89. Efficacy and Tolerability of Voriconazole (VOR) vs. Isavuconazole (ISA) Prophylaxis (px) in Preventing Invasive Fungal Infections (IFI) in Lung Transplant Recipients (LTR)

Abstract

BackgroundIFI is a significant complication following lung transplant (LT). VOR was universal antifungal px in our LT program from 2004 to October 2015, at which time px was changed to ISA. We compared the efficacy and tolerability of VOR vs. ISA px in LTR.MethodsWe reviewed all LTR from September 2013 to February 2018 who received VOR or ISA Px. The standard duration of px was 3 or 4 months following basiliximab and alemtuzumab induction, respectively. All patients were followed for ≥1 years post-Tx. IFI was defined by revised EORTC/MSG criteria.ResultsIn total, 310 LTR were included, 149 and 161 of whom received ISA and VOR px, respectively. There was no difference in demographics, underlying diseases, single vs. double LT, or induction therapy (alemtuzumab vs. basiliximab) between the 2 groups. At 1-year after LT, 9% (14) and 8% (13) of patients in ISA and VOR groups developed IFI, respectively (P = 0.5). 5% (7) and 3% (5) of patients developed breakthrough (BT) IFI during ISA and VOR px, respectively (P = 0.6; Figure 1, P = 0.4, Kaplan-–Meier). ISA BT included pneumonia (PNA, 2), endobronchial IFI (2), mediastinitis (1), chest wall IFI (1), and candidemia (1). ISA BT patients were infected with Aspergillus fumigatus (3; 2 with ISA MIC = 0.5 µg/mL, 1 MIC = 1 µg/mL), black mould (1), and yeasts (3; 2 C. glabrata, 1 C. albicans). VOR BT IFI included PNA (2), endobronchial IFI (1), empyema (1), and chest wall IFI (1). VOR BT IFIs were due to A. ustus, A. niger, A. lentulus, black mould, and Rhizopus spp (1 each). All Aspergillus VOR BT isolates exhibited VOR MIC ≥2 µg/mL. Patients with IFI were more likely to have positive pre-LT respiratory fungal culture (P = 0.01) and grade ≥3 ischemic reperfusion injury (IRI) post-LT (P = 0.01). VOR and ISA were prematurely discontinued in 53% (85) and 14% (21) of patients due to adverse events, respectively (P < 0.0001). Hepatotoxicity was more common with VOR (22%, 35) than ISA (5%, 7) (P < 0.0001). IFI was an independent risk factor for death at 1 year (Figure 2, P < 0.0001, Kaplan–Meier).ConclusionISA was as effective as VOR in preventing IFI in LTR, and significantly better tolerated. Pre-LT fungal culture positivity and grade ≥3 IRI post-LT were risk factors for the development of IFI. IFI within 1-year post-LT had a significant impact on mortality DisclosuresFernanda P. Silveira, MD, MS, FIDSA, Ansun: Grant/Research Support; Qiagen: Grant/Research Support; Shire: Grant/Research Support; Whiscon: Grant/Research Support.