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.

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Background Previous studies suggested that 6-12 months of universal or targeted azole prophylaxis is effective in preventing coccidioidomycosis for various organ transplant recipients. However, limited reports have described outcomes with longer prophylactic durations or using mold-active azoles in lung transplant recipients. Therefore, the purpose of this study was to investigate the incidence of coccidioidomycosis and tolerability of universal lifelong azole therapy in this high-risk patient population. Methods This study was an IRB-approved, retrospective cohort study of lung transplant recipients transplanted from January 2013 through December 2018. Adult recipients who were initiated on azole antifungal prophylaxis were eligible for inclusion. Recipients who died or received pre-emptive or definitive treatment for coccidioidomycosis during the transplant admission, or who received a previous transplant were excluded from the study. Outcomes were assessed through December 2019 or until the time of coccidioidomycosis diagnosis, death, second transplant, or date lost to follow-up. Results Of 544 lung transplants completed between 2013-2018, 493 patients were included with a mean age at transplant of 62 ± 11; 57.3% were male, 88.6% were white, and 77.1% developed post-transplant diabetes. The majority of patients ( > 70%) lived in Arizona or California pre-transplant and at 1-year post-transplant, and most patients had primary transplant indication of COPD and/or pulmonary fibrosis (~75%). One proven coccidioidomycosis infection and one new asymptomatic seropositivity for Coccidioides (incidence 0.2% each) occurred during the study period with median follow-up duration of 31 months. Azole therapy changes were common but permanent discontinuation was rare (1.4%) with reasons for azole switch varying among the different agents as summarized in Table 1. Table 1. Comparison of azole antifungal exposures and reasons for discontinuation Conclusion Lifelong azole antifungal prophylaxis was well-tolerated and effectively protected lung transplant recipients at an Arizona transplant center against coccidioidomycosis. Thus, in the absence of documented intolerance or contraindication, universal lifelong azole antifungal prophylaxis should be considered for all lung transplant recipients residing in a coccidioidomycosis-endemic area. Disclosures Michael D. Nailor, PharmD, BCPS (AQ-ID), AbbVie (Consultant)Merck (Consultant)Shionogi (Consultant) Rajat Walia, MD, Astellas (Consultant, Speaker)