Clinical Phenotypes and Glycopeptide Escalation Patterns in Pediatric Febrile Neutropenia: 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 non-specific 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). Materials and Methods: We conducted a retrospective cohort study including 106 FN episodes experienced by 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 the initiation of vancomycin or teicoplanin within 48 hours. Associations with clinical outcomes on day 7 and AKI were evaluated using multivariable cluster-robust 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. Conclusion: Pediatric FN comprises distinct clinical phenotypes that differentially drive antibiotic escalation behavior and renal injury risk. A phenotype-informed approach may help to optimize escalation decisions and potentially reduce preventable toxicity. However, given the observational design of this study, these associations should be interpreted with caution.