Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial.
BACKGROUND
Among persons who receive solid organ transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective.


OBJECTIVE
To evaluate the efficacy and safety of prophylactic fluconazole in liver transplant recipients.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
University-affiliated transplantation center.


METHODS
212 liver transplant recipients who received fluconazole (400 mg/d) or placebo until 10 weeks after transplantation.


METHODS
Fungal colonization, proven superficial or invasive fungal infection, drug-related side effects, and death.


RESULTS
Fungal colonization increased in patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003).


CONCLUSIONS
Prophylactic fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.
Winston
D J
DJ
Department of Medicine, University of California, Los Angeles, Medical Center, 90095, USA.
Pakrasi
A
A
Busuttil
R W
RW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016572:Cyclosporine / Q000097:blood; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000382:microbiology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000517:prevention & control*; D016016:Proportional Hazards Models; D012640:Seizures / Q000139:chemically induced; D018709:Statistics, Nonparametric; D014202:Tremor / Q000139:chemically induced
D000935:Antifungal Agents; D016572:Cyclosporine; D015725:Fluconazole