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Antimicrob. Agents Chemother. doi:10.1128/AAC.00638-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Efficacies of Ceftobiprole Medocaril and Comparators in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Osteomyelitis

Department of Orthopaedic Surgery, The University of Missouri, Columbia, Missouri; Basilea Pharmaceutica AG, Basel, Switzerland

^* To whom correspondence should be addressed. Email: calhounj{at}health.missouri.edu.

	Abstract

The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand white rabbits were determined after subcutaneous administration of prodrug ceftobiprole medocaril. Serum exposure (C_max, C_trough, AUC) to ceftobiprole at 20 and 80 mg/kg was dose-proportional, and there was no accumulation of ceftobiprole following repeated q6h injections of the antibiotic. Ceftobiprole titers in tibial matrix and marrow were 3.2 ± 1.3 µg/g and 11.2 ± 6.5 µg/g, respectively, in uninfected animals treated with 20 mg/kg of antibiotic; and 13.4 ± 7.3 µg/g and 66.3 ± 43.2 µg/g, respectively, in uninfected animals treated with 80 mg/kg of antibiotic. No differences in ceftobiprole titer were observed between right and left tibiae for either bone matrix or marrow. The efficacies of four weeks of treatment with ceftobiprole (40 mg/kg sc q6h), vancomycin (30 mg/kg sc q12h), or linezolid (60 mg/kg po q8h) were compared using a rabbit model of MRSA tibial osteomyelitis. Following ceftobiprole treatment bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; mean ceftobiprole titers were 3-5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.