Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae

We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 mu g/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 mu g/ml). Middle ear infection was induced by bilateral transbullar challenge with 107 bacteria per ear, Antibiotic treatment was administered subcutaneously at 2 h postinfection, Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples, With the cefriaxone-susceptible strain (MIC, 0.5 mu g/ml), we tested doses of 5 to 100 mg/kg of body weight, With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls, Similar efficacy was obtained with a dose of 100 mgikg against the two ceftriaxone-resistant strains, Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mgikg (peak level of total drug, 268 +/- 33 mu g/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 mu g . h . ml(-1)) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg, Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.