When azoles cannot be used: the clinical effectiveness of intermittent liposomal amphotericin prophylaxis in haematology patients

Background Patients unable to take azoles are a neglected group lacking a standardized approach to antifungal prophylaxis. We evaluated the effectiveness and safety of intermittent liposomal amphotericin (L-AMB) prophylaxis in a heterogenous group of haematology patients. Methods A retrospective cohort of all haematology patients who received a course of intravenous L-AMB defined as 1mg/kg thrice weekly, from 1 July 2013-30 June 2018 were identified from pharmacy records. Outcomes included breakthrough-invasive fungal disease (BIFD), reasons for premature discontinuation and acute kidney injury. Results There were 198 patients who received 273 courses of L-AMB prophylaxis. Using a conservative definition, the BIFD rate was 9.6% (n=19/198) occurring either during L-AMB prophylaxis or up to 7 days from cessation in patients who received a course. Probable/proven-BIFD occurred in 13 patients (6.6%, 13/198), including molds in 54% (n=7) and non-albicans Candidaemia in 46% (n=6). Cumulative incidence of BIFD was highest in patients with acute myeloid leukaemia (6.8%) followed by acute lymphoblastic leukaemia (2.7%) and allogeneic stem cell transplantation (2.5%). The most common indication for L-AMB was chemotherapy or anticancer drug-azole interactions (75% of courses) dominated by vincristine or acute myeloid leukaemia clinical trials, followed by gut absorption concerns (13%) and liver function abnormalities (8.8%). Acute kidney injury using a modified international definition, complicated 27% of courses but was not clinically significant accounting for only 3.3% (9/273) of discontinuations. Conclusions Our findings demonstrate a high rate of BIFD among patients receiving L-AMB prophylaxis. Pragmatic trials will help find the optimal regimen of L-AMB prophylaxis for the many clinical scenarios where azoles are unsuitable, especially as targeted anticancer drugs increase in use.