C312 - Isavuconazole Prophylaxis in Heart Transplant Recipients to Prevent Invasive Fungal Infections

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Author Block: A. Kluener¹, A. R. Shields², P. Gillespie³, J. Hughes¹, T. Grome¹, R. Dowling¹, M. Javorski¹, J. Cafardi¹, G. Bhat¹, ¹The Christ Hospital, Cincinnati, OH, ²University of Cincinnati, The Christ Hospital, Cincinnati, OH, ³The Christ Hopital, Cincinnati, OH
*Purpose: Heart transplant recipients face a high risk of invasive fungal infections (IFIs), particularly from Candida and Aspergillus species. Conventional prophylaxis with voriconazole or posaconazole is frequently limited by hepatotoxicity, QTc prolongation, and drug interactions with calcineurin inhibitors. Isavuconazole (ISA) offers broad antifungal coverage with a more favorable safety and pharmacokinetic profile, including QT-shortening effects and fewer drug interactions. The purpose of this study is to assess the efficacy and tolerability of ISA prophylaxis for prevention of IFIs in adult heart transplant recipients.
*Methods: This was a single-center retrospective study in 53 consecutive adult orthotopic heart transplant (OHT) recipients who were initiated on systemic antifungal prophylaxis within 7 days post-transplant (n=30) compared to OHT patients who did not receive systemic antifungal prophylaxis (n=20). Three patients who did not meet 3-month post-transplant prophylaxis were excluded. After initial cases of aspergillosis, an aggressive screening protocol was implemented as well as use of ISA for prophylaxis. Analysis included incidence of IFI within 180 days, incidence of invasive aspergillosis, breakthrough fungal infections, survival, discontinuation of ISA due to adverse effects or cost (cost effectiveness and toxicity analysis pending), and calcineurin inhibitor and mycophenolate mofetil dose adjustments.
*Results: 50 patients received an OHT at our single center from November 2022 until August 2025 (30 received ISA). The patients without systemic prophylaxis were generally an earlier cohort of patients. Demographics and immunosuppression are in Table 1 below. Results and Outcomes are shown in Table 2. There were 4 cases of aspergillosis, all occurring in patients without ISA prophylaxis. Death due to aspergillosis occurred in 2 patients without systemic prophylaxis and no patients who received ISA and the deaths occurred at days 84 and 377 post-OHT.
*Conclusions: Isavuconazole prophylaxis in OHT patients provides effective IFI and mortality prevention with no cases of aspergillosis compared to 20% developing aspergillosis and 2 deaths in patients without isavuconazole prophylaxis and with less interactions and likely improved tolerability compared with traditional azoles. Prospective randomized data and full cost effectiveness analyses are warranted to define optimal duration and patient selection.