Colonization and infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in ICU patients: what impact on outcomes and carbapenem exposure?

J Antimicrob Chemother. 2016 Apr;71(4):1088-97. doi: 10.1093/jac/dkv423. Epub 2016 Jan 10.

Abstract

Objectives: It remains uncertain whether colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-PE) affect the outcomes for ICU patients. Our objectives were to measure the effects of ESBL-PE carriage and infection on mortality, ICU length of stay (LOS) and carbapenem exposure in this population.

Methods: A cause-specific hazard model based on prospectively collected data was built to assess the impact of ESBL-PE colonization and infection on competing risks of death and ICU discharge at day 28 in a multicentre cohort of ICU patients. Carbapenem exposure during the ICU stay was compared between infected carriers, uninfected carriers and non-carriers.

Results: Among the 16,734 included patients, 594 (3.5%) were ESBL-PE carriers, including 98 (16.4%) with one or more ESBL-PE infections during the ICU stay. After adjustment for baseline and time-dependent confounders, ESBL-PE infections increased the probability of death at day 28 [adjusted cause-specific hazard ratio (aCSHR), 1.825, 95% CI 1.235-2.699, P = 0.0026] and the ICU LOS (aCSHR for discharge alive at day 28, 0.563, 95% CI 0.432-0.733, P < 0.0001). ESBL-PE carriage without infection extended the LOS (aCSHR, 0.623, 95% CI, 0.553-0.702, P < 0.0001), without affecting mortality (aCSHR, 0.906, 95% CI, 0.722-1.136, P = 0.3916). Carbapenem exposure increased in both infected and uninfected carriers when compared with non-carriers (627, 241 and 69 carbapenem days per 1000 patient days, respectively, P < 0.001).

Conclusions: ESBL-PE infections increased carbapenem consumption, LOS and day 28 mortality. ESBL-PE infections were rather infrequent in carriers; however, even ESBL-PE carriage without infection increased carbapenem exposure and delayed discharge, thereby amplifying the selective pressure and the colonization pressure in the ICU.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Cause of Death
  • Cross Infection*
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae Infections / drug therapy
  • Enterobacteriaceae Infections / epidemiology*
  • Enterobacteriaceae Infections / microbiology*
  • Female
  • Hospital Mortality
  • Humans
  • Intensive Care Units*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Outcome Assessment, Health Care
  • Population Surveillance
  • Proportional Hazards Models
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / genetics

Substances

  • Carbapenems
  • beta-Lactamases