Development of resistance in Pseudomonas aeruginosa to broad-spectrum cephalosporins via step-wise mutations.
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 > or = 32 mg/L) to ceftazidime compared with none, five (31%) and ten (60%) strains becoming resistant to cefepime, cefpirome and cefotaxime (MIC > or = 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.
Gradelski
E
E
Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
Fung-Tomc
J
J
Huczko
E
E
Kessler
R E
RE
D002511:Cephalosporins / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics
D002511:Cephalosporins