Preventing Fungal Infections in Lung Transplant Recipients: Isavuconazole as Effective as Voriconazole but Better Tolerated

Adverse events led to premature discontinuation in 14% (21) of ISA patients and 53% (85) of patients receiving VOR prophylaxis.

Isavuconazole (ISA) was as effective as voriconazole (VOR) in preventing invasive fungal infections (IFI) in lung transplant recipients, and patients also appeared to tolerate the treatment better.

In findings presented at IDWeek 2019, investigators with the University of Pittsburgh sought to compare the efficacy and tolerability of 2 antifungal prophylaxis regimens instituted at their health care facility. From 2004 to 2015, VOR was the universal agent used in the lung transplant program. The switch to ISA was made in October 2015.

The research team reviewed all lung transplant recipients who received ISA and VOR prophylaxis between September 2013 and February 2018. Each agent was administered for 3 or 4 months following basiliximab and alemtuzumab induction, and patients were monitored for > 1 year post-transplant. Investigators relied on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria to define IFI.

A total of 310 lung transplant recipients were included in the study—149 of whom received ISA prophylaxis and 161 of whom received VOR prophylaxis. No major differences were recorded among the groups when it came to demographics, underlying diseases, single vs. double lung transplant, or induction therapy (alemtuzumab vs basiliximab).

Nine percent (14) of patients in the ISA group developed an IFI as of the 1-year post-transplant mark compared with 8% (13) of patients in the VOR group (p = 0.5). During prophylaxis, 5% (7) and 3% (5) of patients receiving ISA and VOR developed breakthrough IFI, respectively (p = 0.6; p = 0.4).

The breakthrough infections developed by patients receiving ISA included pneumonia (PNA, 2), endobronchial IFI (2), mediastinitis (1), chest wall IFI (1), and candidemia (1). Pathogens in this group included Aspergillus fumigatus (3; 2 with ISA minimum inhibitory concentration [MIC] = 0.5 µg/mL, 1 MIC = 1 µg/ml), black mold (1), and yeasts (3; 2 Candida glabrata, 1 C albicans).

Breakthrough infections developed by patients receiving VOR included PNA (2), endobronchial IFI (1), empyema (1), and chest wall IFI (1). The infections were due to A ustus, A niger, A lentulus, black mold, and Rhizopus spp (1 each).

Patients with IFI more often had a positive pre-lung transplant respiratory fungal culture (p = 0.01) and grade ≥ 3 ischemic reperfusion injury post-LT (p = 0.01).

Adverse events led to premature discontinuation in 14% (21) of ISA patients and 53% (85) of patients receiving VOR prophylaxis (p < 0.0001), with hepatoxicity more common in the VOR group (22%, 35) than ISA (5%, 7) (p < 0.0001). At the 1-year mark, IFI was considered an independent risk factor for death (p < 0.0001).

“ISA was as effective as VOR in preventing IFI in [lung transplant recipients], and significantly better tolerated,” investigators concluded. “Pre-[lung transplant] fungal culture positivity and grade ≥3 [ischemic reperfusion injury] post-LT were risk factors for development of IFI. IFI within 1-year post-[lung transplant] had significant impact on mortality.”

The study, Efficacy and Tolerability of Voriconazole (VOR) versus Isavuconazole (ISA) Prophylaxis (px) in Preventing Invasive Fungal Infections (IFI) in Lung Transplant Recipients (LTR), was presented on Thursday, October 3, 2019, at IDWeek in Washington, DC.