Isavuconazole in Lung Transplant Recipients: A Retrospective Case Series to Appraise Clinical Efficacy

Purpose Lung transplant patients are at increased susceptibility to fungal infections. Isavuconazole, a triazole anti-fungal with broad-spectrum activity against medically important fungal pathogens, received a marketing authorisation in the U.K. in 2015. The use of isavuconazole has advantages over voriconazole and posaconazole as it presents a more favourable toxicity profile. There is some, but very limited data appraising its clinical effectiveness, but this is predominantly in the context of anti-fungal prophylaxis. This research looks to review the experience of a single centre by reviewing clinical outcome data in lung transplant patients who received isavuconazole as treatment for invasive fungal infections. Methods We performed a single-centre retrospective study to describe the clinical outcome data from patients commenced on treatment with Isavuconazole for invasive fungal infections between October 2016 and December 2019. We assessed outcomes at 3 months and 6 months post-commencement of treatment including patient reported improvement of presenting symptoms, stability or improvement in lung function (FEV1), radiological improvement or histocytoloical resolution on bronchoscopy (including galactomannan and persistent invasion of fungal hyphae/pseudohyphae or features in keeping with fungal infection). Results Fifty patients were treated with isavuconazole during the study period. Eleven patients were excluded from analysis (two due to transfer of care to a different centre and nine due to early treatment cessation). Of the thirty-nine patients, twenty-six were treated for possible and thirteen were treated for proven invasive fungal infection. A range of fungal isolates were encountered. Treatment success was observed in 60% (n=24). Isavuconazole was well tolerated by most patients (n = 37). Conclusion Isavuconazole is well tolerated and appears effective in the management of invasive fungal infection after lung transplantation. The limitations of this study are that it is a single centred, retrospective study, however, is the largest case series to date where clinical effectiveness of Isavuconazole has been appraised.