Clinical Phenotypes and Glycopeptide Escalation Patterns in Pediatric Febrile Neutro-penia: Associations With Short-Term Outcomes and Acute Kidney Injury Risk

Objective: Febrile neutropenia (FN) in pediatric oncology is a clinically heterogeneous syndrome in which early antibiotic escalation decisions are frequently driven by nonspecific severity cues. We aimed to identify baseline clinical phenotypes of pediatric FN, to describe early glycopeptide escalation patterns across these phenotypes, and to examine their associations with short-term outcomes and acute kidney injury (AKI). Methods: We conducted a retrospective cohort study including 106 FN episodes in 82 pediatric oncology patients initially treated with piperacillin-tazobactam monotherapy. Baseline clinical and laboratory variables available within the first 6 hours of FN onset were used for unsupervised k-means clustering to derive latent clinical phenotypes. Early glycopeptide escalation was defined as initiation of vancomycin or teicoplanin within 48 hours. Associations with day-7 clinical outcomes and AKI were evaluated using cluster-robust multivariable regression and inverse probability of treatment weighting. Results: Three distinct FN phenotypes were identified: a high-inflammatory/mucositis-dominant phenotype (39.6%), a hemodynamically severe phenotype (22.6%), and a lower-severity phenotype (37.7%). Early glycopeptide escalation occurred in 26.4% of episodes and was disproportionately concentrated in the high-inflammatory and hemodynamically severe phenotypes. AKI developed in 10.4% of FN episodes and clustered predominantly within escalation-prone phenotypes. After adjustment, early escalation was not associated with improved day-7 clinical success but was associated with a higher observed risk of AKI. Conclusions: Pediatric FN comprises distinct clinical phenotypes that differentially drive antibiotic escalation behavior and renal injury risk. A phenotype-informed approach may help optimize escalation decisions and potentially reduce preventable toxicity. However, given the observational design, these associations should be interpreted with caution.