Intensive therapy with ceftobiprole medocaril of experimental foreign-body infection by methicillin-resistant Staphylococcus aureus.

Abstract

The therapeutic activity of ceftobiprole medocaril, the water-soluble prodrug of ceftobiprole, was compared to that of vancomycin in a rat tissue cage model of chronic methicillin-resistant Staphylococcus aureus (MRSA) foreign-body infection. The MICs and MBCs of ceftobiprole and vancomycin in Mueller-Hinton broth for strain MRGR3 were 1 and 4 and 1 and 2 microg/ml, respectively. In vitro elimination rates of strain MRGR3 of 4 and 8 microg/ml of ceftobiprole or vancomycin were equivalent. After 2 weeks of infection, mean +/- standard error of the mean viable counts of strain MRGR3 were 6.83 +/- 0.11 log CFU/ml of tissue cage fluid (n = 87). High-dose regimens of ceftobiprole medocaril (equivalent to 150 mg/kg of ceftobiprole) or 50 mg/kg vancomycin produced nearly identical average peak and trough levels of ceftobiprole and vancomycin in tissue cage fluid, which exceeded the MBC of either antibiotic towards strain MRGR3 for > or =75% of each dosing interval. After 7 days of therapy with ceftobiprole medocaril or vancomycin, average counts of MRGR3 decreased significantly (P < 0.02) by 0.68 +/- 0.28 (n = 29) and 0.88 +/- 0.22 (n = 28) log CFU/ml of tissue cage fluid, respectively, compared with cages of untreated animals, but were not significantly different from each other. No resistant mutants were detected on ceftobiprole-supplemented agar following therapy with this cephalosporin. The in vivo activity of ceftobiprole medocaril against chronic MRSA foreign-body infections was equivalent to that of vancomycin and did not lead to the emergence of resistant subpopulations.

• Authors: Pierre Vaudaux, Asllan Gjinovci, Manuela Bento, Dongmei Li, Jacques Schrenzel, Daniel P Lew
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 9 Pg. 3789-93 (Sep 2005) ISSN: 0066-4804 [Print] United States
• PMID: 16127054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cephalosporins
• ceftobiprole
• Vancomycin
• ceftobiprole medocaril

Topics

• Animals
• Cephalosporins (pharmacokinetics, pharmacology, therapeutic use)
• Foreign Bodies (complications)
• Methicillin Resistance
• Microbial Sensitivity Tests
• Mutation (genetics)
• Rats
• Rats, Wistar
• Staphylococcal Infections (drug therapy, etiology)
• Staphylococcus aureus (drug effects, genetics)
• Vancomycin (therapeutic use)