Early Discontinuation of Empiric Antibiotics in Pediatric Haploidentical Hematopoietic Cell Transplant Recipients with Febrile Neutropenia.

Abstract

Febrile neutropenia (FN) is common in children, adolescents, and young adults (CAYA) undergoing hematopoietic cell transplant (HCT), particularly following allogeneic haploidentical HCT (haplo-HCT). Optimal empiric antibiotic duration for FN is not well established in this population. A retrospective quasi-experimental study was conducted among CAYA undergoing haplo-HCT between 2010 and 2022 who experienced FN. In 2017 a guideline was implemented for discontinuation of empiric antibiotics within 72 hours of FN in patients without identified infection regardless of persistence of fever. We compared patients who underwent haplo-HCT pre-implementation (Pre-I) vs. post-implementation (Post-I) of this guideline. The primary outcome was days of therapy (DOT). Secondary outcomes included incidence of bloodstream infections (BSI), ICU admission, and mortality from 72 hours of FN onset until neutrophil engraftment. A Desirability of Outcome Ranking (DOOR) with a modified Response Adjusted for Duration of Antibiotic Risk (RADAR) approach using DOT was applied to comprehensively assess outcomes. Patients in Post-I (n=82) had fewer DOT compared to Pre-I (n=90) with a median difference of 8 days (p<0.01). There were no significant differences in BSI incidence, ICU admission, or mortality between groups. The DOOR-modified RADAR analysis demonstrated Post-I was associated with a 70% (95% CI = 61, 78%) probability of experiencing a more favorable clinical outcome compared to the Pre-I group (p <0.01). Early antibiotic discontinuation appears safe and feasible in CAYA haplo-HCT recipients with FN, significantly reducing antibiotic exposure without increasing adverse outcomes. Large prospective multicenter trials are needed to confirm these findings.