Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes

J Antimicrob Chemother. 2012 Mar;67(3):707-14. doi: 10.1093/jac/dkr511. Epub 2011 Dec 18.

Abstract

Objectives: We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival.

Methods: Patients ≥16 years of age with first episodes of candidaemia during 2001-09 were included. Clinical data were collected retrospectively, including time to appropriate antifungal therapy and patient survival.

Results: The study population included 446 patients [243 (54%) female, mean age 53 years] with candidaemia, 380 (85%) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50%) followed by Candida glabrata (99, 22%), Candida parapsilosis (59, 13%), Candida tropicalis (48, 11%) and Candida krusei (6, 1%). Appropriate antifungal therapy consisted of fluconazole (177, 40%), an echinocandin (125, 28%), amphotericin B (41, 9%) and voriconazole (6, 1%); 97 (22%) failed to receive appropriate antifungal therapy. The 30 day mortality was 34% (151/446) and there was no clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30 day survival. On multivariable Cox regression, increased APACHE II score [hazard ratio (HR) 1.11, 95% CI 1.09-1.13, P<0.001], cirrhosis (HR 2.15, 95% CI 1.48-3.13, P<0.001) and HIV infection (HR 2.03, 95% CI 1.11-3.72, P=0.02) were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received ≥24 h of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 h of a positive blood culture being drawn (30 day mortality for early treatment: 27% versus 40%, P=0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95% CI 1.01-1.98, P=0.045).

Conclusions: Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects*
  • Candida albicans / isolation & purification
  • Candidemia / drug therapy*
  • Candidemia / mortality
  • Candidemia / pathology
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Antifungal Agents