Ceftobiprole, a broad-spectrum
cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in a subcutaneous skin
infection model with Staphylococcus aureus Smith OC 4172 (
methicillin-susceptible S. aureus [MSSA]), S. aureus OC 8525 (MRSA), Pseudomonas aeruginosa OC 4351 (having an inducible
AmpC beta-lactamase), and P. aeruginosa OC 4354 (overproducing
AmpC beta-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). 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 was
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.