Time to Antibiotics in Pediatric Patients with Fever in Neutropenia
during Chemotherapy for Cancer -- Data from the Prospective Multicenter
SPOG 2015 FN Definition Study
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.