Fluoroquinolone-Free Prophylaxis and Impact on Bacterial Infections, Resistance, and Survival in Allo-HSCT: 5-Year Follow-up of the BATMO Protocol (Best Anti-microbical Therapy Trapianto di Midollo Osseo).

BACKGROUND: Infectious complications and antimicrobial resistance (AMR) are leading causes of morbidity and non-relapse mortality (NRM) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The BATMO protocol, implemented in 2019, removed fluoroquinolone prophylaxis and introduced a personalized, stewardship-based antimicrobial approach. METHODS: We retrospectively analyzed 323 allo-HSCT recipients transplanted between 2016 and 2023 at a single center, comparing outcomes in patients before (n = 115) and after (n = 208) BATMO implementation. Primary endpoints included overall survival (OS), NRM, incidence and microbiology of bloodstream infections (BSIs), antimicrobial resistance trends, and carbapenem use. Kaplan-Meier and cumulative incidence methods were employed. RESULTS: Despite a significant increase in 30-day Gram-negative BSI incidence post-BATMO (24% vs 15%, P = .03), OS and NRM were similar between the two cohorts. Notably, the post-BATMO cohort included a substantially higher proportion of high-risk transplants, with a marked increase in haploidentical procedures and broader use of post-transplant cyclophosphamide. Interestingly, fluoroquinolone-resistant E. coli strains declined from 100% to 46% (P = .003), and overall Gram-negative resistance dropped from 75% to 36% (P = .006). Use of carbapenems remained unchanged (43% vs 53%, P = .1). CONCLUSIONS: The BATMO protocol demonstrates that withdrawal of fluoroquinolone prophylaxis and implementation of a targeted antimicrobial strategy can reduce resistance without compromising transplant outcomes. These findings support the long-term safety and efficacy of stewardship-based approaches in allo-HSCT.