版權(quán)說(shuō)明:本文檔由用戶提供并上傳,收益歸屬內(nèi)容提供方,若內(nèi)容存在侵權(quán),請(qǐng)進(jìn)行舉報(bào)或認(rèn)領(lǐng)
文檔簡(jiǎn)介
Clinicalmanagementofdiphtheria
Guideline
2February2024
worldHealth
organization
Clinicalmanagementofdiphtheria:guideline,2February2024
WHO/Diph/Clinical/2024.1
?WorldHealthOrganization2024
Somerightsreserved.ThisworkisavailableundertheCreativeCommonsAttribution-NonCommercial-ShareAlike3.0IGOlicence(CCBY-NC-SA3.0IGO;
/licenses/by-nc-sa/3.0/igo
).
Underthetermsofthislicence,youmaycopy,redistributeandadapttheworkfornon-commercialpurposes,pro-videdtheworkisappropriatelycited,asindicatedbelow.Inanyuseofthiswork,thereshouldbenosuggestionthatWHOendorsesanyspecificorganization,productsorservices.TheuseoftheWHOlogoisnotpermitted.Ifyouadaptthework,thenyoumustlicenseyourworkunderthesameorequivalentCreativeCommonslicence.Ifyoucreateatranslationofthiswork,youshouldaddthefollowingdisclaimeralongwiththesuggestedcitation:“ThistranslationwasnotcreatedbytheWorldHealthOrganization(WHO).WHOisnotresponsibleforthecontentorac-curacyofthistranslation.TheoriginalEnglisheditionshallbethebindingandauthenticedition
AnymediationrelatingtodisputesarisingunderthelicenceshallbeconductedinaccordancewiththemediationrulesoftheWorldIntellectualPropertyOrganization(
/amc/en/mediation/rules/
).
Suggestedcitation.Clinicalmanagementofdiphtheria:guideline,2February2024.Geneva:WorldHealthOrgani-
zation;2024(WHO/DIPH/Clinical/2024.1).Licence:
CCBY-NC-SA3.0IGO
.
Cataloguing-in-Publication(CIP)data.CIPdataareavailableat
/iris
.
Sales,rightsandlicensing.TopurchaseWHOpublications,see
/bookorders
.Tosubmitrequestsforcommercialuseandqueriesonrightsandlicensing,see
/copyright
.
Third-partymaterials.Ifyouwishtoreusematerialfromthisworkthatisattributedtoathirdparty,suchastables,figuresorimages,itisyourresponsibilitytodeterminewhetherpermissionisneededforthatreuseandtoobtainpermissionfromthecopyrightholder.Theriskofclaimsresultingfrominfringementofanythird-party-ownedcom-ponentintheworkrestssolelywiththeuser.
Generaldisclaimers.ThedesignationsemployedandthepresentationofthematerialinthispublicationdonotimplytheexpressionofanyopinionwhatsoeveronthepartofWHOconcerningthelegalstatusofanycountry,terri-tory,cityorareaorofitsauthorities,orconcerningthedelimitationofitsfrontiersorboundaries.Dottedanddashedlinesonmapsrepresentapproximateborderlinesforwhichtheremaynotyetbefullagreement.
Thementionofspecificcompaniesorofcertainmanufacturers’productsdoesnotimplythattheyareendorsedorrecommendedbyWHOinpreferencetoothersofasimilarnaturethatarenotmentioned.Errorsandomissionsexcepted,thenamesofproprietaryproductsaredistinguishedbyinitialcapitalletters.
AllreasonableprecautionshavebeentakenbyWHOtoverifytheinformationcontainedinthispublication.How-ever,thepublishedmaterialisbeingdistributedwithoutwarrantyofanykind,eitherexpressedorimplied.Theresponsibilityfortheinterpretationanduseofthemateriallieswiththereader.InnoeventshallWHObeliablefordamagesarisingfromitsuse.
Contact
cmtm@
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
3of27
Sections
1.Summaryoftheguideline 4
2.Abbreviations 6
3.Introduction 7
4.Clinicalcharacterization 8
5.Recommendationforantibioticstreatment 9
6.Recommendationsfordiphtheriaantitoxin(DAT) 14
6.1Mechanismofactionofdiphtheriaantitoxin(DAT) 14
6.2Diphtheriaantitoxinsensitivitytesting:rationale 14
6.3RecommendationonDATsensitivitytesting 14
6.4RecommendationonDATdose 17
7.Methods:howthisguidelinewascreated 21
8.Howtoaccessandusetheguideline 23
9.Uncertainties,emergingevidenceandfutureresearch 24
10.Authorship,contributionsandacknowledgements 25
References 26
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
4of27
1.Summaryoftheguideline
Clinicalquestion:Whatistheroleofantibioticsanddiphtheriaantitoxin(DAT)inthetreatmentofdiphtheria?
Context:Thisclinicalpracticeguidelinehasbeenrapidlydevelopedrecognizingtheglobalincreaseindiphtheriaoutbreaks.
OutbreaksofdiphtheriainNigeria,Guineaandneighbouringcountriesin2023havehighlightedtheurgentneedforevidence-basedclinicalpracticeguidelinesforthetreatmentofdiphtheria.Giventhesporadicnatureofoutbreaks,manycliniciansintheaffected
regionshavenevermanagedacutediphtheriaanditsrelatedcomplications.ThediphtheriacasedefinitionisprovidedintheWHOdocument:
Diphtheria:VaccinePreventableDiseasesSurveillanceStandards
(1).
Scope:Thisguidelinefocusesontheclinicalmanagementofrespiratorydiphtheriaanddoesnotprovideadviceonvaccination.
SeeWHOLaboratorymanualforthediagnosisofdiphtheriaandotherrelatedinfections(2).
Newrecommendations:
?Inpatientswithsuspectedorconfirmeddiphtheria,WHOrecommendsusingmacrolideantibiotics(azithromycin,erythromycin)inpreferencetopenicillinantibiotics[Strongrecommendation,lowcertaintyevidence].
?Inpatientswithsuspectedorconfirmeddiphtheria,WHOrecommendsnottoperformroutinesensitivitytestingpriortoadministrationofdiphtheriaantitoxin(DAT)[Strongrecommendation,moderatecertaintyevidence].
?Inpatientswithsuspectedorconfirmedsymptomaticdiphtheria,WHOsuggestsanescalatingdosingregimenfordiphtheria
antitoxin(DAT)whichisbasedondiseaseseverityandtimesincesymptomonset,incomparisonwithafixeddoseforallpatients[conditionalrecommendation,verylowcertaintyevidence].
Characteristicofdiphtheriadisease
Doseofdiphtheriaantitoxin(IU)
?Laryngitisorpharyngitis
and
?Duration<48hours
20000
?Nasopharyngealdisease(extensivepseudomembrane)
and
?duration<48hours
40000
Oneormoreof:
?Diffuseswellingoftheneck
?Anydisease≥48hours
?Severedisease(respiratorydistress,shock)
80000
Aboutthisguideline:Thisguidelinewasdevelopedaccordingtostandardsandmethodsfortrustworthyguidelines.These
guidelinesarebasedonthesynthesisoftheavailableevidenceonthehealtheffectsofinterventions,andthegradingofthecertaintyofthatevidenceusingtheGRADE(GradingofRecommendationsAssessment,Development,andEvaluation)approach.The
synthesizedandgradedevidenceonthehealtheffectsofinterventions,aswellasanyevidenceoncontextualfactors,isusedto
developanevidence-to-decision(EtD)frameworkforeachrecommendation(3).ThejudgementonthedifferentfactorsintheEtD
framework(includingthecertaintyofevidence)facilitatesthedeterminationofthestrengthanddirectionofeachrecommendation(4).
Expertinputisimportantfortheinterpretationoftheevidence,andthedevelopmentofguidancemayrelyonexpertopinion,
particularlyinareaswheretheevidenceiscurrentlyweak,scarceorabsent.Forexample,theDATdosingrecommendations
presentedintheguidelinesarebasedonaconsiderationoftheevidencegainedfromobservationaldataaswellasthetechnicalknowledgeandexperienceoftheGuidelineDevelopmentGroup(GDG).Detailsofcontributorsareavailableonline
here
.
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
5of27
Updateandaccess:Thelivingguidelineiswritten,disseminated,andupdatedonanonlineplatform(MAGICapp,
/#/guideline/7759
),withauser-friendlyformatandeasy-to-navigatestructurethataccommodatesdynamicallyupdatedevidenceandrecommendations,focusingonwhatisnewwhilekeepingexistingrecommendationsupdatedwithinthe
guideline.Thisformatshouldalsofacilitateadaptation,whichisstronglyencouragedbyWHO,tocontextualizerecommendationsfromahealthcaresystemperspectivetomaximizecountryimpact.
Aplannedupdateisalreadyongoingtoaddressclinicalquestionsrelatedtothepreventionofinfectioninclosecontactsofpeoplewithdiphtheria.
Broadercontext:
TheguidelinecloselyalignswiththeWHOHealthEmergenciesProgrammegoalofstrengtheningpreparation,preparedness,responseandresilienceinresponsetohealthemergencies,particularlytheabilityofmemberstatestoprovidesafeandscalablecare(5).
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
6of27
2.Abbreviations
AMR
antimicrobialresistance
AST
antibioticsensitivitytesting
DAT
diphtheriaantitoxin
DOI
declarationofinterest
DST
drugsensitivitytesting
ETD
evidencetodecision
GDG
guidelinedevelopmentgroup
SAE
seriousadverseevent
WHO
WorldHealthOrganization
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
7of27
3.Introduction
Whattriggeredthisguideline?
Despitetheimplementationofdiphtheriavaccinationearlylastcenturytherehascontinuedtobeoutbreaksofdiphtheriainregions
wherevaccinecoverageisnotoptimal.VaccinecoveragehasbeennegativelyimpactedbytheCOVID-19pandemic,population
displacement,andstructuraldisruptionofhealthsystems.Thereisnowaprolongedoutbreakofdiphtheriainmultiplecountriesin
WestAfricaandsporadicoutbreaksinallWHOregions.Althoughdiphtheriaisbothpreventableandtreatable,successfultreatmentdependsonrapidrecognitionoftheclinicalsyndromeaswellasrapidimplementationoftheappropriatetreatment,whichincludesthetimelyadministrationoftheappropriateantibioticsandDAT.AccesstoDAThasbeenachallengeduetolimitedglobalsupplyand
rapiddistributionsystems.
TheWHOClinicalmanagementofdiphtheriaguidelineaimstoprovide,inasinglereference,thelatestevidence-based
recommendationstosupportcliniciansintheireffortstoprovideacutetreatmentfordiphtheria.Thisguidelinerespondstodirectrequestsfromcliniciansandhealthministriesofaffectedcountries.Currently,cliniciansincountriesaffectedbytheoutbreakhavelimitedornoclinicalexperiencemanagingpatientswithdiphtheriaandlimitedaccesstoantimicrobialsusceptibilitytesting.
Whataretheguideline'sobjectives?
?Toprovideevidence-basedandcontext-sensitiverecommendationsontheappropriatechoice(s)fordiphtheriaclinicalmanagementincludingtheuseofdiphtheriaantitoxin(DAT)andantibiotics.
?TosupporttheadaptationbyWHOMemberStatesoftheseevidence-basedguidelinesintonationaldiphtheriapoliciesfortheclinicalmanagementofdiphtheria.
?Toinformtheclinicalresearchagendabyidentifyingknowledgegapswhichlimitourcapacitytoproduceevidence-basedrecommendations.
Whoisthisguidelinefor?
Theprimaryaudiencefortheguidelineisclinicianstreatingpatientswithdiphtheria.Theguidelineisalsointendedforusebyhealthmanagersatfacilityorjurisdictionleveltodeveloplocaltoolsorprotocolstoassistcliniciansinmanagingpatientswithdiphtheriaandorientprocurementandallocationofrecommendedtreatments.Furthermore,theguidelineisintendedtoguideresearchersand
researchfunderstoaddressthehighlightedevidencegapsanduncertainties.
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
8of27
4.Clinicalcharacterization
Clinicalcharacterization
RespiratorydiphtheriaiscausedbystrainsofCorynebacteriumdiphtheriae,whichhaveaffinityfortheupperrespiratorytract(noseandthroat)andproduceatoxinwhichcauseslocaldiseaseand,inseverecases,airwaycompromiseandsystemiccomplications.Diphtheriaoccurswhenthebacterialtoxininflamestheepithelialmucosal,causinganexudatewhichcanhaveacharacteristic
greyish-white“pseudomembrane”inthepharynx,nasopharynx,tonsils,orlarynx(oracombinationofthese).Thefibrinous
pseudomembranecanleadtorespiratoryobstruction.Thetoxindisruptsproteinsynthesisandcausescelldeathleadingtothe
breakdownoftheepithelium,andsubsequentspreadtolocallymphnodescancauseaswollenneck.Spreadofthetoxininthebloodcanaffectthemyocardium(heart),kidneys,andnervoussystem.C.diphtheriaecanalsocauseskinandwoundinfections.Cutaneousdiseaseisnotfurtherdiscussedinthisguideline.
TheseverityofdiphtheriaisdescribedinpreviousWHOoperationalguidance.
?Milddisease:localizedlaryngealorpharyngealdiseaseof2daysduration;
?Severe/extensivedisease:durationof3ormoredays,ordiffuseneckswelling(thesocalled“bullneck”),orrespiratorydistress,orhemodynamicinstability”(6)(7).
Arecentsystematicreviewsuggeststhecasefatalityratioinunvaccinatedindividualsinfectedwithtoxin-producingstrainsis
29%(8).Casefatalityratiosinresource-limitedsettingsarehighlyvariablebut,insomeoutbreaks,canbeashighas50%(9)(10).
Transmission:Diphtheriaspreadsfrompersontopersonmostlythroughtheair,andlessfrequentlybydirectcontact.Theincubationperiodisusuallyfrom2to5days.
Currenttreatmentsinclude:
?neutralizationofunboundtoxinwithDAT;
?antibioticstopreventfurtherbacterialgrowth;
?monitoringandsupportivecaretopreventandtreatcomplications,e.g.airwayobstruction,myocarditis.Inpatientswithimminentairwayobstruction,urgentairwayinterventionmaybelifesaving.Thepossibleoptionsincludebasicairwaymanouevres,
endotrachealintubation,cricothyroidotomy(needleorsurgicalapproach),andtracheostomy.Therisksandbenefitsofeachapproachwilldependontheexperienceofthetreatingmedicalpersonnel.
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
9of27
5.Recommendationforantibioticstreatment
Antibioticsareusedtopreventfurtherbacterialgrowthandtoxinproductionreducingtheriskfromfurtherorgandamage,andtoreducebacterialtransmissiontoothers.Historically,penicillinshavebeenused(includingbenzylpenicillin,procainepenicillinandpenicillinV),butmacrolideshavealsobeenemployed(forexample,erythromycinorazithromycin).Antimicrobialresistance
prevalenceamongststrainsofC.diphtheriaeoccurstobothclasses,andisvariablebyregionandovertime.Localresistancepatternscanthereforeonlybeknownbybacterialsusceptibilitytesting.Recentstudieshavedemonstratedincreasedresistancetopenicillin
overthemacrolideclassofantibiotics(11).Antibioticsarealsousedtopreventthedevelopmentofdiphtheriainclosecontactsofinfectiouspatients;WHOrecommendationsonthistopicareunderdevelopment.
Strongrecommendationfor
Inpatientswithsuspectedorconfirmeddiphtheria,WHOrecommendsusingmacrolideantibiotics(azithromycin,erythromycin)inpreferencetopenicillinantibiotics[Strongrecommendation,lowcertaintyevidence].
Remarks:
?AntibioticsshouldbeadministeredalongsideDATandshouldnotbedelayed.
?Recentevidencesuggeststhatthereisincreasingresistancetopenicillinsandlessresistancetomacrolideantibiotics.Localantimicrobialsusceptibilitytestingisvitaltoensuretheongoingappropriateuseofantibiotics.Adviceonlaboratorytestinginoutbreaksisavailable
here
.
?Thechoiceofmacrolidewilldependonavailabilityandfeasibility.
Practicalinfo
Macrolideantibioticsincludeazithromycinanderythromycin.Parenteraladministrationofmacrolideantibioticsispossible;however,itistypicallyindicatedforwhereoraladministrationisnotpossible,suchaswhenpatientisunabletoswalloworalmedications.Thechoiceofmacrolidewillbebasedonavailabilityandfeasibility.Dosingrecommendationareasfollows:
?Azithromycin:administerorallyorintravenouslyonceaday.
?Forchildren:10–12mg/kgoncedaily(maximum500mgperday).
?Foradults:500mgoncedaily.
?Erythromycin:administerorallyorintravenouslyeverysixhours.
?Dose(childrenandadults):10–15mg/kgevery6hours,maximum500mgperdoseor2gramsaday.
Penicillinantibiotics
Weareprovidingpracticalinformationonpenicillinforthescenariowheremacrolideantibioticsarenotavailableandsusceptibilitytestingdemonstratessensitivitytopenicillin.Penicillincanbegivenorallyorparentally(intravenousorintramuscular).Parenteraladministrationisusedprimarilytoachieveadequatetissueconcentrations,especiallyinpatientswithseveredisease.
?Procainebenzylpenicillin(penicillinG):administerbyintramuscularinjection.
?Dose(childrenandadults):50mg/kgoncedaily.Maximumis1.2gperday.
?Aqueousbenzylpenicillin(penicillinG):administerbyintramuscularinjectionorslowintravenousinfusion.
?Dose(childrenandadults):100000units/kgperdayindivideddoseof25000IU/kgevery6hours.Maximumis4MIUor
2.4gperday.
?PhenoxymethylpenicillinV:administerorally.
?Dose(childrenandadults):50mg/kgperdayindivideddosesadministeredevery6hours(eachdose10–15mg/kg.Maximum500mgperdose).
Inadiphtheriaoutbreakitisimportantthatantibioticstewardshipandmonitoringareimplementedparticularlyinrelationtoanychangesinantibioticresistance,whichcanbedeterminedbyantibioticsensitivitytesting.
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
10of27
Evidencetodecision
Benefitsandharms
Substantialnetbenefitsoftherecommendedalternative
Inpatientswithsuspectedorconfirmeddiphtheria,theGDGdeemedtheuseofantibioticstobethestandardofcareovernoantibiotics.Theuseofmacrolides,comparedwithpenicillins,probablydoesnotaffectmortalityorrateofseriousside-effects,buterythromycinmayincreasetherateofgastrointestinalside-effects.Thetreatmenteffectofmacrolideantibiotics,comparedwithpenicillinantibiotics,isveryuncertainfortheoutcomesofrateofmyocarditis,hospitalization,needforairwayintervention,newcasesofdiphtheria,ortreatmentfailure.However,thepointestimateoftreatmentfailurefavursmacrolidesoverpencillins.
Thetreatmentburdenofpenicillinsissubstantiallygreaterthanthatofazithromycin,includingtheneedformorefrequent
dosesofpenicillinsgenerally,andtheneedforintravenousadministrationofbenzylpenicillinspecifically.Thoughtheriskof
antibioticresistancewasuncertainanddependentonlocalresistancepatternsthepanelnotedthatcurrentdatasuggeststhattheriskofpenicillinresistanceishigherthanmacrolideresistance,thereforesuggestingpotentialbenefitsofmacrolide
therapy.
Inthecircumstanceswhereantitoxinisunavailableandunlikelytobeaccessibleinashortperiod,thereisaspeculativebenefitofdualantibiotictreatment.Insuchcases,wherebacteriologicalsusceptibilityisunknown,cliniciansmightchoose,pendingsusceptibilitydata,totreatconcurrentlywithbothmacrolideandbeta-lactamantibiotics.
CertaintyoftheEvidence
Low
Theevidencesummaryfortheprioritizedoutcomeswerelargelyinformedbyonerandomizedclinicaltrial(n=86)whichcomparedpenicillin(benzylpenicillinfollowedbypenicillinV)witherythromycinforthetreatmentofdiphtheria.
Certaintyofevidencewasratedas:moderateformortality(rateddownforimprecision),verylowformyocarditis(rateddown
forimprecisionandriskofbias),verylowforhospitalizationandairwayintervention(rateddownforimprecisionand
indirectness),verylowfornewcasesofdiphtheria(rateddownforimprecisionandindirectness)andverylowfortreatment
failure(rateddownforriskofbias,imprecision,andindirectness).Thecertaintyofevidencewasratedas:moderateforseriousside-effects(rateddownforriskofbias),lowforgastrointestinalside-effects(rateddownforriskofbias,imprecision),highforburdenoftreatment,andverylowforantibioticresistance.
Valuesand
preferences
Nosubstantialvariabilityexpected
Patientsplaceahighvalueonreceivingfewerdosesandoraldrugtreatment,ratherthanmultipledosesandparenteraldrugadministration,andtoalesserextentonthespeculativepossibilityofgreatereffectivenesswithmacrolidetreatment.The
panelfeltthatconsiderationsofantimicrobialresistancewereasormoreimportantthanindividualpatientconsiderations.
Resources
Importantissues,orpotentialissuesnotinvestigated
Theresourcesrequiredtoroutinelyusepenicillinantibiotictreatment,withfrequentintramuscularorintravenousdosing,aresubstantiallygreaterthanwithadaily,oraltreatmentsuchasazithromycin.
Theavailabilityandreliabilityofmicrobiologicalsusceptibilitytestingforisolatestoguidetherapywillnotalwaysbeavailableinatimelyfashion,particularlyinoutbreaksettings.Therefore,cliniciansshouldadministertheantibioticwiththelowest
probabilityofresistance.
Equity
Importantissues,orpotentialissuesnotinvestigated
TheGDGdiscussedatlengththeavailabilityofbothpencillinandmacrolideantibiotics,andhowtherewerenosignificant
equity-relatedconcernsastoaccessibilityofthetwotreatmentsinmostsettings.Treatmentburdenbeinghigherwith
penicillinsledconsiderationsforpreferenceofmacrolides,whichhasequityimplicationsforaccessinghealthcareresources.
TheGDGdiscusseddataondiphtheriaresistancetobeta-lactamand/ormacrolideantibiotics,andthepossibilityof
widespreaduseofmacrolidesinworseningantimicrobialresistance,andworseninghealthequitylongerterm.Theagreed
11of27
valuesandpreferencesstatementheavilyweighedontheconsiderationsoftheGDG,whereantibioticresistancewasseenas,ormoreimportantthan,individualpatientconsiderations.TheGDGmadeastrongrecommendationfortheuseof
macrolides,giventhefeasibilityofimplementationandthelikelylimitedimpactofmacrolideusageindiphtheriaoutbreaksonwiderresistancepatterns.
Acceptability
Importantissues,orpotentialissuesnotinvestigated
TheGDGremarkedthatintravenousdosingmaybeappropriateforpatientswhoareseverelyillandadmittedtohospital,orwhomaybeunabletotolerateorallyadministeredmedications.Inaddition,somepanelistscommentedonthepotentialforconcomitantuseofpenicillinandmacrolideantibioticsforseverelyillpatientswhensusceptibilitypatternsareunknown,andparticularlyduringtheearlyphasesofoutbreakswhenDATmaybeunavailable.
Thereareknowngastrointestinalside-effectsofmacrolides,whichmayimpactacceptabilityoftherecommendation,butthesearenotserious(12).
Theacceptabilityofimplementationwasaprimaryconsiderationinmakingrecommendingadministrationofmacrolides,specificallyoralazithromycinratherthanintravenousorintramuscularpenicillin.
ThecurrentWHOAWaReantibioticbookdoesnotlistdiphtheriaasanindicationforazithromycin,andthiswasnoted(13).
Feasibility
Importantissues,orpotentialissuesnotinvestigated
Thefeasibilityofimplementingmacrolideantibiotics,comparedwithpenicillinantibiotics,isveryhigh.Forpatientswhoareseverelyill,feasibilityconsiderationsarelessrelevant,asintravenousroutesofadministrationmaybepreferredandare
availableforeitherantibiotic.Treatmentofseverelyillpatientslargelyfocusedonthepotentiallyhighburdenofresistancetobeta-lactamantibiotics.
Inadiphtheriaoutbreakitisimportantthatantibioticstewardshipandmonitoringareimplementedparticularlyinrelationtoanychangesinantibioticresistance,whichcanbedeterminedbyantibioticsensitivitytesting.
Justification
WhenmovingfromtheevidencetoarecommendationtheGDGemphasizedtherelativetreatmentburdenofpenicillinsand
macrolides.TheGDGdiscussedtheknownandvariableepidemiologyofantibioticresistanceinCorynebacteriumdiphtheriae,inadditiontonocompellingadverseclinicalconsequencesofmacrolideuse.
Typically,WHOdoesnotmakestrongrecommendationswithlowcertaintyevidence.Oneexceptioniswhenlowevidence
suggestsequivalenceorbenefitofatherapy(inthiscasemacrolidesequivalentorsuperiortopenicillins)andthereishigh
certaintyevidenceoflessharmwiththattherapy.Inthiscase,wehavehighcertaintyevidenceofthehigherburdensassociatedwithpenicillinparenteraltherapymultipletimesaday.
TheGDGmadeastrongrecommendationfortheuseofmacrolides,giventhefeasibilityofimplementationandthelikelylimitedimpactofmacrolideusageindiphtheriaoutbreaksonwiderresistancepatterns.
Clinicalquestion/PICO
Population:Personswithsuspectedorconfirmeddiphtheria
Intervention:Macrolideantibiotic
Comparator:Penicillinantibiotic
Clinicalmanagementofdiphtheria:guideline-WorldHealthOrganization(WHO)
12of27
Summary
Fullsummaryoftheevidencesynthesisisavailablehere.(14)
Outcome
Timeframe
Studyresultsandmeasurements
Comparator
Penicillin
Intervention
Macrolide
CertaintyoftheEvidence
(Qualityof
evidence)
Summary
Mortality
10days
Relativerisk1
Basedondatafrom86
participantsin1studies.
1(Randomized
controlled)
10
per1000
Difference:
10
per1000
0fewerper1000
CI95%
Moderate
Duetoseriousimprecision.2
Thechoiceofantibiotic
probablydoesnotaffect
mortality.
Myocarditis
Basedondatafrom86participantsin1studies.
68
per1000
Difference:
0
per1000
68fewerper1000
(CI95%166
fewer—29more)
Verylow
Duetoserious
imprecision,Due
toseriousriskof
bias4
Weareveryuncertainif
thechoiceofantibiotic
affectstherateof
myocarditis.
3
(Randomized
controlled)
Treatmentfailure
asinferredfrom
non-clearanceof
colonisationat
day8(higher
valuesuggests
moretreatment
failure)5
Serioussideeffects
Relativerisk
Basedondatafrom238participantsin1studies.
Basedondatafrom86participantsin1studies.
160
per1000
Difference:
0
per100
Difference:
80
per1000
80fewerper1000
(CI95%173fewer—8more)
0
per100
0fewerper100
CI95%
Verylow
Duetoseriousrisk
ofbias,Dueto
serious
indirectness,Due
toserious
imprecision6
Moderate
Duetoseriousrisk
ofbias8
Weareuncertainif
choiceofantibioticaffects
therateoftreatment
failure.
Thechoiceofantibiotic
probablydoesnotaffect
therateofseriousside
effects.
7
(Randomized
controlled)
Gastrointestinalsideeffects
Relativerisk
溫馨提示
- 1. 本站所有資源如無(wú)特殊說(shuō)明,都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請(qǐng)下載最新的WinRAR軟件解壓。
- 2. 本站的文檔不包含任何第三方提供的附件圖紙等,如果需要附件,請(qǐng)聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
- 3. 本站RAR壓縮包中若帶圖紙,網(wǎng)頁(yè)內(nèi)容里面會(huì)有圖紙預(yù)覽,若沒(méi)有圖紙預(yù)覽就沒(méi)有圖紙。
- 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
- 5. 人人文庫(kù)網(wǎng)僅提供信息存儲(chǔ)空間,僅對(duì)用戶上傳內(nèi)容的表現(xiàn)方式做保護(hù)處理,對(duì)用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯,并不能對(duì)任何下載內(nèi)容負(fù)責(zé)。
- 6. 下載文件中如有侵權(quán)或不適當(dāng)內(nèi)容,請(qǐng)與我們聯(lián)系,我們立即糾正。
- 7. 本站不保證下載資源的準(zhǔn)確性、安全性和完整性, 同時(shí)也不承擔(dān)用戶因使用這些下載資源對(duì)自己和他人造成任何形式的傷害或損失。
最新文檔
- PEP小學(xué)四年級(jí)英語(yǔ)第五單元電子備(新版) 全冊(cè)
- 人教版數(shù)學(xué)初中七年級(jí)下冊(cè)全冊(cè)教案
- 百年亨氏三次經(jīng)營(yíng)危機(jī)啟示研究:穿越周期的經(jīng)營(yíng)密碼
- 2025高考物理步步高同步練習(xí)選修3第三章 熱力學(xué)定律熱力學(xué)第二定律含答案
- 寶鋼股份ESG 信息披露分析
- 2024云邊一體化人工智能算力資源開(kāi)放與適配平臺(tái)模型服務(wù)標(biāo)準(zhǔn)
- 大學(xué)美育 課件 第四篇第二章第一節(jié) 高鐵之美
- 函數(shù)的表示法同步練習(xí) 高一上學(xué)期數(shù)學(xué)人教A版(2019)+必修第一冊(cè)
- 大學(xué)美育 課件 第三編 第四章 第二節(jié) 服飾增色
- 糖類 同步練習(xí) 高二化學(xué)人教版(2019)選擇性必修3
- 2024-2030年中國(guó)人力資源行業(yè)市場(chǎng)發(fā)展前瞻及投資戰(zhàn)略研究報(bào)告
- 全國(guó)法律職業(yè)資格考試試卷(一)綜合測(cè)試(附答案和解析)
- 2023年贛州銀行校園招聘考試真題
- 2024年高考新課標(biāo)全國(guó)卷政治試題分析及2025屆高考復(fù)習(xí)備考建議
- 制藥工藝的改進(jìn)與創(chuàng)新
- 五年級(jí)上冊(cè)音樂(lè)說(shuō)課稿《 第五課 真善美的小世界》湘藝版
- 公立醫(yī)院醫(yī)療服務(wù)價(jià)格制度
- 泥塑工作坊工作計(jì)劃
- 投標(biāo)服務(wù)方案及承諾
- 偏差行為、卓越一生3.0版
- 一氧化碳檢測(cè)報(bào)警器標(biāo)準(zhǔn)裝置技術(shù)報(bào)告
評(píng)論
0/150
提交評(píng)論