When Azoles Cannot Be Used: The Clinical Effectiveness of Intermittent Liposomal Amphotericin Prophylaxis in Hematology Patients

R Batchelor; C Thomas; B J Gardiner; S J Lee; S Fleming; A Wei; J Coutsouvelis; M Ananda-Rajah

doi:10.1093/ofid/ofab113

When Azoles Cannot Be Used: The Clinical Effectiveness of Intermittent Liposomal Amphotericin Prophylaxis in Hematology Patients

Open Forum Infect Dis. 2021 Mar 8;8(7):ofab113. doi: 10.1093/ofid/ofab113. eCollection 2021 Jul.

Authors

R Batchelor¹, C Thomas¹, B J Gardiner^{2

3}, S J Lee^{2

3}, S Fleming^{4

5}, A Wei^{4

5}, J Coutsouvelis^{6

7}, M Ananda-Rajah^{1

2

3}

Affiliations

¹ Department of General Medicine, Alfred Health, Melbourne, Victoria, Australia.
² Department of Infectious Diseases Alfred Health Melbourne, Victoria, Australia.
³ Central Clinical School, Monash University, Clayton, Victoria, Australia.
⁴ Australian Centre for Blood Diseases, Alfred Health Melbourne, Victoria, Australia.
⁵ Department of Haematology, Alfred Health Melbourne, Victoria, Australia.
⁶ Pharmacy Department, Alfred Health Melbourne, Victoria, Australia.
⁷ Centre for Medicine Use and Safety, Monash University Parkville, Victoria, Australia.

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 B (L-AMB) prophylaxis in a heterogenous group of hematology patients.

Methods: A retrospective cohort of all hematology patients who received a course of intravenous L-AMB, defined as 1 mg/kg thrice weekly from July 1, 2013 to June 30, 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 of 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 of 198), including molds in 54% (n = 7) and non-albicans Candidemia in 46% (n = 6). Cumulative incidence of BIFD was highest in patients with acute myeloid leukemia (6.8%) followed by acute lymphoblastic leukemia (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 leukemia 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 of 273) of discontinuations.

Conclusions: Our findings demonstrate a high rate of BIFD among patients receiving L-AMB prophylaxis. Pragmatic trials will help researchers find the optimal regimen of L-AMB prophylaxis for the many clinical scenarios in which azoles are unsuitable, especially as targeted anticancer drugs increase in use.

Keywords: antifungal prophylaxis; breakthrough fungal infection; invasive fungal disease; liposomal amphotericin B; malignant hematology.