Abstract
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.
Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single‐centre retrospective study in Korea and clinical considerations