title: 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.
authors.affiliation: UMR-MD1, Aix-Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lavigne
authors.forename: Albert
authors.initials: A
authors.lastname: Sotto
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Nicolas-Chanoine
authors.forename: Nicole
authors.initials: N
authors.lastname: Bouziges
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
authors.forename: Anne
authors.initials: A
authors.lastname: Davin-Regli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D021902:Enterobacter aerogenes / Q000187:drug effects* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D005260:Female; D005602:France; D015964:Gene Expression Regulation, Bacterial; D006785:Hospitals, University; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D018272:Porins / Q000378:metabolism*; D012641:Selection, Genetic; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018272:Porins; D015378:Imipenem