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

Abstract

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 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) 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 microgram/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 mg/kg 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 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.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.

In Vivo Efficacies of Amoxicillin and Cefuroxime against Penicillin-Resistant Streptococcus pneumoniae in a Gerbil Model of Acute Otitis Media

“…It is also common that the cefuroxime MICs for such strains are higher than those of amoxicillin (12). In addition, this strain was able to induce AOM in gerbils, as described by other investigators (3,10).…”

“…AOM induced in gerbils is a well-established model for studying AOM as well as for comparing the efficacies of different antimicrobial regimens (3,10).…”

Management of Infections Due to Antibiotic-Resistant Streptococcus pneumoniae

“…However, efficacy for antibiotic-resistant pneumococci was not assessed. In the gerbil model, a single 100mg/kg dose of ceftriaxone was effective in treating otitis media due to S. pneumoniae strains resistant to penicillin and ceftriaxone (MIC of both antibiotics ϭ 8.0 g/ml) (18 tained, and treatment with ceftriaxone (50 mg/kg) once daily for 3 days was administered. Thirty-six children had S. pneumoniae isolates for which the penicillin MICs were Ն1 g/ml.…”