Introduction
Febrile neutropenia (FN) is a common complication of chemotherapy in the
setting of pediatric malignancy.1 It is the leading
cause of emergency hospitalization and infection-related mortality among
these patients.1,2 As many as one third of pediatric
oncology patients receiving chemotherapy or hematopoietic stem cell
transplantation (HSCT) experience at least one instance of FN, with
similar rates of FN in both leukemic and solid tumor
disease.2,3 While the majority of FN episodes are not
associated with significant bacterial infection, bacterial bloodstream
infections (BSI) are the leading infectious cause of FN and thus account
for significant morbidity and mortality.2,4 Given the
mortality associated with bacterial BSIs, current standard of care calls
for inpatient observation and empiric broad spectrum antibiotics for
patients with FN which decreases mortality from BSI but also results in
hospitalization and antibiotic therapy for many patients with more
benign causes of their FN. For this reason, substantial efforts have
been made to establish and validate reliable clinical decision rules
(CDRs) to predict bacteremia and severe bacterial infections (SBI) in
neutropenic patients. These CDRs most commonly utilize a combination of
patient/disease related factors, presenting signs/symptoms, and results
of laboratory tests and biomarkers.5-11 Despite these
efforts, no singular CDR has emerged as a superior method for risk
stratification with current recommendations suggesting institutions
adopt a CDR on a case-by-case basis taking into account institutional
resources and local validation.1
Acetaminophen is widely utilized for symptom control in patients with FN
due to its analgesic and antipyretic effects. It has been shown to
significantly lower peak temperatures in FN compared to placebo and is a
first-line agent for temperature control in FN.12-14Many CDRs utilize peak temperatures or set temperature cutoffs (ex. ≥
39.0°C) in an attempt to gauge the likelihood of bacteremia or severe
bacterial infection in FN.5,15-18 Despite the
widespread use of acetaminophen in FN and the utilization of temperature
for FN risk stratification, using fever responsiveness to acetaminophen
as a means of risk stratification or a predictor of bacteremia has not
yet been investigated.