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
In brief
Antibiotic de-escalation safe in 95% of pediatric fever-neutropenia episodes
In a multicenter trial of 231 children with cancer whose febrile neutropenia was classified as fever of unknown origin and showed early improvement, narrowing antibiotics achieved uneventful recovery in 95% of cases, matching the 96% rate with unchanged therapy. The results support cautious antimicrobial de-escalation as a stewardship option, pending larger studies to confirm impact on resistance.
- Journal
- Antibiotics (Basel, Switzerland) (Q1)
- Published
- 13 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Carolina Ibáñez, Romina Valenzuela, Marlon Barraza, Ana M Álvarez, Ernesto Paya, Verónica Contardo, et al.
- PMID
- 42650704
- DOI
- 10.3390/antibiotics15080779
Why clinicians should know about it
- Picked for Microbiology (medical) (top studies of the week, 30 August 2026): High-quality evidence in a top journal
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 30 August 2026): Antimicrobial adjustment in pediatric FN, not adult ICU
Abstract
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 48-72 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 48-72 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 0.95-1.06); absolute risk difference 0.01, (95%CI -0.05-0.06). 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.