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Time to Antibiotics in Pediatric Patients with Fever in Neutropenia during Chemotherapy for Cancer -- Data from the Prospective Multicenter SPOG 2015 FN Definition Study
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  • Christa Koenig,
  • Claudia Kuehni,
  • Nicole Bodmer,
  • Philipp Agyeman,
  • Marc Ansari,
  • Jochen Rössler,
  • Nicolas von der Weid,
  • Roland Ammann
Christa Koenig
Inselspital University Hospital Bern

Corresponding Author:christa.koenig@insel.ch

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Claudia Kuehni
University of Bern Institute of Social and Preventive Medicine
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Nicole Bodmer
University Children's Hospital Zürich
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Philipp Agyeman
Inselspital University Hospital Bern
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Marc Ansari
University Hospitals of Geneva Child and Adolescent Department
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Jochen Rössler
Inselspital University Hospital Bern
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Nicolas von der Weid
University Children’s Hospital Basel
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Roland Ammann
Inselspital University Hospital Bern
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Abstract

Background. Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. Procedure. We analyzed the association between time from recognition of fever to start of antibiotics (F-TTA) and SRE (death, admission to intensive care unit (ICU), severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation. Results. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. F-TTA (median, 120min; interquartile range, 49 to 180min) was not associated with SRE, with a trend for less SREs in episodes with longer F-TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. Conclusion. We found little evidence that longer TTA leads to a higher risk of poor clinical outcome in pediatric patients with FN, except for those with severe disease at presentation. We saw strong evidence for triage bias which could only be partially adjusted.