Safety and efficacy of short courses of antibiotic therapy in high-risk febrile neutropenic pediatric patients

The majority of children and adolescents treated for acute leukemia experiences at least one infectious episode during neutropenia [1].According to pediatric-specific guidelines, these patients are promptly hospitalized and receive empirical broad-spectrum antibiotics [2, 3], which further impairs the quality of life of patients and increases the risk of resistant pathogens [4].Pediatric-specific guidelines strongly recommend for both high-and low-risk patients who have been clinically well, are afebrile for at least 24 h and have negative blood cultures at 48-72 h, to discontinue empirical antibiotic therapy if there is evidence of marrow recovery [3].However, only in low-risk febrile neutropenic patients, a conditional recommendation was made for the discontinuation of antibiotics in this setting when there is no evidence for marrow recovery.We expanded the recommendation to stop empirical antibiotic therapy irrespective of hematological recovery in our institution to high-risk patients defined by long periods of therapy-induced neutropenia (e.g., 10 days) [5,6], such as patients with high-risk acute lymphoblastic leukemia (HR-ALL), acute myeloid leukemia (AML) or relapsed acute leukemia, and performed a retrospective audit to assess safety (e.g., mortality) and efficacy (e.g., readmission) of this approach.This retrospective, single-center audit evaluated all consecutive patients <18 years treated for HR-ALL, AML or relapsed acute leukemia who had presented in stable condition with febrile neutropenia in order to assess outcome of antibiotic discontinuation and hospital discharge prior to hematological recovery.Patients were treated between April 2020 and March 2025 according to Berlin-Frankfurt-Mnster (BFM)-based protocols, e.g., AIEOP-BFM-ALL2017 (EudraCT-2016-001935-12), AML-BFM-2017-Registry (DRKS 00013030) or INTREALL2010HR (EudraCT-2012-000810-12).Written informed consent for data collection and analysis was obtained within the consent procedure for cancer treatment and medical care approved by the local institutional review board (e.g., A105/18, 349/17, 16/0040).Clinical and microbiological data during intensive chemotherapy was extracted from the medical information system and entered in a secured database.The primary endpoint of the analysis was overall survival of the episode of infection.Secondary endpoints included readmission for suspected infection, or the days without antibiotic therapy from discharge until neutrophil recovery.Prophylactic anti-infective measures for high-risk patients included systemic trimethoprim/sulfamethoxazole twice weekly and mold-active antifungal prophylaxis, but no systemic antibiotics [5,7].Diagnostics and first line therapy of febrile neutropenic