*Purpose: Invasive fungal diseases (IFD) are a leading cause of infection related morbidity and mortality in lung transplant (LT) recipients. Data regarding outcomes of breakthrough IFD while on triazole prophylaxis are limited.

*Methods: A retrospective chart review was performed identifying LT recipients who had a positive diagnostic test for filamentous fungi (molds) from 2012-2017. IFD were defined by criteria established by the International Society for Heart and Lung Transplantation. Primary outcome was response to antifungal therapy defined by consensus criteria of Mycoses Study Group and European Organization for Research and Treatment of Cancer. Secondary outcomes involving chronic lung allograft dysfunction (CLAD) and rejection were assessed.

*Results: 553 LT recipients were identified. Of these, 122 (22%) had positive diagnostic testing for molds. There were 28 IFD (28/122 [23%]; 28/553 [5%]). Remaining 94 LT patients met criteria for colonization. All patients with IFD were receiving triazole prophylaxis. Median time to diagnosis of IFD was 166 days. Aspergillus was the most common pathogen (23/28 [82%] of IFD) followed by 1 case each of Ochroconis gallopava, Mucorales order, Alternaria species, and Purpureocillium lilacinum. Of those with IFD, 25 (89%) were changed to voriconazole (N=20) or posaconazole (N=5). No patient was switched to amphotericin B. A complete or partial response was observed in 19/28 (68%) IFD. Despite these favorable responses, 1-year all-cause mortality was significantly higher in those with IFD compared to those with fungal colonization (18 vs. 3%; p=0.015). There was no difference in development of CLAD between patients with IFD and those with fungal colonization (43 vs. 36%; p=0.52) and no difference in need for treatment of rejection in the subsequent 6 months after positive diagnostic testing for molds (36 vs. 30%; p=0.55). Interestingly, 44/94 (47%) who met criteria for colonization were switched to targeted therapy. Compared to those who were colonized and not switched to any targeted therapy, no difference in 1-year mortality was observed (2 vs. 4%; p=0.69).

*Conclusions: Favorable response to alternative triazole therapy was observed in LT recipients with breakthrough IFD on triazole prophylaxis. We did not observe abundant difficult-to-treat molds and azole resistance requiring amphotericin B. LT patients meeting criteria for colonization have similar positive outcomes whether they do or do not receive targeted therapy. This may pose an opportunity for antimicrobial stewardship.

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