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The effects of co-amoxiclav (AMC) and amoxicillin (AMX) therapy on the nasopharyngeal flora of children with acute otitis media (AOM) were compared. Nasopharyngeal culture for aerobic and anaerobic bacteria were obtained before therapy and 2–4 days after completion of antimicrobial therapy in 25 patients treated with either antibiotic. After therapy, 16 (64%) of the 25 patients treated with AMX and 23 (92%) of the 25 patients treated with AMC were considered clinically cured. Polymicrobial aerobic–anaerobic flora were present in all instances. A significant reduction in the number of both aerobic and anaerobic isolates occurred after therapy in those treated with AMX (177 isolates versus 133, P< 0.005) and AMC (172 isolates versus 60, P< 0.001). However, the number of all isolates recovered after therapy in those treated with AMC was significantly lower (60 isolates) than in those treated with AMX (133 isolates, P < 0.001). The recovery of known aerobic pathogens (e.g. Streptococcus pneumoniae, Staphylococcus aureus, β-haemolytic streptococci, Haemophilus species and Moraxella catarrhalis) and penicillin-resistant bacteria after therapy was lower in the AMC group than in the AMX group (P < 0.005). This study illustrates the greater ability of AMC, compared with AMX, to reduce the number of potential nasopharyngeal pathogens and penicillin-resistant bacteria in children with AOM.