Comparative study of five plasmid-mediated ceftazidimases isolated in Klebsiella pneumoniae

• Published in: Journal of antimicrobial chemotherapy 1989-10, Vol.24 (4), p.509-521
• Main Authors: Sirot, D., Chanal, C., Labia, R., Meyran, M., Sirot, J., Cluzel, R.
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Autoradiography; beta-Lactamases - genetics; beta-Lactamases - isolation & purification; beta-Lactamases - metabolism; Biological and medical sciences; Blotting, Southern; Ceftazidime - pharmacology; Culture Media; DNA, Bacterial - analysis; DNA, Bacterial - genetics; Drug Resistance, Microbial; Electrophoresis, Agar Gel; Isoelectric Focusing; Kinetics; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - enzymology; Klebsiella pneumoniae - genetics; Medical sciences; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Pharmacology. Drug treatments; Plasmids
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/24.4.509

Five plasmid-mediated β-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 selftransferable plasmids of 85 kb (CAZ-2, CAZ-3) or ≥ 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 β-lactamases hydrolysed all β-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 β-lactamases CAZ-4 and CAZ-5, MICs of aztreonam were the highest ( ≥ 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 β-lactams for CAZ-4 and CAZ-5 producers. The enzymes CAZ-1, CAZ-2 and CAZ-3 derived from TEM β-lactamase whereas CAZ-4 and CAZ-5 derived from SHV-1 enzyme.