| Title | In Vivo Activity of Ceftobiprole in Murine Skin Infections Due to Staphylococcus aureus and Pseudomonas aeruginosa. | | Author(s) | Fernandez J, Hilliard JJ, Abbanat D, Zhang W, Melton JL, Santoro CM, Flamm RK, Bush K | | Institution | Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Raritan, New Jersey. | | Source | Antimicrob Agents Chemother 2009 Nov 2. | | Abstract | Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (30), was evaluated in a subcutaneous skin infection model with Staphylococcus aureus Smith OC 4172 (MSSA), S. aureus OC 8525 (MRSA), P. aeruginosa OC 4351 (inducible AmpC beta-lactamase), and P. aeruginosa OC 4354 (overproducing AmpC beta-lactamase). In the MSSA and MRSA infection models, ceftobiprole, dosed as the prodrug ceftobiprole medocaril, was more effective in reducing CFU/g skin (P < 0.001) than cefazolin, vancomycin, or linezolid based on the dose-response profiles. Skin lesion volumes in MSSA-infected animals treated with ceftobiprole were 19 to 29% smaller than cefazolin, vancomycin, or linezolid treated animals (P < 0.001). In MRSA infections, lesion size in ceftobiprole-treated mice was 34% smaller than with cefazolin or linezolid treatment (P < 0.001). Against P. aeruginosa, ceftobiprole at similar doses was as effective as meropenem-cilastatin in reductions of CFU/g skin, despite 8 and 32-fold lower MICs for meropenem; both treatments were more effective than cefepime (P < 0.001) against the inducible and overproducing AmpC beta-lactamase strains of P. aeruginosa. Ceftobiprole was similar to meropenem-cilastatin and 47 to 54% more effective than cefepime (P < 0.01) in reducing the size of the lesion caused by either strain of P. aeruginosa in this study. These studies indicate that ceftobiprole is effective in reducing both bacterial load and lesion volume associated with infections due to MSSA, MRSA, and P. aeruginosa in this murine model of skin and soft tissue infection. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19884364 |
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