Principles of infectious disease and management of febrile neutropenia

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What are typical infectious complications in pediatric oncology patients?

Typical infectious complications include bacterial sepsis, systemic or organ-specific infections caused by either primary or reactivated viruses (e.g., cytomegalovirus [CMV], Epstein-Barr virus [EBV]), respiratory viruses (e.g., influenza, respiratory syncytial virus [RSV]), and invasive fungal infections (e.g., Candida , Aspergillus sp.)

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How does bacterial infectious risk vary across the spectrum of oncology patients?

The risk of infection coincides with the intensity of chemotherapy, leading to profound myelosuppression, mucositis, and nutritional deficiencies. Bacteremia is most common in relapsed acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) followed by allogeneic hematopoietic stem cell transplantation (HSCT). Estimates of bacterial infections vary by study and year published but can approach 50% in relapsed ALL and AML. Embryonal central nervous system (CNS) tumors and high-risk neuroblastoma are other high-risk diagnoses. Across all conditions, indwelling foreign devices such as central venous catheters and ventriculoperitoneal shunts increase infection risk.

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What is the recommended empiric antibiotic coverage for febrile neutropenia?

Antibiotic coverage should be based on the local hospital antibiogram and should offer combined coverage for:

• Pseudomonas and related gram-negative organisms

• The majority of typical gram-positive organisms, including Staphylococcus aureus and Viridans group Streptococci.

Therefore antibiotics should include an antipseudomonal agent, which has additional gram-positive coverage, typically a penicillin (piperacillin-tazobactam) or cephalosporin (cefepime). Vancomycin is not routinely indicated as empiric coverage for stable febrile children with neutropenia unless there is a high probability of a resistant gram-positive pathogen (e.g., signs of catheter site infection, skin and soft tissue infection, and/or a previous history of methicillin-resistant Staphylococcus aureus [MRSA] or resistant viridans group Streptococci ).

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