Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination.
OBJECTIVE
Infections caused by Candida spp. are a major cause of morbidity and mortality in critically ill patients and usually develop from endogenous colonization. We assessed the effectiveness of adding fluconazole to a selective digestive decontamination regimen to prevent candidal infections.


METHODS
We performed a prospective, randomized, double-blind, placebo-controlled trial among medical and surgical intensive care unit patients at a large university hospital.


METHODS
All adult patients mechanically ventilated for at least 48 h with an expectation to remain so for at least an additional 72 h, and receiving selective decontamination of the digestive tract.


METHODS
Patients were randomly assigned fluconazole 100 mg daily (n=103) or placebo (n=101).


RESULTS
Candida infections occurred less frequently in the fluconazole group (5.8%) than in the placebo group (16%; rate ratio 0.35; Cl(95) 0.11-0.94). Some 90% of candidemia episodes occurred in the placebo group (rate ratio for fluconazole use 0.10; Cl(95) 0.02-0.74). The rate of treatment failure, development of candidal infection, or increased colonization, was 32% in the fluconazole group and 67% in the placebo group (P<0.001). Crude in-hospital mortality was similar in the two groups (39% fluconazole vs. 41% placebo).


CONCLUSIONS
Prophylactic use of fluconazole in a selected group of mechanically ventilated patients at high risk for infection reduces the incidence of Candida infections, in particular candidemia.
Garbino
Jorge
J
Division of Infectious Diseases, Department of Internal Medicine, University of Geneva Hospitals, 1211 Geneva 14, Switzerland.
Lew
Daniel P
DP
Romand
Jacques-A
JA
Hugonnet
Stéphane
S
Auckenthaler
Raymond
R
Pittet
Didier
D
D000368:Aged; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000382:microbiology / Q000517:prevention & control*; D016009:Chi-Square Distribution; D016638:Critical Illness; D003666:Decontamination / Q000379:methods; D004064:Digestive System / Q000382:microbiology; D004311:Double-Blind Method; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D009355:Neomycin / Q000627:therapeutic use; D011113:Polymyxins / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
D000935:Antifungal Agents; D011113:Polymyxins; D014640:Vancomycin; D015725:Fluconazole; D009355:Neomycin