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.
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