Experience with isavuconazole in lung transplant recipients with Aspergillus isolation in respiratory tract specimens: A multicenter, observational study.
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.
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).
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%.
ISA was well tolerated in LuTRs and proved to be effective for the treatment of invasive Aspergillus syndromes.
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).
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%.
ISA was well tolerated in LuTRs and proved to be effective for the treatment of invasive Aspergillus syndromes.
Authors
Silva Silva, López-Medrano López-Medrano, de Pablo de Pablo, Gutiérrez-Villanueva Gutiérrez-Villanueva, Fernández-Cruz Fernández-Cruz, Cano Cano, Ruiz-Arabi Ruiz-Arabi, Torre-Cisneros Torre-Cisneros, Monforte Monforte, Berastegui Berastegui, Len Len, Brandariz-Núñez Brandariz-Núñez, Sousa-Regueiro Sousa-Regueiro, Aguilar-Pérez Aguilar-Pérez, Fernández-Ruiz Fernández-Ruiz, Aguado Aguado
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