Double-blind Placebo-Controlled Trial of Fluconazole to Prevent Candidal Infections in Critically Ill Surgical Patients

Ann Surg. 2001 Apr;233(4):542-8. doi: 10.1097/00000658-200104000-00010.


Objective: To evaluate the prophylactic use of enteral fluconazole to prevent invasive candidal infections in critically ill surgical patients.

Summary background data: Invasive fungal infections are increasingly common in the critically ill, especially in surgical patients. Although fungal prophylaxis has been proven effective in certain high-risk patients such as bone marrow transplant patients, few studies have focused on surgical patients and prevention of fungal infection.

Methods: The authors conducted a prospective, randomized, placebo-controlled trial in a single-center, tertiary care surgical intensive care unit (ICU). A total of 260 critically ill surgical patients with a length of ICU stay of at least 3 days were randomly assigned to receive either enteral fluconazole 400 mg or placebo per day during their stay in the surgical ICU at Johns Hopkins Hospital.

Results: The primary end point was the time to occurrence of fungal infection during the surgical ICU stay, with planned secondary analysis of patients "on-therapy" and alternate definitions of fungal infections. In a time-to-event analysis, the risk of candidal infection in patients receiving fluconazole was significantly less than the risk in patients receiving placebo. After adjusting for potentially confounding effects of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, days to first dose, and fungal colonization at enrollment, the risk of fungal infection was reduced by 55% in the fluconazole group. No difference in death rate was observed between patients receiving fluconazole and those receiving placebo.

Conclusions: Enteral fluconazole safely and effectively decreased the incidence of fungal infections in high-risk, critically ill surgical patients.

Publication types

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

MeSH terms

  • Aged
  • Antifungal Agents / therapeutic use*
  • Candidiasis / epidemiology
  • Candidiasis / prevention & control*
  • Critical Illness*
  • Double-Blind Method
  • Female
  • Fluconazole / therapeutic use*
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Surgical Procedures, Operative*
  • Time Factors


  • Antifungal Agents
  • Fluconazole