Universal lifelong fungal prophylaxis and risk of coccidioidomycosis in lung transplant recipients living in an endemic area

Background Lung transplant recipients residing in the endemic region are vulnerable to severe morbidity and mortality from Coccidioides. As infection risk persists beyond the first post-transplant year, investigations evaluating extended prophylaxis durations are needed. The purpose of this study is to assess the incidence of coccidioidomycosis among lung transplant recipients receiving universal lifelong azole antifungal prophylaxis. Methods Recipients transplanted 2013-2018 and initiated on azole antifungal prophylaxis at a lung transplantation center in Arizona were included and followed through 2019 or until death, second transplant, or loss to follow-up. Recipients who died or received treatment for coccidioidomycosis during the transplant admission, or who had received a previous transplant were excluded. The primary outcome was proven or probable coccidioidomycosis with new asymptomatic seropositivity assessed secondarily. Results A total of 493 lung transplant recipients were included, with 82% initiated on itraconazole prophylaxis, 9.3% on voriconazole, and 8.5% on posaconazole. Mean age at transplant was 62 years, 77% were diabetic, and 8% were seropositive for Coccidioides pre-transplant. After a median follow-up of 31 months, one proven infection and one case of new asymptomatic seropositivity (1/493 each, 0.2% incidence) occurred during the study period. The single coccidioidomycosis case occurred 5 years post-transplant in a patient who had azole prophylaxis stopped several months prior. Although within-class switches were common throughout the study period, permanent discontinuation of azole prophylaxis was rare (1.4% at end of follow-up). Conclusions Universal lifelong azole prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients residing in endemic regions.