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An adaptive response of Enterobacter aerogenes to imipenem: regulation of porin balance in clinical isolates.

Abstract
Imipenem (IPM) is a carbapenem antibiotic frequently used in severe hospital infections. Several reports have mentioned the emergence of resistant isolates exhibiting membrane modifications. A study was conducted between September 2005 and August 2007 to survey infections due to Enterobacter aerogenes in patients hospitalised in a French university hospital. Resistant E. aerogenes clinical isolates obtained from patients treated with IPM and collected during the 3 months following initiation of treatment were phenotypically and molecularly characterised for β-lactamases, efflux pumps activity and outer membrane proteins. Among the 339 patients infected with E. aerogenes during the study period, 41 isolates (12.1%) were resistant to extended-spectrum cephalosporins and 17 patients (5.0%) were treated with IPM. The isolates from these 17 patients presented TEM-24 and basal efflux expression. Following IPM treatment, an IPM-intermediate-susceptible (IPM-I) isolate emerged in 11 patients and an IPM-resistant (IPM-R) isolate in 6 patients. A change in the porin balance (Omp35/Omp36) was observed in IPM-I isolates exhibiting ertapenem resistance. Finally, a porin deficiency (Omp35 and Omp36 absence) was detected in IPM-R isolates associated with efflux pump expression. This study indicates that the alteration in porin expression, including the shift of porin expression and lack of porins, contribute to the E. aerogenes adaptive response to IPM treatment.
AuthorsJean-Philippe Lavigne, Albert Sotto, Marie-Hélène Nicolas-Chanoine, Nicole Bouziges, Jean-Marie Pagès, Anne Davin-Regli
JournalInternational journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 41 Issue 2 Pg. 130-6 (Feb 2013) ISSN: 1872-7913 [Electronic] Netherlands
PMID23280442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Chemical References
  • Anti-Bacterial Agents
  • Porins
  • Imipenem
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents (pharmacology)
  • Child
  • Child, Preschool
  • Drug Resistance, Bacterial
  • Enterobacter aerogenes (drug effects, isolation & purification)
  • Enterobacteriaceae Infections (microbiology)
  • Female
  • France
  • Gene Expression Regulation, Bacterial
  • Hospitals, University
  • Humans
  • Imipenem (pharmacology)
  • Infant
  • Infant, Newborn
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation
  • Porins (metabolism)
  • Selection, Genetic
  • Young Adult

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