Unlike in adults, however, beta-D-glucan testing should not be relied on for clinical decisions in this scenario, the panelists advise in their paper in the Journal of Clinical Oncology online September 17.
“We have created an evidence-based guideline for the management of pediatric FN (fever and neutropenia),” write Dr. Lillian Sung, at the Hospital for Sick Children in Toronto, Ontario, Canada, and colleagues.
“Some recommendations are similar to those of adult guidelines, such as choice of empiric antibacterials and criteria for their modification. Some similar recommendations have benefitted from a pediatric-specific focus, such as consideration of outpatient management and oral antibacterial therapy,” the authors explain. “However, there are key distinctions.”
The guideline covers three main areas: the initial presentation of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation, ongoing management, and empiric antifungal treatment.
Regarding the initial presentation, the guideline includes validated risk-stratification strategies that should be adopted routinely. For high-risk febrile neutropenia, empiric monotherapy with an antipseudomonal beta-lactam or carbapenem is recommended. Addition of a second agent should be reserved for patients who are clinically unstable or when resistant infection is likely.
Ongoing management depends on the patient’s response. Double coverage, if initiated, can be discontinued after 24-72 hour if the patient is afebrile with evidence of marrow recovery and negative blood cultures. If fever persists and the patient becomes clinically unstable, initial empiric antibacterial regimen should be escalated to include coverage for resistant Gram-negative, Gram-positive, and anaerobic bacteria, the guideline recommends.
The risk of invasive fungal disease, the panelists note, is highest in children with AML or relapsed acute leukemia, those receiving highly myelosuppressive chemotherapy for other malignancies, and those undergoing allogeneic hematopoietic stem-cell transplantation with persistent fever despite prolonged broad-spectrum antibiotic therapy. All other patients should be considered low risk for fungal infection, according to the guideline.
Galactomannan screening to support a diagnosis of aspergillosis should be undertaken in children at high risk for invasive fungal disease, but not routinely in low-risk children, the experts advise. As mentioned, beta-D-glucan testing should not be used in children “until further pediatric evidence has accumulated.”
Empiric treatment with caspofungin or liposomal amphotericin B should be started in high-risk children with persistent or recurrent fever, and can be considered for low-risk children.
While they note that their recommendations are based on the best available evidence, Dr. Sung and colleagues conclude: “Future iterations of this guideline will need to incorporate evolving and emerging evidence as research is conducted in pediatric FN (fever and neutropenia).”