Abstract
BACKGROUND: 10 days of amoxicillin/clavulanic acid high dose and 5 days of cefdinir have been the preferred first- or second-line antibiotics for treatment of children with acute otitis media (AOM) since 2004, as recommended by the American Academy of Pediatrics in the USA, but no head-to-head comparison study has been done. OBJECTIVE: The purpose of the study was to compare the clinical efficacy of amoxicillin/clavulanic acid high-dose therapy for 10 days with cefdinir therapy for 5 days for AOM at recommended doses. METHODS: This was an investigator-blind trial in young children 6-24 months old with no history of recurrent AOM who were randomly assigned to amoxicillin/clavulanic acid (80 mg/kg/day amoxicillin) or cefdinir (14 mg/kg/day), both in two divided doses. The diagnosis of AOM was based on specific clinical criteria by validated otoscopists at two AOM research centres. The outcome measure for clinical cure was resolution of all symptoms and signs of AOM except for persistence of middle-ear effusion at test-of-cure (TOC) 11-14 days after initiation of antibiotic treatment. Clinical failure was defined as persistence of symptoms and signs of AOM and the need for additional antibiotic therapy. Subjects lost to follow up or who had not taken at least 80% of the prescribed medication were classified as having an indeterminate response. Compliance was monitored using Medical Electronic Monitoring System (MEMS) caps and antibiotic bottle volume measurement at the TOC visit. A logistic regression model was used to estimate the association of age with cure rate. Full interactions in terms of age with treatment were included to estimate any age gradient differential. RESULTS: A total of 330 children (average age 13.1 months) with AOM were studied. At TOC, 256 children had clinical cure, 69 had clinical failure, and 5 were lost to follow-up. High-dose amoxicillin/clavulanic acid-treated children had a better cure rate (86.5%) than cefdinir-treated patients (71.0%; p = 0.001). Cefdinir was correlated with less frequent cure outcomes as children increased in age between 6 and 24 months. The odds ratios for clinical cure per increasing month of age estimated from a logistic regression model for amoxicillin/clavulanic acid high dose and cefdinir treatment groups was 0.992 (95% CI 0.932, 1.056), p > 0.05 and 0.932 (95% CI 0.881, 0.986), p = 0.01. The differences in the odds ratios are significant at p < 0.002, indicating a stable clinical cure rate across the ages of children studied for amoxicillin/clavulanic acid and decreasing clinical cure rates as children increased in age for cefdinir. CONCLUSION: In children with bona fide AOM for whom clinical outcomes are assessed by validated otoscopists, 10 days of high-dose amoxicillin/clavulanic acid is significantly more effective than 5 days of cefdinir as therapy for AOM. Because of the identified age effect (correlated to child weight), higher doses of cefdinir may have led to a different conclusion; 10 days of cefdinir may also have led to a different conclusion.