Combined Activity of Clavulanic Acid and Ticarcillin Against Ticarcillin-Resistant, Gram-Negative Bacilli

Abstract

Fifty-one clinical isolates of ticarcillin-resistant, gram-negative bacilli were tested for susceptibility to combinations of ticarcillin and clavulanic acid (BRL 14151), a potent beta-lactamase inhibitor. Minimal inhibitory concentrations (MICs) were measured by a microdilution method, and minimal bactericidal concentrations for selected strains were measured by the broth dilution method. Ticarcillin MICs were ≥128 μg/ml for all and ≥512 μg/ml for 38 (75%) of the strains. Thirty-nine strains of Enterobacteriaceae tested included Escherichia coli (14), Klebsiella pneumoniae (16), Citrobacter sp. (3), Enterobacter sp. (3), Salmonella enteritidis (1), Serratia marcescens (1), and Proteus mirabilis (1). Ticarcillin MICs for 34 strains (88%) were lowered at least threefold by the addition of 1.0 μg of clavulanic acid per ml. Against 33 strains (85%), the MICs were 64 μg or less per ml in the presence of 5 μg of clavulanic acid per ml. In contrast, the MICs for seven of eight strains of Pseudomonas aeruginosa were unaffected by the addition of up to 10 μg of clavulanic acid per ml. Ticarcillin with 5 μg of clavulanic acid per ml was bactericidal against ticarcillin-resistant (MIC ≥ 2,048 μg/ml) E. coli, K. pneumoniae, Enterobacter , and P. mirabilis .