Antibiotics for otitis media with effusion in children

94 Pages·2016·0.97 MB·English

CochraneDatabaseofSystematicReviews
Antibiotics for otitis media with effusion in children (Review)
VenekampRP,BurtonMJ,vanDongenTMA,vanderHeijdenGJ,vanZonA,SchilderAGM
VenekampRP,BurtonMJ,vanDongenTMA,vanderHeijdenGJ,vanZonA,SchilderAGM.
Antibioticsforotitismediawitheffusioninchildren.
CochraneDatabaseofSystematicReviews2016,Issue6.Art.No.:CD009163.
DOI:10.1002/14651858.CD009163.pub3.
www.cochranelibrary.com
Antibioticsforotitismediawitheffusioninchildren(Review)
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARYOFFINDINGSFORTHEMAINCOMPARISON . . . . . . . . . . . . . . . . . . . 4
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Analysis1.1.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome1
CompleteresolutionofOMEat2to3months. . . . . . . . . . . . . . . . . . . . . . . 69
Analysis1.2.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome2
Adverseeffects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Analysis1.3.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome3
CompleteresolutionofOMEat2to4weeks. . . . . . . . . . . . . . . . . . . . . . . . 71
Analysis1.4.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome4
CompleteresolutionofOMEatmorethan6months. . . . . . . . . . . . . . . . . . . . . 72
Analysis1.5.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome5
CompleteresolutionofOMEatendoftreatment(10to14days). . . . . . . . . . . . . . . . . 73
Analysis1.6.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome6
CompleteresolutionofOMEatendoftreatment(4weeks). . . . . . . . . . . . . . . . . . . 74
Analysis1.7.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome7
CompleteresolutionofOMEatendoftreatment(3months). . . . . . . . . . . . . . . . . . 75
Analysis1.8.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome8
CompleteresolutionofOMEatendoftreatment(6months). . . . . . . . . . . . . . . . . . 75
Analysis1.9.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome9
Insertionofventilationtubes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Analysis1.10.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome10
Tympanicmembranesequelae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Analysis1.11.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome11
AOMwithin4to8weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Analysis1.12.Comparison1Antibioticsversusplacebo,notreatmentortherapyofunproveneffectiveness,Outcome12
AOMwithin6months. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Analysis2.1.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome1CompleteresolutionofOMEat2to3months. . . . . . . . . . . . . . 79
Analysis2.2.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome2Adverseeffects. . . . . . . . . . . . . . . . . . . . . . . . . 80
Analysis2.3.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome3CompleteresolutionofOMEat2to4weeks. . . . . . . . . . . . . . . 81
Analysis2.4.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome4CompleteresolutionofOMEatmorethan6months. . . . . . . . . . . . 82
Antibioticsforotitismediawitheffusioninchildren(Review) i
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Analysis2.5.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome5CompleteresolutionofOMEatendoftreatment(10to14days). . . . . . . . 83
Analysis2.6.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome6CompleteresolutionofOMEatendoftreatment(4weeks). . . . . . . . . . 84
Analysis2.7.Comparison 2Sensitivity analysis -Antibiotics versusplacebo, notreatmentortherapyofunproven
effectiveness,Outcome7AOMwithin4to8weeks. . . . . . . . . . . . . . . . . . . . . 84
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 90
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Antibioticsforotitismediawitheffusioninchildren(Review) ii
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Antibiotics for otitis media with effusion in children
RoderickPVenekamp1,MartinJBurton2,ThijsMAvanDongen3,GeertJvanderHeijden4,AlicevanZon3,AnneGMSchilder3,5
1Julius Center for Health Sciencesand Primary Care & Departmentof Otorhinolaryngology, University Medical Center Utrecht,
Utrecht,Netherlands.2UKCochraneCentre,Oxford,UK.3DepartmentofOtorhinolaryngology&JuliusCenterforHealthSciences
and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. 4Department of Social Dentistry, Academic Center
forDentistryAmsterdam(ACTA),Amsterdam,Netherlands.5evidENT,EarInstitute,FacultyofBrainSciences,UniversityCollege
London,London,UK
Contactaddress:RoderickPVenekamp,JuliusCenterforHealthSciencesandPrimaryCare&DepartmentofOtorhinolaryngology,
UniversityMedicalCenterUtrecht,Heidelberglaan100,Utrecht,3508GA,[email protected].
Editorialgroup:CochraneENTGroup.
Publicationstatusanddate:Newsearchforstudiesandcontentupdated(nochangetoconclusions),publishedinIssue6,2016.
Reviewcontentassessedasup-to-date: 14April2016.
Citation: Venekamp RP, Burton MJ, van Dongen TMA, van der Heijden GJ, van Zon A, Schilder AGM. Antibiotics for
otitis media with effusion in children. Cochrane Database of Systematic Reviews 2016, Issue 6. Art. No.: CD009163. DOI:
10.1002/14651858.CD009163.pub3.
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Otitismediawitheffusion(OME)ischaracterisedbyanaccumulationoffluidinthemiddleearbehindanintacttympanicmembrane,
withoutthesymptomsorsignsofacuteinfection.SincemostcasesofOMEwillresolvespontaneously,onlychildrenwithpersistent
middleeareffusionandassociatedhearinglosspotentiallyrequiretreatment.PreviousCochranereviewshavefocusedontheeffectiveness
of ventilation tube insertion, adenoidectomy, nasal autoinflation, antihistamines, decongestants and corticosteroids in OME. This
review,focusingontheeffectivenessofantibioticsinchildrenwithOME,isanupdateofaCochranereviewpublishedin2012.
Objectives
Toassessthebenefitsandharmsoforalantibioticsinchildrenupto18yearswithOME.
Searchmethods
TheCochraneENTInformationSpecialistsearchedtheENTTrialsRegister;CentralRegisterofControlledTrials(CENTRAL2016,
Issue3);PubMed;OvidEMBASE;CINAHL;WebofScience;ClinicalTrials.gov;ICTRPandadditionalsourcesforpublishedand
unpublishedtrials.Thedateofthesearchwas14April2016.
Selectioncriteria
Randomisedcontrolledtrialscomparingoralantibioticswithplacebo,notreatmentortherapyofunproveneffectivenessinchildren
withOME.
Datacollectionandanalysis
WeusedthestandardmethodologicalproceduresexpectedbyCochrane.
Antibioticsforotitismediawitheffusioninchildren(Review) 1
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Mainresults
Twenty-five trials(3663 children)wereeligible for inclusion. Two trialsdid notreporton any of theoutcomes of interest, leaving
23trials(3258children)coveringarangeofantibiotics,participants,outcomemeasuresandtimepointsforevaluation.Overall,we
assessedmoststudiesasbeingatlowtomoderateriskofbias.
Wefoundmoderatequalityevidence(sixtrialsincluding484children)thatchildrentreatedwithoralantibioticsaremorelikelyto
havecompleteresolutionattwotothreemonthspost-randomisation(primaryoutcome)thanthoseallocatedtothecontroltreatment
(riskratio(RR)2.00,95%confidenceinterval(CI)1.58to2.53;numberneededtotreattobenefit(NNTB)5).However,thereis
evidence(albeitoflowquality;fivetrials,742children)indicatingthatchildrentreatedwithoralantibioticsaremorelikelytoexperience
diarrhoea,vomitingorskinrash(primaryoutcome)thanthoseallocatedtocontroltreatment(RR2.15,95%CI1.29to3.60;number
neededtotreattoharm(NNTH)20).
Inrespectofthesecondaryoutcomeofcompleteresolutionatanytimepoint,wefoundlowtomoderatequalityevidencefromfive
meta-analyses,includingbetweentwoand14trials,ofabeneficialeffectofantibiotics,withaNNTBrangingfrom3to7.Timeperiods
rangedfrom10to14daystosixmonths.
In terms of other secondary outcomes, only two trials (849 children) reported on hearing levels at two to four weeks and found
conflicting results. None of the trials reporteddata on speech,language and cognitive developmentor quality of life.Low quality
evidencedidnotshowthatoralantibiotics wereassociated withadecreaseintherateofventilationtube insertion(twotrials,121
children)orintympanicmembranesequelae(onetrial,103children),whilelowqualityevidenceindicatedthatchildrentreatedwith
antibioticswerelesslikelytohaveacuteotitismediaepisodeswithinfourtoeightweeks(fivetrials,1086children;NNTB18)and
withinsixmonthspost-randomisation(twotrials,199children;NNTB5).Itshould,however,benotedthatthebeneficialeffectof
oralantibioticsonacuteotitismediaepisodeswithinfourtoeightweekswasnolongersignificantwhenweexcludedstudieswithhigh
riskofbias.
Authors’conclusions
Thisreviewpresentsevidenceofbothbenefitsandharmsassociatedwiththeuseoforalantibioticstotreatchildrenupto16years
withOME.AlthoughevidenceindicatesthatoralantibioticsareassociatedwithanincreasedchanceofcompleteresolutionofOME
atvarioustimepoints,wealsofoundevidencethatthesechildrenaremorelikelytoexperiencediarrhoea,vomitingorskinrash.The
impactofantibioticsonshort-termhearingisuncertainandlowqualityevidencedidnotshowthatoralantibioticswereassociated
withfewerventilationtubeinsertions.Furthermore,wefoundnodataontheimpactofantibioticsonotherimportantoutcomessuch
asspeech,languageandcognitivedevelopmentorqualityoflife.
Eveninsituationswhereclearandrelevantbenefitsoforalantibioticshavebeendemonstrated,thesemustalwaysbecarefullybalanced
againstadverseeffectsandtheemergenceofbacterialresistance.Thishasspecificallybeenlinkedtothewidespreaduseofantibiotics
forcommonconditionssuchasotitismedia.
PLAIN LANGUAGE SUMMARY
Antibioticsforotitismediawitheffusion(’glueear’)inchildren
Reviewquestion
Thisreviewcomparedtheeffectsoforalantibioticsagainstplacebo,notreatmentorothertherapiesinchildrenwithotitismediawith
effusion(OME)or’glueear’.
Background
Glueearisoneofthemostcommonconditionsofearlychildhood.Glueearmeansthatthereisfluidinthemiddleearspacebehind
the eardrum. This may cause hearing difficulties that may in turn affect children’s behaviour, language and progress at school. In
approximatelyoneinthreechildrenwithglueear,bacteriaareidentifiedinthemiddleearfluid.Therefore,peoplehavesuggestedthat
antibioticsmaybebeneficialinchildrenwithglueear.
Studycharacteristics
Thisreviewincludedevidenceavailableupto14April2016.Intotal25studies(3663children)wereeligibleforinclusion.Twostudies
didnotreportonanyoftheoutcomesofinterest,leaving23studies(3258children).Overall,weassessedmoststudiesasbeingatlow
Antibioticsforotitismediawitheffusioninchildren(Review) 2
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
tomoderateriskofbias.Inthe23studiesmanydifferentantibioticswereusedandthechildrenwereofdifferentagesandhadsuffered
fromglueearforvariouslengthsoftime.Theylookedatthebenefitsatvarioustimepointsafterthetreatmentwasgiven.
Keyresults
Themostimportantoutcomesthatwemeasuredwerethedifferenceintheproportionofchildrenwhonolongerhadglueeartwoto
threemonthsafterthetreatmentwasstartedandadverseeffectsofantibiotics(diarrhoea,vomitingorskinrash).
Wefoundmoderatequalityevidence(sixtrialsincluding484children)thatchildrentreatedwithoralantibioticsaremorelikelyto
haveglueearresolvedtwotothreemonthsafterthetreatmentwasstartedthanthoseallocatedtocontroltreatment.Thenumberof
childrenneededtotreatforonebeneficialoutcome(NNTB)wasfive.However,thereisevidence(albeitoflowquality;fivetrials,742
children)indicatingthatchildrentreatedwithoralantibioticsaremorelikelytoexperiencediarrhoea,vomitingorskinrashthanthose
allocatedtocontroltreatment.Thenumberofchildrenneededtotreatforoneharmfuloutcome(NNTH)was20.
Inrespectofthesecondaryoutcomeofhavingglueearresolvedatanytimepoint,wefoundlowtomoderatequalityevidencefrom
fiveofouranalyseswherewecombineddatafromstudies(meta-analyses),whichincludedbetweentwoand14studies,ofabeneficial
effectofantibiotics,withaNNTBrangingfromthreetoseven.Timeperiodsrangedfrom10to14daystosixmonths.
In terms of other secondary outcomes, only two trials (849 children) reported on hearing levels at two to four weeks and found
conflicting results. None of the trials reporteddata on speech,language and cognitive developmentor quality of life.Low quality
evidencedidnotshowthatoralantibioticswereassociatedwithfewerventilationtube(grommet)insertions(twotrials,121children)or
inadverseconsequencesforthetympanicmembrane(eardrum)(onetrial,103children).Lowqualityevidenceindicatedthatchildren
treatedwithoralantibioticswerelesslikelytohaveacuteotitismedia(earinfection)episodeswithinfourtoeightweeks(fivetrials,
1086children;NNTB18)andwithinsixmonthsaftertreatmentwasstarted(twotrials,199children;NNTB5).Itshouldhowever
benotedthatthebeneficialeffectoforalantibioticsonearinfectionepisodeswithinfourtoeightweekswasnolongersignificantwhen
studieswithhighriskofbiaswereexcluded.
Qualityoftheevidence
Moderate quality evidence isavailable thatchildrenwith glue ear dobenefit fromoral antibiotics in termsof resolving glue ear at
varioustimepointsandreducingacuteotitismediaepisodesduringfollow-upcomparedwithcontroltreatment.Lowqualityevidence
isavailablethatchildrentreatedwithoralantibioticsaremorelikelytoexperiencediarrhoea,vomitingandskinrashthanthosereceiving
thecontroltreatment.Currentlyonlytwotrialshaveassessedtheimpactoforalantibioticsonhearingandtheseshowedconflicting
results (low quality evidence). Low quality evidence did not show that oral antibiotics were associated with fewer ventilation tube
insertionsorinadverseconsequencesforthetympanicmembrane.
Antibioticsforotitismediawitheffusioninchildren(Review) 3
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
CoAn SUMMARY OF FINDINGS FOR THE MAIN COMPARISON [Explanation]
pyright©20tibioticsfor Antibioticscomparedtoplacebo,notreatmentortherapyofunproveneffectivenessforotitismediawitheffusioninchildren
1o
6Thtitis
em Patientorpopulation:childrenwithotitismediawitheffusion
Ce
ocdia Setting:community,primarycare,secondarycareandtertiarycare
hraneCowitheffu CInotemrpvaernitsioonn::palnatcibeibooti,cnsotreatmentortherapyof unproveneffectiveness
llabosion Outcomes Anticipatedabsoluteeffects∗(95%CI) Relativeeffect ofparticipants Qualityoftheevidence Comments
ratioinch (95%CI) (studies) (GRADE)
n.ild
Pubren Riskwithcontroltreat- Riskwithantibiotics
lis(R ment
he
ev
die
bw
y) Complete resolution of Studypopulation RR2.00 484 ⊕⊕⊕(cid:13) TheNNTBbasedonthe
Jo
h OMEat2to3months (1.58to2.53) (6RCTs) moderate1 study population risk
n
W 247per1000 493per1000 was 1/(493-247)*1000
ile (390to624) =4.07
y
&
S
on Adverseeffects Studypopulation RR2.15 742 ⊕⊕(cid:13)(cid:13) TheNNTHbasedonthe
s
,L (1.29to3.60) (5RCTs) low2 study population risk
td. 45per1000 97per1000 was 1/(97-45)*1000 =
(54to149) 19.23
Complete resolution of Studypopulation RR1.98 2091 ⊕⊕(cid:13)(cid:13) TheNNTBbasedonthe
OMEat2to4weeks (1.47to2.67) (14RCTs) low2 study population risk
203per1000 403per1000 was 1/(403-203)*1000
(299to543) =5.00
Complete resolution of Studypopulation RR1.75 606 ⊕⊕(cid:13)(cid:13) TheNNTBbasedonthe
OME at more than 6 (1.41to2.18) (5RCTs) low2 study population risk
months 255per1000 445per1000 was 1/(445-255)*1000
(359to555) =5.26
Insertion of ventilation Studypopulation RR0.90 121 ⊕⊕(cid:13)(cid:13) -
tubes (0.46to1.78) (2RCTs) low3
4
CA
on
pyright©20tibioticsfor 185per1000 1(8657tpoe3r3100)00
1o
6Thetitism Tympanic membrane Studypopulation RR0.42 103 ⊕⊕(cid:13)(cid:13) -
Ce
ocdia sequelae (0.18to1.01) (1RCT) low4
hrw 275per1000 115per1000
aneith (49to277)
Coeffu
llabosion *Theriskintheinterventiongroup(andits95%confidenceinterval)isbasedontheassumedriskinthecomparisongroupandtherelativeeffectof theintervention(andits
rain 95%CI).
tioch
n.ild
Pubren CI:confidenceinterval;NNTB:numberneededto treat tobenefit;NNTH:numberneededto treat toharm;OME:otitis mediawitheffusion;RCT:randomisedcontrolled trial;
lis(R RR:riskratio
he
ev
die
byw) GRADEWorkingGroupgradesofevidence
Jo Highquality:Weareveryconfidentthatthetrueeffectliesclosetothatof theestimateof theeffect
h
n
W Moderate quality:We are moderately confident in the effect estimate:The true effect is likely to be close to the estimate of the effect,but there is a possibility that it is
ile substantiallydifferent
y
& Lowquality:Ourconfidenceintheeffectestimateislimited:Thetrueeffectmaybesubstantiallydifferentfrom theestimateof theeffect
S
o Verylowquality:Wehaveverylittleconfidenceintheeffectestimate:Thetrueeffectislikelytobesubstantiallydifferentfrom theestimateof effect
n
s
,
L
td 1Wedowngradedtheevidencefrom hightomoderatequalityduetostudylimitations(riskof bias).
.
2We downgraded the evidence from high to low quality due to study limitations (risk of bias) and inconsistency of effect
estimatesacrossindividualtrials.
3Wedowngradedtheevidencefrom hightolow qualityduetostudylimitations (riskof bias)andimpreciseeffectestimates
acrossindividualtrials.
4We downgraded the evidence from high to low quality due to concerns around directness of evidence: one trial included
participantsparticularlyatriskforsuppurativeotitismedia(AustralianAboriginalchildreninruralAustralia)andhadalimited
numberof children,leadingtoanimpreciseeffectestimate.
5
Howtheinterventionmightwork
BACKGROUND
TherationaleforusingantibioticsinOMEisthepotentialbacte-
rialoriginofthedisease;abacterialpathogenisidentifiedinthe
middleearfluidofapproximatelyoneinthreechildrenwithOME
Descriptionofthecondition (Poetker 2005). Successful eradication of bacteria may promote
fasterresolutionofmiddleearfluidandpreventionofsecondary
complications.However,notallOMEcasesareofbacterialorigin
andthereforethepotentialbenefitsofantibioticsneedtobebal-
Symptoms,prevalenceandaetiology
ancedbothagainstthewell-recognisedadverseeffectsandthein-
Otitismediawitheffusion(OME)or’glueear’isoneofthemost creasedriskofbacterialresistance(Costelloe2010;ECDC2011;
commondiseasesofearlychildhood.OMEischaracterisedbyan Gillies2015;Laxminarayan2013).
accumulationoffluidinthemiddleearbehindanintacttympanic
membrane, without the symptoms or signs of acute infection (
Gates2002;Shekelle2002). Whyitisimportanttodothisreview
ThepotentialabsenceofsymptomsofOMEmakesitdifficultto
In2004, Rosenfeldreviewedtheeffectsof antibiotic therapyin
estimateitstrueprevalence,butinthefirstyearoflifemorethan
OMEandconcludedthatthereisevidenceforashort-termbenefit,
50%ofchildrenwillexperienceanepisodeofOME,increasing
butlonger-termbenefitsareuncertain(Rosenfeld2004).Mandel
tomorethan60%bytwoyearsofage(Casselbrant2003).
etalcametoasimilarconclusionintheirreview(Mandel2004).
WhenOMEisnewlydetected,naturalresolution(i.e.disappear-
After 2004, the effectiveness of antibiotics in the management
anceofthefluidfromthemiddleearspace)withinthreemonths
ofOMEhadnotbeenreviewedsystematicallyuntiltheoriginal
isseenin28%ofchildren.Ratesofimprovementorspontaneous
publicationofthisreview(vanZon2012).Thisisanupdateof
resolutioninchildrenwithOMEobservedafteranepisodeofacute
thatreview.
otitismedia(AOM)aremuchhigher(Rosenfeld2003).However,
recurrence of OME is also common, with an estimated rate of
50%within24months(Teele1989).
In most cases, OME causes mild hearing impairment of short
duration. When experienced in early life and when episodes of OBJECTIVES
(bilateral)OMEpersistorrecur,theassociatedhearinglossmay
Toassessthebenefitsandharmsoforalantibioticsinchildrenup
besignificantandhaveanegativeimpactonspeechdevelopment
to18yearswithOME.
andbehaviour(Gouma2011;Roberts2004;Sabo2003;Shekelle
2002).
AlthoughthepathophysiologyofOMEisnotfullyunderstood,
METHODS
bothmiddleearinflammationandEustachiantubedysfunction
arelikelytobecontributoryfactors(Rovers2004).
Criteriaforconsideringstudiesforthisreview
Descriptionoftheintervention
Typesofstudies
Since most casesof OME will resolve spontaneously, only chil-
Randomised controlled trials (RCTs). We excluded quasi- and
dren with persistent middle ear effusion and associated hear-
cluster-RCTs.Ifcross-overtrialswereavailable,weonlyincluded
inglosspotentiallyrequiretreatment.Tothatendtherearetwo
thosewheredatafromthefirstphasewereavailable.
management options: surgical and non-surgical. There are two
Cochranereviewsaddressingdifferentsurgicalinterventions:ven-
tilationtubes(grommets)(Browning2010),andadenoidectomy Typesofparticipants
(vandenAardweg2010).Thecombinationofthetwoisaddressed Childrenaged18yearsorunderwithadiagnosisofunilateralor
in an individual patient data meta-analysis (Boonacker 2014). bilateral OME at time of randomisation. The clinical diagnosis
The following non-surgical interventions have been addressed of OME hadtobe made by tympanometry alone or in combi-
in different Cochrane reviews: antihistamines and/or deconges- nationwithotoscopy(includingpneumaticotoscopyandotomi-
tants(Griffin2011),intranasalandoralcorticosteroids(Simpson croscopy).Weexcludedstudiesofchildrenwithventilationtubes
2011),andnasalautoinflation(Perera2013).Avarietyofantibi- present,thosewithchronicsuppurativeotitismedia,knownim-
oticsdirectedatthemicrobialpathogenscausingupperrespiratory munodeficiency, Down syndrome or craniofacial anomalies, in-
tractinfectionsarebeingusedandareconsideredinthisreview. cludingcleftpalate.
Antibioticsforotitismediawitheffusioninchildren(Review) 6
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Typesofinterventions Searchmethodsforidentificationofstudies
TheCochraneENTInformationSpecialistconductedsystematic
searchesfor randomised controlledtrials and controlledclinical
Intervention trials. There were no language, publication year or publication
statusrestrictions.Thedateofthesearchwas14April2016.
Oralantibiotics(ofalltypesandcoursesofanyduration).
Electronicsearches
Control TheInformationSpecialistsearched:
• theCochraneENTTrialsRegister(searched14April2016);
Placebo,notreatmentor therapyofunproveneffectiveness(an-
• theCochraneCentralRegisterofControlledTrials
tihistamines, decongestants, mucolytics and intranasal corticos-
(CENTRAL2016,Issue3);
teroids).Weexcludedstudiesinwhich oneantibiotic was com-
• PubMed(1946to14April2016);
paredwithanother.
• OvidEMBASE(1974to2016week15);
We analysed antihistamines, decongestants, mucolytics and in-
• OvidCABAbstracts(1910to2016week13);
tranasalcorticosteroidsasthesamecomparatorasplaceboandno
• EBSCOCINAHL(1982to14April2016);
treatmentastheyarenotproventobeeffectiveinchildrenwith
• LILACS,lilacs.bvsalud.org(searched14April2016);
OME(Griffin2011;Pignataro1996;Simpson2011).
• KoreaMed(searchedviaGoogleScholar14April2016);
Participantswereallowedtoreceiveadditionalmedicaltherapies
• IndMed,www.indmed.nic.in(searched14April2016);
providedsuchadjunctinterventions werethesameinthetreat-
• PakMediNet,www.pakmedinet.com(searched14April
mentandinthecontrolgroupsandthattheadditionaltherapies
2016);
wereoneofthoseofunproveneffectiveness(seeabove).
• WebofKnowledge,WebofScience(1945to14April
2016);
• ClinicalTrials.gov(searchedviatheCochraneRegisterof
Typesofoutcomemeasures
Studies14April2016);
Weanalysedtheoutcomeslistedbelowinthereview,butwedid • WorldHealthOrganization(WHO)InternationalClinical
notusethemasabasisforincludingorexcludingstudies. TrialsRegistryPlatform(ICTRP),www.who.int/ictrp(searched
14April2016);
• ISRCTN,www.isrctn.com(searched14April2016);
Primaryoutcomes • GoogleScholar,scholar.google.co.uk(searched14April
2016);
• CompleteresolutionofOME(completetreatmentsuccess)
• Google,www.google.com(searched14April2016).
attwotothreemonthspost-randomisation.
Insearchespriorto2015,wealsosearchedBIOSISPreviews1926
ThisisdefinedasresolutionofOMEintheaffectedearinchildren toFebruary2012.
with unilateral OMEat randomisation and resolution of OME The Information Specialist modelled subject strategies for
in both ears in children with bilateral OME at randomisation; databasesonthesearchstrategydesignedforCENTRAL.Where
ineithercase,thediagnosishavingbeenmadebytympanometry appropriate,theywerecombinedwithsubjectstrategyadaptations
aloneorincombinationwithotoscopy. ofthehighlysensitivesearchstrategy designedbyCochrane for
• Adverseeffects,specificallydiarrhoea,vomitingorskinrash. identifyingrandomisedcontrolledtrialsandcontrolledclinicaltri-
als(asdescribedintheCochraneHandbookforSystematicReviewsof
InterventionsVersion5.1.0,Box6.4.b.(Handbook2011).Search
Secondaryoutcomes strategiesformajordatabasesincludingCENTRALareprovided
inAppendix1.
• CompleteresolutionofOME(completetreatmentsuccess)
atallpossibletimepoints.
• Hearinglevel. Searchingotherresources
• Languageandspeechdevelopment. Wescannedthereferencelistsofidentifiedpublicationsforaddi-
• Cognitivedevelopment. tionaltrialsandcontactedtrialauthorswherenecessary.Inaddi-
• Qualityoflife. tion,theInformationSpecialistsearchedPubMed,TheCochrane
• Insertionofventilationtubes. LibraryandGoogletoretrieveexistingsystematicreviewsrelevant
• Tympanicmembranesequelae. tothissystematicreview,sothatwecouldscantheirreferencelists
• AOMepisodes. foradditionaltrials.
Antibioticsforotitismediawitheffusioninchildren(Review) 7
Copyright©2016TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.