Clinical Characteristics and Outcomes of Non-Neutropenic Fever in Children with Cancer: An Urban-Single Institution Experience Non-Neutropenic Fever in Pediatric Cancer Patients
Article Sidebar
Main Article Content
Abstract
OBJECTIVE: To evaluate the clinical characteristics and outcomes of pediatric cancer with non-neutropenic fever (NNF) in pediatric cancer patients in the absence of a central venous catheter.
METHODS: This single-center retrospective cohort study enrolled pediatric patients with cancer (age < 18 years) who received chemotherapy treatment at the Department of Pediatrics, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand, from January 2016 to July 2020. Clinical characteristics and outcomes of NNF episodes were described. Descriptive statistics were analyzed.
RESULTS: Fifty-one patients were reviewed, but the 97 NNF episodes were documented from 32 patients. Only One (of the 51 patients) had subcutaneous port. The most frequent cancer diagnosis was acute lymphoblastic leukemia (51%). NNF occurred in 3.8 per 1,000 days of chemotherapy period (95% confidence interval [CI] 3.1–4.6). The most frequently clinically documented infections were respiratory tract infection (35%), urinary tract infection (11%), and gastrointestinal infection (10%). The causative pathogens could not be demonstrated in 67.1% of NNF episodes. The commonly identified pathogens were viruses (12.3%), gram-negative bacteria (10.3%), and gram-positive bacteria (5.2%). Empiric treatment with antibiotic was initiated in 92.8% of the total episodes. Ceftriaxone was the most common antibiotic of choice. Only one episode had a positive hemoculture. Four (4.1%) episodes required intensive care unit admissions, and only one NNF-related mortality due to the human Bocavirus pneumonia and multi-organ failure occurred. The mortality rate of NNF was 3.1%.
CONCLUSION: NNF episodes are common and life-threatening complications among pediatric cancer patients and generally lead to hospitalization. The incidence of NNF was 3.8 per 1,000 days of chemotherapy (95% CI 3.1–4.6). The causative pathogen in 67% of NNF episodes was unknown, and the commonly identified pathogens were viruses. However, many patients did not identify any causative bacteria, and they received intravenous antibiotics and were hospitalized. The results of our study suggest that patients with severe symptoms may indicate early evaluation and prompt management for viral infection, especially in a patient with a negative bacterial culture and poor respond to antibiotic treatment. This study reveals baseline information for future cohorts to provide guideline management of this common complication during cancer treatment.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Erdmann F, Frederiksen LE, Bonaventure A, Mader L, Hasle H, Robison LL, et al. Childhood cancer: survival, treatment modalities, late effects and improvements over time. Cancer Epidemiol 2021;71(Pt B):101733.
Bidwell SS, Peterson CC, Demanelis K, Zarins KR, Meza R, Sriplung H,et al. Childhood cancer incidence and survival in Thailand: a comprehensive population-based registry analysis, 1990-2011. Pediatr Blood Cancer 2019;66(1):e27428.
O'Brien SN, Blijlevens NM, Mahfouz TH, Anaissie EJ. Infections in patients with hematological cancer: recent developments. Hematology Am Soc Hematol Educ Program 2003:438-72.
Loeffen EAH, Knops RRG, Boerhof J, Feijen EAML, Merks JHM, Reedijk AMJ, et al. Treatment-related mortality in children with cancer: Prevalence and risk factors. Eur J Cancer 2019;121:113-22.
Mueller EL, Jacob SA, Cochrane AR, Carroll AE, Bennett WE Jr. Variation in hospital admission from the emergency department for children with cancer: a pediatric health information system study. Pediatr Blood Cancer 2020;67(6):e28140.
Kochanek M, Schalk E, von Bergwelt-Baildon M, Beutel G, Buchheidt D, Hentrich M, et al. Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol 2019;98(5):1051-69.
Ammann RA, Bodmer N, Hirt A, Niggli FK, Nadal D, Simon A, et al. Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study. J Clin Oncol 2010;28(12):2008-14.
Lehrnbecher T, Robinson P, Fisher B, Alexander S, Ammann RA, Beauchemin M, et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol 2017;35(18):2082-94.
Gorelick MH, Owen WC, Seibel NL, Reaman GH. Lack of association between neutropenia and the incidence of bacteremia associated with indwelling central venous catheters in febrile pediatric cancer patients. Pediatr Infect Dis J 1991;10(7):506-10.
Allaway Z, Phillips RS, Thursky KA, Haeusler GM. Nonneutropenic fever in children with cancer: a scoping review of management and outcome. Pediatr Blood Cancer 2019;66(6):e27634.
Esbenshade AJ, Zhao Z, Baird A, Holmes EA, Dulek DE, Banerjee R,et al. Prospective implementation of a risk prediction model for bloodstream infection safely reduces antibiotic usage in febrile pediatric cancer patients without severe neutropenia. J Clin Oncol 2020;38(27):3150-60.
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6(1):2-8.
Bartholomew F, Aftandilian C, Andrews J, Gutierrez K, Luna-Fineman S, Jeng M. Evaluation of febrile, nonneutropenic pediatric oncology patients with central venous catheters who are not given empiric antibiotics. J Pediatr 2015;166(1):157-62.
Beauchemin M, Marshall AF, Ricci AM, Lopez ID, Yao Y, Lee A, et al. Bacteremia in febrile, non-neutropenic, and well-appearing children with cancer. J Pediatr Hematol Oncol 2022;44(1):e194-8.
Karavanaki K, Kossiva L, Sklavou R, Kakleas K, Tsentidis C, Gourgiotis D, et al. Infections in children with cancer: the role of the presence or absence of neutropenia. Pediatr Emerg Care 2021;37(3):155-60.
Ali BA, Hirmas N, Tamim H, Merabi Z, HannaWakim R, Muwakkit S, et al. Approach to non-neutropenic fever in pediatric oncology patients-a single institution study. Pediatr Blood Cancer 2015;62(12):2167-71.
Hijano DR, Maron G, Hayden RT. Respiratory viral infections in patients with cancer or undergoing hematopoietic cell transplant. Front Microbiol 2018;9:3097.
Chemaly RF, Ghantoji SS, Shah DP, Shah JN, El Taoum KK, Champlin RE, et al. Respiratory syncytial virus infections in children with cancer. J Pediatr Hematol Oncol 2014;36(6): e376-81.
Koskenvuo M, Möttönen M, Waris M, Allander T, Salmi TT, Ruuskanen O. Human bocavirus in children with acute lymphoblastic leukemia. Eur J Pediatr 2008;167(9):1011-5.
Christensen A, Kesti O, Elenius V, Eskola AL, Døllner H, Altunbulakli C, et al. Human bocaviruses and paediatric infections. Lancet Child Adolesc Health 2019;3(6): 418-26.