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Patterns and Drivers of Antifungal Prescribing in Acute Leukemia: A Retrospective Cohort Study
Hamish Houston1,2, Peter Dutey-Magni3,4, Matthew Steel2,5
1Department of Clinical Microbiology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
Background:
Patients with hematological malignancy are at high risk of invasive fungal infections (IFIs). Diagnosis is challenging, which can lead to overtreatment. Reducing exposure to inappropriate antifungal prescribing is likely to improve patient safety, but modifying prescribing behavior is difficult. We aimed to describe patterns and drivers of therapeutic antifungal prescribing in a large tertiary hemato-oncology center in the United Kingdom.
Methods:
We studied adults receiving treatment for acute leukemia at our center between 1 April 2019 and 14 October 2022. We developed a reproducible method to analyze 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 (European Organisation for Research and Treatment of Cancer/Mycoses Study Group).
Results:
Two hundred ninety-eight 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% and 77.9%, respectively). Approximately 33% 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 that will likely be useful to target antifungal stewardship programs. The thoracic HRCT report is an important contributor to diagnostic uncertainty.
Insights
Antifungal prescribing for invasive fungal infections (IFIs) in hemato-oncology patients is often not supported by clear diagnostic evidence. Improving diagnostic confidence is key to optimizing antifungal stewardship and patient safety.
Area of Science:
- Hematology
- Oncology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Patients with hematological malignancy face a high risk of invasive fungal infections (IFIs).
- Accurate diagnosis of IFIs is challenging, often leading to overtreatment with antifungals.
- Modifying prescribing behavior for antifungals is difficult, impacting patient safety.
Purpose of the Study:
- To describe patterns and drivers of therapeutic antifungal prescribing.
- To analyze antifungal use in a UK tertiary hemato-oncology center.
- To stratify antifungal use by diagnostic confidence levels.
Main Methods:
- Analysis of routinely collected electronic health record data.
- Study of adult acute leukemia patients (April 2019 - October 2022).
- Development of a reproducible method for analyzing antifungal therapy episodes.
Main Results:
- 21.7% of inpatient antifungal use was for proven/probable IFIs.
- Significant antifungal use occurred without strong infection evidence (81.0% in high-intensity chemotherapy, 77.9% near death).
- Indeterminate high-resolution computed tomography (HRCT) reports increased new antifungal therapy episodes eightfold compared to negative reports.
Conclusions:
- Antifungal stewardship is challenging due to diagnostic uncertainty, especially in critically ill patients.
- The proportion of antifungal therapy for proven/probable infection is a novel metric for stewardship programs.
- Thoracic HRCT reports contribute significantly to diagnostic uncertainty regarding IFIs.
