Development of resistance in Pseudomonas aeruginosa to broad-spectrum cephalosporins via step-wise mutations

• Published in: Journal of antimicrobial chemotherapy 1993-11, Vol.32 (suppl-B), p.75-80
• Main Authors: Gradelski, Elizabeth, Fung-Tomc, Joan, Huczko, Elizabeth, Kessler, Robert E.
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cephalosporins - pharmacology; Drug Resistance, Microbial - genetics; Humans; Medical sciences; Microbial Sensitivity Tests; Mutation; Pharmacology. Drug treatments; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas Infections - microbiology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/32.suppl_B.75

Step-wise resistance to cefepime, ceftazidime, cefotaxime, and cefpirome were determined for 16 Pseudomonas aeruginosa strains by daily transfer for 7 days to fresh media containing two-fold serial dilution of antibiotic. By the third transfer 4 of 16 strains (25%) were resistant (MIC ≥ 32 mg/L) to ceftazidime compared with none, five (31%) and ten (60%) strains becoming resistant to cefepime, cefpirome and cefotaxime (MIC ≥ 64 mg/L), respectively. At the end of the 7 day serial transfer, only four (25%) of the 16 strains were resistant to cefepime, in contrast to nine (56%) cefpirome resistant, 12 (75%) ceftazidime resistant and 13 (81%) cefotaxime resistant. These results are consistent with the infrequent, single-step development of resistance to cefepime, and this may also explain the frequent cefepime susceptibility of cefotaxime/ceftazidime-resistant clinical isolates of P. aeruginosa.