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.