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) ( <0·001). With the 3-day EBAT strategy, an SMC was observed in 12·5% versus 8·9% with the prolonged strategy ( = 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.