Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients

Objective: To evaluate the efficacy and safety of intravenous fluconazole f or the prevention of intra-abdominal Candida infections in high-risk surgic al patients. Design: Randomized, prospective, double-blind, placebo-controlled study. Setting: Two university-affiliate hospitals in Switzerland. Patients: Forty-nine surgical patients with recurrent gastroin-testinal per forations or anastomotic leakages. Interventions: Prophylaxis with intravenous fluconazole (400 mg per day) or placebo continued until resolution of the underlying surgical condition. Measurements and Main Results.. Patients were evaluated daily, and specimen s for culture were obtained three times per week during prophylaxis. The pr imary study end points were the frequency of and the time to intra-abdomina l Candida infections. Secondary end points were the frequency of candidiasi s (intra-abdominal and extra-abdominal) and the emergence or persistence of Candida colonization. Among patients who were not colonized at study entry , Candida was isolated from surveillance cultures during prophylaxis in 15% of the patients in the fluconazole group and in 62% of the patients in the placebo group (relative risk, 0.25; 95% confidence interval, 0.07 to 0.96; p = .04). Candida peritonitis occurred in one of 23 patients (4%) who rece ived fluconazole and in seven of 20 patients (35%) who received placebo (re lative risk, 0.12; 95% confidence interval, 0.02 to 0.93; p = .02). In addi tion, one catheter-related Candida albicans sepsis occurred in a fluconazol e-treated patient. Thus, overall, candidiasis developed in two fluconazole patients and seven placebo patients (relative risk, 0.25; 95% confidence in terval, 0.06 to 1.06; p = .06). C. albicans accounted for 87% of the Candid a species isolated before or during prophylaxis, and all C albicans strains were susceptible to fluconazole, Fluconazole was well tolerated, and adver se events occurred at similar frequencies in both treatment groups. Conclusions: Fluconazole prophylaxis prevents colonization and invasive int ra-abdominal Candida infections in high-risk surgical patients.