Patterns and Drivers of Antifungal Prescribing in Acute Leukemia: A Retrospective Cohort Study

Abstract

Background Patients with haematological malignancy are at high risk of invasive fungal infections (IFI). Diagnosis is challenging which can lead to overtreatment. Reducing exposure to inappropriate antifungal prescribing is likely to improve patient safety, but modifying prescribing behaviour is difficult. We aimed to describe patterns and drivers of therapeutic antifungal prescribing in a large tertiary haemato-oncology centre in the UK. Methods We studied adults receiving treatment for acute leukaemia at our centre between 1st April 2019 and 14th October 2022. We developed a reproducible method to analyse routinely collected data on antifungal therapy episodes in a widely used electronic health record system. We report antifungal use in Days of Therapy stratified by level of diagnostic confidence, as defined by consensus diagnostic guidelines (EORTC/MSG). Results 298 patients were included in the analysis. 21.7% of inpatient antifungal use occurred in cases of proven/probable IFI. Substantial antifungal use occurred in the absence of strong evidence of infection in patients receiving high-intensity first line chemotherapy or approaching death (81.0% & 77.9%). 32.6% of high-resolution computed tomography (HRCT) reports were indeterminate for IFI. Indeterminate reports were around 8 times more likely to be followed by a new antifungal therapy episode than a negative report. Conclusions Antifungal stewardship remains challenging in the absence of reliable diagnostics, particularly in more unwell patients. The proportion of antifungal therapy given for proven/probable infection is a new metric which will likely be useful to target antifungal stewardship programs. The thoracic HRCT report is an important contributor to diagnostic uncertainty.