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

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.

• Authors: William R Miller, Kavindra V Singh, Cesar A Arias, Barbara E Murray
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 62 Issue 11 (11 2018) ISSN: 1098-6596 [Electronic] United States
• PMID: 30150459 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American Society for Microbiology.

Chemical References

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

Topics

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