Association of Time to Antibiotics With Outcome in Pediatric Patients Receiving Chemotherapy for Cancer With Fever in Neutropenia-An International Individual Patient Data Meta-Analysis

PURPOSE: Fever in neutropenia (FN) is a potentially lethal complication of chemotherapy for cancer. Prompt administration of broad-spectrum antibiotics is standard of care. Despite conflicting results on the association of time to antibiotics (TTA) with outcomes, TTA limits are used as FN quality measure both in adult and pediatric oncology. This individual patient data (IPD) meta-analysis studied the association between TTA and outcomes in pediatric patients with FN. PATIENTS AND METHODS: IPD on TTA in pediatric patients with FN receiving chemotherapy for any malignancy was collected internationally. Three-level mixed binomial logistic regression analyzed the association of TTA with safety relevant events (SRE; death, admission to intensive care unit [ICU], bacteremia), primarily in patients with severe disease at presentation and secondarily in all patients. RESULTS: Data on 4006 FN episodes in 2073 patients, diagnosed 2016-2023, were reported from 15 study sites in eight countries. Median TTA was 61 min overall and 53 min in the 345 (8.6%) episodes with severe disease at presentation. Among these with severe disease, an SRE was reported in 119 (34%) episodes. Longer TTA (> 60 vs. ≤ 60 min) was associated with less SRE (odds ratio, 0.41; 95% CI, 0.24-0.70). This primary finding was confirmed in secondary and additional exploratory analyses. CONCLUSION: This large, international and adequately powered IPD meta-analysis found no association between shorter TTA and improved clinical outcomes in pediatric patients with FN. This finding was consistent across analyses. These results challenge the continued use of TTA limits as a quality measure for pediatric oncology centers.