Antibiotic Duration and Outcomes in High-Risk Febrile Neutropenia Patients

This is a multicenter, open-label, randomized controlled trial. Upon confirmation of Gram-negative bacteraemia, eligible patients are randomized 1:1 to one of two treatment strategies:

• Experimental Arm (Personalized Duration): Antibiotic therapy is discontinued once the patient achieves and maintains clinical stability for 72 consecutive hours. Clinical stability is defined as apyrexia (Tc < 38°C) for at least 48 hours and a stable or improving qSOFA score.
• Control Arm (Standard of Care): Antibiotic therapy duration follows local clinical practice, with a suggested minimum duration of 10 days, consistent with current European and Asian hematological guidelines.

In parallel, a prospective observational microbiological sub-study will utilize Shotgun Metagenomic Next-Generation Sequencing (mNGS) to analyze the evolution of the intestinal and blood microbiota. The goal is to compare the rate of MDR organism colonization and the reconstitution of the healthy microbiome between the two antibiotic duration strategies.

All participants will undergo clinical monitoring until day 28. For those enrolled in the sub-study, biological samples (stool, rectal swabs, and blood) will be collected at baseline (V1), at the end of treatment (V4), and at the end of the study (V5). These samples will be analyzed to identify clinically significant bacteria and antibiotic-resistance genes.

Inclusion criteria

• Diagnosed with a hematologic malignancy that is candidate for treatment with chemotherapy or bone marrow transplantation or chimeric antigen receptor T cell therapy (CAR-T)
• Diagnosis of febrile neutropenia defined according to the guidelines of the Infectious Disease Society of America, IDSA; ref: Freifeld, A.G., et al., Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis, 2011. 52(4): p. e56-93.) as: Fever: single record of oral temperature >=38.3°C or a temperature >=38.0°C sustained over a period of one hour; Neutropenia: absolute neutrophil count < 1000 cells/microL; Expected duration of neutropenia >= 7 days
• Diagnosis of bacteraemia defined by positive blood cultures (at least 1 vial positive for a non-contaminating microorganism)
• Isolation of Gram-Negative species

Exclusion criteria

• Contextual diagnosis of pneumonia
• Contextual diagnosis of intra-abdominal infection, in particular: neutropenic enterocolitis/typhlitis or biliary tract infection
• Persistently positive blood cultures at randomization
• Any condition that endangers the safety of the patient based on the judgment of the treating physician