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Peer-reviewedCC BY 4.0Supportive Care in Cancer

Association between time-to-antibiotics and clinical outcomes in neutropenic fever after hematopoietic stem cell transplant

  • Samuel L. Windham1
  • Christopher A. Guidry2
  • Anthony D. Sung3
  • Marin H. Kollef4
  • Steven Q. Simpson5
5 affiliations
  1. 1Division of Infectious Diseases, University of Kansas Medical Center, Kansas City, KS USA
  2. 2Acute Care Surgery Division, University of Kansas Medical Center, Kansas City, KS USA
  3. 3Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS USA
  4. 4Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO USA
  5. 5Present Address: Division of Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, KS USA
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Abstract

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 h preceding fever) with timestamp-validated TTA. Primary outcome was clinical deterioration (new vasopressor requirement ≥ 6 h, 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 h (IQR 0.8–2.2), with 86 (38.4%) receiving antibiotics within one hour. In the primary categorical analysis, TTA was not associated with deterioration (≤ 1 h vs > 1 h, adjusted OR 1.18, 95% CI 0.37–3.78, P = .78); a per-hour continuous parameterization was similarly null (adjusted OR 1.03, 95% CI 0.85–1.24, P = .80). Recognized pathogen bacteremia occurred in 59 episodes (26.3%) and was not associated with 90-day mortality (adjusted OR 1.98, 95% CI 0.50–7.90, P = .33); a sensitivity analysis using any-positive cultures (69/224 [30.8%]) yielded similar findings (OR 1.15, 95% CI 0.31–4.28, P = .84). Of 11 deaths, 10 (91%) occurred without preceding acute deterioration. Pre-antibiotic and post-antibiotic cultures had similar recognized pathogen positivity (27.1% vs 23.5%; adjusted OR 1.03, 95% CI 0.28–3.85, P = .97).

Conclusion: In antibiotic-naïve adult HSCT recipients with neutropenic fever, TTA was not associated with deterioration and bacteremia was not associated with mortality. Per-hour TTA effects were bounded below the minimum detectable effect size, challenging the extrapolation of the 1-h antibiotic rule from septic shock cohorts to this population. Multicenter validation is needed.

Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s00520-026-11141-8.

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Cite

BibTeXRIS
BibTeX
@article{windham2026association,
  title = {{Association between time-to-antibiotics and clinical outcomes in neutropenic fever after hematopoietic stem cell transplant}},
  author = {Samuel L. Windham and Christopher A. Guidry and Anthony D. Sung and Marin H. Kollef and Steven Q. Simpson},
  journal = {Supportive Care in Cancer},
  year = {2026},
  month = oct,
  doi = {10.1007/s00520-026-11141-8},
  url = {https://doi.org/10.1007/s00520-026-11141-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Association between time-to-antibiotics and clinical outcomes in neutropenic fever after hematopoietic stem cell transplant
AU  - Samuel L. Windham
AU  - Christopher A. Guidry
AU  - Anthony D. Sung
AU  - Marin H. Kollef
AU  - Steven Q. Simpson
PY  - 2026
DA  - 2026/10/28
JO  - Supportive Care in Cancer
DO  - 10.1007/s00520-026-11141-8
UR  - https://doi.org/10.1007/s00520-026-11141-8
AB  - 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 h preceding fever) with timestamp-validated TTA. Primary outcome was clinical deterioration (new vasopressor requirement ≥ 6 h, 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 h (IQR 0.8–2.2), with 86 (38.4%) receiving antibiotics within one hour. In the primary categorical analysis, TTA was not associated with deterioration (≤ 1 h vs > 1 h, adjusted OR 1.18, 95% CI 0.37–3.78, P = .78); a per-hour continuous parameterization was similarly null (adjusted OR 1.03, 95% CI 0.85–1.24, P = .80). Recognized pathogen bacteremia occurred in 59 episodes (26.3%) and was not associated with 90-day mortality (adjusted OR 1.98, 95% CI 0.50–7.90, P = .33); a sensitivity analysis using any-positive cultures (69/224 [30.8%]) yielded similar findings (OR 1.15, 95% CI 0.31–4.28, P = .84). Of 11 deaths, 10 (91%) occurred without preceding acute deterioration. Pre-antibiotic and post-antibiotic cultures had similar recognized pathogen positivity (27.1% vs 23.5%; adjusted OR 1.03, 95% CI 0.28–3.85, P = .97).  Conclusion: In antibiotic-naïve adult HSCT recipients with neutropenic fever, TTA was not associated with deterioration and bacteremia was not associated with mortality. Per-hour TTA effects were bounded below the minimum detectable effect size, challenging the extrapolation of the 1-h antibiotic rule from septic shock cohorts to this population. Multicenter validation is needed.  Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s00520-026-11141-8.
SN  - 0941-4355
SN  - 1433-7339
ER  -