Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trialResearch in context
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
EClinicalMedicine, Vol 83, Iss , Pp 103195- (2025)
| 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 |
|---|---|
| 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 |
| Publication Year |
2025
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| Source |
EClinicalMedicine, Vol 83, Iss , Pp 103195- (2025)
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| 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
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| Document Type |
article
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| Language |
English
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| Publisher Information |
Elsevier, 2025.
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| Subject Terms | |
