Diagnosis and Management of Febrile Neutropenia in Pediatric Oncology Patients—A Systematic Review

Abstract

Infectious diseases are associated with a high morbidity and mortality rate among pediatric cancer patients undergoing treatment or receiving a transplant. Neutropenia represents a potentially fatal complication of cancer treatment and is associated with a high risk of developing bacterial infections. Although febrile neutropenia (FN) can affect both adults and children, the latter has a higher chance of infections with an unknown origin. Prompt empiric broad-spectrum antibiotic administration is collectively considered the best therapeutic approach. This review aims to analyze the latest works from the literature regarding the therapeutic strategies, schemes, and approaches and the efficacy of these in pediatric febrile neutropenia. Following PRISMA guidelines, an advanced search on PubMed, Scopus, and Cochrane Library, using the keywords “febrile neutropenia”, “pediatric”, “cancer”, and “oncology”, was performed. A total of 197 articles were found to be eligible. After screening the abstracts and excluding unfit studies, 16 articles were analyzed. There were eight retrospective studies, five prospective studies, and two clinical trials. Altogether, these studies have described around 5000 episodes of FN. The median age of the participants was 7.6 years, and the underlying condition for most of them was acute leukemia. The infectious agent could only be determined in around one-fifth of cases, from which 90% were of bacterial origin. As such, empirical broad-spectrum antibiotics are used, with the most used treatment scheme comprising third- and fourth-generation cephalosporins and antipseudomonal penicillins. In order to improve the treatment strategies of FN episodes and to successfully de-escalate treatments toward narrower-spectrum antibiotics, hospitals and clinics should increase their efforts in identifying the underlying cause of FN episodes through blood culture urine culture and viral tests, wherever infrastructure enables it.

Impact of Time-to-Antibiotic Delivery in Pediatric Patients With Cancer Presenting With Febrile Neutropenia

“…21 Empiric antibiotics are required for severely neutropenic patients with fever because of their risk for severe bacterial infection and the inability to distinguish which patients have a bacterial etiology at fever presentation. 1,2 There exists a small subset of patients with FN who have severe sepsis at presentation for whom quick action is always needed (0.6% of episodes in this cohort). For these patients, antibiotics must be given urgently as this study showed a mortality rate over 57% even when antibiotics were given rapidly.…”

“…Febrile neutropenia (FN) during pediatric cancer therapy can be a life-threatening emergency 1-3 and is also a leading cause of hospital admission. 2,4 Patients are instructed to seek immediate medical evaluation with fever onset, and standard practice mandates empiric intravenous (IV) antibiotics in those who are severely neutropenic (absolute neutrophil count [ANC] <500 cells/µL 1 ). Time to antibiotic (TTA) refers to the time from patient arrival at a medical center until the time when empiric parenteral antibiotics are administered.…”

Application value of metagenomic next-generation sequencing in hematological patients with high-risk febrile neutropenia

“…FN patients with weakened immune systems are particularly vulnerable to fungal and viral infections. Without available evidence, fungi and viruses are rarely identified as the cause of early fever in FN ( Boeriu et al., 2022 ). Traditional methods for detecting fungal and viral infections are limited and often lead to missed diagnoses.…”

The Assessment of Antimicrobial Resistance in Gram-Negative and Gram-Positive Infective Endocarditis: A Multicentric Retrospective Analysis

“…The vast majority of Gram-negative bacteria are considered to be pathogens. Distinguished by their unique cell envelope structure, Gram-negative bacteria are associated with a higher mortality and morbidity rate on a global scale [ 4 , 5 , 6 ]. On the other side, many different Gram-positive bacteria are commonly known for some of the most dangerous community and healthcare-associated resistant infections [ 7 ].…”