title: Comparative study of a novel plasmid-mediated beta-lactamase, CAZ-2, and the CTX-1 and CAZ-1 enzymes conferring resistance to broad-spectrum cephalosporins.
abstract: Infections caused by strains of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins have been observed recently in hospitals in Clermont-Ferrand, France. beta-Lactam resistance resulted primarily from the plasmid-mediated, expanded-spectrum CTX-1 beta-lactamase. Furthermore, since 1987 some K. pneumoniae isolates more resistant to ceftazidime than to other cephalosporins have been observed. This new resistance phenotype was the result of the production of ceftazidimase CAZ-1 and, more recently, CAZ-2. As in CTX-1-producing strains, resistance to beta-lactams resulting from CAZ-2 was associated with resistance to aminoglycosides except gentamicin, sulfonamide, and tetracycline and was transferable to Escherichia coli by conjugation. Agarose gel electrophoresis of plasmid DNA from wild-type strains and transconjugants indicated that CAZ-2 production was mediated by a plasmid of 85 kilobases highly related to plasmid pCFF04 coding for CTX-1 beta-lactamase. The isoelectric point, close to 6.0, of this novel enzyme differed from those of CTX-1 and CAZ-1. Like CAZ-1, the CAZ-2 enzyme efficiently hydrolyzed ceftazidime and aztreonam, but as with CTX-1, cefotaxime gave the maximal reaction rate. For each expanded-spectrum beta-lactamase, the activity of broad-spectrum cephalosporins was restored by clavulanic acid or sulbactam.
authors.affiliation: Service de Bactériologie, Facultés de Médecine et Pharmacie, Clermont-Ferrand, France.
authors.forename: C M
authors.initials: CM
authors.lastname: Chanal
authors.forename: D L
authors.initials: DL
authors.lastname: Sirot
authors.forename: R
authors.initials: R
authors.lastname: Labia
authors.forename: A
authors.initials: A
authors.lastname: Petit
authors.forename: A
authors.initials: A
authors.lastname: Morand
authors.forename: J L
authors.initials: JL
authors.lastname: Sirot
authors.forename: R A
authors.initials: RA
authors.lastname: Cluzel
mesh_terms: D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000302:isolation & purification; D004352:Drug Resistance, Microbial / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D004926:Escherichia coli / Q000235:genetics; D005822:Genetic Vectors; D007525:Isoelectric Focusing; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D010957:Plasmids; D001618:beta-Lactamases / Q000032:analysis / Q000235:genetics*
chemical_list: D002511:Cephalosporins; D004269:DNA, Bacterial; D002442:Ceftazidime; C060182:beta-lactamase CAZ-2; C055184:beta-lactamase TEM-3; D001618:beta-Lactamases; C060181:beta-lactamase CAZ-1; D002439:Cefotaxime