title: Characterisation and clinical features of Enterobacter cloacae bloodstream infections occurring at a tertiary care university hospital in Switzerland: is cefepime adequate therapy?
abstract: Despite many years of clinical experience with cefepime, data regarding the outcome of patients suffering from bloodstream infections (BSIs) due to Enterobacter cloacae (Ecl) are scarce. To address the gap in our knowledge, 57 Ecl responsible for 51 BSIs were analysed implementing phenotypic and molecular methods (microarrays, PCRs for bla and other genes, rep-PCR to analyse clonality). Only two E. cloacae (3.5%) were ESBL-producers, whereas 34 (59.6%) and 18 (31.6%) possessed inducible (Ind-Ecl) or derepressed (Der-Ecl) AmpC enzymes, respectively. All isolates were susceptible to imipenem, meropenem, gentamicin and ciprofloxacin. Der-Ecl were highly resistant to ceftazidime and piperacillin/tazobactam (both MIC₉₀≥256 μg/mL), whereas cefepime retained its activity (MIC₉₀ of 3 μg/mL). rep-PCR indicated that the isolates were sporadic, but Ecl collected from the same patients were indistinguishable. In particular, three BSIs initially due to Ind-Ecl evolved (under ceftriaxone or piperacillin/tazobactam treatment) into Der-Ecl because of mutations or a deletion in ampD or insertion of IS4321 in the promoter. These last two mechanisms have never been described in Ecl. Mortality was higher for BSIs due to Der-Ecl than Ind-Ecl (3.8% vs. 29.4%; P=0.028) and was associated with the Charlson co-morbidity index (P=0.046). Using the following directed treatments, patients with BSI showed a favourable treatment outcome: cefepime (16/18; 88.9%); carbapenems (12/13; 92.3%); ceftriaxone (4/7; 57.1%); piperacillin/tazobactam (5/7; 71.4%); and ciprofloxacin (6/6; 100%). Cefepime represents a safe therapeutic option and an alternative to carbapenems to treat BSIs due to Ecl when the prevalence of ESBL-producers is low.
authors: Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, Get rid of Postfach 61, CH-3010 Bern, Switzerland.
authors: Markus
authors: M
authors: Hilty
authors: Parham
authors: P
authors: Sendi
authors: Salome N
authors: SN
authors: Seiffert
authors: Sara
authors: S
authors: Droz
authors: Vincent
authors: V
authors: Perreten
authors: Andrea M
authors: AM
authors: Hujer
authors: Robert A
authors: RA
authors: Bonomo
authors: Kathrin
authors: K
authors: Mühlemann
authors: Andrea
authors: A
authors: Endimiani
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D016972:Enterobacter cloacae / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D005260:Female; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D007239:Infections / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058889:Molecular Typing; D016019:Survival Analysis; D013557:Switzerland; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D001618:beta-Lactamases