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

Yin LY, Calhoun JH, Thomas JK, Shapiro S, Schmitt-Hoffmann A

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

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 (Cmax, Ctrough, 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 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of antibiotic; and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/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.

Published 11 March 2008 in Antimicrob Agents Chemother.
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