Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae.

OBJECTIVE: To evaluate the rate of bacteriologic failure of amoxicillin-clavulanate in the treatment of acute otitis media (AOM) and to identify the risk factors associated with failure. METHODS: Ninety-nine subjects (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. Tympanocentesis for microbiologic studies was performed in all subjects at enrollment; at 3 to 6 days, during amoxicillin-clavulanate therapy; and at other times when clinically indicated. The subjects were followed up for 1 month. Clinical, bacteriologic, and virologic characteristics of the subjects were analyzed. RESULTS: Bacteriologic failure of treatment occurred in none of 39 subjects (0%) with Streptococcus pneumoniae, two of 25 (8%) with Moraxella catarrhalis, and 11 of 29 (38%) with nontypeable Haemophilus influenzae (NTHi) infection. The failure rate for NTHi was higher than that for other pathogens (p = 0.0007) and was increased when compared with the preceding study period (p = 0.017). Bacteriologic failure was also associated with clinical failure (p = 0.041). In subjects with AOM caused by NTHi the rates of adequate drug compliance were comparable in both success and failure groups. Antimicrobial susceptibility testing by minimum inhibitory concentration and minimum bactericidal concentration (MIC/MBC) assays showed that amoxicillin-clavulanate resistance was not significantly associated with bacteriologic 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 therapy were discordant as determined by outer membrane protein analysis. The bacteriologic failure rate was higher in nonwhite boys (p = 0.026) and in subjects with a history of three or more previous episodes of AOM (p = 0.008). Other factors such as age, bilaterality of disease, polymicrobial infection, and biotype pattern of NTHi were not associated with treatment failure. When children with adequate drug compliance were analyzed separately, only those with concomitant viral infection of the nasopharynx or middle ear were found to be at an increased risk of bacteriologic failure of treatment (p = 0.04). CONCLUSIONS: The bacteriologic failure rate of amoxicillin-clavulanate therapy for AOM caused by NTHi was higher in the current study period than in the preceding period. Factors contributing to treatment failure were race, gender, proneness to otitis, and concomitant viral infection.

Effect of viral respiratory tract infection on outcome of acute otitis media.

We prospectively studied 271 infants and children (2 months to 7 years of age) with acute otitis media (AOM) for viral and bacterial causes, outcome at the end of therapy, and frequency of recurrence within 1 month. Comprehensive virologic methods, including viral antigen detection, cell culture, and serologic studies, were used to diagnose viral infection of the respiratory tract, middle ear, or both. Evidence of viral infection was found in 46% (124/271) of patients with AOM. Sixty-six patients (24%) had virus or viral antigen in the middle ear fluid; 50 of these patients (76%) also had bacteria in middle ear fluid, and 16 (24%) had virus alone. More patients with AOM and combined bacterial and viral infection (51%) had persistent otitis (3 to 12 days after institution of antibiotic treatment), compared with those with only bacterial otitis (35%; p = 0.05) or patients with only viral infection (19%; p less than 0.01). Of patients with only viral infection, 4 of 10 with virus in middle ear fluid had persistent otitis, compared with none of 11 patients who had virus only in nasal wash specimens or whose viral infection was diagnosed only by serologic studies. Our data suggest that viruses interact with bacteria and that concurrent viral infection can significantly worsen the clinical course of bacterial AOM. The presence of virus in middle ear fluid may contribute to the pathogenesis and outcome of bacterial AOM. The mechanism of these interactions deserve further investigation.