Overall Summary of Recommendations* (see PDF version)
*Parenthesis indicates the GRADE strength of recommendation (1=strong, 2=weak) and quality of the evidence (A=high, B=moderate, C=low or very-low).
Initial presentation of FN
Adopt a validated risk stratification strategy and incorporate it into routine clinical management (1C).
Obtain blood cultures at the onset of FN from all lumens of central venous catheters (1C).
Consider peripheral blood culture concurrent with obtaining central venous catheter cultures (2C).
Obtain chest radiography only in symptomatic patients (1B).
Reserve addition of a second Gram-negative agent or a glycopeptide for patients who are clinically unstable, when a resistant infection is suspected, or for centers with a high rate of resistant pathogens (1B).
In children with low-risk FN, consider oral antibiotic administration if the child is able to tolerate this route of administration reliably (2B).
Modification of Treatment
Cessation of Treatment
Ongoing management of FN: 24 to 72 hours after initiation of empiric antibacterial treatment
In patients who are responding to initial empiric antibiotic therapy, discontinue double coverage for Gram-negative infection or empiric glycopeptide (if initiated) after 24 to 72 hours if there is no specific microbiologic indication to continue combination therapy (1B).
Do not modify the initial empiric antibacterial regimen based solely on persistent fever in children who are clinically stable (1C).
In children with persistent fever who become clinically unstable, escalate the initial empiric antibacterial regimen to include coverage for resistant Gram-negative, Gram-positive, and anaerobic bacteria (1C).
Empiric Antifungal Treatment: 96 hours or more after initiation of empiric antibacterial treatment
Patients at IFD high-risk are those with AML, relapsed acute leukemia, those receiving highly myelosuppressive chemotherapy for other malignancies, and allogeneic hematopoietic stem cell transplant recipients with persistent fever despite prolonged (≥ 96 hours) broad-spectrum antibiotic therapy and expected prolonged neutropenia (>10 days). All others should be categorized as IFD low-risk (1B).
In children, do not use ß-D-glucan testing for clinical decisions until further pediatric evidence has accumulated (1C).
In IFD high-risk children with persistent FN beyond 96 hours, perform evaluation for IFD. Evaluation should include CT of the lungs and targeted imaging of other clinically suspected areas of infection (1B). Consider CT of the sinuses in children 2 years of age or older (2C).
Abbreviations: AML – acute myeloid leukemia; CT – computed tomography; FN – fever and neutropenia; GRADE – Grades of Recommendation Assessment, Development and Evaluation; IFD – invasive fungal disease; CNS –central nervous system