EFFECT OF INCREASED DOSAGES OF AMOXICILLIN IN TREATMENT OF EXPERIMENTAL MIDDLE-EAR OTITIS DUE TO PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE

A gerbil model of acute middle ear otitis was used to evaluate the efficacy of increased dosages of amoxicillin in eradicating infection induced by penicillin-resistant Streptococcus pneumoniae. Three different strains were used: (i) a serotype 23 penicillin-susceptible strain; (ii) a serotype 23 penicillin-resistant strain (MIC of penicillin, 2 mug/ml); and (iii) a serotype 19 highly penicillin-resistant strain (MIC of penicillin, 4 to 8 mug/ml). Animals were inoculated bilaterally with 10(7) CFU per ear by transbulla challenge and treated 2 to 4 h postinfection by amoxicillin administrated subcutaneously. The course of the disease was monitored bacteriologically on days 2, 4, and 8 postinfection. The three strains had a similar pathogenicity in untreated animals in terms of the duration of the disease, bacterial counts in middle ear (ME) fluid, and systemic complications. Infection due to the penicillin-susceptible strain was cured after two injections of 2.5 mg/kg of body weight. No bacteria were recovered at day 2 after two injections at 10 and 25 mg/kg with the penicillin-resistant and highly penicillin-resistant strains, respectively. Under these experimental conditions, increased doses of amoxicillin consistent with MICs were able to clear ME infection. Pharmacokinetic parameters of amoxicillin in serum and ME fluid were within the clinical range at the doses used in the study.