title: Ceftobiprole is superior to vancomycin, daptomycin, and linezolid for treatment of experimental endocarditis in rabbits caused by methicillin-resistant Staphylococcus aureus.
abstract: Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P<0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P<0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.
authors.affiliation: Division of Infectious Diseases, San Francisco General Hospital, University of California, San Francisco, Room 3400, Building 30, 1001 Potrero Avenue, San Francisco, CA 94110, USA. pierre.tattevin@chu-rennes.fr
authors.forename: P
authors.initials: P
authors.lastname: Tattevin
authors.forename: L
authors.initials: L
authors.lastname: Basuino
authors.forename: D
authors.initials: D
authors.lastname: Bauer
authors.forename: B A
authors.initials: BA
authors.lastname: Diep
authors.forename: H F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D017576:Daptomycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D023303:Oxazolidinones / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D023303:Oxazolidinones; C443755:ceftobiprole; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin