Experience with isavuconazole in lung transplant recipients with Aspergillus isolation in respiratory tract specimens: A multicenter, observational study

Background: Aspergillus is a life-threatening opportunistic pathogen in lung transplant recipients (LuTRs). Isavuconazole (ISA) is a broad-spectrum triazole with favorable pharmacokinetics and safety profile. The clinical experience with ISA in LuTRs, however, is still limited. Methods: We performed an ambispective observational study from June 2019 to June 2024 in 5 Spanish centers. Adult LuTRs with isolation of Aspergillus spp. in respiratory tract specimens and indication of ISA therapy (either for the treatment of invasive pulmonary aspergillosis [IPA] or tracheobronchial aspergillosis [TBA] or for preemptive therapy) were eligible. The safety outcome comprised the occurrence of treatment-emergent adverse events (trAEs) and the need for modification of tacrolimus dose. Effectiveness outcomes included clinical, mycological, and radiological response at the end of treatment (EoT). Results: Overall, 50 LuTRs were included. ISA was administered for a median duration of 101 days (interquartile range: 27-161) for the treatment of IPA (18 [36.0%]) or TBA (27 [54.0%]) and as preemptive therapy (5 [10.0%]). The incidence rates of any trAE and trAE requiring premature ISA discontinuation were 24.0% and 10.0%, respectively. Most patients (35 [70.0%]) completed the planned course of therapy. Tacrolimus daily dose was reduced by a median of one-third in half of the patients (26/48 [54.2%]). Clinical, mycological, and radiological responses at EoT among were achieved in 66.7%, 84.2%, and 64.3% of evaluable patients, respectively. Aspergillosis-attributable mortality at the end of follow-up was 12.0%. Conclusions: ISA was well tolerated in LuTRs and proved to be effective for the treatment of invasive Aspergillus syndromes.