Azoles or Aerosols: Inhaled Amphotericin B Vs Triazole Antifungals for Prevention of Aspergillosis after Lung Transplant

Document Type

Conference Proceeding

Publication Date

3-6-2026

Publication Title

Am J Health Syst Pharm

Keywords

Pharmacology & Pharmacy

Abstract

Purpose: Fungal infections are a major cause of morbidity and mortality in lung transplant recipients, frequently due to Aspergillus spp. While antifungal prophylaxis is routinely recommended, the optimal strategy remains undefined. Inhaled amphotericin B (iAMB) provides direct pulmonary delivery with minimal systemic absorption, which may reduce adverse effects and improve drug distribution to poorly perfused regions of lung tissue post-transplant. Triazole antifungals offer systemic protection but are limited by toxicity and drug-drug interactions. This study aims to compare the safety and efficacy of iAMB with triazole antifungals for the prevention of invasive pulmonary aspergillosis (IPA) after lung transplantation. Methods: This single-center retrospective analysis included adults who underwent single or bilateral lung transplantation between January 2020 and September 2024 and received at least one month of either iAMB or triazole antifungal prophylaxis. The iAMB regimen consisted of lipid amphotericin B 25mg administered via nebulizer three times weekly for 60 days, then once weekly for 120 days. The dose was increased to 50mg if patients were intubated or had a tracheostomy. Triazole antifungal monotherapy was used when iAMB was not feasible. Exclusion criteria included multiorgan transplant, pre-transplant recipient colonization or donor cultures with Aspergillus, combination prophylaxis for over one month, or death during index admission. The primary outcome was IPA within 1 year. Secondary outcomes included non-Aspergillus invasive fungal infections (IFI), adverse effects, acute rejection, and all-cause mortality within 1 year of transplant. Results: Of the 85 patients included, 69 received iAMB and 15 received triazole antifungals. Baseline characteristics were similar between groups except for sex (male: 58.0% iAMB vs 93.3% triazole antifungals, p=0.010). Agents used in the triazole antifungal group included posaconazole (5/15, 33.3%), voriconazole (4/15, 26.7%), isavuconazonium sulfate (3/15, 20.0%), and itraconazole (3/15, 20.0%). IPA occurred in more patients in the iAMB group than the triazole antifungal group (11.6% vs 6.7%; p=1.000). Breakthrough IPA occurred on itraconazole in the triazole antifungal group. Non-Aspergillus IFI was more frequent with iAMB (26.1% vs 6.7%; p = 0.172), mainly related to empyema or surgical site infections (10/18, 55.6%) and caused by Candida species (14/18, 77.8%). Triazole antifungal therapy was discontinued more often (26.7% vs 2.9%; p=0.008), primarily due to adverse effects including gastrointestinal intolerance, elevated liver function enzymes, and visual disturbances associated with itraconazole and voriconazole. Respiratory adverse effects were uncommon with iAMB (3/69, 4.3%) and led to drug discontinuation in one patient. There were no significant differences in antibody mediated rejection, T-cell-mediated rejection, or all-cause mortality within 1 year. Conclusion: Both iAMB and triazole antifungal monotherapy were effective for IPA prophylaxis. Lack of systemic activity with iAMB may increase extrapulmonary IFI risk, though this could not be confirmed due to limited power. iAMB was better tolerated with fewer discontinuations. These findings highlight the need to balance tolerability and systemic coverage using patient-specific factors when selecting antifungal prophylaxis in lung transplant recipients.

Volume

83

First Page

S806

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