the american college of obstetricians and gynecologists ...pharm.cch.org.tw/files/antimicro3/16.pdf · the american college of obstetricians and gynecologists ... , cefuroxime , ampicillin

1472 VOL. 117, NO. 6, JUNE 2011 OBSTETRICS & GYNECOLOGY

P RAC T I C EBUL L E T I N

the american college of obstetricians and gynecologistswomen’s health care physicians

BackgroundEffectiveprophylacticantibioticagentsareactiveagainstmostbutnotallpotentialpathogens,whichusuallyareendogenous flora. The goal of antibiotic prophylaxisis to prevent infection, not to cure or treat disease. Incontrasttothetherapeuticuseofantibiotics,prophylaxismustbeadministeredbeforethepotentialexposure,andusually for a short duration (less than 24 hours). Thegoalofprophylacticantibioticuseistohavetherapeutictissue levels in place at the time microbial contamina-tionmightoccur.Delayingadministrationbyevenafewhours reducesor eliminates thebenefit ofprophylaxis.Ideally, theagentofchoiceshouldbelongacting,nar-rowly focused on the likely bacteria, inexpensive, andhavealowincidenceofadverseeffects.

Resistance Risks of Prophylactic AntibioticsAlthough the risks of inappropriate antibiotic use maybe difficult to recognize in any individual patient, thebroader effect of the increasing use of antibiotics canbe seen in the hospital setting. Antimicrobial prophy-laxishasbeenshowntoresultinmarkedchangesinanindividual’s skin flora,with increases in resistant floraseenpostoperatively(1).Thisappearstobetheresultofselectionof resistant endogenous florabyprophylacticantibiotics, as well as the nosocomial acquisition ofresistantmicro-organisms.

In labor and delivery, awareness of the potentialadverseeffectsof resistantbacterial infectionsonneo-nates has been increasing. A comparison of very lowbirthweightneonates(lessthan1,500g)bornbetween

Use of Prophylactic Antibiotics in Labor and DeliveryThe use of antibiotics to prevent infections during the antepartum, intrapartum, and postpartum periods is distinctly different from the use of antibiotics to treat established infections. For many years, the use of prophylactic antibiot-ics was thought to have few adverse consequences. Concerns about the emergence of resistant strains of common bacteria, in addition to the emergence of strains with increased virulence, have resulted in increased scrutiny of the use of antibiotics, particularly in the hospital setting. In labor and delivery, awareness of the potential adverse effects of resistant bacterial infections on neonates has been growing. Finally, cost is an element to consider in the use and choice of prophylactic agents. The purpose of this Practice Bulletin is to present a review of clinical situations in which prophylactic antibiotics are frequently prescribed and to weigh the evidence supporting the use of antibiotics in these scenarios.

Number 120, JuNe 2011 (Replaces Committee Opinion Number 445, November 2009 and Committee Opinion Number 421, November 2008)

clinical management guidelines for obstetrician–gynecologists

Committee on Practice Bulletins––Obstetrics.ThisPracticeBulletinwasdevelopedbytheCommitteeonPracticeBulletins––Obstetricswiththeassis-tanceofAmyMurtha,MD,andNeilSilverman,MD.Theinformationisdesignedtoaidpractitionersinmakingdecisionsaboutappropriateobstetricandgynecologiccare.Theseguidelinesshouldnotbeconstruedasdictatinganexclusivecourseoftreatmentorprocedure.Variationsinpracticemaybewar-rantedbasedontheneedsoftheindividualpatient,resources,andlimitationsuniquetotheinstitutionortypeofpractice.

VOL. 117, NO. 6, JUNE 2011 Practice Bulletin Use of Prophylactic Antibiotics in Labor and Delivery 1473

1998and2000withthosebornbetween1991and1993found an important reduction in early-onset neonatalsepsisfromgroupBstreptococci(GBS),butanincreaseinsepsiscausedbyEscherichia coli(2).

ChangeshavebeenreportedinresistancepatternsofisolatedstrainsofE coliinnewborns,particularlyaftermaternalantibioticadministration (3–8).The increasesinE coli sepsisandtheincreasingresistancetoampicil-linareprimarilyconfinedtothepretermpopulationandlowbirthweightpopulationalthoughaneffectonterminfants has been suggested as well (9–10). Sepsis inverylowbirthweightneonateswithampicillin-resistantE coliismorelikelytobefatalthaninfectionwithsus-ceptiblestrains(7).InadditiontoresistantE coli,somestudiesshowthatupto30%ofGBSisolatesareresistanttoerythromycinandclindamycin.TheseresultshaveledtosignificantchangesinintrapartumprotocolsdesignedtopreventinvasiveneonatalGBSdisease(11–14).

In the past, resistance has been countered by thedevelopmentofnewclassesofdrugsormodificationsofolderdrugs.However,itseemsincreasinglyunlikelythatthe pharmaceutical industry will be able to keep pacewiththerapidemergenceofresistantorganisms(15).Inthepasttwodecades,forexample,increasingdifficultieshave been encountered in treating multidrug-resistanttuberculosis as well as increasingly resistant strains ofStaphylococcus aureus, enterococci, andStreptococcus pneumoniae(16).

The potential for the development of resistantorganisms is also a financial consideration when plan-ningprophylacticantibioticstrategies.Thecostimplica-tionsofmethicillin-resistantS aureus(MRSA)infectiontreatmentamongobstetricpatientshavebeenestimatedtobemorethan$8millionannuallyintheUnitedStatesalone(17).

Antibiotic Allergy and Anaphylaxis RisksOther risksofantibioticadministration includeallergicreactions or anaphylaxis, although the true incidencesof these risks are unclear. Approximately 25% of allpatients requiring antimicrobial therapy in the hospitalreport an allergy to at least one antibiotic, typicallypenicillin,althoughonly4%ofthosepatientshavedocu-mentationastothespecifictypeofallergicreaction(18).Anaphylaxis to penicillin is estimated to occur in 1 in2,500–25,000patients,withlessseverereactionsoccur-ring in approximately 10% of patients (9). It has beenestimatedthatapproximately5%ofpatientsreceivinganantibioticinthehospitalwillhaveasignificantadversereaction (19). Skin reactions (urticaria, rash, pruritus)to cephalosporinsoccur in1–3%ofpatients;however,the risk of anaphylaxis is thought to be much lower(0.001–0.1%) (20).Acaseofanaphylaxis topenicillin

after administration for GBS prophylaxis has beenreported,and thereare reportsofexfoliativedermatitisand severe immune hemolytic anemia associated withcephalosporintherapy(20–22).Althoughtheseinstanc-esareuncommon,antibioticuseshouldbelimitedtothespecificindicationsasoutlined.

Pharmacokinetics of AntibioticsIt has long been assumed that the pharmacokinetics ofantibiotics differ between pregnant and nonpregnantpatients. As a result of the increase in the glomerularfiltrationrate thatbeginsearly in the first trimesterdur-ing pregnancy, those medications that are excreted byrenalfiltrationmaybeexpectedtohaveshorterhalf-livesandmaybeexpectedtoreachlowerpeakserumlevelsinpregnant women. Because of the increased plasma vol-ume in pregnancy, the volume of distribution is greaterandtheconcentrationofplasmaproteinsislowerthaninthe nonpregnant state, which potentially leads to lowerplasmaandserumlevelsofantibiotics.Hormone-mediatedincreasesinbindingproteinsalsomayresultinchangesinthe distribution of drugs, whereas decreases in gastricemptyingtimeandchangesingastricaciditymaychangetheoralabsorptionofdrugs.Overall,theseconsiderationsarebelievedtoresultinareductionintheamountofthedrugavailabletothewomanand,potentially,aneedforincreasedantibioticdosagesduringpregnancy.

Whentherapeuticlevelsofantibioticsintheamni-otic cavity are desired, agents known to have efficienttransplacental transfer should be used. Examples ofsuchclinicalsituationsincludeprophylaxisforpretermpremature rupture of membranes (PROM) to prolongthelatencyperiodaswellasmaternal intrapartumpro-phylaxis for GBS. Antibiotics that are known to reachfetalconcentrationsof30–90%ofmaternalseruminthesecondtrimesterandbeyondincludeampicillin,cepha-lothin, clindamycin, and the aminoglycosides (23, 24).Antibioticsthatdonotappeartocrosstheplacentawellincludeerythromycinandazithromycin.(23–25).

Highdosesofprophylacticantibioticsalsomaybeindicatedinthecontextofanobesepatient(bodymassindex [BMI] greater than 30). Although this issue hasnot been studied extensively in pregnant patients, inpatientsundergoingbariatricsurgery,forexample,asin-glepreoperative2-gdoseofcefazolinresultedinintra-operativeserumandtissuelevelscomparablewiththoseseen in nonobese patients given a 1-g dose (26, 27).Comparably, increases in both volume of distributionanddrugclearanceforcephalosporinshavebeendemon-stratedinobesepatients(27–29).Therefore,adjustmentofsingle-dosepreoperativeantibioticprophylaxisinthecontextofmaternalobesityseemsreasonablebasedoncurrentlyavailablepharmacokineticdata(26,30).

1474 Practice Bulletin Use of Prophylactic Antibiotics in Labor and Delivery OBSTETRICS & GYNECOLOGY

Clinical Considerations and Recommendations

Isantibioticprophylaxisappropriateforpatientsundergoingcesareandelivery?

The single most important risk factor for infection inthepostpartumperiodiscesareandelivery,withratesofpostoperative infection significantly higher than wouldbe predicted compared with rates from other surgicalprocedures(31–33).Aswithotherelective,noninfectedsurgical cases, antimicrobial prophylaxis is recom-mended forallcesareandeliveriesunless thepatient isalreadyreceivinganantibioticregimenwithappropriatecoverage (eg, for chorioamnionitis), and such prophy-laxis should be administered within 60 minutes beforethestartofthecesareandelivery(34).Whenthisisnotpossible (eg, need for emergent delivery), prophylaxisshouldbeadministeredassoonaspossibleaftertheinci-sionismade.

ArecentCochranereviewincluded86studieswithmore than 13,000 participants enrolled in randomizedclinicaltrialstoevaluatetheeffectofprophylacticanti-bioticsinbothemergentandnonemergentcesareandeliv-eries.Thisreviewfoundsignificantreductionsinoverallfebrilemorbidity,woundcomplications,andendometritiswith theuseofprophylacticantibiotics. In thisanalysis,the risk of endometritis after elective cesarean delivery,for example, was reduced by 76% (relative risk [RR]0.24;95%confidenceinterval[CI],0.25–0.35).Allriskreductionsremainedsignificantregardlessofthetypeofcesareandelivery(emergentorelective)(35).Inaddition,arecentreviewofmorethan9,000U.S.womenundergo-ingatermprelaborcesareandeliveryshowedsignificantreductions in both postpartum endometritis and woundcomplicationswhenantibioticprophylaxiswasreceived.This study, conducted through the Eunice Kennedy Shriver National Institute of Child Health and HumanDevelopment-sponsored Maternal–Fetal Medicine UnitsNetwork,demonstratedsignificantreductionsinmorbid-ity outcomes in the face of very low baseline rates forthese complications after nonlabor cesarean deliveries(2.6% for endometritis and 1% for wound infections).These risk reductions remained significant when theanalysis was controlled for patients who had rupture ofmembranes,butnotlabor,beforetheirsurgery(36).

Timing and Choice of Antibiotic RegimenAntibiotics that are effective against gram-positivebacteria, gram-negative bacteria, and some anaerobicbacteria, are mainly used for prophylaxis for cesareandelivery. A variety of antibiotics have been shown to

be efficacious for prophylaxis, including cefazolin,cefotetan, cefuroxime, ampicillin, piperacillin, cefoxi-tin, and ampicillin–sulbactam. One retrospective studyof 2,280 nonelective cesarean deliveries reported thatcefazolin, a first-generation cephalosporin, and cefoxi-tin, a second-generation cephalosporin, were equallyefficacious in preventing endometritis, with cefazolincosting80%lessthancefoxitin(37).Similarly,ameta-analysisof51antibiotictrialsconfirmedthatampicillinand first-generation cephalosporins had comparableefficacy when compared with second-generation andthird-generation cephalosporins for cesarean deliveryprophylaxis(38).Ampicillin,however,wouldbealessappropriate choice for surgical prophylaxis comparedwithcefazolinbecauseofitsmuchshorterhalf-life.Thissame review demonstrated no differences in efficacywhen first-generation cephalosporins were comparedwith broader-spectrum second-generation cephalospo-rins or third-generation cephalosporins for the purposeofsurgicalprophylaxisingeneral.

Single-dose therapyhasbeen shown tobe as effi-cacious as multidose therapy in most studies (39–42).Single-dose therapyalso reducescosts,potential toxic-ity,andtheriskofcolonizationwithresistantorganisms.Therefore,asingledoseofatargetedantibiotic,suchasa first-generation cephalosporin, is the first-line anti-biotic of choice, unless significant drug allergies arepresent. For women with a history of a significantpenicillinorcephalosporinallergy(anaphylaxis,angio-edema, respiratory distress, or urticaria), a single-dosecombinationofclindamycinwithanaminoglycosideisareasonablealternativeforcesareandeliveryprophylaxis.

Extended-spectrum antibiotics, such as azithromy-cin,havebeensuggestedbysomeinvestigatorsasalter-natives or adjuncts to first-generation cephalosporinsfor cesarean delivery prophylaxis, administered eitherbeforeorafterumbilicalcordclamping.Inonereview,thebenefitofpostincisionadministrationofazithromy-cinappearedtobecomparabletopreincisionalcefazolin(43).Atpresent,theadvantageofthisstrategyremainsunproved and further systematic study is necessarybeforeitsroutineadoption.

Afterasingle1-g intravenousdoseofcefazolin,atherapeutic level is maintained for approximately 3–4hours. A higher dose may be indicated if a woman isobese. Although no specific dose has been studied inobesepregnantpatients, aspreviouslymentioned,con-siderationshouldbegiventousingahigherdoseofpre-operativeantibioticsforsurgicalprophylaxisforwomenwithaBMIgreaterthan30oranabsoluteweightmorethan100kg(27).Furtherstudyisneededtodeterminewhether additionallyaugmenteddosagesarewarrantedinpatientsatorabovedefinitionsofextremelymorbid


or World Health Organization class III, obesity (BMIgreaterthan40–45).

The most appropriate timing for administration ofprophylactic antibiotics alsohasbeen increasingly stud-ied. A recent meta-analysis of three randomized trials(44–46),withacombinedsamplesizeof749participants,supported the use of antibiotic prophylaxis for cesar-ean delivery administered up to 60 minutes before skinincision rather than after umbilical cord clamping (47).Antibioticprophylaxisbeforeskinincisionwasfoundinthis study and a later systematic review to decrease theincidenceofpostpartumendometritisandtotalinfectiousmorbiditieswithoutaffectingneonataloutcomes(47,43).Two subsequent retrospective cohort studies from largecenters evaluated the effect of policy change at theseinstitutions from administering antibiotics after umbili-cal cord clamping to administering preincisional cesar-eanprophylaxistoallpatients.Thesetwostudies,withacombined sample sizeof10,326women, reinforced thefindingsoflowratesofbothsurgicalsiteinfectionsandoverall maternal infectious morbidities with presurgicalprophylaxis.Nodifferencesinratesofneonatalintensivecareunitadmission,neonatalsepsis,orsuspectedsepsiswere reported between the treatment groups, although,aswithotherstudies,powercalculationswerenotbasedonevaluationofthesesecondaryneonataloutcomes(48,49). In addition, a retrospective case–control study of1,600patientswhounderwentcesareandeliveryshowedthatantibioticprophylaxisadministeredmorethan1hourbefore incision was associated with double the rate ofsurgical site infections compared with timing within 1hourofincision(RR,2.1;CI,1.2–3.8)(50).Asforsurgi-calprophylaxisingeneral,patientswithlengthysurgicalproceduresorthosewhoexperienceexcessivebloodlossshould receive an additional intraoperative dose of theantibioticusedforpreincisionprophylaxis(51).

Doescolonizationwithmethicillin-resistantS aureusaffectantibioticprophylaxisforcesareandelivery?

The epidemiology of MRSA infections has changedfromprimarilyhospital-acquiredinfectionamongillorimmunocompromisedpatientstoinfectionsrelatedtotheemergenceofmorevirulentMRSAstrainsoverthepast10years,whichconstitutesamajorpublichealthprob-lemnolongerconfinedtointensivecareunitsorhealthcareinstitutionsingeneral(52–55).Inonerecentsurvey,MRSAisolationamongpatientswithculture-confirmedsurgicalsiteinfectionincreasedfrom16%to21%overa5-yearstudyperiod(56).Methicillin-resistantS aureushasbeenassociatedwithseriouspostpartuminfections,particularlyaftercesareandelivery(57,58),andsurveil-

lance studies have detected MRSA colonization ratesofupto10%inrectovaginalswabspecimensandupto2%ofnasalswabspecimensinasymptomaticpregnantwomenat term (59,60).Despite these increasingcon-cerns, there are currently insufficient data in pregnantpatientstowarrantorrecommendscreeningallwomenpreoperatively for MRSA colonization status, particu-larly because most colonized patients will not developinvasivedisease.

Although intranasal or topical (skin wash) antimi-crobial decolonization protocols have been studied forthepreventionofrecurrentskinandsofttissueinfectionsamongMRSAcarriers,theoverallefficacy,optimaldos-age and duration for these regimens remains uncertain(61). In the context of skin and soft tissue infectionsalone, nasal mupirocin has been shown to decrease theprevalenceofnasalMRSAcolonization,butnottoreducetheincidenceoffirst-timeskinandsofttissueinfections(62).Inaddition,concernsabouthighlevelsofmupirocinresistancehavebeenraisedbyanalysisofMRSAisolatesinsomecommunitysettings(63).Althoughapreoperativeskinpreparationusingchlorhexidinealcoholwasshowntoreduceratesofsurgicalinfectionscomparedwithpovi-doneiodine(64),chlorhexidineskinwipesusedalonehadnoeffectonloweringskinandsofttissueinfectionsratesamongMRSAcarriers (65).Finally,aCochrane reviewfoundnobenefit fromoralantibiotics foreradicationofMRSAcolonizationamongpatientsinthehealthcareset-ting(66),andoralantibioticsarenotcurrentlyroutinelyrecommended for the purpose of MRSA decolonization(61).

In addition, any potential benefit of preoperativedecolonization protocols for MRSA carriers may belimited in obstetric populations to women who have aplannedcesareandeliveryandwhoareknownbeforethedelivery tobeMRSAcolonized(definedas thosewitha historyofMRSA infectionor positive culture in thepast).RoutinescreeningofobstetricpatientsforMRSAcolonizationisnotrecommended.However,inobstetricpatients known to be MRSA colonized, considerationmay be given to adding a single dose of vancomycinto the recommended antibiotic prophylaxis regimenfor women undergoing cesarean delivery (cefazolinor an alternative for patients with b-lactam allergies).Vancomycinalonedoesnotprovidesufficientcoverageforsurgicalprophylaxisingeneral.

Isantibioticprophylaxisappropriateforpatientswithpretermprematureruptureofmembranes?

ForpatientswithPROMatlessthan37weeksofgesta-tion, antibiotic prophylaxis is indicated to prolong the


andonerecentretrospectivereviewoftheuseofamoxi-cillin–clavulanicaciddidnotdemonstrateanassociationwithnecrotizingenterocolitis(77).

The Eunice Kennedy Shriver National Institute ofChild Health and Human Development-sponsoredMaternal–Fetal Medicine Units Network Trial, as wellas the Society of Obstetricians and Gynaecologists ofCanada have recommended the use of prophylacticantibiotics for preterm PROM when fetal lung matu-rity is not documented and delivery is not imminent,with options including a regimen of both amoxicillinand erythromycin for a total of 7 days (78). Severalrecent studies have attempted to determine whether ashorter duration of 7 days of antibiotic therapy couldbe adequate after preterm PROM, but they have beenofinadequatesizeandpowertodemonstrateequivalenteffectivenessinreducinginfantmorbidity(79,80).

Recently revised guidelines from the Centers forDiseaseControlandPreventionrecommendthatwomenwith preterm PROM who are not in labor shouldreceive a regimen that will include adequate intrave-nous GBS coverage for at least the first 48 hours ofpreterm PROM latency prophylaxis, pending the GBStest results obtainedon admission.However,GBS testresultsshouldnotaffecttheoveralldurationofantibiotictherapy.Ifthepatientcompletesthefull7-daycourseofantibioticprophylaxisandremainswithoutevidenceofinfectionorlabor,intrapartumGBSprophylaxisshouldthen be managed by the results of the baseline GBStestatthetimeofpretermPROMunless5weekshavepassed(anegativeGBStestresultisconsideredvalidfor5weeks)(13,14).

Isantibioticprophylaxisappropriateforpretermlabor?

Antibioticuseintendedonlyforpregnancyprolongationin women with preterm labor with intact membranesdoesnothaveshort-termneonatalbenefitsandmaybeassociated with long-term harm. Thus, antibiotic pro-phylaxisshouldnotbeusedforpregnancyprolongationinwomenwithpretermlaborandintactmembranes(72,73, 76). This recommendation is distinct from recom-mendations for antibiotic use for preterm PROM andGBScarrierstatus(7,13,81).

In cases of preterm labor with intact membranes,intravenous GBS prophylaxis should be administereduntil GBS test results are available unless the patienthas had a negative GBS test result within the preced-ing5weeks.IftheGBStestresultobtainedatthetimethepatientwasadmittedispositivebuttruelabordoesnotensue, theGBSprophylaxisshouldbestoppedandrestartedattheonsetoftruelabor(13).

latencyperiodbetweenmembraneruptureanddelivery(13,67)(seeBox1).Numeroustrialshaveevaluatedtheprophylactic use of intravenous and oral antibiotics toprolong latency and to improve maternal and neonataloutcomes after preterm PROM (68–73). Regardlessof the antibiotic prescribed or the duration of treat-ment, most trials described a statistically significantprolongationofthelatencyperiodbutgenerallydidnotshow an improvement in neonatal outcome. However,a Maternal–Fetal Medicine Units Network multicentertrial did demonstrate a reduction in neonatal morbid-ityandmortalitywithantibioticprophylaxis, includingreductionsinrespiratorydistresssyndrome,necrotizingenterocolitis, intraventricular hemorrhage, and early-onsetsepsis(72).Inthisstudy,neonatesofGBS-positivewomendidnotreceivethesamebenefit,andnoneofthepatientsreceivedantenatalcorticosteroids.

Several meta-analyses have concluded that anti-biotic prophylaxis after preterm PROM is effective inprolongingpregnancy,reducingmaternalinfectiouscom-plications, and reducing neonatal infectious morbidity(73–75). However, a large multicenter trial from theUnitedKingdomreportedthatpregnancywasprolongedbytheuseoferythromycin,amoxicillin–clavulanicacid,orboth,but thatonly theuseoferythromycin resultedin reduced neonatal morbidity (76). A review of thecurrentliteraturedoesnotrevealaconsistentpatternofincreasedriskwithbroader-spectrumantibiotictherapy,

Box 1. Recommendations for Use of Antibiotics in Women With Preterm Premature Rupture of

Membranes or Preterm Labor

For patients with preterm labor with intact membranes—• Use intrapartum antibiotics to prevent group B strep-

tococcal perinatal infection.• Do not use antibiotics to prolong pregnancy.For patients with acute infections requiring antibiotic

treatment during pregnancy—• Erythromycin, or amoxicillin–clavulanate, or both

may be given if appropriate based on known or anticipated bacterial sensitivities to these agents.

For patients with preterm premature rupture of membranes—• Use antibiotics to prevent group B streptococcal

perinatal infection.• Use broad-spectrum antibiotics during conservative

management to prolong pregnancy and decrease short-term neonatal complications for preterm premature rupture of membranes.


Arecentmulticenter,randomizedclinicaltrialpro-vided a 7-year follow-up of a large group of patientsreceivingantibiotics(placeboversusoralerythromycin,amoxicillin–clavulanate,orboth)forpretermlaborwithintactmembranes.Fromthistrial,3,196children(71%of thoseenrolled) had outcome information available(82).Despitebeingcomparableinacutemorbiditiesandmortality, the studygroupswere significantlydifferentin terms of long-term follow-up data. Infants exposedprenatallytoerythromycin,hadmorefunctionalimpair-ment(42.3%versus38.3%)andmildfunctionalimpair-ment (23.9% versus 21.3%) compared with those whohadnotreceivederythromycin.Thesedatareinforcethelack of benefit and potential harm in using antibioticprophylaxisforpretermlaborwithintactmembranes,incontrasttoitsusewithpretermPROM.

Isantibioticprophylaxisappropriateforpreventionofbacterialendocarditisatthetimeofdelivery?

Infectiveendocarditisprophylaxis isnot recommendedfor either vaginal delivery or cesarean delivery in theabsenceofinfection,exceptpossiblyforthesmallsubsetofpatients athighestpotential risk for adverse cardiacoutcomeswhoareundergoingvaginaldelivery(83,84).Joint statements from the American Heart Associationand the American College of Cardiology recommendthis approach for threemain reasons:1)most casesofendocarditisarenotattributabletoaninvasiveprocedure(whether dental, gastrointestinal, or genitourinary), butrather are the result of randomly occurring bacteremiafrom routine daily activities; 2) prophylaxis may onlypreventasmallnumberofcasesofinfectiveendocarditisinwomenundergoinggenitourinaryprocedures;and3)theriskofantibiotic-associatedadverseeventsexceedsthebenefit, ifany,fromprophylacticantibiotictherapy(83,85).Mitralvalveprolapseisnotconsideredalesionthateverneedsinfectiveendocarditisprophylaxis.

Onlycardiacconditionsassociatedwiththehighestrisk of adverse outcomes from endocarditis are appro-priateforinfectiveendocarditisprophylaxis,andthisisprimarilyforpatientsundergoingdentalproceduresthatinvolvemanipulationofgingivaltissueortheperiapicalregion of teeth, or perforation of the oral mucosa (seeBox2).However,becauseofthepotentialforsignificantmorbidityandmortality,basedonexpertopinionandalimited retrospective study of women with congenitalheartdisease(86),theAmericanHeartAssociationandthe American College of Cardiology recommend thattheuseofprophylacticantibiotictherapybeconsideredforvaginaldelivery inpatientswith thehighest riskofadverse outcomes from endocarditis. Those at highest

risk are women with cyanotic cardiac disease, or pros-theticvalves,orboth(84).Forthosenotalreadyreceiv-ingintrapartumantibiotictherapyforanotherindicationthat would also provide coverage against endocarditis,antibiotic regimens for endocarditis prophylaxis canbeadministered as close to 30–60 minutes before antici-patedtimeofdeliveryasisfeasible.

In patients with one of these high-risk conditionsandwhohaveanestablished infection thatcould resultinbacteremia,suchaschorioamnionitisorpyelonephri-tis,theunderlyinginfectionshouldbetreatedtopreventinfection or sepsis, but specific additional endocarditisprophylaxis is not recommended (83). In such cases,the regimen being used to treat the established infec-tionwillalmostuniformlyalreadycontainanagentthatis recommended as a single-dose for prophylaxis with

Box 2. Cardiac Conditions With High Risk of Endocarditis in the Presence of Bacteremia

Prophylaxis against infective endocarditis is reasonable for the following patients at highest risk of adverse out-comes from infective endocarditis who undergo dental procedures that involve manipulation of either gingival tissue or the periapical region of teeth or perforation of the oral mucosa*:• Patients with prosthetic cardiac valve or prosthetic

material used for cardiac valve repair • Patients with previous infective endocarditis • Patients with CHD

— Unrepaired cyanotic CHD, including palliative shunts and conduits

— Completely repaired congenital heart defect repaired with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure.

— Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (both of which inhibit endothelialization)

• Cardiac transplant recipients with valve regurgitation due to a structurally abnormal valve.

Abbreviation: CHD, congenital heart disease.

*Prophylaxis against infective endocarditis is not recommended for nondental procedures in the absence of active infection.

Data from Nishimura RA, Carabello BA, Faxon DP, et al. ACC/AHA 2008 guideline update on valvular heart disease: focused update on infective endocarditis. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: endorsed by the Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Angiography, and Society of Thoracic Surgeons. Circulation 2008;118:887–96.


dental procedures (ampicillin or amoxicillin, cefazo-lin or ceftriaxone, clindamycin, or azithromycin) (seeTable 1). Multiple-dose combination regimens are nolonger indicated or recommended for prophylaxis eveninthecontextofinvasivedentalprocedures.

Isantibioticprophylaxisappropriateforpatientsundergoingrepairofthird-degreelacerationsorfourth-degreelacerations?

Theuseofprophylacticantibioticsinthesettingofsig-nificantperinealtraumahasnotbeenextensivelystudied.Asinglerandomizedtrialsuggeststhatasingledoseofasecond-generationcephalosporin(cefotetanorcefoxitin),or of clindamycin if the patient was penicillin allergic,was protective against perineal wound complications(8.2%inthetreatmentgroupat2weeks,comparedwith24.1%inthecontrolgroup;P=0.04,RR0.34;95%CI,0.12–0.96).However,thisstudyhadafollow-uplossrateof27%,and its findingshavenotbeen replicated (87).In a recentmeta-analysis, additional data regarding theuse of prophylactic antibiotics in this setting were felttobenecessarybeforerecommendationscouldbemade(88).

Isantibioticprophylaxisappropriateforpatientsundergoingcervicalcerclage?

Evidenceisinsufficienttorecommendperioperativeanti-biotic prophylaxis at the time of prophylactic or emer-gency cervical cerclage. Few studies have specificallyevaluated theuseofprophylactic antibioticsduring theperformanceofaprophylacticcervicalcerclage.Becausethe rate of complications (including infectious compli-cations) after prophylactic cerclage (when performedbeforeanyevidenceofcervicaldilationorshortening)islow(1–5%),astudywithasufficientlylargesamplesizetodeterminewhetherprophylacticantibiotictherapyisofbenefitwouldbeextremelydifficulttoimplement(89).

Cerclage performed later in pregnancy, and whencervicaldilationandeffacementarepresent,hasahighrate of complications, including chorioamnionitis andrupture of membranes (89, 90). In addition, the risk ofpre-existing, often subclinical, chorioamnionitis as acause of the cervical insufficiency is significant, aver-aging approximately 33% (89, 91). Randomized trialsof cerclage in both high-risk individuals and low-riskindividualswithcervicalshorteninghavenotuniformlyincludedantibioticprophylaxisaspartoftheirprotocolsand, therefore, the current evidence is insufficient torecommendantibioticprophylaxisforeitherprophylacticor emergency cerclage (92, 93). If prophylaxis is usedin such a situation, it should be guided by the generalprinciples previously outlined, particularly a focused-coveragespectrumandshortduration.

Similarly,consistentdataare lacking regarding theuse of antibiotic prophylaxis for abdominal cerclage.Whenperformedvialaparotomy,however,routinepro-phylaxiswouldnotbeindicated,inaccordancewithrec-ommendationsforothergynecologicsurgicalproceduresthatdonotinvolvethevagina.Similarly,incaseswherethis procedure is performed laparoscopically, antibioticprophylaxis,asforotherlaparoscopicprocedures,isnotindicated(51).

Isantibioticprophylaxisappropriateforpatientsundergoingmanualremovaloftheplacenta?

Severalstudiesdocumenttheincreasedriskofpostpartumendometritis after manual removal of the placenta dur-ing cesarean delivery, even in the presence of antibioticprophylaxis (94–96).Although it iscommonpractice toadminister prophylactic antibiotics to patients who givebirth vaginally and in whom a manual removal of theplacentahasbeenperformed,nodataexisttosupportthispractice.

Table 1. Antibiotic Prophylaxis Appropriate for Infective Endocarditis

Regimen (Preferable Treatment of Antibiotic 30–60 Minutes Treatment Antibiotic Before Procedure)

Intravenous therapy Ampicillin 2 g intravenously or Cefazolin or ceftriaxone* 1 g intravenously

Allergic to penicillin or ampicillin† Cefazolin or ceftriaxone* 1 g intravenously* or Clindamycin† 600 mg intravenously*

Oral Amoxicillin 2 g

*This regimen does not cover enterococcus. Vancomycin can be used if enterococcus is of concern.†Cephalosporins should not be used in patients with a significant sensitivity to penicillins.


Inobesepatients(BMIgreaterthan30)undergoingcesareandelivery,considerationshouldbegiventousing a higher dose of preoperative antibiotics forsurgicalprophylaxis.

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asaconsequenceofantimicrobialprophylaxis.RevInfectDis1991;13(suppl10):S805–9.(LevelIII)

2. StollBJ,HansenN,FanaroffAA,WrightLL,CarloWA,Ehrenkranz RA, et al. Changes in pathogens causingearly-onset sepsis in very-low-birth-weight infants. NEnglJMed2002;347:240–7.(LevelII-3)

3. StiverHG,ForwardKR,TyrrellDL,KripG,LivingstoneRA,Fugere P, et al. Comparative cervical microflora shiftsaftercefoxitinorcefazolinprophylaxisagainst infectionfollowingcesarean section.AmJObstetGynecol1984;149:718–21.(LevelI)

4. TowersCV,CarrMH,PadillaG,AsratT.Potentialcon-sequencesofwidespreadantepartaluseofampicillin.AmJObstetGynecol1998;179:879–83.(LevelII-3)

5. TerroneDA,RinehartBK,EinsteinMH,BrittLB,MartinJN Jr, Perry KG. Neonatal sepsis and death caused byresistant Escherichia coli: possible consequences ofextendedmaternalampicillinadministration.AmJObstetGynecol1999;180:1345–8.(LevelIII)

6. FriedmanS,ShahV,OhlssonA,MatlowAG.Neonatalescherichiacoliinfections:concernsregardingresistancetocurrenttherapy.ActaPaediatr2000;89:686–9.(LevelIII)

7. Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B,Romaguera J, O’Sullivan MJ, et al. Risk factors andopportunitiesforpreventionofearly-onsetneonatalsep-sis: a multicenter case-control study. Pediatrics 2000;105:21–6.(LevelII-2)

8. Towers CV, Briggs GG. Antepartum use of antibioticsand early-onset neonatal sepsis: the next 4 years. Am JObstetGynecol2002;187:495–500.(LevelII-3)

9. VeraniJR,McGeeL,SchragSJ.Preventionofperinatalgroup B streptococcal disease—revised guidelines fromCDC, 2010. Division of Bacterial Diseases, NationalCenter for Immunization and Respiratory Diseases,Centers for Disease Control and Prevention (CDC).MMWRRecommRep2010;59(RR-10):1–36.(LevelIII)

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11. PearlmanMD,PiersonCL,FaixRG.Frequentresistanceof clinical group B streptococci isolates to clindamy-cin and erythromycin. Obstet Gynecol 1998;92:258–61.(LevelIII)

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Summary of Recommendations and Conclusions

The following recommendations are based ongoodandconsistentscientificevidence(LevelA):

Antimicrobial prophylaxis is recommended for allcesarean deliveries unless the patient is alreadyreceivingappropriateantibiotics(eg,forchorioam-nionitis) and that prophylaxis should be adminis-tered within 60 minutes before the start of thecesareandelivery.

Forcesareandeliveryprophylaxis,asingledoseofatargetedantibiotic,suchasafirst-generationceph-alosporin,isthefirst-lineantibioticofchoice,unlesssignificantdrugallergiesarepresent.

Antibioticprophylaxisisindicatedforpatientswithpreterm PROM to prolong the latency periodbetweenmembraneruptureanddelivery.

Antibioticprophylaxisshouldnotbeusedforpreg-nancy prolongation in women with preterm laborandintactmembranes.Thisrecommendationisdis-tinct from recommendations for antibiotic use forpretermPROMandGBScarrierstatus.

Thefollowingrecommendationsarebasedonlim-itedorinconsistentscientificevidence(LevelB):

Forwomenwithahistoryofasignificantpenicillinorcephalosporinallergy(anaphylaxis,angioedema,respiratorydistress,orurticaria),asingle-dosecom-binationofclindamycinwithanaminoglycosideisareasonablealternativechoice forcesareandeliveryprophylaxis.

Infectiveendocarditisprophylaxisisnolongerrec-ommendedforeithervaginalorcesareandeliveryinthe absence of infection except possibly for thesmallsubsetofpatientsathighestpotentialriskofadversecardiacoutcomeswhoareundergoingvagi-naldelivery.

Thefollowingrecommendationsarebasedprimar-ilyonconsensusandexpertopinion(LevelC):

Evidence is insufficient to recommend antibioticprophylaxis for either prophylactic or emergencycerclage.


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The MEDLINE database, the Cochrane Library, and theAmerican College of Obstetricians and Gynecologists’own internal resources anddocumentswereused to con-ductaliteraturesearchtolocaterelevantarticlespublishedbetween January 1990–January 2011. The search wasrestricted to articles published in the English language.Priority was given to articles reporting results of originalresearch, although review articles and commentaries alsowereconsulted.Abstractsofresearchpresentedatsympo-siaandscientificconferenceswerenotconsideredadequatefor inclusion in this document. Guidelines published byorganizationsorinstitutionssuchastheNationalInstitutesof Health and the American College of Obstetricians andGynecologistswerereviewed,andadditionalstudieswerelocated by reviewing bibliographies of identified articles.Whenreliable researchwasnotavailable,expertopinionsfromobstetrician–gynecologistswereused.

Studieswerereviewedandevaluatedforqualityaccordingto the method outlined by the U.S. Preventive ServicesTaskForce:

I Evidence obtained from at least one properlydesignedrandomizedcontrolledtrial.

II-1 Evidence obtained from well-designed controlledtrialswithoutrandomization.

II-2 Evidence obtained from well-designed cohort orcase–controlanalyticstudies,preferablyfrommorethanonecenterorresearchgroup.

II-3 Evidenceobtainedfrommultipletimeserieswithorwithouttheintervention.Dramaticresultsinuncon-trolled experiments also could be regarded as thistypeofevidence.

III Opinionsofrespectedauthorities,basedonclinicalexperience,descriptivestudies,orreportsofexpertcommittees.

Basedon thehighest levelofevidencefoundin thedata,recommendationsareprovidedandgradedaccordingtothefollowingcategories:

LevelA—Recommendationsarebasedongoodandcon-sistentscientificevidence.

LevelB—Recommendationsarebasedonlimitedorincon-sistentscientificevidence.

LevelC—Recommendations arebasedprimarilyoncon-sensusandexpertopinion.

Copyright June 2011 by the American College of Obstet-riciansandGynecologists.Allrightsreserved.Nopartof thispublication may be reproduced, stored in a retrieval system,posted on the Internet, or transmitted, in any form or by anymeans, electronic, mechanical, photocopying, recording, orotherwise,withoutpriorwrittenpermissionfromthepublisher.

Requests for authorization to make photocopies should bedirectedtoCopyrightClearanceCenter,222RosewoodDrive,Danvers,MA01923,(978)750-8400.

The American College of Obstetricians and Gynecologists 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920

Useofprophylacticantibioticsinlaboranddelivery.PracticeBulletinNo.120.AmericanCollegeofObstetriciansandGynecologists.ObstetGynecol2011;117:1472–83.

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