Comparative study of five plasmid-mediated ceftazidimases isolated in Klebsiella pneumoniae.
Five plasmid-mediated beta-lactamases conferring a high level of resistance to ceftazidime were isolated from Klebsiella pneumoniae strains. These ceftazidimases (CAZ) differed in their isoelectric point (from 5.3 to 8.2) and were encoded by large self-transferable plasmids of 85 kb (CAZ-2, CAZ-3) or greater than or equal to 150 kb (CAZ-1, CAZ-4, CAZ-5). The 85 kb plasmids seemed closely related to pCFF04 encoding CTX-1 enzyme and belonged to the same incompatibility group 7 or M. These beta-lactamases hydrolysed all beta-lactams with the exception of cephamycins and carbapenems. For CAZ-1, CAZ-2 and CAZ-3 producers, MICs of ceftazidime (32-256 mg/l) were higher than MICs of cefotaxime (0.12-2 mg/l) and aztreonam (1-16 mg/l). For the strains producing the beta-lactamases CAZ-4 and CAZ-5, MICs of aztreonam were the highest (greater than or equal to 256 mg/l). The impaired activities of cephalosporins and monobactams were restored equally well by 2 mg/l of clavulanate, sulbactam and CL-298741 for CAZ-2 producing strains (wild type and transconjugant). Sulbactam (2 mg/l) had a lower protective effect than other inhibitors on ceftazidime for CAZ-1 and CAZ-3 producing K. pneumoniae. The protective effect of sulbactam (2 mg/l) was lower than that of the other inhibitors on all beta-lactams for CAZ-4 and CAZ-5 producers. The enzymes CAZ-1, CAZ-2 and CAZ-3 derived from TEM beta-lactamase whereas CAZ-4 and CAZ-5 derived from SHV-1 enzyme.
Sirot
D
D
Service be Bactériologie, Faculté de Médecine, Clermont-Ferrand, France.
Chanal
C
C
Labia
R
R
Meyran
M
M
Sirot
J
J
Cluzel
R
R
D001345:Autoradiography; D015139:Blotting, Southern; D002442:Ceftazidime / Q000494:pharmacology*; D003470:Culture Media; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D004352:Drug Resistance, Microbial; D004587:Electrophoresis, Agar Gel; D007525:Isoelectric Focusing; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D001618:beta-Lactamases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D003470:Culture Media; D004269:DNA, Bacterial; D002442:Ceftazidime; D001618:beta-Lactamases