The purpose of this study was to assess if utilizing fluconazole for prophylaxis of invasive fungal infections (IFIs) in high risk liver transplant recipients is effective.

This retrospective study included patients who received a liver transplant between January 2013 and November 2015 at Emory University Hospital. Patients in the fluconazole group were excluded if they received antifungal therapy prior to transplantation or less than one week of prophylaxis post-transplant. Patients are determined to be high risk if they exhibit at least one to two of the following risk factors: re-operation, renal dysfunction, intra-operative transfusion requirements greater than ten units, broad spectrum antibiotic use within 14 days of transplant, or biliary leakage.

Fluconazole 400 mg daily, with renal adjustments, is used for 21 days in patients meeting high risk criteria. The primary outcome was the difference in the rate of clinically relevant fungal infections within six months of transplantation between those who received fluconazole prophylaxis and those who did not. The secondary outcomes were incidence of inherently resistant fungal infections, acute cellular rejection, hospitalizations and mortality within one year, and supratherapeutic calcineurin inhibitor levels.

After transplant, 106 patients received fluconazole, of which 47 met inclusion criteria and were compared to a control group of 47 patients. In the fluconazole group, 10.6% of patients experienced an IFI compared to 2.1% in the no fluconazole group (p=0.204). There was no statistically significant difference in fluconazole resistant fungal infections, 8.5% in the fluconazole group versus 0% in the no fluconazole group (p=0.117). A difference was seen in micafungin use, 14.9% versus 0% (p=0.012) and readmission, 83% versus 44.7% (p<0.001), respectively. No difference was seen in mortality. Of patients on tacrolimus, 55.6% in the fluconazole group had a tacrolimus level of greater than 15 ng/mL compared to 23.4% in the no fluconazole group (p=0.003).

The incidence of IFI post-liver transplant in those with pre-existing risk factors who have received fluconazole prophylaxis has been reported to be 6%, which is similar to the 10.6% observed in this study. While potentially effective in preventing fungal infections, fluconazole use was associated with supratherapeutic tacrolimus levels and a higher rate of inherently resistant fungal infections, although not statistically significant.

CITATION INFORMATION: Roach K., Todd S., Lyon M., Subramanian R. Impact of Fluconazole Prophylaxis on Fungal Infections in Liver Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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