Characteristics of aztreonam as a substrate, inhibitor and inducer for ².-lactamases

Abstract

Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined ²-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of ²-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A ²-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range. However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A ²-lactamases. Aztreonamwas extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the ²-lactamase. Whilethe MICs of aztreonam in the cases of the constitutive producers of class C ²-lactamaseswere evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable ²-lactamgave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonasaeruginosa, aztreonam was confirmed to be a poor inducer of ²-lactamases. © 1990, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.