title: Plasmid-mediated resistance to expanded-spectrum cephalosporins among Enterobacter aerogenes strains.
abstract: Resistance to expanded-spectrum cephalosporins commonly develops in Enterobacter aerogenes during therapy due to selection of mutants producing high levels of the chromosomal Bush group 1 beta-lactamase. Recently, resistant strains producing plasmid-mediated extended-spectrum beta-lactamases (ESBLs) have been isolated as well. A study was designed to investigate ESBL production among 31 clinical isolates of E. aerogenes from Richmond, Va., with decreased susceptibility to expanded-spectrum cephalosporins and a positive double-disk potentiation test. Antibiotic susceptibility was determined by standard disk diffusion and agar dilution procedures. Beta-lactamases were investigated by an isoelectric focusing overlay technique which simultaneously determined isoelectric points (pIs) and substrate or inhibitor profiles. Decreased susceptibility to cefotaxime, ceftazidime, and aztreonam (MIC range, 1 to 64 microg/ml) was detected and associated with resistance to gentamicin and trimethoprim-sulfamethoxazole. All strains produced an inducible Bush group 1 beta-lactamase (pI 83). Twenty-nine of the 31 isolates also produced an enzyme similar to SHV-4 (pI 7.8), while 1 isolate each produced an enzyme similar to SHV-3 (pI 6.9) and to SHV-5 (pI 8.2). The three different SHV-derived ESBLs were transferred by transconjugation to Escherichia coli C600N and amplified by PCR. Plasmid profiles of the clinical isolates showed a variety of different large plasmids. Because of the linkage of resistance to aminoglycosides and trimethoprim-sulfamethoxazole with ESBL production, it is possible that the usage of these drugs was responsible for selecting plasmid-mediated resistance to extended-spectrum cephalosporins in E. aerogenes. Furthermore, it is important that strains such as these be recognized, because they can be responsible for institutional spread of resistance genes.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Pitout
authors.forename: K S
authors.initials: KS
authors.lastname: Thomson
authors.forename: N D
authors.initials: ND
authors.lastname: Hanson
authors.forename: A F
authors.initials: AF
authors.lastname: Ehrhardt
authors.forename: P
authors.initials: P
authors.lastname: Coudron
authors.forename: C C
authors.initials: CC
authors.lastname: Sanders
mesh_terms: D002511:Cephalosporins / Q000494:pharmacology*; D003227:Conjugation, Genetic / Q000187:drug effects*; D004269:DNA, Bacterial / Q000032:analysis; D004352:Drug Resistance, Microbial / Q000235:genetics; D004754:Enterobacter / Q000145:classification / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics*; D016133:Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002511:Cephalosporins; D004269:DNA, Bacterial; C062759:beta-lactamase CAZ-5; D001618:beta-Lactamases