Open AccessIn Vivo Activity of Ceftobiprole in Murine Skin Infections Due to Staphylococcus aureus and Pseudomonas aeruginosa
Author(s) -
Jeffrey Fernandez,
Jamese J. Hilliard,
Darren Abbanat,
Wenyan Zhang,
John L. Melton,
Colleen M. Santoro,
Robert K. Flamm,
Karen Bush
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00642-09
Subject(s) - staphylococcus aureus , linezolid , microbiology and biotechnology , cefazolin , cefepime , pseudomonas aeruginosa , vancomycin , meropenem , cephalosporin , methicillin resistant staphylococcus aureus , antibiotics , medicine , biology , imipenem , antibiotic resistance , bacteria , genetics
Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistantStaphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in a subcutaneous skin infection model withStaphylococcus aureus Smith OC 4172 (methicillin-susceptibleS. aureus [MSSA]),S. aureus OC 8525 (MRSA),Pseudomonas aeruginosa OC 4351 (having an inducible AmpC β-lactamase), andP. aeruginosa OC 4354 (overproducing AmpC β-lactamase). In the MSSA and MRSA infection models, ceftobiprole, administered as the prodrug ceftobiprole medocaril, was more effective in reducing CFU/g skin (P < 0.001) than were cefazolin, vancomycin, or linezolid based on the dose-response profiles. Skin lesion volumes in MSSA-infected animals treated with ceftobiprole were 19 to 29% lower than those for cefazolin-, vancomycin-, or linezolid-treated animals (P < 0.001). In MRSA infections, lesion size in ceftobiprole-treated mice was 34% less than that with cefazolin or linezolid treatment (P < 0.001). AgainstP. 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 was cefepime (P < 0.001) against the inducible and overproducing AmpC β-lactamase strains ofP. 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 ofP. 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, andP. aeruginosa in this murine model of skin and soft tissue infection.