Antibacterial prophylaxis and antimicrobial stewardship in the era of innovative therapies for haematological malignancies: transplantation, cellular therapies and new drugs

Abstract Antibacterial prophylaxis has long been a cornerstone of supportive care in patients with haematological malignancies undergoing intensive chemotherapy and haematopoietic stem cell transplantation (HSCT), particularly in the setting of prolonged and profound neutropenia. However, the widespread use of fluoroquinolone (FQ) prophylaxis has increasingly raised concerns related to antimicrobial resistance, microbiota disruption, drug-related toxicity, and Clostridioides difficile infection, challenging its universal application. At the same time, the therapeutic landscape of haematology is rapidly evolving, with the introduction of novel agents and cellular therapies such as chimeric antigen receptor (CAR) T cells, bispecific antibodies (BsAbs), antibody–drug conjugates, and immune-based treatments, each associated with distinct patterns of immunosuppression and infectious risk. In this narrative review, we critically examine the role of antibacterial prophylaxis through the lens of antimicrobial stewardship, integrating evidence from traditional chemotherapy and transplantation with emerging data from innovative therapies. We summarize current guideline recommendations, real-world evidence, and recent studies questioning the net benefit of routine FQ prophylaxis, particularly in settings with high resistance prevalence. Alternative strategies, including non-FQ agents and selective omission of prophylaxis, are also discussed. Overall, available evidence supports a shift from universal prophylaxis toward a risk-adapted, individualized approach that accounts for treatment modality, expected duration and depth of neutropenia, patient-specific factors, and local epidemiology. Embedding antibacterial prophylaxis decisions within structured antimicrobial stewardship programs is essential to balance infection prevention with long-term patient safety and resistance containment in modern haematological practice.