title: 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 < or =4 and < or =8 microg/mL, respectively, although MIC90 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, beta-hemolytic and viridans group streptococci, inhibiting >98% of isolates at < or =0.5 microg/mL. Although ceftobiprole was generally inactive against Enterococcus faecium, the majority of Enterococcus faecalis strains (95.7%) were inhibited at < or =4 microg/mL. This agent was similar in potency to the "3rd- and 4th-generation" cephems (MIC50 values, < or =0.06 microg/mL) for all tested Enterobacteriaceae. Although cefepime provided enhanced coverage against Klebsiella spp. (86.5% at < or =8 microg/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 (MIC50, 2 microg/mL) and 2-fold more potent than cefepime. None of these agents inhibited >45% of Acinetobacter spp. at 8 mug/mL. Ceftobiprole is a new anti-MRSA beta-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.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA. thomas-fritsche@jmilabs.com
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fritsche
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000382:microbiology; D002511:Cephalosporins / Q000494:pharmacology*; D005060:Europe; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007843:Latin America; D008826:Microbial Sensitivity Tests; D009656:North America
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C443755:ceftobiprole