BACTERIOLOGICAL FAILURE OF AMOXICILLIN-CLAVULANATE IN TREATMENT OF ACUTE OTITIS-MEDIA CAUSED BY NONTYPABLE HAEMOPHILUS-INFLUENZAE

Objective: To evaluate the rate of bacteriologic failure of amoxicilli n-clavulanate in the treatment of acute otitis media (AOM) and to iden tify the risk factors associated with failure. Methods: Ninety-nine su bjects (mean age, 21.4 months) with AOM were treated with amoxicillin- clavulanate in two prospective study trials that compared efficacy of two experimental antibiotics with amoxicillin-clavulanate. Tympanocent esis for microbiologic studies was performed in all subjects at enroll ment; at 3 to 6 days, during amoxicillin-clavulanate therapy; and at o ther times when clinically indicated. The subjects were followed up fo r 1 month. Clinical, bacteriologic, and virologic characteristics of t he subjects were analyzed. Results: Bacteriologic failure of treatment occurred in none of 39 subjects (0%) with Streptococcus pneumoniae, t wo of 25 (8%) with Moraxella catarrhalis, and 11 of 29 (38%) with nont ypeable Haemophilus influenzae (NTHi) infection. The failure rate for NTHi was higher than that for other pathogens (p = 0.0007) and was inc reased when compared with the preceding study period (p = 0.017). Bact eriologic failure was also associated with clinical failure (p = 0.041 ). In subjects with AOM caused by NTHi the rates of adequate drug comp liance were comparable in both success and failure groups. Antimicrobi al susceptibility testing by minimum inhibitory concentration and mini mum bactericidal concentration (MIC/MBC) assays showed that amoxicilli n-clavulanate resistance was not significantly associated with bacteri ologic failure of treatment. However, in two subjects, MIC/MBC of the NTHi isolates during therapy were higher than MIC/MBC of the isolates before therapy; these strains of isolates pretherapy and during therap y were discordant as determined by outer membrane protein analysis. Th e bacteriologic failure rate was higher in nonwhite boys (p = 0.026) a nd in subjects with a history of three or more previous episodes of AO M (p = 0.008). Other factors such as age, bilaterality of disease, pol ymicrobial infection, and biotype pattern of NTHi were not associated with treatment failure. When children with adequate drug compliance we re analyzed separately, only those with concomitant viral infection of the nasopharynx or middle ear were found to be at an increased risk o f bacteriologic failure of treatment (p = 0.04). Conclusions: The bact eriologic failure rate of amoxicillin-clavulanaie therapy for AOM caus ed by NTHi was higher in the current study period than in the precedin g period. Factors contributing to treatment failure were race, gender, proneness to otitis, and concomitant viral infection.