Febrile Neutropenia in Adults With Hematological Malignancies: Pathogen Distribution, Resistance Patterns, and Predictors of 28-Day Mortality

Background: Patients with hematological malignancies remain particularly vulnerable to severe infections, and the management of febrile neutropenia (FN) is increasingly challenged by the rising burden of multidrug-resistant pathogens, especially in high-resistance settings. Objectives: To evaluate causative pathogens, antimicrobial resistance patterns, and independent predictors of 28-day infection-related mortality in FN episodes among adults with hematological malignancies. Methods: We retrospectively reviewed 240 FN episodes from 170 adult patients followed at a tertiary university hospital between April 2022 and September 2024. Independent predictors of infection-related mortality were identified using multivariable logistic regression with generalized estimating equations. Results: Fever of unknown origin accounted for 45.4% of episodes, clinically documented infection for 29.2%, and microbiologically documented infection for 25.4%. Gram-negative bacteria predominated among culture-positive episodes (76.0%), with Escherichia coli (45.3%) and Klebsiella spp. (24.0%) as the most frequent isolates. Resistance to third-generation cephalosporins and carbapenems in Klebsiella reached 83.3% and 77.8% (14/18), respectively. No Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus was recovered. All Candida isolates were fluconazole-resistant, while none showed resistance to echinocandins or amphotericin B. Invasive pulmonary aspergillosis developed in 21 episodes (8.8%). The 28-day infection-related mortality was 22.4% (38/170). On multivariable analysis, low baseline platelet count (OR=0.988; p=0.014), low lymphocyte count (OR=0.163; p=0.037), and prolonged neutropenia (OR=1.018; p=0.018) emerged as independent mortality predictors. Conclusions: The high carbapenem resistance in Klebsiella and universal fluconazole resistance among Candida isolates reflect a substantial resistance burden. Low platelet count, low lymphocyte count, and prolonged neutropenia emerged as independent mortality predictors, underscoring the need for empirical strategies guided by local surveillance and individualized risk-based approaches.