Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trialResearch in context
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...
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| author | 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 Nick Daneman Asgar Rishu Ruxandra Pinto Benjamin Rogers Yahya Shehabi Rachael Parke Deborah J. Cook Yaseen Arabi John Muscedere Steven Reynolds Richard Hall Dhiraj Bhatia Dwivedi Colin McArthur Shay McGuinness Dafna Yahav Bryan Coburn Anna Geagea Pavani Das Phillip Shin Michael Detsky Andrew Morris Michael Fralick Jeff E. Powis Christopher Kandel Wendy Sligl Sean M. Bagshaw Nishma Singhal Emilie Belley-Cote Richard Whitlock Kosar Khwaja Susan Morpeth Alex Kazemi Tony Williams Derek R. MacFadden 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 Todd C. Lee Emily G. McDonald 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 Josef Prazak Brenda Reeve Edward Litton Sylvain Lother Anand Kumar Ryan Zarychanski Tomer Hoffman David L. Paterson Peter Daley Robert J. Commons Emmanuel Charbonney Jean-Francois Naud Sally Roberts Ravindranath Tiruvoipati Sachin Gupta Gordon Wood Omar Shum Spiros Miyakis Peter Dodek Clement Kwok Linda R. Taggart Stephanie Smith Karen Doucette Robert A. Fowler |
| author_facet | 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 Nick Daneman Asgar Rishu Ruxandra Pinto Benjamin Rogers Yahya Shehabi Rachael Parke Deborah J. Cook Yaseen Arabi John Muscedere Steven Reynolds Richard Hall Dhiraj Bhatia Dwivedi Colin McArthur Shay McGuinness Dafna Yahav Bryan Coburn Anna Geagea Pavani Das Phillip Shin Michael Detsky Andrew Morris Michael Fralick Jeff E. Powis Christopher Kandel Wendy Sligl Sean M. Bagshaw Nishma Singhal Emilie Belley-Cote Richard Whitlock Kosar Khwaja Susan Morpeth Alex Kazemi Tony Williams Derek R. MacFadden 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 Todd C. Lee Emily G. McDonald 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 Josef Prazak Brenda Reeve Edward Litton Sylvain Lother Anand Kumar Ryan Zarychanski Tomer Hoffman David L. Paterson Peter Daley Robert J. Commons Emmanuel Charbonney Jean-Francois Naud Sally Roberts Ravindranath Tiruvoipati Sachin Gupta Gordon Wood Omar Shum Spiros Miyakis Peter Dodek Clement Kwok Linda R. Taggart Stephanie Smith Karen Doucette Robert A. Fowler |
| author_sort | Sean W.X. Ong |
| collection | DOAJ |
| 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<2: RD −2.38, 95% CI −5.0 to 0.23; score ≥2: RD −0.65, 95% CI −5.06 to 3.77; p = 0.24). Results were consistent across sensitivity analyses including imputation for missing data and restricting analyses to gram-negative BSI. Interpretation: The decision rules included in our analyses did not identify a subgroup of patients within BALANCE that would benefit from 14 (vs 7) days of treatment. 7-day treatment duration is sufficient for most patients with uncomplicated non-S. aureus/lugdunensis BSI. Future research could explore data-driven machine-learning approaches to identify comprehensive combinations of patient characteristics that may guide individualised duration of antibiotic therapy. Funding: The BALANCE trial was funded by the Canadian Institutes of Health Research, Health Research Council of New Zealand, Australian National Medical Research Council, Physicians Services Incorporated Ontario and Ontario Ministry of Health and Long-term Care Innovation Fund. SWXO conducted this study as part of his PhD studies, with funding from: the Emerging & Pandemic Infections Consortium (University of Toronto, Canada); Connaught International Scholarship (University of Toronto, Canada); the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST; Government of Ontario, Canada); and the Melbourne Research Scholarship (University of Melbourne, Australia). VML is supported by Clinical Research Scholar—Junior 2 program (FRQ-S). |
| format | Article |
| id | doaj-art-76bc971defd249d48ce4f8d9d6867213 |
| institution | OA Journals |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-76bc971defd249d48ce4f8d9d68672132025-08-20T02:11:26ZengElsevierEClinicalMedicine2589-53702025-05-018310319510.1016/j.eclinm.2025.103195Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trialResearch in contextSean W.X. Ong0Ruxandra Pinto1Asgar Rishu2Steven Y.C. Tong3Robert J. Commons4John M. Conly5Gerald A. Evans6Michael Fralick7Christopher Kandel8Philippe R.S. Lagacé-Wiens9Todd C. Lee10Sylvain A. Lother11Derek R. MacFadden12John C. Marshall13Valérie Martel-Laferrière14Michael Mayette15Emily G. McDonald16John D. Neary17Josef Prazak18Edward Raby19Adrian Regli20Benjamin A. Rogers21Stephanie Smith22Linda R. Taggart23Han Ting Wang24Terence Wuerz25Dafna Yahav26Paul J. Young27Robert A. Fowler28Nick Daneman29Nick DanemanAsgar RishuRuxandra PintoBenjamin RogersYahya ShehabiRachael ParkeDeborah J. CookYaseen ArabiJohn MuscedereSteven ReynoldsRichard HallDhiraj Bhatia DwivediColin McArthurShay McGuinnessDafna YahavBryan CoburnAnna GeageaPavani DasPhillip ShinMichael DetskyAndrew MorrisMichael FralickJeff E. PowisChristopher KandelWendy SliglSean M. BagshawNishma SinghalEmilie Belley-CoteRichard WhitlockKosar KhwajaSusan MorpethAlex KazemiTony WilliamsDerek R. MacFaddenLauralyn McIntyreJennifer L.Y. TsangFrancois LamontagneAlex CarignanJohn MarshallJan O. FriedrichRobert CironeMark DowningChristopher GrahamJoshua DavisErick DuanJohn NearyGerald EvansBasem AlraddadiSameera Al JohaniClaudio MartinSameer ElsayedIan BallFrançois LauzierAlexis F. TurgeonHenry Thomas StelfoxJohn ConlyTodd C. LeeEmily G. McDonaldRichard SullivanJennifer GrantIlya KaganPaul YoungCassie LawrenceKevin O'CallaghanMatthew EustaceKeat ChoongPierre AslanianUlrike BuehnerTom HaveyAlexandra BinnieJosef PrazakBrenda ReeveEdward LittonSylvain LotherAnand KumarRyan ZarychanskiTomer HoffmanDavid L. PatersonPeter DaleyRobert J. CommonsEmmanuel CharbonneyJean-Francois NaudSally RobertsRavindranath TiruvoipatiSachin GuptaGordon WoodOmar ShumSpiros MiyakisPeter DodekClement KwokLinda R. TaggartStephanie SmithKaren DoucetteRobert A. FowlerInstitute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Infectious Diseases, University of Melbourne, At the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, AustraliaInstitute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, CanadaDepartment of Infectious Diseases, University of Melbourne, At the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, AustraliaGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia; General and Subspecialty Medicine, Grampians Health, Ballarat, Victoria, AustraliaDepartment of Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, CanadaDivision of Infectious Diseases, Department of Medicine, Queen's University, Kingston, Ontario, CanadaDivision of General Internal Medicine, Sinai Health System, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Infectious Diseases, Michael Garron Hospital, Toronto, Ontario, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University, Montreal, CanadaDepartment of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaDivision of Infectious Diseases, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaInterdepartmental Division of Critical Care Medicine and Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, CanadaDivision of Microbiology and Infectious Diseases, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, CanadaUniversity of Sherbrooke, Sherbrooke, Quebec, CanadaDivision of General Internal Medicine, McGill University Health Centre, Montreal, Quebec, CanadaDivision of General Internal Medicine, Department of Medicine, McMaster University, Hamilton, Ontario, CanadaDepartment of Intensive Care Medicine, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Western Australia, AustraliaIntensive Care Unit, SJOG Murdoch Hospital, Perth, Western Australia, AustraliaMonash University School of Clinical Sciences at Monash Health, Melbourne, Victoria, AustraliaDivision of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, CanadaDivision of Infectious Diseases, Unity Health Toronto, Toronto, Ontario, CanadaDepartment of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal, Montréal, Quebec, CanadaDepartment of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaInfectious Diseases Unit, Sheba Medical Center, Ramat-Gan, IsraelIntensive Care Unit, Wellington Hospital, Wellington, New Zealand; Medical Research Institute of New Zealand, Wellington, New ZealandInstitute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Corresponding author. Interdepartmental Division of Critical Care, D-wing, Rm. 503, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5, Canada.Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Corresponding author. Division of Infectious Diseases, H-wing, Rm. 259, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5, Canada.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<2: RD −2.38, 95% CI −5.0 to 0.23; score ≥2: RD −0.65, 95% CI −5.06 to 3.77; p = 0.24). Results were consistent across sensitivity analyses including imputation for missing data and restricting analyses to gram-negative BSI. Interpretation: The decision rules included in our analyses did not identify a subgroup of patients within BALANCE that would benefit from 14 (vs 7) days of treatment. 7-day treatment duration is sufficient for most patients with uncomplicated non-S. aureus/lugdunensis BSI. Future research could explore data-driven machine-learning approaches to identify comprehensive combinations of patient characteristics that may guide individualised duration of antibiotic therapy. Funding: The BALANCE trial was funded by the Canadian Institutes of Health Research, Health Research Council of New Zealand, Australian National Medical Research Council, Physicians Services Incorporated Ontario and Ontario Ministry of Health and Long-term Care Innovation Fund. SWXO conducted this study as part of his PhD studies, with funding from: the Emerging & Pandemic Infections Consortium (University of Toronto, Canada); Connaught International Scholarship (University of Toronto, Canada); the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST; Government of Ontario, Canada); and the Melbourne Research Scholarship (University of Melbourne, Australia). VML is supported by Clinical Research Scholar—Junior 2 program (FRQ-S).http://www.sciencedirect.com/science/article/pii/S2589537025001270Bloodstream infectionsAntibiotic durationClinical trialHeterogeneity of treatment effectAntimicrobial stewardship |
| spellingShingle | 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 Nick Daneman Asgar Rishu Ruxandra Pinto Benjamin Rogers Yahya Shehabi Rachael Parke Deborah J. Cook Yaseen Arabi John Muscedere Steven Reynolds Richard Hall Dhiraj Bhatia Dwivedi Colin McArthur Shay McGuinness Dafna Yahav Bryan Coburn Anna Geagea Pavani Das Phillip Shin Michael Detsky Andrew Morris Michael Fralick Jeff E. Powis Christopher Kandel Wendy Sligl Sean M. Bagshaw Nishma Singhal Emilie Belley-Cote Richard Whitlock Kosar Khwaja Susan Morpeth Alex Kazemi Tony Williams Derek R. MacFadden 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 Todd C. Lee Emily G. McDonald 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 Josef Prazak Brenda Reeve Edward Litton Sylvain Lother Anand Kumar Ryan Zarychanski Tomer Hoffman David L. Paterson Peter Daley Robert J. Commons Emmanuel Charbonney Jean-Francois Naud Sally Roberts Ravindranath Tiruvoipati Sachin Gupta Gordon Wood Omar Shum Spiros Miyakis Peter Dodek Clement Kwok Linda R. Taggart Stephanie Smith Karen Doucette Robert A. Fowler Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trialResearch in context EClinicalMedicine Bloodstream infections Antibiotic duration Clinical trial Heterogeneity of treatment effect Antimicrobial stewardship |
| 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 |
| title_full | 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_fullStr | 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_full_unstemmed | 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_short | 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_sort | identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection an exploratory post hoc analysis of the balance randomised clinical trialresearch in context |
| topic | Bloodstream infections Antibiotic duration Clinical trial Heterogeneity of treatment effect Antimicrobial stewardship |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025001270 |
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identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT markdowning identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT christophergraham identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT joshuadavis identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT erickduan identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT johnneary identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT geraldevans identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT basemalraddadi identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT sameeraaljohani identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT claudiomartin identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT sameerelsayed identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT ianball identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT francoislauzier identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT alexisfturgeon identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT henrythomasstelfox identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT johnconly identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT toddclee identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT emilygmcdonald identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT richardsullivan identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT jennifergrant identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT ilyakagan identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT paulyoung identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT cassielawrence identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT kevinocallaghan identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT mattheweustace identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT keatchoong identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT pierreaslanian identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT ulrikebuehner identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT tomhavey identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT alexandrabinnie identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT josefprazak identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT brendareeve identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT edwardlitton identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT sylvainlother identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT anandkumar identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT ryanzarychanski identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT tomerhoffman identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT davidlpaterson identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT peterdaley identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT robertjcommons identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT emmanuelcharbonney identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT jeanfrancoisnaud identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT sallyroberts identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT ravindranathtiruvoipati identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT sachingupta identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT gordonwood identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT omarshum identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT spirosmiyakis identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT peterdodek identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT clementkwok identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT lindartaggart identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT stephaniesmith identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT karendoucette identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext AT robertafowler identifyingheterogeneityoftreatmenteffectforantibioticdurationinbloodstreaminfectionanexploratoryposthocanalysisofthebalancerandomisedclinicaltrialresearchincontext |