*Purpose: IFI is a significant complication following lung transplant (LT). VOR was universal antifungal (AF) px in our LT program from 2004-09/2015, at which time px was changed to ISA. We compared efficacy and tolerability of VOR vs ISA px in LTR

*Methods: We reviewed all LTR from 09/2013-02/2018 who received VOR or ISA px post-Tx. The standard duration of px was 3 or 4 months following basiliximab and alemtuzumab induction, respectively. All patients (pts) were followed for ≥ 1-yr post-Tx. IFI was defined by revised EORTC/MSG criteria

*Results: 300 LTR were included in the analysis. 144 and 156 LTR received ISA and VOR px, respectively. There was no difference in underlying diseases, single vs double LT, or induction therapy (alemtuzumab or basiliximab) between the 2 groups. At 1-yr after LT, the IFI prevalence rate was 8% in both the ISA (11/144, 95% CI 3.2- 12.0%) and VOR (12/156, 95% CI 3.5-11.9%) groups (p=1.0). 70% (16/23) of IFIs were invasive mold infection (IMI, 8 in each group) and 30% (7/23) were invasive yeast infection (IYI, 3 and 4 in ISA and VOR groups, respectively). The median times to IMI and IYI were 2.4 months (0.36 to 11.4) and 2.7 months (0.2 to 5.6), respectively (p=0.13). 3% of pts in each group (ISA 5/144 and VOR 5/156) had breakthrough (BT) IFI (p=1.0). 70% (7/10) of BT IFI were due to molds (Cladophialophora boppi, Aspergillus fumigatus, histopathology with fungal hyphae in ISA group and A. fumigatus, Cladosporium spp, A. niger, Rhizopus microsporus in VOR group), and 30% (3/10) were due to yeasts (2 Candida glabrata in ISA group and 1 C. glabrata + C. parapsilosis co-infection in VOR group). ISA BT IFI included endobronchial infections (3) and candidemia (2). VOR BT IFIs included chest wall infections (3), pneumonia (1) and empyema (1). Possible etiologies for px failure were reduced ISA susceptibility in ISA group and sub-therapeutic VOR level in VOR groups. The African American race, positive mold culture at Tx, grade 4 ischemic reperfusion injury, packed red blood cell transfusions during Tx and cold ischemic time were significantly associated with BT IFI. ISA and VOR were prematurely discontinued in 10% and 36% due to side effects, respectively (p=0.0001). Hepatotoxicity and neurotoxicity were more common in VOR (18% and 10% respectively) than ISA (5%, 0% respectively) (both p<0.0001). AF px ≥90 days was associated with less IFI (p=0.04). 1-year mortality rates were 10% and 12% in ISA and VOR groups, respectively (p=0.54). IFI was an independent risk factor for death. Patients with IFI had significantly longer hospital stay than those without IFI (p=0.0005)

*Conclusions: Isavuconazole is a reasonable option for antifungal prophylaxis following lung transplantation. Multi-center clinical trials are needed to define optimal antifungal prophylaxis strategies for lung transplant recipients

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