Essentials for Selecting Antimicrobial Therapy for

EssentialsforSelectingAntimicrobialTherapyforIntra-AbdominalInfectionsStijnBlot,JanJ.DeWaeleandDirkVogelaersFacultyofMedicine&HealthSciences,GhentUniversity,Ghent,BelgiumContentsAbstract.................................................................................e171.Introduction..........................................................................e182.TheChallengeofDefinitions.............................................................e192.1Primary,SecondaryandTertiaryPeritonitis/ComplicatedvsNon-ComplicatedIntra-AbdominalInfection(IAI)......................................................e192.2AnAlternativeCategorizationofIAI..................................................e193.AntimicrobialTherapy..................................................................e203.1GeneralConsiderations............................................................e203.2FactorstoTakeintoAccountwhenSelectingEmpiricalAntimicrobialTherapyforIAI........e213.2.1MicrobiologicalConsiderations................................................e213.3Patient-RelatedFactors............................................................e263.3.1UnderlyingCo-Morbidities.....................................................e263.3.2PenicillinAllergy.............................................................e273.3.3SeverityofDiseaseExpression..................................................e274.RecentlyIntroducedAgents.............................................................e284.1Doripenem.......................................................................e284.2Moxifloxacin......................................................................e284.3Tigecycline.......................................................................e285.DirectedTherapy......................................................................e286.DurationofAntimicrobialTherapyforIAI..................................................e297.Conclusion...........................................................................e29AbstractIntra-abdominalinfection(IAI)isacomplexdiseaseentityinwhichdif-ferentaspectsmustbebalancedinordertoselecttheproperantimicrobialregimenanddeterminedurationoftherapy.Acurrentclassificationindicatesdifferentfacesofperitonitis.Primaryperitonitisimpliesanintactgastro-intestinaltractwithoutovertbarrierdisruption.Secondaryperitonitisreferstolocalizedordiffuseperitonealinflammationandabscessformationduetodisruptionoftheanatomicalbarrier.Tertiaryperitonitisincludescasesthatcannotbesolvedbyasingleorevensequentialsurgicalintervention,oftenincombinationwithsequentialcoursesofantimicrobialtherapy.Themostfrequentlyusedclassificationdistinguishes‘uncomplicated’and‘compli-cated’IAI.InuncomplicatedIAI,theinfectiousprocessiscontainedwithinasingleorgan,withoutanatomicaldisruption.IncomplicatedIAI,diseaseisextended,witheitherlocalizedorgeneralizedperitonitis.However,thereex-istsmorethanasingledimensionofcomplexityinIAI,includingseverityofTHERAPYINPRACTICEDrugs2012;72(6):e17-e320012-6667/12/0006-0017Adisª2012Blotetal.,publisherandlicenseeSpringerInternationalPublishingAG.ThisisanopenaccessarticlepublishedunderthetermsoftheCreativeCommonsLicense‘‘Attribution-NonCommercial-NoDerivative3.0’’()whichpermitsnon-commercialuse,distribution,andreproduction,providedtheoriginalworkisproperlycitedandnotaltered.diseaseexpressionthroughsystemicinflammation.AsthecurrentlyusedclassificationsofIAIofteninciteconfusionbymixingelementsofanatomicalbarrierdisruption,severityofdiseaseexpressionand(thelikelihoodof)re-sistanceinvolvement,weproposeanalternativeforthecurrentwidelyac-ceptedclassification.Wesuggestabandoningtheterms‘uncomplicated’and‘complicated’IAI,astheymerelyconfusetheissue.Furthermore,theterm‘tertiaryperitonitis’shouldlikewisebediscarded,asthissimplyreferstotreatmentfailureofsecondaryperitonitisresultinginastateofpersistentinfectionand/orinflammation.Hence,anatomicaldisruptionanddiseaseseverityshouldbeseparatedintodifferentphenotypesforthesamediseaseincombinationwitheitherpresenceorabsenceofriskfactorsforinvolvementofpathogensthatarenotroutinelycoveredinfirst-lineantimicrobialregi-mens(Pseudomonasaeruginosa,enterococci,Candidaspeciesandresistantpathogens).Generally,theseriskfactorscanbebroughtbacktorecentex-posuretoantimicrobialagentsandsubstantiallengthofstayinhealthcaresettings(5–7days).Assuch,wedevelopedagridbasedonthedifferentcomponentsoftheclassification:(i)anatomicaldisruption;(ii)severityofdiseaseexpression;and(iii)eithercommunity-acquired/early-onsethealth-care-associatedoriginorhealthcare-associatedoriginand/orrecentanti-microbialexposure.ThegridallowsphysicianstodefinetheindexcaseofIAIinamoreunequivocalwayandtoselectthemostconvenientempiricalantimicrobialregimens.Thegridadvisesonthenecessityofcoveringnoso-comialGram-negativebacteria(includingP.aeruginosa),enterococciandyeasts.ThebasisofantimicrobialtherapyforIAIisthatbothGram-negativeandanaerobicbacteriashouldalwaysbecovered.Inrecentyears,somenew