Antimicrobial activity of ceftobiprole, a novel anti–methicillin-resistant Staphylococcus aureus cephalosporin, tested against contemporary pathogens: results from the SENTRY Antimicrobial Surveillance Program (2005–2006)

Abstract

Ceftobiprole is a 1st-in-class anti–methicillin-resistant Staphylococcus aureus (MRSA) extended-spectrum cephalosporin currently in clinical trials for the treatment of complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia. This agent is also active against other prominent Gram-positive and Gram-negative pathogens, making it an attractive candidate for broad-spectrum therapy. We evaluated the in vitro potency of ceftobiprole tested against the most commonly occurring bacterial pathogens as part of a global surveillance study for the years 2005 to 2006 (>60 medical centers in North America, Latin America, and Europe). All isolates (40 675) were susceptibility tested using reference broth microdilution methods. Ceftobiprole inhibited 100% and >99% of tested S. aureus and coagulase-negative staphylococci at ≤4 and ≤8 μg/mL, respectively, although MIC 90 values for oxacillin-resistant strains were 4-fold and 8-fold higher than oxacillin-susceptible isolates for the 2 groups. Ceftobiprole was also broadly active against Streptococcus pneumoniae, β-hemolytic and viridans group streptococci, inhibiting >98% of isolates at ≤0.5 μg/mL. Although ceftobiprole was generally inactive against Enterococcus faecium, the majority of Enterococcus faecalis strains (95.7%) were inhibited at ≤4 μg/mL. This agent was similar in potency to the “3rd- and 4th-generation” cephems (MIC 50 values, ≤0.06 μg/mL) for all tested Enterobacteriaceae. Although cefepime provided enhanced coverage against Klebsiella spp. (86.5% at ≤8 μg/mL versus 76.9–81.7% for ceftobiprole and ceftazidime), ceftobiprole and cefepime were superior to ceftazidime against Enterobacter spp. and Citrobacter spp. Against Pseudomonas aeruginosa, ceftobiprole was equal in potency to ceftazidime (MIC 50, 2 μg/mL) and 2-fold more potent than cefepime. None of these agents inhibited >45% of Acinetobacter spp. at 8 μg/mL. Ceftobiprole is a new anti-MRSA β-lactam with recognized activity against the most commonly occurring Enterobacteriaceae and P. aeruginosa, similar to that of extended-spectrum cephems. These characteristics warrant continued evaluation of the agent as empiric therapy for cSSSIs, and in pneumonia, especially in those institutions/regions where MRSA and P. aeruginosa may be prevalent.