Association Between Time-to-Antibiotics and Clinical Outcomes in Neutropenic Fever After Hematopoietic Stem Cell Transplant

Background: Guidelines recommend empiric antibiotics within one hour for neutropenic fever, extrapolated primarily from sepsis literature. Whether modest variation in time-to-antibiotics (TTA) affects outcomes in antibiotic-naïve hematopoietic stem cell transplant (HSCT) recipients remains unclear. Methods: We conducted a retrospective cohort study of neutropenic fever episodes occurring within 30 days of HSCT at a single academic center (2018–2022). We included antibiotic-naïve episodes (no intravenous antibiotics in the 24 hours preceding fever) with timestamp-validated TTA. Primary outcome was clinical deterioration (new vasopressor requirement ≥6 hours, mechanical ventilation, or 90-day mortality). Secondary analyses examined bacteremia and blood culture yield. Results: Among 224 antibiotic-naïve episodes, 17 (7.6%) experienced clinical deterioration. Median TTA was 1.2 hours (IQR 0.8–2.2). TTA was not associated with deterioration (adjusted OR 1.03 per hour, 95% CI 0.85–1.24, P=.79). In the full cohort (N=272), bacteremia occurred in 81 episodes (29.8%) and was not associated with 90-day mortality (adjusted OR 1.24, 95% CI 0.38–4.09, P=.72); findings were similar when restricted to true bacterial pathogens (OR 1.64, 95% CI 0.40–6.78, P=.49). Of 15 deaths, 14 (93%) occurred without preceding acute deterioration. Pre-antibiotic cultures had numerically higher positivity than post-antibiotic cultures (33.7% vs 23.5%; adjusted OR 0.70, 95% CI 0.21–2.39, P=.57), though small number of post-antibiotic cultures limits conclusions. Conclusion: In antibiotic-naïve HSCT recipients with neutropenic fever, we found no significant associations between TTA and clinical deterioration or between bacteremia and mortality. These hypothesis-generating findings suggest that in closely monitored patients receiving rapid empiric therapy, modest timing variation may not critically influence outcomes.