Outpatient Management of Febrile Neutropenia in Children with Cancer

Abstract

The objectives of this article are to review the studies that have examined the safety and feasibility of outpatient management for children with febrile neutropenia, and to provide recommendations as to which patient populations and treatment strategies are most appropriate for this approach. The outpatient strategies have included either complete outpatient management or employment of early discharge, with the latter methodology predominating in most published studies. Common criteria relied upon to identify children with febrile neutropenia at low risk of serious infections included evidence of hematopoietic recovery and/or an absolute monocyte count >/=100/mm(3), and the absence of both comorbidity and culture positivity. A wide variety of different antibacterial regimens have been employed, with some trials investigating either early discontinuation of treatment or conversion to an oral administration strategy. Trials performed to date among this low risk population indicate a very low rate of readmission and/or complications. Some studies have also estimated substantial overall cost savings with this approach. However, many of these trials are significantly underpowered to detect the low rate of serious complications in the pediatric population with febrile neutropenia. At present, the available evidence indicates that a carefully chosen subpopulation of children with febrile neutropenia can be safely managed on an outpatient basis. Regardless of setting, current clinical guidelines for febrile neutropenia management indicate that all children with febrile neutropenia should be managed with appropriate antibacterial therapy until resolution of febrile neutropenia. Treatment with either an oral antibacterial regimen as initial therapy, or early discontinuation of antibacterial therapy in the outpatient setting should remain investigational at the present time.

Low risk episodes of fever and neutropenia in pediatric oncology: Is outpatient oral antibiotic therapy the new gold standard of care?

“…In the pediatric literature, there is no consensus on whether oral antibiotics in an outpatient setting are the new gold standard of therapy for FN: in their review on this issue, Holdsworth et al 4 conclude that “the available evidence indicates that a carefully chosen subpopulation of children with LRFN can be safely managed on an outpatient basis,” despite stating that there is no validated set of criteria reliably identifying pediatric oncology patients with LRFN, and that many of the trials studying outpatient management and/or oral anti‐microbial therapy were significantly underpowered to detect the low rate of serious complications. Orudjev and Lange 3 come to a similar conclusion, while Mullen 15 states that “pediatric cancer patients with LRFN can be prospectively identified and safely treated as outpatients with oral antibiotics.”…”

“…It is evident that at least the two criteria of chronic obstructive pulmonary disease and age, and thus the whole risk prediction score itself, cannot be directly applied to children and adolescents with FN. In pediatric oncology, criteria—basing on characteristics accessible at presentation with FN and within the first hours of follow‐up—to predict bacteremia and/or infectious complications in general, have been developed and/or validated in many single center studies, see, e.g., 3,4,18 for overviews. This has led to a multitude of different risk scores and criteria.…”

“…Different steps of modification of the initial gold standard of care, according to the risk of complications of the respective episode, have been developed and studied so far. They range from; (1) strategies of early discharge (e.g., 72 hr after admission) before resolution of severe neutropenia in episodes with a favorable clinical course, with or without continuation of antibiotic therapy, see 3,4 for overviews, (2) therapy with oral instead of intravenous broad‐spectrum antibiotics in patients with a supposed low risk for bacterial infections and complications (LRFN), be it from the very beginning as inpatients 5,6, or as outpatients after an initial inpatient observation period with intravenous antibiotics (sequential approach) 7–9, to (3) complete abstention from anti‐microbial therapy in a well‐defined inpatient population with very low risk for bacterial infections 10.…”

“…Early discharge strategies are scientifically well founded and broadly applied in clinical practice, see the reviews of Orudjev and Lange 3 and Holdsworth et al 4, and the 2002 guidelines of the Infectious Diseases Society of America 11. The concept of complete abstention from anti‐microbial therapy 10, on the other hand, is far away from broad clinical application.…”

Prospective audit of treatment of paediatric febrile neutropenia in Australasia

“…Not surprisingly, outpatient treatment of low‐risk episodes of fever and neutropenia is substantially less costly than inpatient therapy, and is preferred by most families 2,8 . Additional benefits of outpatient treatment are a reduction in nosocomial infection risk, reduced administration of broad‐spectrum antibiotics and associated drug resistance, and a reduction in treatment‐related toxicity 9 …”