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

Gjinovci, Asllan
Bento, Manuela
Published in Antimicrobial Agents and Chemotherapy. 2005, vol. 49, no. 9, p. 3789-3793
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.
Keywords AnimalsCephalosporins/pharmacokinetics/pharmacology/ therapeutic useForeign Bodies/ complicationsMethicillin ResistanceMicrobial Sensitivity TestsMutation/geneticsRatsRats, WistarStaphylococcal Infections/ drug therapy/ etiologyStaphylococcus aureus/drug effects/geneticsVancomycin/therapeutic use
PMID: 16127054
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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 https://archive-ouverte.unige.ch/unige:7652

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Deposited on : 2010-06-21

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