Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 62, Issue 11, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01158-18
Keywords
Staphylococcus aureus; animal models; cefazolin; clavulanic acid; infective endocarditis; inoculum effect
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Funding
- NIH-NIAID [R21/R33 AI121519, K24 AI121296]
- UTHealth Presidential award
- University of Texas System STARS award
- UTHealth Center for Antimicrobial Resistance and Microbial Genomics (CARMiG) seed funds
- Achaogen
- Merck
- Paratek Pharmaceuticals
- MeMed
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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 log(10) CFU/g) compared to that with cefazolin alone (2 +/- 0.6 log(10) CFU/g; P < 0.0001). The addition of a beta-lactamase inhibitor may be a viable strategy for overcoming the CzIE.
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