www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Efficacy
of
topical
clotrimazole
vs.
topical
tolnaftate
in
the
treatment
of
otomycosis.
A
randomized
controlled
clinical
trial
夽
Lesly
Jimenez-Garcia
a,
Erika
Celis-Aguilar
a,∗,
Gaudencio
Díaz-Pavón
a,
Victor
Mu˜
noz
Estrada
b,
Ángel
Castro-Urquizo
a,
Nemiliztli
Hernández-Castillo
a,
Ernesto
Amaro-Flores
aaUniversidadAutónomadeSinaloa,CentrodeInvestigaciónyDocenciaenCienciasdelaSalud,OtolaryngologyDepartment,
Culiacán,Mexico
bUniversidadAutónomadeSinaloa,CentrodeInvestigaciónyDocenciaenCienciasdelaSalud,MycologyDepartment,Culiacán,
Mexico
Received22May2018;accepted11December2018 Availableonline18February2019
KEYWORDS Otomycosis; Antifungals; Topicaltolnaftate; Clotrimazolecream Abstract
Introduction:Otomycosis,aninfectionoftheearcanalbyfungi,isprevalentinhotandhumid weather.Nevertheless,thereisnotsufficientevidencefortheeffectivenessofdifferenttopical antifungaltreatments.Tolnaftate,isatopicalantifungalagentdescribedtobeeffectiveinthe treatmentofotomycosis.Currentlytherearenotsufficientstudiesthatproveitsefficacy. Objectives:Tocomparetheefficacyofclotrimazoleandtolnaftateadministrationinthe treat-mentofotomycosis.
Materialandmethods: Acontrolled,randomizedandopenclinicaltrialincludedpatients diag-nosedwithfungalexternalotitiswhoweretreatedwithtopicalantifungals,randomizedintotwo treatmentgroups:(1)clotrimazolecream;(2)tolnaftatesolution.Theyweremicroscopically evaluated at one and two weeks of treatment to determine resolution of disease. Recur-rence andcomplicationswere recorded.Demographicandclinical variableswere collected andanalyzed.Follow-upandfinaloutcomes(absenceofinfection)werecompared between groups.
Results:Fortyeightpatientswereincluded, 28intheclotrimazolegroupand20inthe tol-naftategroup.Springwastheweathermostcommonlyassociatedwithotomycosis,whileotic manipulationwastheriskfactormorecommoninbothgroups.Predominantsymptomswere itchingandoticfullness.Aspergillusnigerorganismwasisolatedmostfrequently.Treatment
夽 Pleasecitethisarticleas:Jimenez-GarciaL,Celis-AguilarE,Díaz-PavónG,Mu˜nozEstradaV,Castro-UrquizoA,Hernández-CastilloN,
etal.Efficacyoftopicalclotrimazolevs.topicaltolnaftateinthetreatmentofotomycosis.Arandomizedcontrolledclinicaltrial.BrazJ
Otorhinolaryngol.2020;86:300---7.
∗Correspondingauthor.
E-mail:erikacelis@hotmail.com(E.Celis-Aguilar).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial. https://doi.org/10.1016/j.bjorl.2018.12.007
1808-8694/©2019Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
withclotrimazoleresultedin75%resolutionvs45%resolutionwithtreatmentwithtolnaftate atoneweekoftreatment (p=0.007).The Tolnaftatetreatment groupdemonstrated higher recurrenceratesandtreatmentfailures,20%and15%respectively.
Conclusions: Clotrimazolecreamtreatmentismoreeffectivethantolnaftateforuncomplicated otomycosis.Morestudiesareneededtocorroborateourresults.
© 2019 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/). PALAVRAS-CHAVE Otomicoses; Antifúngicos; Tolnaftatotópico; Clotrimazole(creme)
Eficáciadoclotrimazoltópicoversustolnaftatotópiconotratamentodaotomicose: umensaioclínicocontroladorandomizado
Resumo
Introduc¸ão: Otomicose,umainfecc¸ãofúngicadocanalauditivoexterno,éprevalenteem cli-mas quentes eúmidos. Noentanto, aliteraturanão apresenta evidências suficientessobre osdiferentestratamentosantifúngicostópicos.Otolnaftatoéumantifúngicotópicodescrito como eficaznotratamentodaotomicose;entretanto,suaeficácianãoestásuficientemente comprovada.
Objetivo: Compararaeficáciadousodeclotrimazoletolnaftatonotratamentodaotomicose. Materialemétodo: Ensaioclínicocontroladoerandomizado;incluiupacientesdiagnosticados comotiteexternafúngicatratadoscomantifúngicostópicos,randomizadosemdoisgruposde tratamento:1)clotrimazole(creme);2)soluc¸ãodetolnaftato.Elesforamavaliados microscopi-camenteumaeduassemanasapósoiníciodotratamentoparaavaliararesoluc¸ãodadoenc¸a. Recorrênciaeintercorrênciasforamregistradas;alémdisso,asvariáveisdemográficase clíni-casforamcoletadaseanalisadas.Osdadosdoacompanhamentoedesfechosfinais(ausência deinfecc¸ão)foramcomparadosentreosgrupos.
Resultados: Oestudoincluiu48pacientes,28dosquaisforamalocadosaogrupoclotrimazole e20aogrupotolnaftato.Aprimaverafoiaestac¸ãomaiscomum;amanipulac¸ãofoiofatorde riscomaiscomumemambososgrupos.Ossintomasmaiscomunsforamcoceiraeplenitude auricular.Aspergillusnigerfoiomicro-organismomaiscomumenteisolado.Apósumasemana,o tratamentocomclotrimazolapresentouumataxaderesoluc¸ãode75%vs.45%comotratamento comtolnaftato(p=0,007).Otratamentocomtolnaftatoapresentoumaiorestaxasderecidiva efalhas:20%e15%,respectivamente.
Conclusões: Emcasosdeotomicosenãocomplicada,ousodeclotrimazol(creme)émaiseficaz doqueodetolnaftato.Maisestudossãonecessáriosparacorroborarospresentesresultados. © 2019 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http://
creativecommons.org/licenses/by/4.0/).
Introduction
Otomycosisisatermusedtodescribetheepithelial infec-tionoftheExternalAuditoryCanal(EAC)causedbyyeastand filamentousfungi,1,2whichaccountsfor9%ofexternalotitis
diagnoses.Fungiareusuallyfoundintheouterearas colo-nizersbecausethissurfacecontainsthenecessary require-mentsfortheirgrowth:proteins,carbohydrates,humidity, temperatureandadequatePh.3Predisposingfactorsinclude
residingintropicalandhumidclimates,theuseoflong-term antibioticorsteroidtherapy,aweakenedimmunesystem, lack of hygiene, a working environment withexposure to dust,foreignbodies inthe EAC,cleaning of theEAC with swabs,geneticfactors,seborrheicdermatitisandthe pres-enceofcerumen,allofwhichfavorthegerminationofthe spores and conidia of the prevalent fungi.2,4---8 Speciesof
Aspergillus(60---90%),usuallyA.niger,andCandidaspecies (10---40%)arethemostcommonlycultivatedpathogens.2---5,7,8
CarefuldebridementoftheEACiscrucialtofacilitatethe eliminationoftheinfectiousorganismandtoallowtopical medicationstoreachthe targettissue. Topical treatment curesmostcases,althoughrecurrenceratesarehigh.5Many
agentswithdifferentantifungalpropertieshavebeenused withvaryingsuccessrates,sothereisnoconsensusonthe mosteffectiveagent.Theobjectiveofthisstudyisto com-paretheefficacyoftheadministrationoftopicalantifungal medications,Clotrimazolecreamvs.Tolnaftatesolution,in thetreatmentoffungalotitisexterna.
Methods
A controlled, randomized, open clinical trial was con-ductedintheotorhinolaryngologyandheadandnecksurgery
departmentof a second level hospitalcenter fromMarch 2016toJuly 2017.Patientsdiagnosedwithclinical otomy-cosis(visualizationcompatiblewithfungaldebriswasdone throughmicroscopicexamination)wereassignedtooneof twotreatment groups according toacomputer-generated randomizationtable. Demographic and clinical data were collected, and two samples of affected EAC were taken fromeachpatientwiththehelpofanearpickand/or suc-tioncleanerandthenplacedinasteriletransportmedium for directmicroscopic examination andculturing in order to identify the pathogenic fungi involved. For the direct examination, thematerial wasmixed withsaline solution ona slide, covered witha coverslip andvisualized under theopticalmicroscopeat10×and40×magnifications.For theculture,thesamplewasimplantedinaSaboraud dex-troseagarmediumincubatedat27---30◦Cforaminimumof 7days.Allpatients underwentEAC cleaning and debride-ment. Clotrimazole cream was appliedto the patients in Group1andleftfor7days;afterthattime,creamresidue wasremoved fromthe EAC,and theotic conditionswere re-evaluated.PatientsinGroup2wereinstructedtoapply Tolnaftatesolution,2dropsevery12hfor7days,afterwhich timetheoticconditionswerere-evaluated.Theideal clini-calfinaloutcomeconsistedofanasymptomaticpatientwith clean and dry external auditory canal confirmed through microscopic examination. In both groups, if the infection continued,theEACwascleanedagainandasecond treat-mentwiththe samedrugwasadministered. Patientswho presented infection data after two courses of treatment were switched to the drug used by the other group. Dry earcare and avoidance of identified predisposing factors wereadvised. The degree of improvementwas evaluated by comparing the symptoms and findings in the physical examination every week as well as one week after the resolution of the infectious disease to assess resolution or relapse.Since drugs in the imidazole group have been foundinmultiple studiestobeeffectivein thetreatment of otomycosis, clotrimazole was used as the standard of care.
Thestudywassubmittedforevaluationandapprovalby the Ethics Committee of our hospital with number 0149, andinallcases,aninformedconsentformwassigned.This researchadherestotheDeclarationofHelsinkioftheWorld MedicalAssociation.
ThedatacollectedwereenteredintoanSPSSdatabase, demographic variables and baseline characteristics were analyzed,includingmeasuresofcentraltendencyanddata dispersion,analysisofcategoricalvariablesusingChisquare and comparison of continuous variables withStudent’s
t-test.Ap<0.05wasconsideredsignificant.Intentiontotreat analysis was performed; lost follow-up cases were con-sidered failure cases, as long as one follow-up visit was undertaken.
Asamplesizeof25 patientswascalculatedinorderto findequivalencebetweenmedications.Twentyfivepatients weredeterminedin samplesizecalculation,withapower of 90%. Difference of effect between medications was estimated as −0.05 and 0.15, clotrimazol difference was assumed in 0.5, and calculations were made through a Z
testandasignificanceof0.05.
Results
Figure1presentstheflowdiagramofthepresentstudy.Of the48patientsstudied,28patientswererandomlyselected tobeincludedinGroup1(Clotrimazole)and20inGroup2 (Tolnaftate)accordingtothecomputerrandomization pro-gram. Table 1 shows the demographic characteristics and risk factorsfoundineach group.Ofthetotal48 patients, 30(62.5%)weremaleand18(37.5%)werefemale,witha male/femaleratioof1.6:1.Agesrangedfrom12to77years withanaverageof41.70±17.44years.Themostaffected agegroupwas50---59,whichrepresented20.83%(n=10)of allpatients.TheClotrimazolegrouphadmoremalepatients thantheTolnaftategroup(p=0.034).
Two patients were eliminated. One patient was elimi-natedduetoacomplicationatfirstweekoftreatmentand evidenceofabacterialinfection.Theotherpatientdidnot completethefirstfollow-upvisit.
Themain occupationsof thepatients werehousewives 18.75% (n=9) andstudents18.75% (n=9),whichwas non-significantbetweenthegroups oftreatment(p=0.892).In both treatment groups, themajority of patients reported living inthecity,representing 91.6%of thecases(n=44). Overall, spring was the season withthe highest infection rate,with43.75%(n=21)ofthecases,followedbywinter, with27.08%(n=13).
The most frequent symptoms were pruritus 77.08% (n=37),oticfullness72.91%(n=35)andhearingloss62.5% (n=30).Therewerenosignificantdifferencesbetweenthe groupsinthedistributionoftheinitialsymptoms(Table2). The physical examination findings of the EAC (Fig. 2a) showed obstruction by ceruminous material, white 85.4% (n=41),black10%(n=5)andyellowhyphae2%(n=1),and abundantdesquamation2%(n=1).
Thedirect exam mycologicalstudy ofthe sampleswas positivein95.8%(n=46)ofthecasesandshowedthat45.8% (n=22)ofthepatientspresentedmycelialfungalstructures and41.6%(n=20)ofthepatientspresentedcharacteristics ofAspergillus.ThesedataaresummarizedinTable3.Inthe microscopicstudyofthecultures,thegenusmostfrequently foundwereAspergillus,91.6%(n=44)(Table4).
Regarding the results of the treatment (Table 5), the infectionsofpatientstreatedwithclotrimazolecream com-pletelyresolvedwithoneweekoftreatmentin75%ofthe cases(n=21),whileintheTolnaftategroup,resolutiononly occurredin45%ofthepatients(n=9).Inbothgroups,the infection resolution after the first and second weeks of treatmentshowedastatisticallysignificantdifference,with
p-valuesof0.007and0.009,respectively.
Group2showeda15%(n=3)treatmentfailurerate,and in 5%(n=1)ofpatients, theinfectionwasnotresolvedin the first week of treatment and presented complications (tympanicperforationandbacterialovergrowth).However, despite inadequate follow up (n=3), twenty patients in Group 2wereincluded in theanalysisunderthe principle oftheintentiontotreat.
Inpatientswhocontinuedtopresentclinical manifesta-tionsafterthefirstweekoftreatment,themostprevalent symptom waspruritus with 41.66% (n=20) (Table5).The resolutionwasevaluatedaccordingtothedisappearanceof
Evaluated for inclusion n=57
Excluded n=0 DO not meet crteria (n=7)
DO not consent(n=0) Other reasons (n=0)
Assigned to intervention group 1 Tx Clotrimazole (n=28) Received assigned intervention (n=28) Did not receive aasigned intervention (n=0)
Assigned to intervention group 2 Tx Tolnaftate (n=22)
Received assigned intervention (n=22) Did not receive aasigned intervention
(n=0) Randomized (n=50) Analysis F ollo w-up Assignment Inclusion Analyzed (n=20) included in analysis by intent to treat (ITT)
Excluded from the analysis (n=2)
Analyzed (n=28) Excluded from the analysis
(n=0)
Lost in follow-up (n=3) Eliminated (n=2) Interrupt intervention (n=1) due to
complication Lost in follow-up (n=0)
Interrupt intervention (n=0)
Figure1 Flowchartofthestudy.
Table1 BaselinedemographiccharacteristicsandriskfactorsinClotrimazoleandTolnaftategroups.
Demographiccharacteristics Group1Clotrimazole(n=28) Group2Tolnaftate(n=20) p-value
Gender(male) 21(75%) 9(45%) 0.034
Ageinyears(average) 42.75 40.25 0.665
Diabetic 2(7.14%) 0 0.222
Useofearphones 7(25%) 7(35%) 0.452
Useofhearingaid 1(3.5%) 1(5%) 0.807
Earmanipulationwithobjects 23(82.14%) 14(70%) 0.324
Swimming 1(3.5%) 0 0.393
Placeofresidencewithunpavedstreets 16(57.14%) 14(70%) 0.324
symptomsandthepresentationofanEACfreeofhyphaeor clinicalsignsofinfectionunderthemicroscope(Fig.2b).
Discussion
The treatment options for otomycosis are multiple, and someofitstreatmentsdonothaveclearscientificsupport yet,asinthecaseofTolnaftate.Ontheotherhand,azoles
have been reported by some studies tobe very effective in the treatment of otomycosis. In the present study, it wasdecidedtocompareTolnaftateagainstClotrimazoleto determinetheefficacyofbothmedicationsinacontrolled clinicaltrial.
Regarding theepidemiology of thisdisease, the preva-lenceofotomycosis is closely relatedtothegeographical area; our weather has a warm, sub-humid climate and
Table2 ClinicalcharacteristicsinClotrimazoleandTolnaftategroups.
Clinicalcharacteristics Group1
Clotrima-zole (n=28) Group2 Tolnaftate (n=22) p-value
Seasonwhensymptomsappeared(spring) 10(35.7%) 11(55%) 0.397
Averageevolutiontime(days) 82.89 96.15 0.318
Affectedside(right) 13(46.4%) 10(50%) 0.316
Pain 18(64.2%) 11(55%) 0.517 Hearingloss 18(64.2%) 12(60%) 0.762 Pruritus 19(67.8%) 18(90%) 0.072 Otorrhea 5(17.8%) 3(15%) 0.793 Tinnitus 10(35.7%) 10(50%) 0.322 Opticalfullness 22(78.5%) 13(65%) 0.297 Vertigo 6(21.4%) 7(35%) 0.297 Othersymptoms 2(7.14%) 0 0.222
Figure2 (a)Differenttypesofhyphaesinfectingtheexternalauditorycanal.Examplesofmicroscopicviewofpatientsinthis studyattimeofinclusion.(b)Microscopicvisualizationaftertreatment.Nohyphaearefoundorpathologyintheexternalauditory canal.
Table3 SamplefindingsfromdirectmicroscopicexaminationinClotrimazolGroup,TolnaftateGroupandtotal.
Directexammicroscopicfindings Total Group1Clotrimazole Group2Tolnaftate p-value
Aspergillus 20(41.6%) 15(53.5%) 5(25%)
Mycelium 22(45.8%) 11(39.2%) 11(55%)
Alternaria 1(2.08%) 1(3.57%) 0
Filaments 1(2.08%) 1(3.57%) 0
Hyalinehyphaspotted 1(2.08%) 0 1(5%)
Microconidia 1(2.08%) 0 1(5%)
Negative 2(4.16%) 0 2(10%)
Table4 OrganismsisolatedinculturesinClotrimazolegroup,Tolnaftategroupandtotal.
Total Group1Clotrimazole Group2Tolnaftate p-value
Aspergillus 44(91.6%) 25(89%) 19(95%) A.niger 16 8(28.5%) 8(40%) A.flavus 9 5(17.8%) 4(20%) A.terreous 8 5(17.8%) 3(15%) A.nidulans 8 6(21.4%) 2(10%) A.fumigatus 3 1(3.57%) 2(10%) Candida 2(4%) 2(7.14%) 0 Nogrowth 2(4%) 1(3.57%) 1(5%) Total 48(100%) 28(100%) 20(100%) 0.715
Table5 ComparisonoftreatmentresultsinpatientswithClotrimazolorTolnaftatetreatments. Group1 Clotrima-zole (n=28) Group2 Tolnaftate (n=20) p-value
Resolutionafter1stweekoftreatment 21(75%) 9(45%) 0.007
Additionalpatientswithresolutionafter2ndweekoftreatment 5(17.8%) 7(35%) 0.009
Recurrence 2(7.14%) 4(20%) 0.117
Numberofrecurrences 1(2)a 1(3)b 0.220
2(1)c
Changeintreatment 0 2(10%) 0.103
Complications 0 1(5%) 0.254
a ThetwopatientsintheClotrimazoleGroupwhopresentedrecurrenceonlyexperienceditonetimeeach. Ofthe4patientsinGroup2whopresentedrecurrence.
b 3hadrecurrenceononeoccasion. c 1presenteditontwooccasions.
presentsoptimalclimatologicalconditionsforthegrowthof pathogenicfungi.Moststudiesontheetiologyofotomycosis havebeenperformedinareasofhighheatandhumidityin additiontodust.4,9---17 Theprevalencebygendervarieswith
respecttodifferentstudies; in ourstudy,maleswere the mostaffected(62.5%),witharatiosimilartothatreported byViswanatha18;thisdifferencewasstatisticallysignificant
(p=0.034).Withregardtoagegroups,patientsintheir50s were more affected, which coincides with the results of Viswanatha.18
The high prevalence of otomycosis in the summer has beenreportedbyseveralauthors;19---21however,inthisstudy,
thehighestincidenceoccurredinthespringinbothgroups, withnostatisticallysignificance.
Otomycosisis mainlyreportedasunilateralin immuno-competentpatients,22however,Prasad8mentionedthat5%
of cases are bilateral, which is similar to our findings of 6%.Themostfrequentsignsandsymptomsreportedinthe literaturearepruritus,otalgia,otorrhea,oticfullness, hear-ing loss and tinnitus,2,6,8,20,23,24 all of which were present
in ourpatients withoutstatistically significant differences betweengroups.
Generally,otomycosisdiagnosisisbasedonclinical find-ings, however, in this study it was also confirmed by mycological laboratory findings. In the direct examina-tion, 100% of the samples from Group 1 and 90% of the samples from Group 2 demonstrated fungal structures.
Culturefindingsvarywidely.Forexample,Hueso-Gutiérrez25
reportedonly22.6% positive cultures,while other studies have achieved yields close to 79%, and in this study the yield was high, confirming the diagnosis in 96% of cases. Several studies report that the most frequently isolated fungi(genus) areAspergillus andCandida,the most com-mon species being A. niger and C. albicans.2,8,9,14,16,22,26
Araiza27 reportedA.flavusasthemostcommonpathogen
inMexico City.In ourstudy,the mostfrequent genus was
Aspergillus,89.2%in Group1and95% inGroup2. Inboth groups,themostcommonspecieswasA.niger, correspond-ing to that reported by other studies in hot and humid regions.
Treating otomycosis is difficult due tohigh recurrence rates.6Failuretorespondtotheinitialtreatmenthasbeen
reportedupto13%byHo2andrecurrencesvaryfrom5%to
15%.28,29
The treatment recommendationsaretocontrol predis-posingfactors,localdebridementandtheuseofantifungal agents, which was done with our patients from the first dayofassessment.Duringthefirstweekoftreatment, sub-jectivecharacteristicswereevaluated,withpruritusbeing themostfrequentsymptominbothgroups,similartothat reportedintheliterature.
Regarding antifungals, the imidazole group showed an 80%resolutionrateintheinitialapplicationwithscant prob-abilityofrecurrenceaccordingtotheMalikstudy.12Onthe
otherhand,JackmannamedClotrimazoleasthemost pop-ularand effective treatment,30 and othershave reported
effectivenessratesof50---100%.3,14,16,29Thesefindings
coin-cide with the results of this study, where 82.14% of the casestreatedwithClotrimazolecompletely resolvedafter oneweekoftreatment.Inourstudy,only7.14%of Clotrima-zolepatientspresentedrecurrence,andtheinfectionwas resolvedwithonemoreweekoftreatmentwithoutrequiring treatmentchange. Furthermore,theapplicationof Clotri-mazolewaseasierandlessexpensiveforthepatientbecause itwascarriedoutinthedoctor’sofficeandthepatienthad acheck-upeveryweek.
Regarding Tolnaftate, it has been recommended for refractorycases14;however, our results showed that only
45% of cases resolved after one week of treatment, 20% presentedrecurrence,10%requiredachangeintreatment toClotrimazole, which resolved the infection, and 5% of thecasespresented complications.However,recurrences, changeintreatmentorcomplicationswerenotstatistically significant,probablyduetothesmallsampleofthisstudy.
Furthermore,therewasasignificantdifferencebetween thetwotreatment groups in theresolution of otomycosis after the first and second weeks of treatment. The Tol-naftatetreatmentalsorequiredgreaterpatientadherence becauseitwasappliedathomeevery12hfor 7days.The creamisprobablymoreefficaciousthanthedropsbecauseit coversalltheextensionoftheEACskinandstaysincontact withthissurfaceforalongertime.
Limitations of these studies mainly were the lack of treatment blinding, sinceboth patients and doctorswere awarewhichtreatmentwasassigned.Thedifficultyin blind-ingresided ondifferenttreatment presentations,sincein one group medication cream was applied in the doctor’s officeand theother topicaldrops at home. Furthermore, the latter treatment required more compliancefrom the patient,which wasassessed in subsequent patient visits. Sinceoursampleissmall,morerandomizedcontrolledtrials areneededtocorroborateourresults.
Ontheotherhand,thehighlightsofthisresearchinclude the comparison of two treatment options for otomycosis scarcelydescribedinpreviousliterature,aswellasacareful designofarandomizedcontrolledtrial.
Accordingtotheresultsof thisresearch,weekly appli-cation of Clotrimazole is recommended in patients with uncomplicatedotomycosis.
Conclusions
TreatmentwithClotrimazolecreamismoreeffectivethan treatmentwithTolnaftatesolutionfor uncomplicated oto-mycosis.Morestudiesareneededtocorroborateourresults.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
We would like tothank CIDOCS UAS. Also,special thanks toIvonneCarolinaLeonLeyva,SergioVerdialesLugo,Nidia
KarinaBermudezTirado,IsauraBeatrizZazuetaLopez,Jose MariaAlarid,LuceroEscobarAispuro.
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