Prediction of fungal infection development in febrile neutropenic patients with hematologic malignancies using D-index, C-reactive protein, and procalcitonin levels

Febrile neutropenia is a common complication in patients with hematologic malignancies undergoing chemotherapy and is associated with high morbidity and mortality. Patients with hematologic malignancies and febrile neutropenia are at high risk for invasive fungal infections (IFI). The early diagnosis and prediction of IFIs is quite challenging. This research aimed to evaluate the performance of D-index, in conjunction with C-Reactive Protein (CRP) and Procalcitonin (PCT), in predicting the development of IFI and assessing the risk of IFI for the appropriate initiation of antifungal therapy in febrile neutropenic patients with hematologic malignancies. Between February 2023 and June 2024, a total of 125 febrile neutropenia episodes occurring in 98 patients admitted to the Hematology Department of Pamukkale University Faculty of Medicine Hospital and evaluated by the Infectious Diseases and Clinical Microbiology Department via consultation were included in the study. C-reactive protein (CRP) and procalcitonin (PCT) levels were recorded at the onset of febrile neutropenia, at 48 hours, 72 hours, on day 7, and between days 7 and 10. D-index and cumulative D-index (k-D-index) values, calculated based on a graph plotting daily absolute neutrophil counts, were recorded to identify high-risk patients for IFI. Patients were classified into "possible," "highly probable," and "proven" invasive fungal infections based on host factors, clinical criteria, and mycological criteria as defined by the EORTC/MSG guidelines. In febrile neutropenia episodes complicated by invasive fungal infection (IFI), CRP levels measured at 48 hours, 72 hours, day 7, and between days 7 and 10 were significantly elevated (p=0.001, p<0.0001, p<0.0001, p<0.0001, respectively). PCT levels were generally lower in episodes with IFI development, with the PCT level at 7-10 days significantly lower (p=0.033). D-index values were significantly higher in episodes with IFI development (p=0.018), while k-D-index values were significantly lower in episodes with IFI development (p=0.0001). Triple combinations of D-index and k-D-index with either CRP or PCT values at baseline or 48 hours resulted in an AUC of 0.99, with 100% sensitivity and negative predictive value. The quadruple combination of D-index and k-D-index with CRP and PCT values at 48 or 72 hours resulted in an AUC of 1.00, with 100% sensitivity, specificity, and both negative and positive predictive values. When evaluated alongside clinical, microbiological, and radiological findings, our study emphasizes that the D-index and k-D-index may play a significant role in the early prediction of invasive fungal infections (IFI) and in guiding the initiation of antifungal therapy. In particular, their combination with CRP and PCT appears to substantially enhance diagnostic accuracy. Keywords: Invasive Fungal Infection, Prediction Model, Febrile Neutropenia, D-index, Biomarker