Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis

Abstract

Coccidioides is an endemic fungus which causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016-2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months and 9 months post-transplant, and patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (p=0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.