Stopping antibiotic therapy after 72 h in patients with febrile neutropenia following intensive chemotherapy for AML/MDS (safe study): A retrospective comparative cohort study

Background Induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) is almost universally complicated by febrile neutropenia(FN). Empirical broad-spectrum antibiotic therapy (EBAT) strategies advocated by guidelines result in long periods of broad-spectrum antibiotic therapy. We compared the outcome of AML/MDS patients treated with a 3-day versus a prolonged (until neutrophil recovery) regimen. Methods This is a retrospective comparative cohort study in AML or MDS patients undergoing remission-induction chemotherapy from 2011 to 2019, comparing 2 tertiary care hospitals with different strategies regarding antibiotic treatment for FN. At Erasmus University medical center(EMC), EBAT was stopped after 3 days of FN, in absence of a clinically or microbiologically documented infection. In the University Hospitals Leuven(UZL), a prolonged strategy was used, where EBAT was given until neutrophil recovery. The primary endpoint was a serious medical complication(SMC) defined as death or ICU admission in the 30 days after the start of chemotherapy. Findings 305 and 270 AML or MDS patients received chemotherapy at EMC and UZL, respectively. Broad-spectrum antibiotic treatment was given for a median of 19 days (IQR13-25) at UZL versus 9 days at EMC (IQR5–13) ( p  <0·001). With the 3-day EBAT strategy, an SMC was observed in 12·5% versus 8·9% with the prolonged strategy ( p  = 0·17). The hazard ratio for an SMC was not significantly higher with the 3-day strategy (HR 1·357,95%CI 0·765–2·409). Interpretation This study suggests that during remission induction chemotherapy it is safe to stop antibiotics after 3 days of FN in absence of infection. A comparison of both strategies in a prospective trial should be pursued.