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.

• Authors: B Barry, M Muffat-Joly, J Bauchet, F Faurisson, P Gehanno, J J Pocidalo, C Carbon
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 40 Issue 9 Pg. 1977-82 (Sep 1996) ISSN: 0066-4804 [Print] United States
• PMID: 8878566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cephalosporins
• Ceftriaxone

Topics

• Animals
• Ceftriaxone (administration & dosage, pharmacokinetics, therapeutic use)
• Cephalosporin Resistance
• Cephalosporins (administration & dosage, pharmacokinetics, therapeutic use)
• Chromatography, High Pressure Liquid
• Female
• Gerbillinae
• Half-Life
• Microbial Sensitivity Tests
• Otitis Media (drug therapy, microbiology)
• Penicillin Resistance
• Pneumococcal Infections (drug therapy, microbiology)
• Streptococcus pneumoniae (drug effects)