Scientific article

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

Published inAntimicrobial agents and chemotherapy, vol. 49, no. 9, p. 3789-3793
Publication date2005

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.

  • 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
Citation (ISO format)
VAUDAUX, Pierre et al. Intensive therapy with ceftobiprole medocaril of experimental foreign-body infection by methicillin-resistant Staphylococcus aureus. In: Antimicrobial agents and chemotherapy, 2005, vol. 49, n° 9, p. 3789–3793. doi: 10.1128/AAC.49.9.3789-3793.2005
Main files (1)
ISSN of the journal0066-4804

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