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

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.