In vitro activity profile of ceftobiprole, an anti-MRSA cephalosporin, against recent Gram-positive and Gram-negative isolates of European origin

Objectives: To determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA), for use as a contemporary baseline to help detect any changes in its activity profile throughout the course of clinical development and use. Methods: MICs were determined by broth microdilution testing for ceftobiprole and comparators against 6680 isolates [1201 S. aureus, 460 coagulase-negative staphylococci (CoNS), 526 Streptococcus pneumoniae, 1213 Escherichia coli, 854 Klebsiella pneumoniae, 443 Proteus mirabilis, 406 Enterobacter cloacae, 387 Citrobacter spp., 291 Serratia marcescens, 621 Pseudomonas aeruginosa and 278 Acinetobacter spp.] from 31 sites in 12 countries. Results: Ceftobiprole activity against MRSA (MIC90 2 mg/L) was 4-fold less than the activity against methicillin-susceptible S. aureus (MIC90 0.5 mg/L) and a similar trend was observed for methicillin-resistant CoNS (MIC90 2 mg/L) and methicillin-susceptible CoNS (MIC90 0.25 mg/L). Activity against S. pneumoniae (MIC(90)s: penicillin-susceptible, 0.015 mg/L; -intermediate, 0.25 mg/L; -resistant, 0.5 mg/L) was comparable to that of ceftriaxone. Ceftobiprole activity against Enterobacteriaceae (MIC(90)s: ceftazidime-susceptible, 0.12 mg/L; non-susceptible, > 32 mg/L), P. aeruginosa (MIC(90)s: ceftazidime-susceptible, 8 mg/L, non-susceptible, > 32 mg/L) and Acinetobacter spp. (MIC90: > 32 mg/L for imipenem-susceptible and non-susceptible) was comparable to that of cefepime. As with cefepime, ceftobiprole activity was decreased among cephalosporin-resistant isolates of Gram-negative bacilli [extended-spectrum beta-lactamase (ESBL) or non-ESBL mediated]. Conclusions: Ceftobiprole demonstrated potent in vitro activity against MRSA and showed activity against key Gram-negative bacilli comparable to that of cefepime. Given this broad spectrum of activity, ceftobiprole appears well suited for development and use in the treatment of a variety of healthcare-associated infections.