chorioamnionitis medication

4/19/2015 ChorioamnionitisMedication

http://emedicine.medscape.com/article/973237medication#showall 1/14

ChorioamnionitisMedicationAuthor:MichaelPSherman,MD,FAAPChiefEditor:TedRosenkrantz,MDmore...

Updated:Apr2,2014

MedicationSummaryEarlydelivery,supportivecare,andantibioticadministrationforthemotherwithchorioamnionitisarediscussedinMedicalCare.Theantibioticsusedmostoftentotreatmotherswithacutechorioamnionitisarealsodiscussed.[1]

Thetreatmentofbacterialvaginosishasalsobeendiscussedabovehowever,antibiotictherapyforthisconditionisoftennotsuccessful.[185,186]

Thetreatmentofthepotentiallysepticneonateiscomplex.AnoverviewofthetreatmentforearlyonsetneonatalinfectionissummarizedinMedicalCare.

Maternalantibioticsforchorioamnionitis

Thestandarddrugtreatmentinthemotherwithchorioamnionitisincludesampicillinandanaminoglycoside(ie,usuallygentamicin),althoughclindamycinmaybeaddedforanaerobicpathogens.[1]Clindamycinmayalsobeusedifthemotherisallergictopenicillin,althoughsomeexpertsproposeuseofacephalosporin.Incasesinvolvingprematurelabororpremature,prelaborruptureofmembranes,penicillinorampicillinisfrequentlyadministeredasachemotherapeuticagenttopreventgroupBstreptococcal(GBS)colonizationofthefetus.TheuseofpenicillinaloneissuggestedforGBSchemoprophylaxisduringtheintrapartumperiod.UsingpenicillinratherthanampicillinmayavoidcolonizationofthefetuswithampicillinresistantEcoli.TherationaleforampicillinusewhenmaternalchorioamnionitisissuspectedisthatampicillinwouldtreatGBS,Haemophilusspecies,manyenterococcistrains,andLmonocytogenes.

FormoreinformationonintrapartumantibioticusetopreventGBS,seetheMedscapeReferencetopicBacterialInfectionsandPregnancy.

ClindamycinmaytreatSaureusandanaerobes.Gentamicinprovidesbroadspectrumcoverageagainstgramnegativebacteria.Theseantibioticsshouldbegivenintravenously.Thedrugsmentionedabovearegenerallysafeformotherandfetus.Anabsolutecontraindicationtouseoftheseantibioticsisaknownallergicreactiontothem.Renalfunctionmustalwaysbeconsideredwhenusingantibiotics,especiallyaminoglycosides.

Ifaurinarytractinfectionispresent,theappropriateantibioticorcombinationofantibioticsshouldbeusedtotreatthespecificbacteriumisolatedfromtheurine.

Erythromycinisinfrequentlyusedinwomenallergictopenicillin.Itsabilitytoenterurogenitalsecretionshasbeenquestioned,especiallyinthetreatmentofUreaplasmaurealyticumrelatedorMycoplasmahominisrelatedcolonizationinpregnantwomen.AneffectivetreatmentofUreaplasmaorMycoplasmainfectionsinmothersortheirinfantsisneededbecausethesepotentialpathogenscausesubstantialmorbidityandevenmortalityinthepretermneonate.[62,187]

OftheinvasiveGBSstrainsthatwereisolatedinonestudy,resistancetoeitherclindamycinorerythromycinwasinexcessof20%,whereascolonizingisolatesofGBShadresistanceinmorethan40%ofcases.[188]AreportfromtheCDCnotedthat,of4882isolatesofGBS,15%and32%wereresistanttoclindamycinanderythromycin,respectively.[189]ThissuggeststhaterythromycinorclindamycinusedaschemoprophylaxistopreventGBSinfectioninneonatesisproblematicinwomenwithpenicillinallergy.

Dosagesofantibioticstotreatmaternalchorioamnionitisarenotprovidedbecausethisisapediatricreviewaddressingmaternalchorioamnionitisasitaffectsthenewborninfant.

Supportive,immune,andantibiotictherapyofearlyonsetbacterialinfection

AnextensivediscussionofthemanagementofsepticneonatesisnotpossibleinthisarticlebutisavailableinotherMedscapeReferencechapters(seeNeonatalSepsis).Criticalpointstoensureintactsurvivaloftheneonatearementionedforcompleteness.Forexample,ventilatormanagementandsurfactantreplacementtherapycanbeusedtotreattheneonatewithcongenitalbacterialpneumonia,butacompletediscussionofthetechniquesinvolvedinthistherapyarecoveredinotherarticles.Physiciansandnursesattendingthedeliveryofanewbornwhosemotherissuspectedofhavingchorioamnionitisshouldbereadytoperformafullresuscitation,includingintubation,providingpositivepressureventilation,andtreatmentofhypovolemia,shock,andrespiratoryand/ormetabolicacidosis.LowApgarscoresmaybeanotherindicatorofsepsis.

Afterinitialstabilizationofaneonatewithpotentialinfectioninthedeliveryroom,attentionisdirectedtowardthefollowingvariablesthatinfluencesurvival:

Warmth,monitoringofvitalsigns,andmaintenanceoffluid,electrolytebalance,andcorrectionofsignificantmetabolicacidosisManagementofthecirculation,includingcorrectionofhypovolemiaandenhancementofcardiacperformancewithinotropicdrugsifsepsisrelatedmyocardialdysfunctionisnotedGlucosehomeostasisTreatmentofrespiratorydistressthatmayentailsurfactantreplacement(forpneumonia,respiratorydistresssyndrome)anddifferentmodesofassistedventilation(Inhalednitricoxidemaybeconsideredasatherapyinthepresenceofpulmonaryhypertension.)Assessmentandtreatmentofthrombocytopeniaandcoagulopathy,ifpresent

Theaforementionedelementsofsupportivecareareessentialtoreducingmorbidityandmortality.Whenmyocardial



dysfunction,cardiovascularcollapse,andseverepulmonaryhypertensionarenotreversible,extracorporealmembraneoxygenation(ECMO)maybealifesavingintervention.Incriticallyillsepticneonatesthatareneartermorterm,theimportanceofearlyreferralforECMOcannotbeoverstated.

Pulmonaryhypertensioncancomplicatethemanagementofneonatalsepsis,andinhalednitricoxidemayreversethiscomplication.TheuseofinhalednitricoxideinanonECMOfacilitymaybeproblematic.ThisisparticularlytrueifthesepticneonatedeterioratesandmustbetransferredtoanECMOfacilitywhileoninhalednitricoxidetherapy.ThereferringfacilitymaynothavethecapabilitytoprovideinhalednitricoxideduringtransporttotheECMOfacility.Inthiscircumstance,theseriouslyillinfantmaybecomecriticallyillwiththecessationofinhalednitricoxidetherapyduringtransport.Therefore,guidelinesforreferraltoanECMOcentershouldbeestablishedforeachneonatalICU(NICU)basedonthecenter'sownresourcesandabilitytosafelytransportsuchinfants.

Guidelinesforimmunotherapyinearlyonsetsepsis(EOS)arenotwellestablished.Treatmentsusedincludeadministrationofgranulocyteorgranulocytemacrophagecolonystimulatingfactors(eg,filgrastim,sargramostim)intravenousadministrationofimmunoglobulinG(IgG),[184]particularlyifahightiterIgGantibodyisspecificallydirectedagainstthebacterialpathogenandleukocytetransfusionsfordepletionofneutrophilsinthebonemarrowstoragepool.Despiteresearchoneachoftheseimmunotherapies,noagreementregardingtheirusehasbeenreached.Aneonatologist,pediatricinfectiousdiseasesubspecialist,orbothshouldbeconsultedifimmunotherapyiscontemplated.

Antibiotictherapyforearlyonsetbacterialinfectionoftheneonateusuallyincludestheadministrationofapenicillin(ie,ampicillinismostoftenusedforadditionalcoverageagainstHaemophilusspecies,enterococci,andlisteriosis)andanaminoglycoside(ie,usuallygentamicin).Generally,gentamicinprovidesamplecoverageagainstgramnegativebacteriathatcauseEOS.ThethirdgenerationcephalosporinsshouldbeusedaspartoftheantibioticregimenifresistantEcoliissuspectedbasedonmaternalhistory,amnioticfluidcultures,andtheclinicalpicture.Cefotaximehasbeenadvocatedbyexpertswhenmeningitisissuspectedorwhenanasphyxiatedinfantoranextremelypreterminfantisbeingtreatedandsevererenaldysfunctionmayoccur.

Antibioticadministrationinnewbornsisbasedonbirthweightcriteriaandgestationalageatbirth.Dosesofantibioticschangeaspostnatalageincreaseandrenalfunctionimproves.Administrationofaminoglycosidesshouldincludechangesindosingbasedonpharmacokinetics.

Finaldecisionsaboutantibioticsshouldbebasedonpositivecultureresultsfromappropriateanatomicsites.Ifrenaldysfunctionispresent,antibioticdosagesshouldbeadjustedduringthecourseoftheiradministration.Thisisparticularlytrueforaminoglycosideadministrationinextremelyprematurenewbornsandinnewbornswithurogenitalanomalies.

Recommendationsontheappropriateantibioticdosecanbefoundinsoftcoverneonatologytextbooks(ie,Neonatology:Management,Procedures,OnCallProblems,Diseases,andDrugsorManualofNeonatalCare)andclassictextbooksofneonatalperinatalmedicine.Specifictextbooksaboutantibioticuseinpediatricpatients,includingneonates(ie,Nelson'sPocketbookofPediatricAntimicrobialTherapy),havealsobeenwritten.Forthisarticle,theNEOFAX2009wasusedforselectingthedoseperkilogramandthedosingintervalforspecificantibiotics.ThereviewonantibioticstotreatEOSisnotexhaustive.

Lastly,thephysicianmustconsiderthedurationofantibiotictherapy.Thisisparticularlytruewhendecidingthedurationofantibiotictreatmentforwellappearingtermneonates.Intheeraofmanagedcare,inwhichcostreductionsaretypical,discontinuingantibioticsinhealthytermneonateswithin2448hoursofinitiatingtherapyisprobablysafe.Withcurrentbacteriologictechniques,morethan9095%ofneonatalbloodculturesbecomepositivewithin48hoursofthetimetheyarecultivated.AnegativeCreactiveprotein(CRP)resultwhenreviewedat48hoursafterbirthsuggestsantibiotictreatmentcanbestopped.

Inneonateswithproveninfection,thewellbeingoftheinfectednewbornshouldguidethedurationofantibiotictherapy.Thebacteriumcausingtheinfectionandthesiteoftheinfectionalsoinfluencethedurationofantibiotictherapy.Forexample,bacterialpneumoniaisoftentreatedfor710dayswithantibiotics.Bacteremiaisoftentreatedwithantibioticsfor1014days.Thisdurationisbasedonthepotentialforrecurrencewithshortercoursesoftreatment(ie,10daysofantibioticsisoftenconsideredaminimumforGBSassociatedbacteremia).

Cerebrospinalfluid(CSF)infectionsmayrequireantibiotictherapyfor24weeksbasedonthebacteriumresponsiblefortheinfection,findingsonananalysisofCSFindicatingtheresolutionofinfection,andthepresenceofcomplicationsassociatedwithmeningitis.ForuncomplicatedGBSrelatedinfectionsoftheCSF,2weeksmaybesufficientothergrampositiveandallgramnegativebacteriaoftenrequire34weeksofantibiotictherapy.SurgicalinterventionsforlocalizedCNSinfections(eg,aninfectiousepiduralcollection,brainabscess)orthepresenceofpostinfectioushydrocephalusmayindicateantibiotictherapyneedstobeprovidedforaslongas46weeks.

Thefollowinginformationreviewstheantibioticsthatarecommonlyusedtotreatearlyonsetbacterialinfectionsintheneonate.Theantibioticscoveredarenotexhaustive.Forexample,theuseofazithromycintotreatcongenitalpneumoniacausedbyUrealyticumorMycoplasmaisnotreviewed.Areportthatusedazithromycintotreatpregnantwomenrevealedthisantibioticwaslesseffectivecomparedwithotherantimicrobials.[190]Issuesrelatedtoinfectionscausedbythesemicrobesandotherspecialbacteriainneonatesmayrequireconsultationwithaneonatologistorapediatricinfectiousdiseasessubspecialist.

AntibioticAgents

ClassSummary

Empiricantimicrobialtherapymustbecomprehensiveandshouldcoveralllikelypathogensintheclinicalsetting.AntibioticcombinationsareusuallyrecommendedforseriousGramnegativebacillaryinfections.Thisapproachensurescoverageforabroadrangeoforganismsandpolymicrobialinfections.Inaddition,itpreventsresistanceinbacterialsubpopulationsandprovidesadditiveorsynergisticeffects.Onceorganismsandsensitivitiesareknown,theuseofantibioticmonotherapyisthenrecommended.Theexceptionwouldbebacteriathatcouldattainahighlyresistantplasmidagainstantimicrobials.[191]InformationaboutantimicrobialsusedtotreatneonatesandthesourceforthisreviewisNEOFAX2009.[192]

AqueouscrystallinepenicillinGisconsideredthefirstlineagentforGBS.Ampicillinmaybeused,however,recentconcernsurroundsampicillinresistantEcoliinfections.Othermodifiedpenicillinssuchasoxacillinornafcillin(antistaphylococcal),netilmicin(antipseudomonalorotherGramnegativeentericbacteria),andpiperacillin(antipseudomonal)arenottypicallyusedasfirstlineantibioticsfortreatmentofearlyonsetneonatalinfections.The



aforementionedmodifiedpenicillinsaredesignedtotreatinfectionscausedbypenicillinresistantbacteriathatcanexpressbetalactamase.Thesemodifiedpenicillinsareusuallyreservedforthetreatmentofpostnatallyacquiredinfectionsinhospitalizedneonates.Methicillinresistantstaphylococcalinfectionshaveemergedinpregnantwomen,andneonateswithEOSwhohavethesestaphylococciarereportedsuchinfectionsrequiretreatmentwithvancomycin.

Viewfulldruginformation

PenicillinG,aqueouscrystalline(Pfizerpen)

AqueouscrystallinepenicillinG(penG)administeredIVistheDOCforGBSbacteremiaormeningitis.PenGisalsoknownasbenzylpenicillin.DonotconfusepenGwithbenzathineorprocainepenicillinusedonlyforIMinjectionspenGistheoriginalantibioticinthepenicillinclassandinhibitssynthesisofthebacterialcellwall.PenGmayprovideadequatecoverageforSpneumoniaewhenitisacauseofearlyonsetbacterialinfectioninneonates(infrequent)butthisbacteriumcanalsohaveresistancetopenG.


Ampicillin

Amorebroadspectrumaminopenicillinusedformanyyearsaseitheradefinitiveoraprophylactictherapyforearlyonsetbacterialinfectionofneonates(ie,GBSandsusceptibleEcoli).MayprovideadditionalcoverageagainstHaemophilusspecies,manyenterococci,otherstreptococci,Listeriamonocytogenes,andalimitednumberofsusceptiblegramnegativeentericbacteria.IndicatedforneonatalbacteremiaormeningitisduetoGBS.

Cefotaxime(Claforan)

Athirdgenerationcephalosporinwithenhancedpotencyagainstmanygramnegativebacteria.Generallyconsideredinactiveagainstenterococci,Listeria,andmoststrainsofpseudomonadsandbacteroides.Someexpertsconsiderthisantibioticthepreferredtherapyforneonatalmeningitiscausedbygramnegativebacteriaifthebacteriumissensitivetoit(andinconjunctionwithanaminoglycoside).ThispreferenceisbasedonmoreeffectiveCNSpenetrationofcefotaxime.Indicatedwhenaminoglycosidesmaybecontraindicated(eg,significantrenalfailure)orwhenaminoglycosidesmayhaveenhancedtoxicity.


Gentamicin

Gentamicinisoneoftheaminoglycosideantibiotics(ie,amikacin,netilmicin,andtobramycin).Generally,gentamicinhasactivityagainstPseudomonasaeruginosa,whereaskanamycindoesnot.Firstchoiceforprophylacticordefinitivetherapyofearlyonsetbacterialinfectionsinneonatesbecauseithasbroadactivityagainstmanygramnegativebacilli.Amikacinandtobramycinareusuallyreservedtotreatnosocomialinfectionscausedbygramnegativebacteriathatareresistanttogentamicin.

Aminoglycosidesshouldnotbeusedalonetotreatinfectionspotentiallycausedbygrampositivebacteria.Thus,apenicillinisalwaysincludedinthetreatmentofearlyonsetbacterialinfectionsinneonates.Furthermore,topreventtheemergenceofhighlyantibioticresistantgramnegativebacteria,nosocomialinfectionsinhospitalizedneonatesshouldneverbetreatedwithanaminoglycosidealone.Asecondantibioticshouldbeadministeredinadditiontotheaminoglycoside,anditsmechanismofactionthatcausesmicrobialdeathshouldbedifferentfromthatoftheaminoglycoside.

Thisantibiotichasablackboxwarning.Elevatedbloodconcentrationsofaminoglycosidesmaycausesignificantinjurytothekidneyandthevestibular/auditorynerve.Concurrentuseoffurosemideorotherloopdiureticsanduseofvancomycincanincreasenephrotoxicity.Thus,peakandtroughlevelsofaminoglycosidesinneonatalseramustbemeasurediftheiruseisgoingtoexceedaninitialperiodofprophylaxis(ie,48hafterbirth)toexcludesepsis.

Aminoglycosidesdemonstrateconcentrationdependentkillingofbacteria,suggestingapotentialbenefitrelatedtohigherserumconcentrationsthatareachievedwithlessfrequentdosing(eg,oncedailyadministration).

ContributorInformationandDisclosuresAuthorMichaelPSherman,MD,FAAPProfessor,DepartmentofChildHealth,UniversityofMissouriColumbiaSchoolofMedicineNeonatologist,Women'sandChildren'sHospitalProfessorEmeritus,DepartmentofPediatrics,UniversityofCalifornia,Davis,SchoolofMedicine

MichaelPSherman,MD,FAAPisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,AmericanAssociationfortheAdvancementofScience,AmericanAssociationofImmunologists,AmericanPediatricSociety,AmericanSocietyforMicrobiology,AmericanThoracicSociety,EuropeanSocietyforPaediatricResearch,PediatricInfectiousDiseasesSociety,PerinatalResearchSociety,SocietyforPediatricResearch,andWesternSocietyforPediatricResearch

Disclosure:Nothingtodisclose.

Coauthor(s)NaomiFLauriello,MDAssistantProfessorofNeonatology,UniversityofMissouriWomen'sandChildren'sHospital

NaomiFLauriello,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics

Disclosure:MedIQHonorariaSpeakingandteaching

KatsufumiOtsuki,MD,PhDAssociateProfessor,Chief,DepartmentofObstetricsandGynecology,ShowaUniversityKotoToyosuHospital,Japan




SpecialtyEditorBoardTedRosenkrantz,MDProfessor,DepartmentsofPediatricsandObstetrics/Gynecology,DivisionofNeonatalPerinatalMedicine,UniversityofConnecticutSchoolofMedicine

TedRosenkrantz,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,AmericanMedicalAssociation,AmericanPediatricSociety,ConnecticutStateMedicalSociety,EasternSocietyforPediatricResearch,andSocietyforPediatricResearch


MaryLWindle,PharmDAdjunctAssociateProfessor,UniversityofNebraskaMedicalCenterCollegeofPharmacyEditorinChief,MedscapeDrugReference


ArunKPramanik,MD,MBBSProfessorofPediatrics,LouisianaStateUniversityHealthSciencesCenter

ArunKPramanik,MD,MBBSisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,AmericanThoracicSociety,NationalPerinatalAssociation,andSouthernSocietyforPediatricResearch


CarolLWagner,MDProfessorofPediatrics,MedicalUniversityofSouthCarolina

CarolLWagner,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,AmericanChemicalSociety,AmericanMedicalWomen'sAssociation,AmericanPublicHealthAssociation,AmericanSocietyforBoneandMineralResearch,AmericanSocietyforClinicalNutrition,MassachusettsMedicalSociety,NationalPerinatalAssociation,andSocietyforPediatricResearch


ChiefEditorTedRosenkrantz,MDProfessor,DepartmentsofPediatricsandObstetrics/Gynecology,DivisionofNeonatalPerinatalMedicine,UniversityofConnecticutSchoolofMedicine

TedRosenkrantz,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofPediatrics,AmericanMedicalAssociation,AmericanPediatricSociety,ConnecticutStateMedicalSociety,EasternSocietyforPediatricResearch,andSocietyforPediatricResearch


AdditionalContributorsResearchbytheauthor,MichaelSherman,issupportedbyNIHgrantR44HD057744andagrantfromtheGerberFoundation.TheauthorappreciatesthereviewofthemanuscriptundertakenbyJanSherman,RN,NNP,PhD,andherhelpfulrecommendationsforimprovement.

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