Patient Outcomes With Febrile Neutropenia Based on Time to Antibiotics in the Emergency Department

Abstract

Objective: Although bacteremia in pediatric oncology patients with febrile neutropenia (FN) is not uncommon, sepsis and mortality are rare. Because of the lack of clinically meaningful decision tools to identify high-risk patients with bacteremia, time to antibiotic administration (TTA) is increasingly considered an important quality and safety measure in the emergency department. Because little evidence exists suggesting that this benchmark is beneficial, we sought to determine whether TTA of 60 minutes or less is associated with improved outcomes. Methods:We retrospectively reviewed patients presenting to a pediatric emergency department with FN from November 2013 to June 2016. Clinical outcomes including mortality, pediatric intensive care unit admission, imaging, fluid resuscitation of 40 mL/kg or greater in the first 24 hours, and length of stay were compared between TTA of 60 minutes or less and more than 60 minutes.Results: One hundred seventy-nine episodes of FN were analyzed. The median TTA was 76 minutes (interquartile range, 58-105). The incidence of bacteremia was higher in patients with TTA of more than 60 minutes (12% vs 2%, P = 0.04), but without impact on mortality, pediatric intensive care unit admission, fluid resuscitation, or median length of stay. The median TTA was not different for those who were and were not bacteremic (91 vs 73 minutes, P = 0.11).Conclusions: Time to antibiotic administration of more than 60 minutes did not increase mortality in pediatric oncology patients with FN. Our study adds to the existing literature that TTA of 60 minutes or less does not seem to improve outcomes in pediatric FN. Further larger studies are required to confirm these findings and determine which features predispose pediatric FN patients to morbidity and mortality.

Impact of Time-to-Antibiotic Delivery in Pediatric Patients With Cancer Presenting With Febrile Neutropenia

“…These results are in accordance with several recent studies assessing the impact of TTA in smaller cohorts of pediatric patients with FN. 23,26,32 A few FN studies have shown an association between a prolonged TTA and some adverse clinical outcomes but have not been consistent. 39 Fletcher et al showed in 1,628 FN episodes a multivariate association between a composite outcome (death, ICU admission or receiving >40 mL/kg IVF) in those receiving antibiotics between 60 and 120 minutes (32.9% of the cohort) versus ≤60 minute (20% of the cohort), P 5 .048.…”

“…These results are in accordance with several recent studies assessing the impact of TTA in smaller cohorts of pediatric patients with FN. 23,26,32…”

“…The evidence dictating the optimal TTA in adult and pediatric patients with FN is largely based on a few studies with small sample sizes and inconsistent findings associating a shorter TTA with decreased mortality or other adverse outcomes, frequently finding no associations. 5,7,11,17,[20][21][22][23][24][25][26][27][28][29][30][31][32] Additionally, a significant confounding factor in the assessment of TTA is triage bias, wherein patients who are severely ill appearing at presentation to a medical center will consistently receive immediate medical attention, leading to a faster TTA. 5 Although the intent of TTA metric of <60 minutes in pediatric patients with FN is to improve care, the inverse may paradoxically result when clinicians, who are under some pressure to meet this high-priority institutional standard, place orders for broad-spectrum antibiotics.…”

Effect of Prearrival Orders on Time to Antibiotics for Immunocompromised Oncology Patients Presenting to the Emergency Department With Fever

“…8,9 Other studies examining outcome have not demonstrated similar benefits in terms of mortality or reduced need for ICU level of care. 10,11 Nevertheless, the window of "antibiotics within 60 minutes" continues to be viewed as a quality of care metric for immunocompromised oncology patients with fever. [12][13][14] There are a number of published studies highlighting efforts to reduce the time to antibiotics for febrile pediatric oncology patients.…”

“…Some have demonstrated that lower TTA is associated with reduced rates of mortality, reduced need or time in intensive care unit (ICU) settings, reduced hospitalization length of stay, and, as a result, lower overall cost of care 8,9 . Other studies examining outcome have not demonstrated similar benefits in terms of mortality or reduced need for ICU level of care 10,11 . Nevertheless, the window of “antibiotics within 60 minutes” continues to be viewed as a quality of care metric for immunocompromised oncology patients with fever 12–14 …”