title: Activity of cefepime against ceftazidime- and cefotaxime-resistant gram-negative bacteria and its relationship to beta-lactamase levels.
abstract: One hundred clinical isolates resistant to ceftazidime and/or cefotaxime were examined for susceptibility to cefepime. The most frequently encountered ceftazidime-cefotaxime-resistant strains belonged to the genera Enterobacter, Pseudomonas, and Citrobacter. Among these strains, 92% were resistant to cefoperazone, 91% were resistant to cefotaxime, 84% were resistant to ceftazidime, and 6% were resistant to cefepime. Of the members of the family Enterobacteriaceae, 57% were resistant to ceftriaxone. The six strains resistant to cefepime were all Pseudomonas aeruginosa and were resistant to both cefotaxime and ceftazidime. Cefepime-resistant P. aeruginosa strains had exceptionally high levels of beta-lactamase activity, higher than the levels found in strains resistant to ceftazidime but susceptible to cefepime. The beta-lactamases from the cefepime-resistant strains were type I (Richmond-Sykes), were constitutively produced, and did not have increased affinity or hydrolytic activity for cefepime. Thus, cefepime was active against most gram-negative bacteria which have developed resistance to the broad-spectrum cephalosporins, and resistance to cefepime in P. aeruginosa appears to be associated with higher beta-lactamase levels than in cefepime-susceptible strains.
authors.affiliation: Department of Microbiology, Bristol-Myers Company, Wallingford, Connecticut 06492.
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
authors.forename: T J
authors.initials: TJ
authors.lastname: Dougherty
authors.forename: F J
authors.initials: FJ
authors.lastname: DeOrio
authors.forename: V
authors.initials: V
authors.lastname: Simich-Jacobson
authors.forename: R E
authors.initials: RE
authors.lastname: Kessler
mesh_terms: D001424:Bacterial Infections / Q000382:microbiology; D001426:Bacterial Proteins / Q000378:metabolism; D000077723:Cefepime; D002439:Cefotaxime / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002511:Cephalosporins / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004790:Enzyme Induction / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002511:Cephalosporins; D000077723:Cefepime; D002442:Ceftazidime; D001618:beta-Lactamases; D002439:Cefotaxime