Sodium Clavulanate Potentiation of Cephalosporin Activity Against Clinical Isolates of Cephalothin-resistant Klebsiella Pneumoniae

Plasmid-carrying Klebsiella pneunomiae clinical isolates with agar dilution minimum inhibitory concentrations (MIC) of 32 mug/ml or greater were tested for in vitro potentiation of cephalothin activity by clavulanic acid (BRL-14151), an inhibitor of beta-lactamases. The addition of 10 mug of clavulanate per ml caused greater than a 500-fold reduction in geometric mean cephalothin agar dilution MIC, with lesser but significant reductions resulting from clavulanate concentrations of 5 or 1 mug/ml. Clavulanate-potentiated reduction of cephalothin MICs in broth against resistant Klebsiella were comparable to reduction in agar dilution MICs as a rule. However, a low concentration (1 mug/ml) of clavulanate produced cephalothin MICs in broth several-fold higher than by the agar dilution method. Modest cephalothin-potentiating effects of clavulanate on cephalothin-susceptible strains and on cefoxitin against cephalothin-resistant Klebsiella strongly suggested that the major effect of clavulanate was beta-lactamase inhibition.