\gb-Lactam Resistance in Nocardia brasiliensis is Mediated by -Lactamase and Reversed in the Presence of Clavulanic Acid

Abstract

Forty clinical isolates and the type strain of Nocardia brasiliensis were screened for susceptibility to 20 β-lactams. Isolates exhibited a single pattern of resistance, with large zones of inhibition by disk diffusion and low MICs by broth and agar dilutions only to cefotaxime, ceftriaxone, ceftizoxime, Augmentin®, and Timentin®. All strains produced β-lactamase, with five different enzyme patterns by isoelectric focusing. Despite the differences in their isoelectric points, the enzymes had the same substrate profiles, with equivalent activity against penicillin, ampicillin, cefamandole, cephalothin, and cephalordine. In an in vitro assay, the enzymes were highly susceptible to clavulanic acid. The MIC₅₀ and MIC₉₀ for the combination of amoxicillin and clavulanic acid (Augmentin) was 2 and 4 µg/ml, respectively, compared with 16 µg/rnl for both values for amoxicillin alone. These studies suggest that β-lactamase is the major mechanism of β-lactam resistance in this species and that Augmentin is the first oral β-lactam with good potential for treating infections due to N. brasiliensis.