{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:28:37Z","timestamp":1786613317689,"version":"build-2736575974"},"reference-count":23,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010751","name":"Fondecyt","doi-asserted-by":"publisher","award":["1200964"],"award-info":[{"award-number":["1200964"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010751","name":"Fondecyt","doi-asserted-by":"publisher","award":["1251720"],"award-info":[{"award-number":["1251720"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: The objective of this study is to evaluate the efficacy and safety of maintaining antimicrobial (AM) therapy or adjusting AM therapy during episodes of febrile neutropenia (FN) catalogued as a fever of unknown origin (FUO) in children with cancer. Methods: This is a prospective, multicenter, noninferiority, randomized study, approved by ethics committee, in children with episodes of FN in eight hospitals in Chile. Microbiological and molecular samples were drawn at admission. Patients with FUO (negative bacterial and viral study with no clinical focus suggesting infection) and favorable evolution during the first 48\u201372 h of AM therapy were randomized 1:1 to maintain or adjust treatment, reducing the number and spectrum of AMs. The primary endpoint was the percentage of episodes with an uneventful resolution; the secondary endpoints were the re-adjustment of AM therapy, days of fever\/hospitalization\/AM therapy, days of vancomycin and meropenem per 1000 days of neutropenia, number of AMs after randomization, pediatric intensive care unit (PICU) admission, sepsis, and death. Results: A total of 266 of 939 FN episodes recruited between March 2021 and January 2024 were catalogued as FUO, of which 231 had a favorable evolution at 48\u201372 h and were randomized, 111 to maintain and 120 to adjust AM therapy. Both groups presented the same percentage of uneventful resolution, with 106 (96%) in the group that maintain AM therapy and 114 (95%) in the adjusted group (p = 1.00); relative risk 1.01, (95%CI 0.95\u20131.06); absolute risk difference 0.01, (95%CI \u22120.05\u20130.06). Conclusions: The main finding of this study demonstrates that adjusting antimicrobial therapy appears safe in carefully selected FUO cases with a favorable early evolution, during episodes of FN catalogued as FUO in children with cancer. These findings open an opportunity to new AM stewardship strategies in this population, with a possible future impact on AM resistance.<\/jats:p>","DOI":"10.3390\/antibiotics15080779","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Adjusting Antimicrobial Therapy in Episodes of Fever and Neutropenia Catalogued as Fever of Unknown Origin in Children with Cancer: A Randomized Clinical Trial"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6259-9862","authenticated-orcid":false,"given":"Carolina","family":"Ib\u00e1\u00f1ez","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-7686","authenticated-orcid":false,"given":"Romina","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon","family":"Barraza","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital San Juan de Dios, Santiago 8320000, Chile"},{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-3342","authenticated-orcid":false,"given":"Ernesto","family":"Paya","sequence":"additional","affiliation":[{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"},{"name":"Department of Pediatrics, Hospital Dr. Exequiel Gonz\u00e1lez Cort\u00e9s, Faculty of Medicine, Universidad de Chile, Santiago 8900000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Contardo","sequence":"additional","affiliation":[{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"},{"name":"Department of Pediatrics, Hospital Dr. Roberto del R\u00edo, Faculty of Medicine, Universidad de Chile, Santiago 8380000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-5035","authenticated-orcid":false,"given":"Valentina","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"},{"name":"Department of Pediatrics, Hospital Dr. S\u00f3tero del R\u00edo, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica, Santiago 8200000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ducasse","sequence":"additional","affiliation":[{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"},{"name":"Department of Pediatrics, Hospital Gustavo Fricke, Vi\u00f1a del Mar 2520000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"},{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Coria","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"de la Maza","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"},{"name":"Department of Pediatrics, Hospital San Borja Arriar\u00e1n, Faculty of Medicine, Universidad de Chile, Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Inostroza","sequence":"additional","affiliation":[{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"},{"name":"Department of Pediatrics, Hospital de Antofagasta, Antofagasta 1240000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"Santolaya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centro de Investigaci\u00f3n Cl\u00ednica Avanzada (CICA), Hospital Dr. Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago 7500000, Chile"},{"name":"Committee of Infectious Diseases, National Child Program of Antineoplastic Drugs (PINDA), Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1007\/s00431-021-04056-5","article-title":"Trends in bacterial bloodstream infections and resistance in immuno-compromised patients with febrile neutropenia: A retrospective analysis","volume":"180","author":"Raad","year":"2021","journal-title":"Eur. 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