RECRUITINGINTERVENTIONAL

Antibiotic Duration and Outcomes in High-Risk Febrile Neutropenia Patients

Appropriate Management of Bacteriemic Febrile Neutropenia in High-Risk Hematological Patients. Relationship Between Duration of Antibiotic Administration, Outcome and Resistance Profile

About This Trial

The goal of this clinical trial is to learn if a personalized duration of antibiotic therapy, based on clinical stability, is as effective as a standard duration of at least 10 days in hospitalized patients with hematologic malignancies (such as leukemia or lymphoma) who develop febrile neutropenia and Gram-negative bacteraemia. The main questions it aims to answer are: * Can a personalized antibiotic duration increase the number of days free from anti-Gram-negative therapy within 28 days without compromising patient safety? * How does the duration of antibiotic therapy (short vs. prolonged) affect the rate and modality of gut microbiota reconstitution? Researchers will compare: * Group A (Personalized Duration): Antibiotics are stopped after the patient maintains clinical stability (no fever and stable vital signs) for 72 consecutive hours. * Group B (Standard of Care): Antibiotics are continued for a standard duration, typically at least 10 days, based on current clinical surveys and physician decision. Participants will: * Be randomized to receive either the personalized or the standard duration of antibiotic therapy once a Gram-negative infection is confirmed in the blood. * Be monitored for 28 days to assess for new fever episodes, recurrence of infection, and overall survival. * If participating in the microbiological sub-study, provide biological samples (blood, feces, and rectal swabs) at specific time points (at the onset of fever, at the end of treatment, and at day 28). * Undergo specialized laboratory testing (Whole Metagenomic Sequencing) on the collected samples to evaluate the evolution of their intestinal and blood microbiota and the presence of antibiotic-resistant genes.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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 Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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

Treatments Being Tested

OTHER

Clinical Stability-Driven Antibiotic Discontinuation Strategy

A therapeutic strategy where the duration of antibiotic treatment for Gram-negative bacteraemia is determined by the achievement of clinical stability (defined as apyrexia for 48h and stable/improved qSOFA score) maintained for 72 consecutive hours

OTHER

Standard of Care Antibiotic Duration

This intervention follows the standard clinical practice for treating Gram-negative bacteraemia in hematological patients. The duration of therapy is not fixed by a stability-driven rule but is based on the treating physician's decision, with a suggested minimum of 10 days.

Locations (1)

Microbiology and Virology - IRCCS Humanitas Research Hospital

Rozzano, Milan, Italy