pneumoniae

Chlamydia pneumoniae

H. influenzae

Legionella pneumophilia

Klebsiella pneumoniae

(alcoholics)

No Recent antibiotic therapy:*

Ceftriaxone 1 g IV daily

PLUS

'Doxycycline'100 mg PO/IV q12h

For severe PCN allergy:

Levofloxacin 750 mg PO/IV daily

OR

MoxifloxacinID-R: SFGH 400 mg PO/IV daily

  • If patient has had recent antibiotic therapy, antibiotics from a different class should be selected (i.e. recent use of a fluoroquinolone should dictate selection of a non-fluoroquinolone regimen, and vice versa).
  • Consider influenza testing and treatment with oseltamivir.
Community-Acquired Pneumonia

Immunocompetent patient – ICU

S. pneumoniae

Mycoplasma pneumoniae

Chlamydia pneumoniae

H. influenzae

Legionella pneumophilia

Klebsiella pneumoniae

(alcoholics)

S. aureus

Ceftriaxone 1 g IV daily

PLUS

Azithromycin 500 mg IV daily

WITH OR WITHOUT*:

Vancomycin

For severe PCN allergy:

Vancomycin

PLUS one of:

Levofloxacin 750 mg IV daily

OR

Moxifloxacin 400 mg IV daily

  • MRSA risk factors: prior influenza, presence cavitary disease, empyema.
  • Consider influenza testing and treatment with oseltamivir.
  • If no microbiologic confirmation of MRSA then discontinue vancomycin.
  • See HCAP for risk factors for infection with Pseudomonas aeruginosa.
Healthcare –associated pneumonia (HCAP):

acquired in long-term care facility where antimicrobials used or Pseudomonas risk factors (see Comments)

S.aureus

S.pneumoniae

H.influenzae 

Antibiotic sensitive enteric gram negative bacilli:

E. coli

Enterobacter aerogenes

Klebsiella pneumoniae

Proteus mirabilis

Serratia marcesans

P. aeruginosa (if risk factors present)

Hemodynamically stable & no Pseudomonas risk factors

Vancomycin

PLUS one of:

Ertapenem 1 g IV daily

WITH OR WITHOUT one of*:

Doxycycline 100 mg IV/PO BID

OR

Levofloxacin 750 mg IV/PO daily

Hemodynamically unstable or Pseudomonas risk factors

Vancomycin

PLUS one of:

Piperacillin/tazobactamID-R: SFGH 4.5 g IV q6h

OR

CefepimeID-R: SFGH VASF 2 g IV q8h-q12h

WITH OR WITHOUT*:

Azithromycin 500 mg IV daily

For severe PCN allergy:

Vancomycin

PLUS one of:

AztreonamID-R: SFGH 2 g IV q8h

WITH OR WITHOUT one of*:

Doxycycline 100 mg IV/PO BID

OR

Azithromycin 500 mg IV daily

  • Pseudomonas risk factors include: structural lung disease, repeated exacerbations of severe COPD leading to frequent steroid and/or antibiotic use, recent mechanical ventilation, recent prior exposure to broad-spectrum antibiotics
  • Avoid using levofloxacin if the patient has recently been treated with a fluoroquinolone.
  • For patients admitted from the community with HCAP and not treated with levofloxacin, consider  adding atypical coverage with doxycycline (floor patients) or azithromycin (ICU patients).
Hospital-acquired pneumonia  EARLY ONSET

including ventilator-associated or less than 5 days of hospitalization, no risk factors for drug-resistant organisms*

S. aureus

S.pneumoniae

H.influenzae 

Antibiotic sensitive enteric gram negative bacilli:

E. coli

Enterobacter aerogenes

Klebsiella pneumoniae

Proteus mirabilis

Serratia marcesans

Vancomycin

PLUS one of

Levofloxacin 750 mg IV daily

OR

Ertapenem 1 g IV daily 

  • Risk factors include recent antibiotic exposure (within 30 days).
  • Consider influenza testing and treatment with oseltamivir when influenza is known to be circulating.
LATE ONSET

including ventilator-associated OR ≥ 5 days of hospitalization or risk factors for resistant organisms*

E. coli

Enterobacter aerogenes

P. aeruginosa

Klebsiella pneumoniae

'S. aureus' 

Vancomycin

PLUS one of:

Piperacillin/tazobactam 4.5 g IV q6h  

OR

Cefepime 2 g IV q8-12h

Alternatively:

Vancomycin

PLUS

Meropenem 1-2 g IV q8h**

For severe PCN allergy:

Vancomycin2

PLUS

Aztreonam 2 g IV q8h

WITH OR WITHOUT***:

Tobramycin

**Consider use in patients with current or recent use (< 7 days) of piperacillin/tazobactam or cefepime and in patients with recent infection with multidrug resistant gram-negative bacteria.

***Weigh risks and benefits of adding aminoglycoside for critical illness, immunocompromise, or history of infection or colonization with drug-resistant Gram-negative rods.

'Septic Shock'

Community onest, no recent healthcare exposure

Enterobacteriaceae

S. aureus

Streptococci spp.

Vancomycin

PLUS one of:

Piperacillin/

TazobactamID-R: SFGH 4.5 g IV q8h

OR

'Ertapenem' 1 g IV daily

For severe PCN allergy:

Vancomycin

PLUS

Metronidazole 500 mg IV/PO q8h

PLUS one of

AztreonamID-R: SFGH 2 g IV q8h

OR

Tobramycin

Healthcare-associated and/or previous antibiotic therapy Enterobacteriaceae

S. aureus

Streptococci spp.

P. aeruginosa

Vancomycin

PLUS

Piperacillin/

Tazobactam 4.5 g IV q6h

OR

Cefepime 2 g IV q8h

For severe PCN allergy:

Vancomycin

PLUS

Metronidazole 500 mg IV q8h

AND

Aztreonam 2 g IV q8h

WITH OR WITHOUT:

Tobramycin

For patients with neutropenia, organ transplant, severe hepatic failure, or current/recent (<7 days) piperacillin/tazobactam or cefepime:

Vancomycin

Plus

Meropenem 1-2 g IV q8h

'Abscess' 'S.aureus' Vancomycin Empirical Gram-negative and/or anaerobic coverage is not routinely indicated.

Incision and drainage is primary therapy for abscesses. After incision and drainage and once patient is stable, switch to oral antibiotics based on culture and susceptibility results.

'Cellulitis' Group A streptococci

Other beta-hemolytic streptococci

S.aureus

Vancomycin

Alternatively:

Cefazolin 1 g IV q8h if patient is stable and cellulitis is not associated with an abscess or other purulent focus of infection

Empirical Gram-negative and/or anaerobic coverage is not routinely indicated.
Necrotizing fasciitis or suspected deep tissue extension Group A streptococci

S. aureus

Anaerobes

Gram-negative rods

Vancomycin

PLUS ONE OF:

Piperacillin/tazobactam 4.5 g IV q6-8h

OR

Ertapenem 1 g IV daily

ALL WITH:

Clindamycin600 – 900 mg IV q8h 

Alternatively if infection is health-care associated:

Vancomycin

PLUS

Meropenem1-2 g IV q8h

PLUS

Clindamycin600-900 mg IV q8h

For severe PCN allergy:

Vancomycin

PLUS

AztreonamID-R: SFGH 2 g IV q8h

PLUS

Clindamycin ID-R: VASF 600-900 mg IV q8h

Clindamycin added for anti-toxin properties. Limited data support use for infections caused by Group A streptococci and Clostridium perfringens. Discontinue clindamycin once adequate surgical debridement is achieved.  

Asymptomatic bacteriuria Enterobacteriaceae

Enterococcusspecies

No treatment required Exceptions: pregnant women, patients having traumatic urologic procedures, recent kidney transplant .
Catheter-associated candiduria Candida species No treatment required Pyuria alone is not an indication for treatment.
Community-acquired Pyelonephritis  Enterobacteriaceae (E. coli) Ceftriaxone

1 g IV q24h

OR

Cefazolin 1g IV q8h (VASF only)

OR

Ertapenem 1g IV daily

For severe PCN allergy:

Vancomycin

PLUS ONE OF EITHER:

Gentamicin

OR

Aztreonam ID-R: SFGH

2 g IV q8h

 Duration of therapy 7-14 days based on clinical response.

Healthcare-associated UTI Enterobacteriaceae (e.g. E. coli)

P. aeruginosa (less common)

Ceftriaxone

1 g IV q24h

OR

Ertapenem 1g IV daily

OR

Piperacillin/tazobactamID-R: SFGH 4.5g IV q8h

For severe PCN allergy:

ONE OF:Criteria: signs and symptoms compatible with a UTI, no other identified source of infection, & ≥ 1000 cfu of ≥ 1 bacterial species on urine culture

Gentamicin

OR

Aztreonam ID-R: SFGH

2 g IV q8h

BOTH WITH OR WITHOUT:

Vancomycin

  • Pyuria alone is not an indication for treatment.
  • A negative urinalysis suggests an alternative source of infection.
  • Remove catheter if possible.
  • Switch to oral therapy when susceptibilities known and patient stable.
  • 7 days of therapy is recommend if patient has prompt resolution of symptoms