A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections

Clin Infect Dis. 2015 Dec 1;61(11):1671-8. doi: 10.1093/cid/civ707. Epub 2015 Aug 13.

Abstract

Background: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy.

Methods: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression.

Results: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result.

Conclusions: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC.

Clinical trials registration: NCT01122368.

Keywords: Preemptive antifungal therapy; gastrointestinal surgery; intensive care; invasive candidiasis; micafungin.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antifungal Agents / administration & dosage
  • Biomarkers / blood
  • Candidiasis, Invasive / drug therapy
  • Candidiasis, Invasive / prevention & control*
  • Double-Blind Method
  • Echinocandins / administration & dosage
  • Female
  • Humans
  • Intensive Care Units
  • Intraabdominal Infections / drug therapy
  • Intraabdominal Infections / prevention & control
  • Intraabdominal Infections / surgery*
  • Lipopeptides / administration & dosage
  • Male
  • Micafungin
  • Middle Aged
  • Postoperative Complications / prevention & control*
  • Pre-Exposure Prophylaxis*
  • Proteoglycans
  • Young Adult
  • beta-Glucans / blood

Substances

  • Antifungal Agents
  • Biomarkers
  • Echinocandins
  • Lipopeptides
  • Proteoglycans
  • beta-Glucans
  • polysaccharide-K
  • Micafungin

Associated data

  • ClinicalTrials.gov/NCT01122368