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.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates

“…Several clinical studies supported the idea that cefepime is a reasonable option for invasive Enterobacter infections, particularly when the local prevalence of ESBL production is low (1,9,10). Recent susceptible breakpoint decreases for cefepime and the lack of need for ESBL detection in Enterobacteriaceae pathogens promote clinical use of cefepime at different dosages, based on MIC values (16).…”

Detection of Curli Biogenesis Genes Among Enterobacter cloacae Isolated From Blood Cultures

“…E. cloacae are often isolated from nosocomial infections, including pneumonia, urinary tract and bloodstream infections. Particularly, E. cloacae are responsible for 3% -6% of bloodstream infections, with approximate mortality rates ranging from 27% to 61% (2). Curli is a new class of bacterial surface structures which is expressed in E. cloacae, Escherichia coli and Salmonella spp.…”

In Vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime

“…On the other hand, AmpCs are not inhibited by inhibitors and do not hydrolyze FEP (1,(3)(4)(5). Therefore, FEP is suggested for the treatment of infections caused by AmpC producers (6)(7)(8).…”

“…(8)(9)(10)(11), Serratia marcescens (12), and Escherichia coli (13)(14)(15)(16)(17). These chromosomal extended-spectrum AmpC ␤-lactamases (cESACs) possess specific amino acid insertions, deletions, duplications, or substitutions in the H-10 helix (also named the R2-loop) that allow better accommodation and hydrolysis of FEP in the serine active site (1,4,11,14).…”

“…However, in only three cases involving infections due to Enterobacter spp., the initial FEP-susceptible (FEP s ) isolates were available for comparison with subsequent isolates expressing the cESAC variants after FEP treatment (8,9,11). To our knowledge, similar clinical cases have not yet been reported for strains producing pESAC enzymes.…”