Ceftobiprole is superior to vancomycin, daptomycin, and linezolid for treatment of experimental endocarditis in rabbits caused by methicillin-resistant Staphylococcus aureus

Antimicrob Agents Chemother. 2010 Feb;54(2):610-3. doi: 10.1128/AAC.00886-09. Epub 2009 Nov 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / therapeutic use*
  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Cephalosporins / therapeutic use*
  • Chromatography, High Pressure Liquid
  • Daptomycin / therapeutic use*
  • Disease Models, Animal
  • Endocarditis, Bacterial / drug therapy*
  • Endocarditis, Bacterial / microbiology
  • Linezolid
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Oxazolidinones / therapeutic use*
  • Rabbits
  • Random Allocation
  • Vancomycin / therapeutic use*

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Cephalosporins
  • Oxazolidinones
  • ceftobiprole
  • Vancomycin
  • Linezolid
  • Daptomycin