Antibiotic therapy in febrile neutropenia in haematological patients: current considerations and future challenges

The management of febrile neutropenia (FN) in oncohematological patients is undergoing a paradigm shift driven by a deeper understanding of patients' pathophysiological heterogeneity, the increasing speed and accuracy of microbiological diagnostics, the emergence of new antibiotics, and the incorporation of predictive artificial intelligence (AI) as a tool to support clinical decision-making. Our objective is to provide an updated and comprehensive overview of the factors influencing antibiotic treatment in FN. We propose that its management should be based on three essential pillars. First, accurate risk stratification for bacterial infection. Second, ensuring that patients receive appropriate empirical antibiotic therapy, tailoring the initial choice according to the results of surveillance cultures from oropharyngeal and/or fecal microbiota. Finally, prioritizing antibiotic choices that preserve intestinal microbiota eubiosis as much as possible. Reducing colonization and overgrowth of facultative aerobic/anaerobic flora (Enterobacteriaceae, non-fermenting Gram-negative bacilli, and Enterococcus spp.) while preserving strict anaerobic flora decreases the risk of bacterial translocation and complications such as graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or loss of CAR-T functionality. This decision model, grounded in objective criteria, aims to balance the need for effective empirical coverage with responsible antibiotic use.