The Effect of Inadequate Initial Empiric Antimicrobial Treatment on Mortality in Critically Ill Patients with Bloodstream Infections: A Multi-Centre Retrospective Cohort Study

PLoS One. 2016 May 6;11(5):e0154944. doi: 10.1371/journal.pone.0154944. eCollection 2016.

Abstract

Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70-1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05-7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anti-Infective Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / mortality
  • Canada
  • Female
  • Fungemia / drug therapy*
  • Fungemia / mortality
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Retrospective Studies

Substances

  • Anti-Infective Agents

Grants and funding

This multicentre observational study was supported by operating funds from the Ontario Ministry of Health and Long-Term Care Academic Health Sciences Alternate Funding Plan Innovation Fund Award (https://ifpoc.org/), and a research grant of Physician Services Incorporated of Ontario (http://psifoundation.org/ForApplicants/HealthResearchGrants.php). ND is supported by a Clinician Scientist salary award from the Canadian Institute of Health Research (http://www.cihr-irsc.gc.ca). DC is a Chair of the Canadian Institutes of Health Research. RAF is supported by a Clinician Scientist salary award from the Heart and Stroke Foundation (Ontario). F. Lauzier and F. Lamontagne hold a career award from the Fonds de recherche du Québec-Santé. SMB holds a Canada Research Chair in Critical Care Nephrology and an Independent Investigator Award from Alberta Innovates – Health Solution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.