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In vivo synergism of ceftobiprole and vancomycin against experimental endocarditis due to vancomycin-intermediate

J M Entenza1, T R Veloso, J Vouillamoz

  • 1Department of Fundamental Microbiology, Biophore-University of Lausanne, CH-1015 Lausanne, Switzerland. jose.entenza@unil.ch

Antimicrobial Agents and Chemotherapy
|July 7, 2011
PubMed

Insights

Ceftobiprole combined with vancomycin shows promise against vancomycin-intermediate Staphylococcus aureus (VISA) infections. Even low doses of ceftobiprole synergized with vancomycin, broadening treatment options for VISA endocarditis.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Microbiology

Background:

  • Vancomycin-intermediate Staphylococcus aureus (VISA) poses a significant challenge in treating serious infections like endocarditis.
  • Limited treatment options exist for VISA infections, necessitating the exploration of novel therapeutic strategies.
  • Ceftobiprole is a cephalosporin with activity against Gram-positive bacteria, including MRSA.

Purpose of the Study:

  • To evaluate the efficacy of ceftobiprole, alone and in combination with vancomycin, against experimental endocarditis caused by VISA strains in a rat model.
  • To investigate potential synergistic interactions between ceftobiprole and vancomycin at subtherapeutic doses.

Main Methods:

  • A rat model of experimental endocarditis was infected with two VISA strains (PC3 and Mu50).
  • Animals were treated with various doses of ceftobiprole (standard, low, very low) and vancomycin (standard), alone or in combination.
  • Treatment regimens simulated human intravenous administration kinetics.

Main Results:

  • Standard-dose ceftobiprole monotherapy demonstrated high efficacy in sterilizing vegetations infected with both VISA strains (86% and 77%).
  • Low-dose ceftobiprole monotherapy was effective against one strain (91%) but less so against the other (25%).
  • Combinations of very low-dose or low-dose ceftobiprole with vancomycin showed synergistic effects, significantly improving vegetation sterilization rates (up to 78% and 83%) compared to monotherapy or controls.

Conclusions:

  • Ceftobiprole monotherapy at standard doses is effective against experimental VISA endocarditis.
  • Subtherapeutic doses of ceftobiprole can synergize with vancomycin, restoring efficacy against VISA infections.
  • Combining ceftobiprole and vancomycin broadens the therapeutic margin for treating VISA infections.

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