A SIMPLE METHOD FOR TESTING THE EFFICACY OF A β-LACTAMASE INHIBITOR AGAINST β-LACTAMASE-PRODUCING GRAM-NEGATIVE BACTERIA

Abstract

The synergistic effect of a β-lactam antibiotic in combination with a β-lactamase inhibitor (cloxacillin) on Gram-negative bacteria producing various types of β-lactamases was studied with respect to the properties of the enzymes by usinga set of bacterial strains we had developed previously for evaluation of β-lactamase stability ofβ-lactam antibiotics1). Cloxacillin showed strong synergy in combination with ampicillin or cephalosporins against typical cephalosporinase-producing bacteria, but not against penicillinase-producing bacteria. Analysis of the results indicated that the efficacy of a competitive inhibitor such as cloxacillin is greatly influenced by the following factors: the affinity or the inhibitor for the enzyme, the difference between the affinity or the inhibitor for the enzyme and that of the combined antibiotic for the enzyme, and the ability of the inhibitor to penetrate the bacterial outer membrane. It was also demonstrated that this information concerning the efficacy of an inhibitor could easily be obtained by using the set of bacterial stra1ns and the methods described.