Prolonged febrile neutropenia in the pediatric patient with cancer

Infectious diseases continue to be major causes of morbidity and mortality in pediatric patients with cancer. Yet not all pediatric patients with cancer with fever and neutropenia are at equal risk for substantial morbidity or mortality from infection. Patients at highest risk for developing infectious complications are those with severe and prolonged neutropenia, substantial medical comorbidity, and hematologic malignancy, or recipients of stem-cell transplantation. These "high-risk" patients also have concomitant host immune deficits as well: severe mucositis, lymphopenia, hypogammaglobulinemia, and gut microbial dysbiosis. Because bacterial and fungal infections are the most common infectious complications, continuation of empirical antibacterial antibiotics that were initiated at the onset of febrile neutropenia and prompt initiation of empirical antifungal therapy in the setting of prolonged fever and neutropenia continue to be the standard of care. In high-risk patients, antibiotic therapy should be maintained until neutrophil counts have recovered. Adjunctive therapies have been shown to be ineffective (e.g., colony-stimulating factors) or necessitate further study (e.g., granulocyte infusions or keratinocyte growth factor treatment to heal mucositis). Prophylactic use of antibacterial and antifungal antibiotics in high-risk patients has shown promise but the fear of inducing antimicrobial-resistant strains remains a deterrent. Finally, the novel concepts of manipulating the host gut microbiota and/or augmenting GI mucosal immunity to prevent invasive bacterial and fungal infections in pediatric patients with cancer offers great promise, but more definitive studies need to be performed.