Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis

Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01158-18. doi: 10.1128/AAC.01158-18. Print 2018 Nov.

Abstract

We tested the ability of clavulanic acid to restore the efficacy of cefazolin against Staphylococcus aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the coadministration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 ± 0.5 log10 CFU/g) compared to that with cefazolin alone (2 ± 0.6 log10 CFU/g; P < 0.0001). The addition of a β-lactamase inhibitor may be a viable strategy for overcoming the CzIE.

Keywords: Staphylococcus aureus; animal models; cefazolin; clavulanic acid; infective endocarditis; inoculum effect.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cefazolin / pharmacology*
  • Clavulanic Acid / pharmacology*
  • Endocarditis / drug therapy*
  • Endocarditis / metabolism
  • Endocarditis, Bacterial / drug therapy*
  • Endocarditis, Bacterial / metabolism
  • Methicillin / pharmacology*
  • Microbial Sensitivity Tests / methods
  • Rats
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / metabolism
  • Staphylococcus aureus / drug effects*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Clavulanic Acid
  • beta-Lactamases
  • Cefazolin
  • Methicillin