title: Inhibitors and inactivators of beta-lactamase from Mycobacterium fortuitum.
abstract: The inhibiting or inactivating effects of some beta-lactam antibiotics on beta-lactamase from Mycobacterium fortuitum were studied. Among all substrates tested, clavulanic acid and sulbactam were the strongest competitive inhibitors of the enzyme although the latter was slightly hydrolyzed. Imipenem and cefoxitin scarcely inhibited the beta-lactamase yet expressed good activity against the microorganism in vitro, suggesting that the effectiveness of these drugs on M. fortuitum might be due to high permeation through the cell wall. All the isoxazolylpenicillins tested and methicillin inactivated the enzyme of M. fortuitum by a first rapid phase of acylation followed by a steady-state process of enzyme reactivation (deacylation). Clavulanic acid and sulbactam showed Ki values for the enzyme inactivation closely corresponding to hematic concentrations achievable in vivo during antibiotic treatment.
authors.affiliation: Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Fattorini
authors.forename: G
authors.initials: G
authors.lastname: Amicosante
authors.forename: D
authors.initials: D
authors.lastname: Fiorentino
authors.forename: N
authors.initials: N
authors.lastname: Franceschini
authors.forename: L
authors.initials: L
authors.lastname: Di Marzio
authors.forename: A
authors.initials: A
authors.lastname: Oratore
authors.forename: G
authors.initials: G
authors.lastname: Orefici
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000201:enzymology*; D009170:Nontuberculous Mycobacteria / Q000201:enzymology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000302:isolation & purification; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases