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

A Schauwvlieghe,A Vlak,B Sciot,A Dunbar,J.J Cornelissen,G Papageorgiou,T Van Der Wel,T Mercier,J Maertens,B.J.A Rijnders,E Storme,R Aerts,I Moors

doi:10.1016/j.eclinm.2021.100855

Abstract

BackgroundInduction 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.MethodsThis 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.Findings305 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).InterpretationThis 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.

Highlights

Patients with Acute Myeloid Leukemia (AML) or myelodysplastic syndrome (MDS), treated with classic “3 + 700 induction chemotherapy, always go through an episode of longstanding neutropenia of three to four weeks
Current strategies towards febrile neutropenia result in long periods of broad-spectrum antibiotics usage with its associated adverse effects, even though an infectious cause can be found in only 20À30% of patients
The policy we investigated here goes one step further because broad-spectrum antibiotics are being stopped after 72 h, even when fever has not resolved

Summary

Introduction

Patients with Acute Myeloid Leukemia (AML) or myelodysplastic syndrome (MDS), treated with classic “3 + 700 induction chemotherapy, always go through an episode of longstanding neutropenia of three to four weeks. Induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) is almost universally complicated by febrile neutropenia(FN). 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 remissioninduction chemotherapy from 2011 to 2019, comparing 2 tertiary care hospitals with different strategies regarding antibiotic treatment for FN. 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

Methods

Results

Conclusion