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Urinarytractinfectionsandasymptomaticbacteriuriainpregnancy

OfficialreprintfromUpToDate
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Urinarytractinfectionsandasymptomaticbacteriuriainpregnancy
Authors
ThomasMHooton,MD
KalpanaGupta,MD,MPH

SectionEditors
StephenBCalderwood,MD
CharlesJLockwood,MD,MHCM

DeputyEditor
AllysonBloom,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2016.|Thistopiclastupdated:Apr29,2016.
INTRODUCTIONUrinarytractinfections(UTIs)arecommoninpregnantwomen.Byconvention,UTIis
definedeitherasalowertract(acutecystitis)oruppertract(acutepyelonephritis)infection.UTIs(acute
cystitisandpyelonephritis)andasymptomaticbacteriuriainpregnantwomenwillbereviewedhere.
Issuesrelatedtourinarytractinfectionsorasymptomaticbacteriuriainotherpopulationsarediscussedindetail
elsewhere.(See"Acuteuncomplicatedcystitisandpyelonephritisinwomen"and"Acuteuncomplicated
cystitisandpyelonephritisinmen"and"Acutecomplicatedcystitisandpyelonephritis"and"Approachtothe
adultwithasymptomaticbacteriuria"and"Asymptomaticbacteriuriainpatientswithdiabetesmellitus"and
"Catheterassociatedurinarytractinfectioninadults".)
EPIDEMIOLOGY
IncidenceandriskfactorsTheincidenceofbacteriuriainpregnantwomenisapproximatelythesameas
thatinnonpregnantwomen,however,recurrentbacteriuriaismorecommonduringpregnancy.Additionally,the
incidenceofpyelonephritisishigherthaninthegeneralpopulation,likelyasaresultofphysiologicchangesin
theurinarytractduringpregnancy.(See'Pathogenesis'below.)
Asymptomaticbacteriuriaoccursin2to7percentofpregnantwomen[1,2].Ittypicallyoccursduringearly
pregnancy,withonlyapproximatelyaquarterofcasesidentifiedinthesecondandthirdtrimesters[3].Factors
thathavebeenassociatedwithahigherriskofbacteriuriaincludeahistoryofpriorurinarytractinfection,pre
existingdiabetesmellitus,increasedparity,andlowsocioeconomicstatus[46].
Withouttreatment,asmanyas30to40percentofpregnantwomenwithasymptomaticbacteriuriawilldevelop
asymptomaticurinarytractinfection(UTI),includingpyelonephritis,duringpregnancy[7].Thisriskisreduced
by70to80percentifbacteriuriaiseradicated(see'Rationalefortreatment'below).Althoughastudyfromthe
Netherlandssuggestedalowrateofpyelonephritisamong208womenwithuntreatedasymptomaticbacteriuria
(2.4percentversus0.6percentamong4035womenwithoutbacteriuria),thisstudyincludedonlylowrisk
womenwithuncomplicatedsingletonpregnancieswithoutdiabetesmellitusorurinarytractabnormalities,andit
isuncertainwhethertheseresultsaregeneralizable[8].
Acutecystitisoccursinapproximately1to2percentofpregnantwomen,andtheestimatedincidenceofacute
pyelonephritisduringpregnancyis0.5to2percent[912].Mostcasesofpyelonephritisoccurduringthe
secondandthirdtrimesters.Asanexample,theincidenceofacutepyelonephritisinpregnancyinthesettingof
routineprenatalscreeningforasymptomaticbacteriuriawasexaminedinaprospectivestudyofageneral
obstetricpopulation[11].Duringthetwoyearstudyperiod,440casesofacutepyelonephritiswereidentifiedin
32,282pregnantwomen(14per1000deliveries).Themajorityofcasesoccurredinthesecondtrimester(53
percent).Inadditiontoprioruntreatedbacteriuria,otherclinicalcharacteristicsthathavebeenassociatedwith
acutepyelonephritisduringpregnancyincludeage<20years,nulliparity,smoking,latepresentationtocare,
sicklecelltrait,andpreexisting(notgestational)diabetes[1113]
PregnancyoutcomesManystudieshavedescribedarelationshipbetweenmaternalurinarytractinfection,
particularlyasymptomaticbacteriuria,andadversepregnancyoutcomes.Studieshavealsosuggestedthat
acutepyelonephritishasasimilarassociation,butthereareseveralvariablesthatpotentiallyconfoundthis
association,suchassocioeconomicstatusandpreviouspretermdelivery.
Untreatedbacteriuriahasbeenassociatedwithanincreasedriskofpretermbirth,lowbirthweight,and
perinatalmortalityinmost[1,7,1419],butnotall[8,20],studies.Asanexample,inametaanalysisof19
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studies,amongwomenwithoutbacteriuria,therisksofpretermbirthandalowbirthweightinfantwereonehalf
andtwothirdstherisksamongwomenwithasymptomaticbacteriuria[19].Otherpregnancycomplications
havealsobeenassociatedwithbacteriuria.Asanexample,acasecontrolstudyofover15,000pregnant
womenfoundanincreasedriskofpreeclampsiawitheitherasymptomaticbacteriuriaorsymptomaticUTI[21].
Nocorrelationhasbeenclearlyestablishedbetweenacutecystitisofpregnancyandincreasedriskoflowbirth
weight,pretermdelivery,orpyelonephritis[16],perhapsbecausepregnantwomenwithsymptomaticlowerUTI
usuallyreceivetreatment.
Pyelonephritis,however,hasbeenassociatedwithadversepregnancyoutcomes.Inan18yearretrospective
studyofover500,000singletonpregnanciesfollowedatalargehealthcaresystemintheUnitedStates,the
rateofpretermbirth,primarilybetweenweeks33and36,washigheramongthe2894womenwhohad
pyelonephritisduringpregnancy(10.3versus7.9percentamongthosewhodidnot,OR1.3,95%CI1.21.5)
[12].Therewerenodifferencesinstillbirthorneonataldeath.Othercomplicationsofpyelonephritisinclude
anemia,sepsis,andrespiratorydistress[11].Maternalmorbidityandobstetricoutcomeswithpyelonephritisdo
notappeartodifferbytrimester[22].
PATHOGENESISTheorganismsthatcausebacteriuriaandurinarytractinfections(UTI)inpregnant
womenareofthesamespeciesandhavesimilarvirulencefactorsasinnonpregnantwomen.Thus,thebasic
mechanismofentryofbacteriaintotheurinarytractislikelytobethesameforbothgroups[23].However,the
smoothmusclerelaxationandsubsequentureteraldilatationthataccompanypregnancyarethoughttofacilitate
theascentofbacteriafromthebladdertothekidney,resultinginthegreaterpropensityforbacteriuriato
progresstopyelonephritisduringpregnancy[14,24].(See"Renalandurinarytractphysiologyinnormal
pregnancy".)
Pressureonthebladderfromtheenlarginguterusmayalsoincreasetheriskofprogressiontopyelonephritis.
Inaddition,theimmunosuppressionofpregnancymaycontribute.Asanexample,mucosalinterleukin6levels
andserumantibodyresponsestoEscherichiacoliantigensappeartobelowerinpregnantwomen[25].
MICROBIOLOGYAsinnonpregnantwomen,E.coliisthepredominanturopathogenfoundinboth
asymptomaticbacteriuriaandurinarytractinfection(UTI)inpregnantwomen.Asanexample,inastudyof
over400casesofpyelonephritis,E.coliaccountedforapproximately70percentofcases[11].Other
organismsresponsibleforinfectionincludedKlebsiellaandEnterobacterspecies(3percenteach),Proteus(2
percent),andgrampositiveorganisms,includinggroupBStreptococcus(10percent).GroupBStreptococcus
inpregnancyisdiscussedindetailelsewhere.(See"GroupBstreptococcalinfectioninpregnantwomen",
sectionon'Urinarytract'.)
Asinothercommunityacquiredinfections,antimicrobialresistanceisanincreasingconcern.Infectionscaused
byextendedspectrumbetalactamase(ESBL)producingstrainsareincreasinginnumber,evenin
uncomplicatedUTIs[26,27].InIndia,ESBLproducinguropathogensisaparticularproblem,eveninpregnant
women[28].
IsolationofmorethanonespeciesorthepresenceofLactobacillusorPropionibacteriummayindicatea
specimencontaminatedbyvaginalorskinflora.However,repeatedisolationofLactobacilluswithhighcolony
countsandwithoutotherorganismsinconsecutiveurineculturesmaynotrepresentsimplecontamination,
althoughthesignificanceofthisfindinginpregnancyisnotknown.
ASYMPTOMATICBACTERIURIA
DiagnosisThediagnosisofasymptomaticbacteriuriaismadebyfindinghighlevelbacterialgrowthonurine
cultureintheabsenceofsymptomsconsistentwithurinarytractinfection(UTI).Detailsonthetimingof
screening,specimencollection,anddiagnosticcriteriaarediscussedbelow.
ScreeningWeagreewiththeguidelinesfromtheInfectiousDiseasesSocietyofAmericathat
recommendscreeningallpregnantwomenforasymptomaticbacteriuriaatleastonceinearlypregnancy[2].
Therationaleforscreeningisthesameasfortreatmentofbacteriuriaandisdiscussedelsewhere.(See
'Rationalefortreatment'below.)
Screeningforasymptomaticbacteriuriaisperformedat12to16weeksgestation(orthefirstprenatalvisit,if
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thatoccurslater)withaurineculture[29].Rescreeningamongthosewhodidnothavebacteriuriaontheinitial
testisgenerallynotperformedinlowriskwomen.Itisreasonabletorescreenwomenathighriskforinfection
(eg,historyofUTIorpresenceofurinarytractanomalies,diabetesmellitus,hemoglobinS,orpretermlabor),
howevertheoptimaltargetpopulationsforthisisuncertain.(See"Initialprenatalassessmentandfirsttrimester
prenatalcare".)
SpecimencollectionThediagnosisofasymptomaticbacteriuriashouldbebasedoncultureofaurine
specimencollectedinamannerthatminimizescontamination.Althoughtheoptimalmethodforcollecting
voidedurineisuncertain,instructingwomentospreadtheirlabiaandcollectamidstreamurine(without
requiringacleancatch)seemsmostreasonable.Routinecatheterizationtoscreenforbacteriuriaisnot
warrantedduetotheriskofintroducinginfection.(See"Samplingandevaluationofvoidedurineinthe
diagnosisofurinarytractinfectioninadults".)
Inordertominimizecontaminationofthevoidedspecimen,itisoftenrecommendedthatthepatientcollecta
cleancatch(afterlocalcleansingoftheurethralmeatusandsurroundingmucosa)midstream(collectionofthe
secondportionofthevoidedurineafterdiscardingtheinitialstream)specimen.However,itisnotclearthat
thesemeasuresreducecontamination.Inastudyof113asymptomaticpregnantwomen,eachwasinstructed
tocollectamidstreamsamplefromthefirstconcentratedmorningurine,amidstreamsample,andaclean
catchmidstreamsample,inthatorder,overthecourseofaday[30].Ratesofmixedgrowthandgrowthofskin
floraoncultureinmidstreamurinewerecomparablewiththoseobservedinthemorningandcleancatch
samples.Overallratesofcontaminationwerehighinallthreesamples,andthewomenweretestedatamean
of32weeksofgestationasopposedtotherecommendedperiodof16weeks.Findingsfromthisandother
studiessuggestthatcollectionofacleancatchvoidedurinespecimenisoflittlevalue[31,32].
Properhandlingandprocessingofthespecimeniscrucialtoavoidfalsepositiveresults.(See"Microbiology
specimencollectionandtransport".)
DiagnosticcriteriaForasymptomaticwomen,bacteriuriaisformallydefinedastwoconsecutivevoided
urinespecimenswithisolationofthesamebacterialstraininquantitativecountsof105colonyformingunits
(cfu)/mLorasinglecatheterizedurinespecimenwithonebacterialspeciesisolatedinaquantitativecountof
102cfu/mL[2].Inclinicalpractice,however,onlyonevoidedurinespecimenistypicallyobtained,and
diagnosis(andtreatmentinitiation)ismadeinwomenwith105cfu/mLwithoutobtainingaconfirmatoryrepeat
culture.Ifbacteriathatarenottypicaluropathogens(suchaslactobacillus)areisolated,treatmentshouldbe
reservedforpatientsinwhomtheorganismgrowsasasingleisolateonconsecutivecultures.
Rapidscreeningtests,suchasdipstick,enzymaticscreen,reagentstrip,orinterleukin8testing,donotcome
closetourinecultureintermsofsensitivityandspecificityfordetectingasymptomaticbacteriuriainpregnant
womenandshouldnotbeused[3335].Inaddition,culturesareusefulinguidingtherapy.Thiscanbe
particularlyimportantinpregnancy,duringwhichthenumberofsafetreatmentalternativesisreduced.
ManagementManagementofasymptomaticbacteriuriainpregnantwomenincludesantibiotictherapy
tailoredtocultureresultsandfollowupculturestoconfirmsterilizationoftheurine.Forthosewomenwith
persistentorrecurrentbacteriuria,prophylacticorsuppressiveantibioticsmaybewarrantedinadditionto
retreatment.
RationalefortreatmentAsymptomaticbacteriuriaduringpregnancyincreasestheriskofpyelonephritis
andhasbeenassociatedwithadversepregnancyoutcomes,suchaspretermbirthandlowbirthweightinfants
(see'Epidemiology'above).Antimicrobialtreatmentreducestheriskofsubsequentdevelopmentof
pyelonephritisandisassociatedwithimprovedpregnancyoutcomes[7,3640].Thiswasillustratedinameta
analysisof14randomizedtrialsofantibiotictreatmentversusplaceboornotreatmentforpregnantwomenwith
asymptomaticbacteriuria[7].Antibiotictherapywasmorelikelytoclearasymptomaticbacteriuria(oddsratio
[OR]0.30,95%CI0.180.53)andtolowertheincidenceofpyelonephritis(OR0.23,95%CI0.130.41).There
wasalsoareductionintheincidenceoflowbirthweightinfantswithantibiotictreatment.However,the
includedstudiesthatevaluatedtheseoutcomesweredeemedtobeofpoorquality.
Similareffectsoftreatmentweresuggestedbyasubsequentprospectivestudyofpregnantwomeninthe
Netherlands(wherescreeningforasymptomaticbacteriuriaisnotperformedroutinely)[8].Womenwith
asymptomaticbacteriuriabetween16and22weeksgestationwhowerenottreatedorreceivedplacebo
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treatmenthadahigherrateofpyelonephritis(2.4percentof208women)comparedwithboththosewho
receivednitrofurantointreatmentforasymptomaticbacteriuria(0percentof40women)andthosewhodidnot
haveasymptomaticbacteriuria(0.6percentof4035women).Likewise,lowbirthweightoccurredin17of208
untreatedorplacebotreatedwomenwithasymptomaticbacteriuria(8percent)comparedwith1of40of
nitrofurantointreatedwomen(2.5percent).Whilethisdifferencewasnotstatisticallysignificant,thestudywas
underpoweredforthisoutcome.Pretermbirthdidnotdifferbetweenthesetwogroups.Notably,thestudy
includedonlywomenwhowereatlowriskforUTI,pretermbirth,orothercomplications,andthe
pyelonephritisratewaslowerthaninpreviousstudiesofpregnantwomenwithasymptomaticbacteriuria[20].
AntimicrobialtreatmentAsymptomaticbacteriuriaistreatedwithanantibiotictailoredtothe
susceptibilitypatternoftheisolatedorganism,whichisgenerallyavailableatthetimeofdiagnosis.Potential
optionsincludebetalactams,nitrofurantoin,andfosfomycin(table1).Thechoiceofantimicrobialagentshould
alsotakeintoaccountsafetyduringpregnancy(includingtheparticularstageofpregnancy).(See'Antibiotic
safetyinpregnancy'below.)
Theoptimaldurationofantibioticsforasymptomaticbacteruriaisuncertain.Shortcoursesofantibioticsare
preferredtominimizetheantimicrobialexposuretothefetus.Shortcourseantibiotictherapyisusuallyeffective
ineradicatingasymptomaticbacteriuriaofpregnancy,althoughsingledoseregimensmaynotbeaseffective
asslightlylongerregimens[4143].Asanexample,inametaanalysisof13studiescomparingsingledose
treatmentwithfourtosevendaytreatments,therewasatrendtowardslowerratesofbacteriuriaclearance
withthesingledoseregimen[43].
Anexceptionissingledosefosfomycin,whichsuccessfullytreatsbacteriuria.Inthreetrialscomparingthis
drugwithothertherapiesadministeredforalongertime,eradicationoftheorganismwascomparable(77to94
percentversus68to94percentwithotheragents)[44].
FollowupBecauseupto30percentofwomenfailtoclearasymptomaticbacteriuriafollowingashort
courseoftherapy[1],afollowupcultureshouldbeobtainedasatestofcure.Wetypicallyperformthisaweek
aftercompletionoftherapy.Inaddition,weusuallyrepeaturineculturesmonthlyuntilcompletionofthe
pregnancybecauseoftheriskofpersistentorrecurrentbacteriuria.
Thereisapaucityofdataandlackofconsensusontheneedforrescreeningortheoptimalrescreening
intervalforwomenwhohaveanegativetestofcure.Ifrescreeningisperformedandpersistentorrecurrent
asymptomaticbacteriuriaisidentified,repeattreatmentiswarranted,asbelow.
ManagementofpersistentbacteriuriaIfthefirstfollowupculture(testofcure)ispositivefor
bacterialgrowth[105cfu/mL]withthesamespecies(persistentbacteriuria),anothercourseofantimicrobial
treatmentbasedonsusceptibilitydatashouldbeadministered:eitherthesameantimicrobialinalongercourse
(eg,sevendays,ifathreedayregimenwasusedpreviously)oradifferentantimicrobialinastandardregimen.
Truepersistentbacteriuriaimpliesinitialtherapywasinadequateandthusrequiresmodificationwithadifferent
therapeuticapproachincontrasttorecurrentbacteriuria(adifferentspeciesisisolatedorthesamespeciesis
isolatedafterdocumentedclearanceoftheinitialbacteriuria).(See'Managementofrecurrentbacteriuria'
below.)
Suppressivetherapymaybeappropriateforwomenwithbacteriuriathatpersistsaftertwoormorecoursesof
therapy.Nitrofurantoin(50to100mgorallyatbedtime)forthedurationofthepregnancymaybeusedifthe
organismissusceptible.Monthlyculturesarenotnecessaryifsuppressivetherapyisadministeredhowever,
breakthroughbacteriuriacanoccurduringsuppressivetherapy,sowegenerallyperformatleastonelater
culture,suchasatthestartofthethirdtrimester,toensuresuppressionisworking.Ifthatfollowupcultureis
positive[105cfu/mL],anothercourseofantimicrobialbasedonsusceptibilitydatashouldbeadministered.
Thesuppressiveregimenshouldbereassessedandadjustedifneededbasedonthesusceptibilitypattern.
ManagementofrecurrentbacteriuriaIfthefirstfollowupcultureispositivewithadifferentspecies
orifthefirstfollowupcultureisnotpositive[<105cfu/mL],butthenasubsequentcultureispositive(withthe
sameordifferentspecies),bothscenariosimplyrecurrentbacteriuria.Treatmentshouldbeadministeredwith
oneoftheregimensusedforaninitialbacteriuricepisode,tailoredtoantimicrobialsusceptibilitytesting(table
1).
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Wetypicallydonotrecommendantibioticprophylaxisforrecurrentasymptomaticbacteriuriabecauseofthe
lackofdatatosupportthispractice.
ACUTECYSTITIS
ClinicalmanifestationsCystitisisasymptomaticinfectionofthebladder.Thetypicalsymptomsofacute
cystitisinthepregnantwomanarethesameasinnonpregnantwomenandincludethesuddenonsetofdysuria
andurinaryurgencyandfrequency.Hematuriaandpyuriaarealsofrequentlyseenonurinalysis.
Systemicsymptoms,suchasfeversandchills,aregenerallyabsentinisolatedcystitis.
DiagnosisAcutecystitisshouldbesuspectedinpregnantwomenwhocomplainaboutdysuria.Although
urinaryfrequencyandurgencyaretypicalfindingsofacutecystitis,theyarealsofrequentlyanormal
physiologicchangeofpregnancyandreportedbypregnantwomenwithoutcystitisorbacteriuria[45].The
presenceoffeverandchills,flankpain,andcostovertebralangletendernessshouldraisesuspicionfor
pyelonephritis(see'Acutepyelonephritis'below).Aurinalysisandurinecultureshouldbeperformedinpregnant
womenwhohavenewonsetdysuria.Specimencollectionisthesameasforasymptomaticbacteriuria.(See
'Specimencollection'above.)
Thediagnosisofacutecystitisisconfirmedbyfindingofbacterialgrowthonurineculture.Priortoconfirming
thediagnosis,empirictreatmentistypicallyinitiatedinapatientwithconsistentsymptomsandpyuriaon
urinalysis(see'Management'below).Asinnonpregnantwomen,pyuriaisusuallypresentinalmostall
pregnantwomenwithsymptomaticurinarytractinfection,anditsabsencestronglysuggestsanalternative
diagnosis.(See"Samplingandevaluationofvoidedurineinthediagnosisofurinarytractinfectioninadults",
sectionon'Interpretationofpyuria'.)
Studiesdefiningthethresholdofbacterialgrowthonvoidedurinethatrepresentssignificantbacteriuriain
pregnantwomenhavenotbeenperformed,butbasedonstudiesinnonpregnantwomen,relativelylowcolony
countscanreflecttruebacteriuriainthepresenceofsymptoms.Innonpregnantwomenwithuncomplicated
cystitis,coliformcolonycountsinvoidedurineaslowas102colonyformingunits(cfu)/mLhavebeennotedto
reflectbladderinfection[4648].Asmostclinicallaboratoriesdonotroutinelyquantifyurineisolatesto102
cfu/mL,itisreasonabletouseaquantitativecount103cfu/mLinasymptomaticpregnantwomanasan
indicatorofsymptomaticUTI.Ifbacteriathatarenottypicaluropathogens(suchaslactobacillus)areisolated,
thediagnosisofcystitisistypicallymadeonlyiftheyareisolatedinhighbacterialcounts(105cfu/mL).(See
"Samplingandevaluationofvoidedurineinthediagnosisofurinarytractinfectioninadults",sectionon
'Definitionofapositiveculture'.)
DifferentialdiagnosisAsinnonpregnantwomen,dysuriainpregnantwomencanbearesultofother
infectiousandnoninfectiousprocesses,suchasvaginitisorurethritis.Similarly,urinaryfrequencyandurgency
maybesymptomsofnormalpregnancyintheabsenceofurinarytractinfection.However,truebacteriuriais
typicallynotpresentinthesesettingsandthusdistinguishesacutecystitis.Ifnotalreadyperformed,testingfor
sexuallytransmittedinfections(suchaschlamydiaandgonorrhea)iswarrantedforpregnantwomenwith
dysuriawithoutbacteriuriaorwomenwhohavepersistentdysuriadespitesuccessfultreatmentofbacteriuria.
(See"Acuteuncomplicatedcystitisandpyelonephritisinwomen",sectionon'Differentialdiagnosis'.)
ManagementManagementofacutecystitisinpregnantwomenincludesempiricantibiotictherapythatis
subsequentlytailoredtocultureresultsandfollowupculturestoconfirmsterilizationoftheurine.Forthose
womenwithpersistentorrecurrentbacteriuria,prophylacticorsuppressiveantibioticsmaybewarrantedin
additiontoretreatment.
AntimicrobialtreatmentAntibiotictreatmentofacutecystitisinpregnantwomenisoftenempiric,
initiatedatthetimeofcomplaintsofdysuria,andthentailoredtothesusceptibilitypatternoftheisolated
organismonceurineculturesreturn.Potentialoptionsforempiricanddirectedtherapyincludebetalactams,
nitrofurantoin,andfosfomycin(table1).Thechoiceofanantimicrobialagentshouldalsotakeintoaccountany
priormicrobiologicaldataanddrugsafetyduringpregnancy(includingtheparticularstageofpregnancy).(See
'Antibioticsafetyinpregnancy'below.)
Forempirictherapy,wetypicallychoosebetweencefpodoxime,amoxicillinclavulanate,andfosfomycin,given
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theirsafetyinpregnancyandthesomewhatbroaderspectrumofactivitycomparedwithotheragents(suchas
amoxicillinorcephalexin).Nitrofurantoinisanotheroptionduringthesecondorthirdtrimesteroriftheothers
cannotbeusedforsomereason(eg,drugallergy).Thechoicebetweenthemshouldbeindividualizedonthe
basisofseveralfactors,includingpatientallergyhistory,localpracticepatterns,localcommunityresistance
prevalence,availability,andcost[49].
Althoughtherearelimiteddatainpregnantwomen,ametaanalysissuggestedthattherearenolarge
differencesinoutcomesbetweendifferentantibioticregimensintermsofcurerates,recurrentinfection,
incidenceofpretermdelivery,andtheneedforachangeofantibiotics[50].Alloftheantibioticsstudiedwere
veryeffectiveandcomplicationswererare.Therewasnotenoughevidencetorecommendaparticular
treatmentscheme.
Forwomenwhoarethoughttobeatriskfororhavedocumentedinfectionwithextendedspectrumbeta
lactamase(ESBL)producingEnterobacteriaceae,nitrofurantoinandfosfomycinareactiveinvitroagainstmany
suchstrainsandarepotentialoraloptions[27,51].
Theoptimaldurationoftreatmentofacutecystitisduringpregnancyisuncertain.Aswithasymptomatic
bacteriuria,shortcoursesofantibioticsarepreferred,tominimizetheantimicrobialexposuretothefetus.We
treatacutecystitiswithathreetosevendaycourseofantibioticsaslongastherearenosymptoms
suggestiveofpyelonephritis(eg,flankpain,nausea/vomiting,fever[>38C],and/orcostovertebralangle
tenderness).Basedondataamongnonpregnantindividuals,thereappeartobenodifferencesbetweenshort
antibioticcourses(threetosevendays)andlongerones[1,49,52].Singledosetherapyisgenerallylimitedto
fosfomycin.
FollowupAswithasymptomaticbacteriuria,afollowupcultureshouldbeobtainedasatestofcure.
Wetypicallyperformthisaweekaftercompletionoftherapy.Inaddition,weusuallyrepeaturinecultures
monthlyuntilcompletionofthepregnancybecauseoftheriskofpersistentorrecurrentbacteriuria.
Managementofpersistentbacteriuriaisdiscussedabove.(See'Managementofpersistentbacteriuria'above.)
ManagementofrecurrentcystitisInwomenwhohaverecurrentcystitisduringpregnancy,antimicrobial
prophylaxisforthedurationofpregnancyisareasonablestrategytopreventadditionalepisodes.Prophylaxis
canbepostcoital,ifthecystitisisthoughttobesexuallyrelated,whichitcommonlyis,orcontinuous
Inthesettingofotherconditionsthatpotentiallyincreasetheriskofurinarycomplicationsduringepisodesof
cystitis(eg,diabetesorsicklecelltrait),prophylaxisfollowingthefirstepisodeofcystitisduringpregnancyis
alsoreasonable.
Thechoiceofantimicrobialusedforprophylaxisshouldbebasedonthesusceptibilityprofileofthecystitis
strains.Ideally,dailyorpostcoitalprophylaxiswithlowdosenitrofurantoin(50to100mgPOpostcoitallyorat
bedtime)orcephalexin(250to500mgPOpostcoitallyoratbedtime)canbeused.
ACUTEPYELONEPHRITIS
ClinicalmanifestationsAcutepyelonephritisisamanifestationofinfectionoftheupperurinarytractand
kidneys.Thetypicalsymptomsofacutepyelonephritisinthepregnantwomanarethesameasinnonpregnant
womenandincludefever(>38Cor100.4F),flankpain,nausea,vomiting,and/orcostovertebralangle
tenderness.Symptomsofcystitis(eg,dysuria)arenotalwayspresent.Pyuriaisatypicalfinding.(See"Acute
uncomplicatedcystitisandpyelonephritisinwomen".)
Mostcasesofpyelonephritisoccurduringthesecondandthirdtrimesters.(See'Incidenceandriskfactors'
above.)
Pregnantwomenmaybecomequiteillandareatriskforbothmedicalandobstetricalcomplicationsfrom
pyelonephritis.Ithasbeenestimatedthatasmanyas20percentofwomenwithseverepyelonephritisdevelop
complicationsthatincludesepticshocksyndromeoritsvariants,suchasacuterespiratorydistresssyndrome
(ARDS)[5355].Asanexample,inaprospectivestudyof440casesofacutepyelonephritisidentifiedamong
32,282pregnantwomeninageneralobstetricpopulation,complicationsincludedanemia(23percent),
bacteremia(17percentintheminorityofpatientswhoweretested),respiratoryinsufficiency(7percent),and
renaldysfunction(2percent)[11].Themechanismofanemiaisnotwellunderstood,buthemolysis,perhaps
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mediatedbyendotoxin,maybeimportant[56].Acuterenalfailureassociatedwithmicroabscessesand
suppurativepyelonephritishasbeendescribedinisolatedcases,independentofsepsis[57].(See"Acute
kidneyinjury(acuterenalfailure)inpregnancy".)
DiagnosisandevaluationAcutepyelonephritisissuggestedbythepresenceofflankpain,
nausea/vomiting,fever(>38Cor100.4F),and/orcostovertebralangletenderness,withorwithoutthetypical
symptomsofcystitis,andisconfirmedbythefindingofbacteriuriainthesettingofthesesymptoms.(See
"Acuteuncomplicatedcystitisandpyelonephritisinwomen".)
Forpregnantwomenwhopresentwithsuchsymptoms,wecheckaurinalysisandurineculture.Pyuriais
presentinthemajorityofwomenwithpyelonephritis,anditsabsencesuggestsanalternativediagnosisor
completeobstruction.Althoughmanypregnantwomenhavebackorflankpainwithoutpyelonephritis,wehave
alowthresholdforevaluationforbacteriuriaandadiagnosisofpyelonephritisinpregnantwomenwiththese
symptoms,giventheriskofcomplicationsandadversepregnancyoutcomeswithuntreatedpyelonephritis.
(See'Pregnancyoutcomes'above.)
Someinvestigatorshavequestionedthevalueofobtainingroutinebloodculturesinpregnantwomenwith
pyelonephritis[58],anddataontheimpactofbloodculturesonoutcomesarelimited[59].Althoughthereisno
evidencethatbacteremiaportendsaworseprognosisorrequireslongertherapyinanotherwisehealthy
pregnantwomanwithpyelonephritis,itisreasonabletoobtainbloodculturesinthosewithsignsofsepsisor
seriousunderlyingmedicalconditionssuchasdiabetes.Othertests,suchasaserumlactatelevel,canalso
beusefulinwomenwithsuspectedsepsistoinformtheseverityofdisease[60].(See"Evaluationand
managementofseveresepsisandsepticshockinadults",sectionon'Assessperfusion'.)
Imagingisnotroutinelyusedtodiagnosepyelonephritis.However,inpatientswithpyelonephritiswhoare
severelyillorwhoalsohavesymptomsofrenalcolicorhistoryofrenalstones,diabetes,historyofprior
urologicsurgery,immunosuppression,repeatedepisodesofpyelonephritis,orurosepsis,imagingofthekidneys
canbehelpfultoevaluateforcomplications.Inpregnantwomen,renalultrasoundisthepreferredimaging
modalityinordertoavoidcontrastorradiationexposure.
DifferentialdiagnosisNephrolithiasiscanpresentwithsignificantflankorbackpainandabnormalfindings
ontheurinalysis,butfeverisuncommonwithuncomplicatedstonedisease.Thiscanalsobedistinguished
frompyelonephritisbyvisualizationofthestonesonrenalultrasound.(See"Diagnosisandacutemanagement
ofsuspectednephrolithiasisinadults".)
Forpregnantwomenpresentingwithfeverand/orflankorbackpain,certainobstetriccomplicationsare
importanttoconsiderinthedifferential:
Intraamnioticinfection,withorwithoutpretermlabor,isanimportantdiagnosticconsiderationinpregnant
womenwhohavefeverandabdominalpain.Thefollowingfeaturessuggestintraamnioticinfectionover
pyelonephritis:presentationwithprematureruptureofmembranes,uterinetendernessand/orfoulodorof
theamnioticfluid,andtheabsenceofbacteriuria.Otherpotentialcausesoffeverandbackorflankpain
intheabsenceofbacteriuriaincludeotherinfections(eg,influenza,pneumonia,appendicitis).(See
"Intraamnioticinfection(chorioamnionitis)",sectionon'Diagnosisofclinicalchorioamnionitis'.)
Placentalabruptionisakeydifferentialdiagnosisofacutebackorabdominalpainduringpregnancy.Back
painisprominentwithabruptionwhentheplacentaisontheposteriorwalloftheuterus.Feverisabsent
andvaginalbleedingisclassicallypresentwithabruption,incontrasttopyelonephritis.Theuterusisoften
firm,andmayberigidandtenderinpatientswithabruption,butisusuallysoftinpatientswith
pyelonephritis.Bothconditionscanbeassociatedwithuterinecontractions.Ifpresent,aretroplacental
hematomaonultrasoundsupportsthediagnosisofabruption.(See"Placentalabruption:Clinicalfeatures
anddiagnosis".)
ManagementManagementofacutepyelonephritisinpregnantwomenincludeshospitaladmissionfor
parenteralantibiotics.Antibiotictherapycanbeconvertedtoanoralregimentailoredtothesusceptibilityprofile
oftheisolatedorganismfollowingclinicalimprovement.Followingthetreatmentcourse,suppressiveantibiotics
aretypicallyusedfortheremainderofthepregnancytopreventrecurrence.

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SiteofcareBaseduponthehigherriskofcomplicationsinpregnantwomen,pyelonephritishas
traditionallybeentreatedwithhospitalizationandintravenousantibioticsuntilthewomanisafebrilefor24to48
hoursandsymptomaticallyimproved[61].Initialoutpatienttherapyofpregnantwomenwithpyelonephritishas
beenattemptedincarefullyselectedpopulations(eg,nounderlyingseriousmedicalconditions,renalorurologic
abnormalities,pregnancycomplications,signsofsepsis,orrecentantibioticuse).However,wesuggestnot
initiatingtherapyofpyelonephritisinpregnantwomenintheoutpatientsettinggiventhelimiteddataevaluating
itssafetyandtheneedforclosemonitoringofthepatient.
Evidenceonthesafetyofoutpatientinitiationofpyelonephritistreatmentduringpregnancyislimitedtotwo
trialsbythesamegroup[62,63].Althoughthestudiessuggestedthatoutpatienttreatmentresultedinsimilar
outcomesasinpatientmanagement,severallimitationsofthestudiescreateuncertaintyaboutthesafetyand
practicalityofoutpatientmanagement:
Inthefirsttrial,120pregnantwomenwithpyelonephritispriorto24weeksgestationwererandomly
assignedtoreceiveanoutpatientregimenconsistingofintramuscularceftriaxonefor2daysfollowedby
oralcephalexinfor10daysoraninpatientregimenconsistingofIVcefazolinfollowedatdischargebyoral
cephalexinfor10days[62].Clinicalresponsestotherapyandbirthoutcomesweresimilarforboth
outpatientsandinpatients.However,sixpatientsinitiallytreatedwithceftriaxonewereultimatelyadmitted
tothehospitalforintravenoustherapy,andonewomandevelopedsepticshockduringtheemergency
departmentobservationperiod.Ofnote,theoutpatientregimenincludedinitialparenteralantibiotics,and
homehealthnursesmonitoredpatientsassignedtotheoutpatientstrategy.
Inthesecondtrial,92womenwhopresentedafter24weeksgestationwerehospitalizedforintramuscular
ceftriaxonefor24hoursandthenrandomlyassignedtoearlydischargeonoralcephalexinorcontinued
hospitalizationuntilafebrilefor48hours[63].Clinicalresponseandbirthoutcomesweresimilarforthose
whocompletedtheassignedstrategy.However,51percentofpatientseitherdidnotqualifyforoutpatient
managementbaseduponstudycriteriaordevelopedcomplications,whichprecludedearlydischargefrom
thehospital.
EmpiricantibioticsParenteral,broadspectrumbetalactamsarethepreferredantibioticsforinitial
empirictherapyofpyelonephritis(table2).Thechoicebetweenthemshouldbeguidedbylocalmicrobiology
andsusceptibilitydataaswellasexpectedpatienttolerance.Fluoroquinolonesandaminoglycosides,whichare
oftenusedforpyelonephritisinnonpregnantindividuals,shouldbeavoidedinpregnancyifpossible.(See
'Antibioticsafetyinpregnancy'below.)
Theefficacyofbetalactamswasdemonstratedinarandomizedtrialof179pregnantwomenwithacute
pyelonephritisbeforethe24thweekofgestation:intravenouscefazolinorintramuscularceftriaxonehad
equivalentefficacytointravenousampicillinplusgentamicin[64].Althoughratesofresistancetofirst
generationcephalosporinshavegenerallybeenlessthan10percentinsurveillancestudies[6568],beta
lactams(includingfirstgenerationcephalosporins)havebeenlesseffectivethantrimethoprim
sulfamethoxazoleorthefluoroquinolonesfortreatmentofcystitisinstudiesofnonpregnantindividuals[69].
Giventhesedataandthepaucityofdataevaluatingnarrowspectrumcephalosporinsinthetreatmentof
pyelonephritis[69],wefavorthirdgenerationcephalosporinsoverfirstorsecondgenerationcephalosporins,
suchascefazolin,fortheempirictreatmentofacutepyelonephritis.
Forwomenwithahistoryofinfectionswithextendedspectrumbetalactamase(ESBL)producing
Enterobacteriaceae(orotherriskfactors),acarbapenemisanappropriatechoiceforempirictherapy.Ofnote,
someanimalstudieshaveshownadversefetaleffectswithimipenemcilastatin,someropenem,ertapenem,or
doripenemarethepreferredcarbapenemsforuseduringpregnancy.(See'Antibioticsafetyinpregnancy'
below.)
DirectedantibiotictherapyandfollowupAswithnonpregnantpatientswithcomplicated
pyelonephritis,pregnantwomengenerallyhavedefiniteimprovementwithin24to48hoursofappropriate
antibiotictherapy.Onceafebrilefor48hours,pregnantpatientscanbeswitchedtooraltherapyguidedby
culturesusceptibilityresultsanddischargedtocomplete10to14daysoftreatment[61].Oraloptionsare
mainlylimitedtobetalactamsor,ifinthesecondtrimester,trimethoprimsulfamethoxazole.Nitrofurantoinand
fosfomycinarenotappropriatefortreatmentofpyelonephritisduetoinadequatetissuelevels.General
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principlesregardingthesafetyofantibioticsinpregnancyarediscussedelsewhere.(See'Antibioticsafetyin
pregnancy'below.)
Ifsymptomsandfeverpersistbeyondthefirst24to48hoursoftreatment,arepeaturinecultureandrenal
ultrasoundshouldbeperformedtoruleoutpersistentinfectionandurinarytractpathology.
Forwomenwhodonotuseantimicrobialprophylaxisforthedurationofpregnancyfollowinganepisodeof
pyelonephritis(see'Preventingrecurrence'below),wegenerallycheckmonthlyurineculturestoevaluatefor
recurrentbacteriuriaandtreatasindicatedbecauseoftheriskofrecurrentpyelonephritis.(See'Asymptomatic
bacteriuria'above.)
ObstetricmanagementPyelonephritisisnotitselfanindicationfordelivery.Ifinductionoflaboror
cesareandeliveryforstandardobstetricalindicationsisplannedinapatientontreatmentforpyelonephritis,we
favorwaitinguntilthepatientisafebrile,aslongasdelayingthedeliveryisrelativelysafeforthemotherand
fetus.
Sincepyelonephritisisassociatedwithpretermbirth,animportantobstetricconsiderationiswhethertocolysis
shouldbeusedwhenpyelonephritistriggerspretermlaboratvariousgestationalages.Tocolysisistypicallynot
administeredafter34weeksgestation.Ifawomanwithuncomplicatedpyelonephritispriortothatgestational
ageexperiencespretermlabor,administrationoftocolysisandsteroidsisreasonabletoattempttoprolongthe
pregnancy.However,ifthepatientisseptic,tocolysisisgenerallyavoided.Pregnantwomenwith
pyelonephritisareatincreasedriskofpulmonaryedemaandacuterespiratorydistresssyndrome(ARDS),
whichmaybeexacerbatedbyadministrationoftocolysiswithorwithoutcorticosteroids.Detaileddiscussionof
thebenefitsandrisksoftocolysisforacutepretermlaborarefoundelsewhere.(See"Inhibitionofacute
pretermlabor",sectionon'Patientselection'.)
PreventingrecurrenceRecurrentpyelonephritisduringpregnancyoccursin6to8percentofwomen
[64,70,71].Asaresult,lowdoseantimicrobialsuppressivetherapywithanagenttowhichtheoriginalorganism
issusceptibleiswarrantedfortheremainderofthepregnancyreasonableoptionsincludenitrofurantoin(50to
100mgorallyatbedtime)orcephalexin(250to500mgorallyatbedtime)[61,72].
Monthlyculturesarenotnecessaryifpreventivetherapyisadministeredhowever,breakthroughbacteriuria
canoccurduringpreventivetherapy,soweusuallyperformatleastonelaterculture,suchasatthestartofthe
thirdtrimester,toensurepreventivetherapyisworking.Ifafollowupcultureispositive(105colonyforming
units/mL),thenacourseofantimicrobialtherapybasedonsusceptibilitydatashouldbeadministered.In
addition,thepreventiveregimenshouldbereassessedandadjustedifneeded.
PREVENTIONINWOMENWITHHISTORYOFRECURRENTUTIAseparateissueisthemanagement
ofpregnantwomenwithahistoryofrecurrenturinarytractinfections(UTIs)priortopregnancy,whichisoften
relatedtosexualintercourse.WeusepostcoitalprophylaxisinpregnantwomenwhohaverecurrentUTIsthat
appeartobetemporallyrelatedtosexualintercourse.Thepreferredregimenisasinglepostcoitaldoseofeither
cephalexin(250mg)ornitrofurantoin(50mg).(See"Recurrenturinarytractinfectioninwomen",sectionon
'Preventionstrategies'.)
ThepotentialefficacyofpostcoitalprophylaxistopreventUTIsduringpregnancywasevaluatedinareportof
33womenwithahistoryofrecurrentUTIswhohad39pregnancies[73].Thewomenweretreatedwithasingle
postcoitaldoseofeithercephalexin(250mg)ornitrofurantoin(50mg).OnlyoneUTIoccurredduring
pregnancythiswasinsharpcontrastto130UTIsduringameanobservationperiodofsevenmonthsbefore
prophylaxis.
ANTIBIOTICSAFETYINPREGNANCYMuchoftheinformationregardingthesafeuseofantibiotics
duringpregnancywasobtaineddecadesago,beforepregnantwomenwereexcludedfromdrugstudies
becauseofconcernsaboutrisktothefetus.Thus,thereislittledirectinformationaboutthesafetyofmany
newerantibioticsinpregnancy,andconcernabouttheuseofcertainantibioticsgenerallyderivesfromindirect
evidence(eg,animalstudies)orobservationalstudiesthatmayhavenumerousconfounders.Overall,the
safestcourseistousetheantibioticsthathavewellestablishedsafetyprofilesinpregnancyandlimittheuse
ofantibioticsofpotentialconcerntocasesinwhichnosaferalternativeexists.(See"Initialprenatal
assessmentandfirsttrimesterprenatalcare",sectionon'Antibiotictherapy'.)
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Itisgenerallyacceptedthatpenicillins(withorwithoutbetalactamaseinhibitors),cephalosporins,and
aztreonamaresafeinpregnancy.However,drugswithveryhighproteinbinding,suchasceftriaxone,maybe
inappropriatethedaybeforeparturitionbecauseofthepossibilityofbilirubindisplacementandsubsequent
kernicterus.Ofthecarbapenems,someanimalstudieshaveshownadversefetaleffectswithimipenem
cilastatin,someropenem,ertapenem,ordoripenemarethepreferredcarbapenemsforuseduringpregnancy.
Fosfomycinisalsogenerallyconsideredsafeinpregnancy[74].Inseveralstudiesofsingledosefosfomycin
duringpregnancy,itwaswelltolerated,andadversefetaleffectswerenotobserved.
Nitrofurantoinisfrequentlyusedduringpregnancy,althoughsomepotentialconcernsexist.Nitrofurantoinwas
associatedwithbirthdefectsinacasecontrolstudy[75],butthisfindingshouldbeinterpretedwithcautionas
multiplecomparisonsinvolvingsmallnumbersofaffectedexposedinfantsmayhaveledbychancetothe
observedassociation.Inaprospectivestudyofpregnantwomenwithasymptomaticbacteriuria,therewereno
congenitalbirthabnormalitiesreportedamongthe40womenwhoreceivednitrofurantoincomparedwith2
amongthe208womenwhoreceivedplaceboornoantimicrobialtreatment[8].Thesafestcourseistoavoid
usingnitrofurantoininthefirsttrimesterifanotherantibioticthatissafeandeffectiveisavailable.Nitrofurantoin
hasalsobeenreportedtocausehemolyticanemiainthemotherandfetuswithG6PDdeficiency[76].Therisk
ofhemolyticanemiaisestimatedtobeonly0.0004percentofcases,butitsuseshouldbeavoidednearterm
forthisreason[72,77].
Useoftrimethoprimsulfamethoxazoleistypicallylimitedtomidpregnancy,avoidingthefirsttrimesterandnear
term.Trimethoprimisgenerallyavoidedinthefirsttrimesterbecauseitisafolicacidantagonist,hascaused
abnormalembryodevelopmentinexperimentalanimals,andsomecasecontrolstudieshavereporteda
possibleassociationwithavarietyofbirthdefects[75].However,itisnotaproventeratogeninhumans.
Womenareroutinelyprescribedfolicacidsupplementationduringpregnancythismaybeparticularlyimportant
inthosewhoaretakingtrimethoprim.Sulfonamidesshouldbeavoidedinthelastdaysbeforedeliverybecause
theycandisplacebilirubinfromplasmabindingsitesinthenewborn,withthetheoreticalincreasedriskfor
kernicterus,althoughkernicterusrelatedsolelytoinuterosulfonamideexposurehasneverbeenreported.
Sulfonamideshavealsobeenassociatedwithbirthdefectsinacasecontrolstudy[75],butthelimitationsof
thestudydiscussedaboveleadtouncertaintyabouttheassociation.
Aminoglycosideshavebeenassociatedwithototoxicityfollowingprolongedfetalexposure[77],andtherefore
shouldbeavoidedunlessintoleranceorresistanceprohibitstheuseoflesstoxicagents.
Tetracyclinesshouldnotbeused,andfluoroquinolonesaregenerallynotusedduringpregnancy.(See"Initial
prenatalassessmentandfirsttrimesterprenatalcare",sectionon'Antibiotictherapy'.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"
and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoread
materials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.
Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepth
informationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
BeyondtheBasicstopics(see"Patientinformation:Urinarytractinfectionsinadolescentsandadults
(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Bacteriuriaoccurscommonlyinpregnancy,typicallyduringearlypregnancy.Withouttreatment,asmany
as30to40percentofpregnantwomenwithasymptomaticbacteriuriawilldevelopasymptomaticurinary
tractinfection(UTI).Thesmoothmusclerelaxationandsubsequentureteraldilatationthatoccursin
pregnancyarethoughttofacilitatetheascentofbacteriafromthebladdertothekidney,accountingfor
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thegreaterriskofpyelonephritis.Additionally,untreatedbacteriuriamaybeassociatedwithanincreased
riskofpretermbirth,lowbirthweight,andperinatalmortality.(See'Epidemiology'aboveand
'Pathogenesis'above.)
Asinnonpregnantwomen,Escherichiacoliisthepredominanturopathogenfoundinbothasymptomatic
bacteriuriaandUTIinpregnantwomen.(See'Microbiology'above.)
Wescreenallpregnantwomenatleastonceforasymptomaticbacteriuria.Screeningforasymptomatic
bacteriuriaisperformedat12to16weeksgestationwithamidstreamurineforculture.Thediagnosisis
madebyfindinghighlevelbacterialgrowth(105colonyformingunits[cfu]/mL)onurinecultureinthe
absenceofsymptomsconsistentwithUTI.(See'Diagnosis'above.)
Managementofasymptomaticbacteriuriainpregnantwomenincludesantibiotictherapytailoredtoculture
results,whichreducestheriskofsubsequentpyelonephritisandisassociatedwithimprovedpregnancy
outcomes.Potentialoptionsincludebetalactams,nitrofurantoin,andfosfomycin(table1).Following
treatment,followupculturesareperformedtoconfirmsterilizationoftheurine.Forthosewomenwith
persistentbacteriuria,prophylacticorsuppressiveantibioticsmaybewarrantedinadditiontoretreatment.
(See'Management'above.)
Acutecystitisshouldbesuspectedinpregnantwomenwhocomplainaboutnewonsetdysuria,
frequency,orurgency.Thediagnosisismadebyfindingofbacterialgrowthonurinecultureinthissetting.
Managementofacutecystitisinpregnantwomenincludesempiricantibiotictherapythatissubsequently
tailoredtocultureresults.Potentialoptionsforempiricanddirectedtherapyincludebetalactams,
nitrofurantoin,andfosfomycin(table1).Aswithasymptomaticbacteriuria,followupculturesare
performedtoconfirmsterilizationoftheurine.Forthosewomenwithpersistentbacteriuriaorrecurrent
cystitis,prophylacticorsuppressiveantibioticsmaybewarrantedinadditiontoretreatment.(See'Acute
cystitis'above.)
Acutepyelonephritisduringpregnancyissuggestedbythepresenceofflankpain,nausea/vomiting,fever
(>38C),and/orcostovertebralangletenderness,withorwithoutthetypicalsymptomsofcystitis,andis
confirmedbythefindingofbacteriuriainthesettingofthesesymptoms.Pregnantwomenmaybecome
quiteillandareatriskforbothmedical(eg,sepsis,respiratoryfailure)andobstetricalcomplicationsfrom
pyelonephritis.(See'Clinicalmanifestations'aboveand'Diagnosisandevaluation'above.)
Managementofacutepyelonephritisinpregnantwomenincludeshospitaladmissionforparenteral
antibiotics,preferablybroadspectrumbetalactams(table2).Antibiotictherapycanbeconvertedtoan
oralregimentailoredtothesusceptibilityprofileoftheisolatedorganismfollowingclinicalimprovement.
Oraloptionsaregenerallylimitedtobetalactamsor,ifinthesecondtrimester,trimethoprim
sulfamethoxazole.Followingthetreatmentcourse,suppressiveantibioticsaretypicallyusedforthe
remainderofthepregnancytopreventrecurrence.(See'Management'above.)
Itisgenerallyacceptedthatpenicillins(withorwithoutbetalactamaseinhibitors),cephalosporins,
aztreonam,andfosfomycinaresafeinpregnancy.Becauseofpossiblebutuncertainassociationswith
adversebirthoutcomes,wegenerallyavoidnitrofurantoinduringthefirsttrimesterandtrimethoprim
sulfamethoxazoleduringthefirsttrimesterandneartermunlessnootheroptionsareavailable.(See
'Antibioticsafetyinpregnancy'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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GRAPHICS
Antibioticsforasymptomaticbacteriuriaandcystitisinpregnancy
Antibiotic
Nitrofurantoin

Dose
100mgorallyevery

Duration
Fivetosevendays

12hours

Notes
Doesnotachieve
therapeuticlevelsin
thekidneyssoshould
notbeusedif
pyelonephritisis
suspected.
Avoiduseduringthe
firsttrimesterifother
optionsareavailable.

Amoxicillin

500mgorallyevery8

Threetosevendays

hoursor

itsutilityamong
gramnegative

875mgorallyevery
12hours
Amoxicillin

500mgorallyevery8

clavulanate

hoursor
875mgorallyevery

Resistancemaylimit

pathogens.
Threetosevendays

12hours
Cephalexin

500mgorallyevery6
hours

Threetosevendays

Cefpodoxime

100mgorallyevery
12hours

Threetosevendays

Fosfomycin

3gorallyassingle

Doesnotachieve

dose

therapeuticlevelsin
thekidneyssoshould
notbeusedif
pyelonephritisis
suspected.

Trimethoprim

800/160mg(one

sulfamethoxazole

doublestrength
tablet)every12

Threedays

Avoidduringthefirst
trimesterandat
term.

hours

Thedurationslistedinthetablearebasedondatafromstudiesconductedinboth
nonpregnantandpregnantwomen.
Graphic98083Version4.0

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Urinarytractinfectionsandasymptomaticbacteriuriainpregnancy

Parenteralregimensforempirictreatmentofpyelonephritisin
pregnancy
Antibiotic

Dose,interval

Mildtomoderatepyelonephritis
Ceftriaxone

1gevery24hours

Cefepime

1gevery12hours

Aztreonam*

1gevery8hours

Ampicillin

12gevery6hours

PLUS

Gentamicin

1.5mg/kgevery8hours

Severepyelonephritiswithanimpairedimmunesystemand/orincompleteurinary
drainage
Piperacillintazobactam

3.375gevery6hours

Meropenem

1gevery8hours

Ertapenem

1gevery24hours

Doripenem

500mgevery8hours

Dosesareforpatientswithnormalrenalfunction.
IfmethicillinresistantS.aureus(MRSA)isknownorsuspected,seetreatmentregimens
outlinedseparatelyintopicsaddressingMRSAmanagement.
*Alternativeinthesettingofbetalactamallergy.
Aminoglycosideshavebeenassociatedwithfetalototoxicitythisregimenshouldbeusedonlyif
intoleranceprecludestheuseoflesstoxicagents.
Graphic56181Version11.0

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ContributorDisclosures
ThomasMHooton,MDConsultant/AdvisoryBoards:Cubist[ComplicatedUTI(Ceftolozane/tazobactam)].
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preventionofUTI)].KalpanaGupta,MD,MPHConsultant/AdvisoryBoards:ParatekPharmaceuticals
MelintaTherapeuticsIterumTherapeuticsTetraphasePharmaceuticals[UTI].StephenBCalderwood,MD
PatentHolder:VaccineTechnologiesInc[Vaccines(Choleravaccines)].EquityOwnership/StockOptions:
Pulmatrix[Infectiousdiseases(Inhaledantimicrobials)]PharmAthene[Anthrax(Antibodytherapies)].Charles
JLockwood,MD,MHCMConsultant/AdvisoryBoards:Celula[Aneuploidyscreening(Nocurrentproductsor
drugsintheUS)].AllysonBloom,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
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