{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:41:05Z","timestamp":1788381665728,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hilfe f\u00fcr krebskranke Kinder Frankfurt e.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Whereas the clinical approach in pediatric cancer patients with febrile neutropenia is well established, data on non-neutropenic infectious episodes are limited. We therefore prospectively collected over a period of 4 years of data on all infectious complications in children treated for acute lymphoblastic or myeloid leukemia (ALL or AML) and non-Hodgkin lymphoma (NHL) at two major pediatric cancer centers. Infections were categorized as fever of unknown origin (FUO), and microbiologically or clinically documented infections. A total of 210 patients (median age 6 years; 142 ALL, 23 AML, 38 NHL, 7 leukemia relapse) experienced a total of 776 infectious episodes (571 during neutropenia, 205 without neutropenia). The distribution of FUO, microbiologically and clinically documented infections, did not significantly differ between neutropenic and non-neutropenic episodes. In contrast to neutropenic patients, corticosteroids did not have an impact on the infectious risk in non-neutropenic children. All but one bloodstream infection in non-neutropenic patients were due to Gram-positive pathogens. Three patients died in the context of non-neutropenic infectious episodes (mortality 1.4%). Our results well help to inform clinical practice guidelines in pediatric non-neutropenic cancer patients presenting with fever, in their attempt to safely restrict broad-spectrum antibiotics and improve the quality of life by decreasing hospitalization.<\/jats:p>","DOI":"10.3390\/antibiotics11070900","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T10:21:33Z","timestamp":1657016493000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Infections during Non-Neutropenic Episodes in Pediatric Cancer Patients\u2014Results from a Prospective Study in Two Major Large European Cancer Centers"],"prefix":"10.3390","volume":"11","author":[{"given":"Stefan","family":"Sch\u00f6ning","sequence":"first","affiliation":[{"name":"Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Barnbrock","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-6511","authenticated-orcid":false,"given":"Konrad","family":"Bochennek","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Gordon","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Program, Department of Pediatric Hematology and Oncology and Center for Bone Marrow Transplantation, University Children\u2019s Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1188-393X","authenticated-orcid":false,"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Program, Department of Pediatric Hematology and Oncology and Center for Bone Marrow Transplantation, University Children\u2019s Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-3439","authenticated-orcid":false,"given":"Thomas","family":"Lehrnbecher","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.7326\/0003-4819-64-2-328","article-title":"Quantitative relationships between circulating leukocytes and infections in patients with acute leukemia","volume":"64","author":"Bodey","year":"1966","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/MOP.0000000000000708","article-title":"Treatment of fever in neutropenia in pediatric oncology patients","volume":"31","author":"Lehrnbecher","year":"2019","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1200\/JCO.2016.71.7017","article-title":"Guideline for the Management of Fever and Neutropenia in Children with Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update","volume":"35","author":"Lehrnbecher","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e270","DOI":"10.1016\/S1470-2045(20)30725-7","article-title":"Eighth European Conference on Infections in Leukaemia (ECIL-8): 2020 Guidelines for the Use of Antibiotics in Paediatric Patients with Cancer or Haematopoietic Cell Transplantation","volume":"22","author":"Lehrnbecher","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1016\/S1470-2045(20)30723-3","article-title":"Eighth European Conference on Infections in Leukaemia (ECIL-8): 2020 Updated Guidelines for Diagnosis, Prevention and Treatment of Invasive Fungal Diseases in Paediatric Patients with Cancer or Al-logeneic Haematopoietic Cell Transplantation","volume":"22","author":"Groll","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/pbc.25275","article-title":"Development and validation of a prediction model for diagnosing blood stream infections in febrile, non-neutropenic children with cancer","volume":"62","author":"Esbenshade","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1002\/cncr.30792","article-title":"Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia","volume":"123","author":"Esbenshade","year":"2017","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1200\/JCO.20.00591","article-title":"Prospective Implementation of a Risk Prediction Model for Bloodstream Infection Safely Reduces Antibiotic Usage in Febrile Pediatric Cancer Patients without Severe Neutropenia","volume":"38","author":"Esbenshade","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/00043426-200308000-00004","article-title":"Evaluation and Treatment of Fever in the Non-Neutropenic Child with Cancer","volume":"25","author":"Salzer","year":"2003","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/MPH.0000000000001878","article-title":"Outcomes and Disposition of Oncology Patients with Non-neutropenic Fever and Positive Blood Cultures","volume":"43","author":"Sharma","year":"2020","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1097\/MPH.0000000000002201","article-title":"Bacteremia in Febrile, Non-neutropenic, and Well-appearing Children with Cancer","volume":"44","author":"Beauchemin","year":"2022","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF02796205","article-title":"Infections in acute leukemia: An analysis of 240 febrile episodes","volume":"17","author":"Jagarlamudi","year":"2000","journal-title":"Med. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1080\/08880018.2019.1667462","article-title":"Etiology, drug sensitivity profiles and clinical outcome of bloodstream infections: A retrospective study of 784 pediatric patients with hematological and neoplastic diseases","volume":"36","author":"Chen","year":"2019","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/cid\/cis774","article-title":"Association Between Corticosteroids and Infection, Sepsis, and Infectious Death in Pediatric Acute Myeloid Leukemia (AML): Results from the Canadian Infections in AML Research Group","volume":"55","author":"Dix","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1097\/INF.0b013e3181e32ab2","article-title":"A Prospective Study of Febrile Episodes in Inpatient Children on Chemotherapy","volume":"29","author":"Ke","year":"2010","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e596","DOI":"10.1097\/MPH.0000000000001935","article-title":"Evaluation of Inflammatory Biomarkers in Pediatric Hematology-Oncology Patients with Bloodstream Infection","volume":"43","author":"Chen","year":"2020","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1002\/pbc.25660","article-title":"Approach to Non-Neutropenic Fever in Pediatric Oncology Patients-A Single Institution Study","volume":"62","author":"Ali","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1007\/s10096-017-3078-5","article-title":"Mortality associated with candidemia in non-neutropenic cancer patients is not less compared to a neutropenic cohort of cancer patients","volume":"36","author":"Goel","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1470-2045(14)70017-8","article-title":"Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation","volume":"15","author":"Groll","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1200\/JCO.2012.42.7161","article-title":"Guideline for the Management of Fever and Neutropenia in Children with Cancer and\/or Undergoing Hematopoietic Stem-Cell Transplantation","volume":"30","author":"Lehrnbecher","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e382","DOI":"10.1038\/bcj.2015.110","article-title":"Infectious complications in children with acute myeloid leukemia: Decreased mortality in multicenter trial AML-BFM 2004","volume":"6","author":"Bochennek","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3389\/fmicb.2019.00681","article-title":"Incidence and Outcome of Invasive Fungal Diseases in Children with Hematological Malignancies and\/or Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Multicenter Study","volume":"10","author":"Lehrnbecher","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Faculty Opinions recommendation of Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"Walsh","year":"2008","journal-title":"Clin. Infect. 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