Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trialResearch in context
| Title: | Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trialResearch in context |
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| Authors: | Sean W.X. Ong; Ruxandra Pinto; Asgar Rishu; Steven Y.C. Tong; Robert J. Commons; John M. Conly; Gerald A. Evans; Michael Fralick; Christopher Kandel; Philippe R.S. Lagacé-Wiens; Todd C. Lee; Sylvain A. Lother; Derek R. MacFadden; John C. Marshall; Valérie Martel-Laferrière; Michael Mayette; Emily G. McDonald; John D. Neary; Josef Prazak; Edward Raby; Adrian Regli; Benjamin A. Rogers; Stephanie Smith; Linda R. Taggart; Han Ting Wang; Terence Wuerz; Dafna Yahav; Paul J. Young; Robert A. Fowler; Nick Daneman; Benjamin Rogers; Yahya Shehabi; Rachael Parke; Deborah J. Cook; Yaseen Arabi; John Muscedere; Steven Reynolds; Richard Hall; Dhiraj Bhatia Dwivedi; Colin McArthur; Shay McGuinness; Bryan Coburn; Anna Geagea; Pavani Das; Phillip Shin; Michael Detsky; Andrew Morris; Jeff E. Powis; Wendy Sligl; Sean M. Bagshaw; Nishma Singhal; Emilie Belley-Cote; Richard Whitlock; Kosar Khwaja; Susan Morpeth; Alex Kazemi; Tony Williams; Lauralyn McIntyre; Jennifer L.Y. Tsang; Francois Lamontagne; Alex Carignan; John Marshall; Jan O. Friedrich; Robert Cirone; Mark Downing; Christopher Graham; Joshua Davis; Erick Duan; John Neary; Gerald Evans; Basem Alraddadi; Sameera Al Johani; Claudio Martin; Sameer Elsayed; Ian Ball; François Lauzier; Alexis F. Turgeon; Henry Thomas Stelfox; John Conly; Richard Sullivan; Jennifer Grant; Ilya Kagan; Paul Young; Cassie Lawrence; Kevin O'Callaghan; Matthew Eustace; Keat Choong; Pierre Aslanian; Ulrike Buehner; Tom Havey; Alexandra Binnie; Brenda Reeve; Edward Litton; Sylvain Lother; Anand Kumar; Ryan Zarychanski; Tomer Hoffman; David L. Paterson; Peter Daley; Emmanuel Charbonney; Jean-Francois Naud; Sally Roberts; Ravindranath Tiruvoipati; Sachin Gupta; Gordon Wood; Omar Shum; Spiros Miyakis; Peter Dodek; Clement Kwok; Karen Doucette |
| Source: | EClinicalMedicine, Vol 83, Iss , Pp 103195- (2025) |
| Publisher Information: | Elsevier |
| Publication Year: | 2025 |
| Collection: | Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: | Bloodstream infections; Antibiotic duration; Clinical trial; Heterogeneity of treatment effect; Antimicrobial stewardship; Medicine (General); R5-920 |
| Description: | Summary: Background: The BALANCE trial demonstrated non-inferiority of 7 (vs 14) day antibiotic durations in patients with uncomplicated non-S. aureus/lugdunensis bacterial bloodstream infections (BSI). However, there may be patient subgroups who benefit from longer durations. We aimed to evaluate if bedside clinical decision rules could identify these subgroups. Methods: In this post-hoc analysis of the multicentre, randomised BALANCE trial (October 17, 2014–May 5, 2023), we applied three clinical decision rules to investigate heterogeneity of treatment effect in 7-day vs 14-day antibiotic durations on 90-day all-cause mortality. We used the rules to categorize patients in BALANCE into different risk groups and calculated the unadjusted absolute risk difference (RD) for 90-day mortality in patients receiving 7- vs 14-day antibiotics within each risk group. Statistical significance was tested using an interaction test. The BALANCE trial is registered with ClinicalTrials.gov (NCT03005145). Findings: 3581 patients were included. All three rules predicted mortality risk, but none identified statistically significant effect modification: (a) static rule (low-risk: RD −0.58, 95% CI −8.91 to 7.73; moderate-risk: RD −.01, 95% CI −3.86 to 1.83; high-risk: RD −2.65, 95% CI −7.12 to 1.81; p = 0.74); (b) dynamic rule (met rule on day 7: RD −2.18, 95% CI −4.81 to 0.45; did not meet rule: RD 1.75, 95% CI −3.89 to 7.40; p = 0.16); and (c) early clinical failure criteria (score |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2589537025001270; https://doaj.org/toc/2589-5370; https://doaj.org/article/76bc971defd249d48ce4f8d9d6867213 |
| DOI: | 10.1016/j.eclinm.2025.103195 |
| Availability: | https://doi.org/10.1016/j.eclinm.2025.103195; https://doaj.org/article/76bc971defd249d48ce4f8d9d6867213 |
| Accession Number: | edsbas.16F7A41D |
| Database: | BASE |