Abstract
BackgroundFebrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim of this study to investigate cytokine profiles as potential biomarkers using in-vitro sepsis models to differentiate between distinct clinical courses of febrile neutropenia (FN).MethodsWe conducted an observational study in FN episodes of pediatric oncology patients. Courses of neutropenia were defined as severe in case of proven blood stream infection or clinical evidence of complicated infection. We collected blood samples at various time points from the onset of FN and stimulated ex vivo with lipopolysaccharide (LPS) and Staphylococcus epidermidis (SE) for 24 h. Twenty-seven cytokine levels were measured in the whole blood culture supernatants by a multiplex immunoassay system.ResultsForty-seven FN episodes from 33 children were investigated. IL-8, IL-1β, and MCP-1 expression increased significantly over time. IL-8, MIP-1α, MIP-1β, MCP-1, and TNF-α showed significantly lower concentration in patients with a clinically severe course of the FN.ConclusionsDistinct patterns of cytokine profiles seem to be able to determine infectious FN and to predict the severity of its clinical course. If these data can be verified in a multi-centre setting, this may finally lead to an individualized treatment strategy facilitating antibiotic stewardship in these patients.
Highlights
Febrile neutropenia is a common and serious complication during treatment of childhood cancer
In the Severe course group (SCG), escalation of antibiotic treatment was performed in 15 episodes and contained Meropenem (13.33%), Teicoplanin (6.67%), Meropenem plus Teicoplanin (20.0%), Vancomycin (20.0%), Vancomycin plus Meropenem (26.67%), and Metronidazole (6.67%)
Children with febrile neutropenia receive broadspectrum antibiotic treatment, bacterial infection cannot be proven in the majority of episodes
Summary
Febrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim of this study to investigate cytokine profiles as potential biomarkers using in-vitro sepsis models to differentiate between distinct clinical courses of febrile neutropenia (FN). The empiric use of broad-spectrum antibiotics in patients with febrile neutropenia leads to a significant decrease in mortality and morbidity [2,3,4,5]. The role of cytokines in the onset of inflammation is well known Their role for the diagnosis and course of bacterial infection has been controversially discussed [12, 16, 18,19,20,21]
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