Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum β-lactamase-producing Enterobacteriaceae

Int J Antimicrob Agents. 2018 Nov;52(5):577-585. doi: 10.1016/j.ijantimicag.2018.06.018. Epub 2018 Jun 30.


Purpose: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E.

Methods: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts.

Results: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. β-lactam/β-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy.

Conclusions: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.

Keywords: carbapenems; extended-spectrum ß-lactamases; sepsis; septic shock; ß-lactam/ß-lactamase inhibitors.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use
  • Decision Support Techniques*
  • Drug Therapy, Combination
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / diagnosis*
  • Enterobacteriaceae Infections / drug therapy
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / mortality*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Sepsis / diagnosis*
  • Sepsis / drug therapy
  • Sepsis / microbiology
  • Sepsis / mortality*
  • Survival Analysis
  • Treatment Outcome
  • beta-Lactamase Inhibitors / therapeutic use
  • beta-Lactamases / metabolism*
  • beta-Lactams / therapeutic use


  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • beta-Lactamases