title: Characteristics of aztreonam as a substrate, inhibitor and inducer for beta-lactamases.
abstract: Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined beta-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of beta-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A beta-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 beta-lactamases. Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the beta-lactamase. While the MICs of aztreonam in the cases of the constitutive producers of class C beta-lactamases were evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable beta-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of beta-lactamases.
authors.affiliation: Division of Microbial Chemistry, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Saitoh
authors.forename: M
authors.initials: M
authors.lastname: Nemoto
authors.forename: A
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Sawai
mesh_terms: D000560:Amdinocillin / Q000494:pharmacology; D001398:Aztreonam / Q000378:metabolism* / Q000494:pharmacology; D002510:Cephalosporinase / Q000096:biosynthesis; D002511:Cephalosporins / Q000494:pharmacology; D002954:Citrobacter / Q000201:enzymology; D004357:Drug Synergism; D004790:Enzyme Induction; D004926:Escherichia coli / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology*; D006868:Hydrolysis; D010405:Penicillinase / Q000096:biosynthesis; D011514:Proteus vulgaris / Q000201:enzymology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D002510:Cephalosporinase; D010405:Penicillinase; D001618:beta-Lactamases; D001398:Aztreonam; D000560:Amdinocillin