Breakthrough invasive fungal infections during posaconazole prophylaxis in patients with hematologic malignancies at a tertiary care center - a 5-year audit from south India.
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PURPOSE: Breakthrough invasive fungal infections (BtIFIs) are an emerging concern in patients with hematological malignancies (HM), despite the use of primary antifungal prophylaxis. Posaconazole (PCZ), a broad-spectrum triazole antifungal, is FDA-approved for primary prophylaxis in high-risk settings. However, data on the real-world burden and characteristics of BtIFIs from low- and middle-income countries (LMICs) are limited. This study aimed to evaluate the incidence, predictors, and microbiological and radiological features of BtIFIs in HM patients receiving PCZ prophylaxis at a tertiary care centre in India. METHODS: Following, Institutional Ethics Committee approval, we enrolled 176 patients on PCZ prophylaxis (adults: 600 mg on day 1, then 300 mg/day; pediatrics: 14 mg/kg on day 1, then 7 mg/kg/day) for IFI prevention during treatment for HM (n = 176) at a tertiary care hospital. We retrospectively reviewed medical records from 2019 to 2023 and prospectively collected data in 2024. Independent sample t-test and a chi-square test were used for statistical analysis. RESULTS: Of 176 patients, 59 (33.5%) developed BtIFIs [culture-proven BtIFI = 20 (33.8%); probable BtIFI = 39 (66.1%)], with an incidence of 336/1000 patients. Aspergillus (46.66%) and Candida (28.88%) spp. were the most commonly isolated pathogens. Severe neutropenia (lasting 5-15 days) was the most significant risk factor for BtIFI (54%, p < 0.001). Comorbidities, Proton Pump Inhibitors (PPIs) and the chemotherapy regimen were not significant risk factors. CONCLUSION: The High incidence of BtIFI observed may be attributed to the unavailability of therapeutic dose monitoring (TDM), variations in pathogenic strains, and environmental factors conducive to fungal infections (warmth and high humidity), implying that strengthened surveillance and prophylaxis strategies are essential.