title: On the kinetic interaction between ceftriaxone and some beta-lactamases.
abstract: The activity of beta-lactamases from Citrobacter diversus ULA-27 on ceftriaxone, a widely recognized third-generation cephalosporin, has been examined and compared to the activity of various other beta-lactamases from different sources. Ceftriaxone (Roche S.p.A. Milan) was found to be resistant to hydrolysis by beta-lactamases from Enterobacter cloacae and Bacillus cereus, but susceptible to beta-lactamases from Mycobacterium fortuitum strain Cow 18 and, mostly, to beta-lactamases from various strains of Citrobacter diversus. Derivatives with substituents in the 3-position of ceftriaxone, namely cefotaxime (Roussel Maestretti S.p.A., Milan) and ceftizoxime (Farmitalia Carlo Erba, Milan), were much less susceptible to hydrolysis by C. diversus ULA-27 enzymes (22 and 6% of ceftriaxone hydrolysis, respectively), the hydrolysis rate being paralleled by differences in MIC values. Ceftriaxone inhibited the activity of E. cloacae beta-lactamases toward cefazolin as substrate, but the inhibition was totally abolished by preincubation of ceftriaxone with the enzyme before addition of the substrate. Overall, the data point to a relevance of C. diversus ULA-27 beta-lactamases in the mechanism of resistance of this strain to the various third-generation cephalosporins.
authors.affiliation: Institute of Biochemistry, University of L'Aquila, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Amicosante
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.forename: N
authors.initials: N
authors.lastname: Franceschini
authors.forename: B
authors.initials: B
authors.lastname: Oliva
authors.forename: B
authors.initials: B
authors.lastname: Segatore
authors.forename: A
authors.initials: A
authors.lastname: Oratore
mesh_terms: D001407:Bacillus / Q000187:drug effects / Q000201:enzymology*; D002443:Ceftriaxone / Q000378:metabolism* / Q000494:pharmacology; D002954:Citrobacter / Q000187:drug effects / Q000201:enzymology; D004754:Enterobacter / Q000187:drug effects / Q000201:enzymology; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D009161:Mycobacterium / Q000201:enzymology*; D009170:Nontuberculous Mycobacteria / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors; D001618:beta-Lactamases / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002443:Ceftriaxone; D001618:beta-Lactamases