Pulsed echinocandin therapy in azole intolerant or multiresistant chronic pulmonary aspergillosis: A retrospective review at a UK tertiary centre

Introduction Chronic pulmonary aspergillosis (CPA) is a fungal disease with high mortality and morbidity. Guidelines suggest treatment with azoles as first-line therapy. However, patients often develop treatment intolerance or increasingly azole resistance. Objectives This retrospective review assesses outcomes in azole resistant or intolerant patients with CPA treated with cyclical echinocandin therapy. Methods We retrospectively examined records of 25 patients with CPA treated with cyclical caspofungin, 6 of whom were either azole-resistant or azole intolerant. Baseline characteristics, high-resolution computed tomography severity scores, forced expiratory volume after 1 minute (FEV1), forced vital capacity (FVC), body mass index and serology (Aspergillus fumigatus-specific IgG, Aspergillus fumigatus-specific IgE, total IgE and CRP) were assessed before and after caspofungin. Results Of the six patients, four (66%) started caspofungin due to intolerance and two (33%) due to pan-azole resistance. On treatment, there was stability in FEV1 with an overall mortality of 33% during the follow-up period with a median survival of 875.5 days (IQR 529-1024). No significant change in serology (A. fumigatus-specific IgG and CRP was seen. Conclusions With pulsed echinocandin therapy, azole-intolerant or pan-resistant CPA patients have similar mortality rates to azole-naive CPA patients. Pulsed echinocandin therapy may present a strategy to stabilize CPA in patients with pan resistance or intolerance to, azole therapy.