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

Rachel D Savage,François Lauzier,Claudio M Martin,Deborah Cook,Nick Daneman,John Muscedere,Asgar H Rishu,John Marshall,Richard Hall,Robert A Fowler,Steven Reynolds,Henry T Stelfox,Anand Kumar,Peter Dodek,Sean M Bagshaw,François Lamontagne,Lauralyn Mcintyre

doi:10.1371/journal.pone.0154944

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.

Highlights

Bloodstream infections (BSI) are associated with considerable morbidity and mortality, with an estimated burden of 575,000–677,000 total episodes and 79, 000–94,000 deaths per year in North America [1]
Some studies have shown that adequate initial empiric antimicrobial therapy improves the prognosis of critically ill patients who have BSIs, others have detected no such association
In our cohort of critically ill, bacteremic patients, 1 in 5 patients experienced a delay in initial adequate antimicrobial treatment, but we did not detect an overall association of inadequate treatment with hospital mortality, similar to other studies which have adjusted for key confounding variables [19,20,21]

Summary

Introduction

Bloodstream infections (BSI) are associated with considerable morbidity and mortality, with an estimated burden of 575,000–677,000 total episodes and 79, 000–94,000 deaths per year in North America [1]. Patients who have ICU-acquired BSIs have a 3-fold higher mortality than ICU patients who do not have BSIs [4]; the attributable cost of these infections is approximately $25,155 CAD per patient in survivors [5]. Some studies have shown that adequate initial empiric antimicrobial therapy improves the prognosis of critically ill patients who have BSIs, others have detected no such association (reviewed in Ramphal [6]). These conflicting findings have prompted a systematic review on the methods used to assess this relationship with the goal of providing recommendations to improve the internal and external validity of future studies [7]

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Discussion

Conclusion