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

We tested the ability of clavulanic acid to restore the efficacy of cefazolin against S. aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the co-administration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 ± 0.5 log₁₀ CFU/g) compared to 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.

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