Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial
Introduction Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance g...
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2025-01-01
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| author | Li Wang Wesley H Self Todd W Rice Matthew W Semler Karen F Miller Cheryl L Gatto Andrea Fletcher Romney M Humphries Joanna L Stollings Adrienne Baughman Jakea Johnson Edward T Qian Mary Lynn Dear David C Gaston Ariel A Lewis George E Nelson Benjamin J Ereshefsky Matthew A Christensen Ritu Banerjee Dan Albert Alison Benton Laura Bobbitt Carleigh Burns Timothy Duff David C. Gaston MLS Sharon Glover Allyson Hobbie Austin Ing Gabriel Kemp Sheryl Mangrum Geoff Mavrak Kelly Moser David Mulherin Shannon Pugh Matthew Rodgers Chrissie Schaeffer Adam Turner Sabrina Shipman Halden Z VanCleave Hamilton Wen Li Wang LaKeysha Wiggins |
| author_facet | Li Wang Wesley H Self Todd W Rice Matthew W Semler Karen F Miller Cheryl L Gatto Andrea Fletcher Romney M Humphries Joanna L Stollings Adrienne Baughman Jakea Johnson Edward T Qian Mary Lynn Dear David C Gaston Ariel A Lewis George E Nelson Benjamin J Ereshefsky Matthew A Christensen Ritu Banerjee Dan Albert Alison Benton Laura Bobbitt Carleigh Burns Timothy Duff David C. Gaston MLS Sharon Glover Allyson Hobbie Austin Ing Gabriel Kemp Sheryl Mangrum Geoff Mavrak Kelly Moser David Mulherin Shannon Pugh Matthew Rodgers Chrissie Schaeffer Adam Turner Sabrina Shipman Halden Z VanCleave Hamilton Wen Li Wang LaKeysha Wiggins |
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| description | Introduction Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes. This manuscript describes the protocol and statistical analysis plan for a randomised trial designed to evaluate the effect of blood cultures plus direct-from-blood bacterial testing results compared with blood culture results alone on antibiotic administration and clinical outcomes.Methods and analysis We are conducting a prospective, single-centre, parallel-group, non-blinded, pragmatic, randomised trial. The trial will enrol 500 adult patients presenting to the emergency department at Vanderbilt University Medical Center with suspected bacterial infection who have been initiated on empiric intravenous vancomycin. Eligible patients are randomised 1:1 to receive Food and Drug Administration-approved direct-from-blood bacterial testing in addition to blood cultures or blood cultures alone. The primary outcome is the time to the last dose of intravenous vancomycin within 14 days of randomisation. The secondary outcome is the time to the last dose of systemic antipseudomonal beta-lactam antibiotics within 14 days of randomisation. Additional outcomes include highest stage of acute kidney injury, lowest platelet count and receipt of kidney replacement therapy within 14 days of randomisation, as well as hospital-free days, intensive care unit-free-days and all-cause, in-hospital mortality within 28 days of randomisation. Enrolment began on 13 December 2023.Ethics and dissemination The trial involves human participants and was approved by the Vanderbilt University Medical Center institutional review board with a waiver of informed consent (IRB#231229). Results will be submitted in a peer-reviewed journal and presented at scientific conferences.Trial registration number NCT06069206. |
| format | Article |
| id | doaj-art-7ae021b715424faaad7e875be4a6ac22 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-7ae021b715424faaad7e875be4a6ac222025-01-15T00:55:09ZengBMJ Publishing GroupBMJ Open2044-60552025-01-0115110.1136/bmjopen-2024-090263Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial Li Wang0Wesley H Self1Todd W Rice2Matthew W Semler3Karen F Miller4Cheryl L Gatto5Andrea FletcherRomney M Humphries6Joanna L Stollings7Adrienne Baughman8Jakea JohnsonEdward T Qian9Mary Lynn Dear10David C Gaston11Ariel A Lewis12George E Nelson13Benjamin J Ereshefsky14Matthew A Christensen15Ritu Banerjee16Dan AlbertAlison BentonLaura BobbittCarleigh BurnsTimothy DuffDavid C. GastonMLS Sharon GloverAllyson HobbieAustin IngGabriel KempSheryl MangrumGeoff MavrakKelly MoserDavid MulherinShannon PughMatthew RodgersChrissie SchaefferAdam TurnerSabrina ShipmanHalden Z VanCleaveHamilton Wen Li WangLaKeysha Wiggins1 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, ChinaDepartment of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USAprofessor of medicineDepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA1 Department of Emergency Medicine, Vanderbilt University, Nashville, Tennessee, USAVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA2Department of Laboratory Medicine, University of California Los Angeles, Los Angeles, USADepartment of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USAclinical fellow of pulmonary and critical careVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USAVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USAIntroduction Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes. This manuscript describes the protocol and statistical analysis plan for a randomised trial designed to evaluate the effect of blood cultures plus direct-from-blood bacterial testing results compared with blood culture results alone on antibiotic administration and clinical outcomes.Methods and analysis We are conducting a prospective, single-centre, parallel-group, non-blinded, pragmatic, randomised trial. The trial will enrol 500 adult patients presenting to the emergency department at Vanderbilt University Medical Center with suspected bacterial infection who have been initiated on empiric intravenous vancomycin. Eligible patients are randomised 1:1 to receive Food and Drug Administration-approved direct-from-blood bacterial testing in addition to blood cultures or blood cultures alone. The primary outcome is the time to the last dose of intravenous vancomycin within 14 days of randomisation. The secondary outcome is the time to the last dose of systemic antipseudomonal beta-lactam antibiotics within 14 days of randomisation. Additional outcomes include highest stage of acute kidney injury, lowest platelet count and receipt of kidney replacement therapy within 14 days of randomisation, as well as hospital-free days, intensive care unit-free-days and all-cause, in-hospital mortality within 28 days of randomisation. Enrolment began on 13 December 2023.Ethics and dissemination The trial involves human participants and was approved by the Vanderbilt University Medical Center institutional review board with a waiver of informed consent (IRB#231229). Results will be submitted in a peer-reviewed journal and presented at scientific conferences.Trial registration number NCT06069206.https://bmjopen.bmj.com/content/15/1/e090263.full |
| spellingShingle | Li Wang Wesley H Self Todd W Rice Matthew W Semler Karen F Miller Cheryl L Gatto Andrea Fletcher Romney M Humphries Joanna L Stollings Adrienne Baughman Jakea Johnson Edward T Qian Mary Lynn Dear David C Gaston Ariel A Lewis George E Nelson Benjamin J Ereshefsky Matthew A Christensen Ritu Banerjee Dan Albert Alison Benton Laura Bobbitt Carleigh Burns Timothy Duff David C. Gaston MLS Sharon Glover Allyson Hobbie Austin Ing Gabriel Kemp Sheryl Mangrum Geoff Mavrak Kelly Moser David Mulherin Shannon Pugh Matthew Rodgers Chrissie Schaeffer Adam Turner Sabrina Shipman Halden Z VanCleave Hamilton Wen Li Wang LaKeysha Wiggins Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial BMJ Open |
| title | Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial |
| title_full | Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial |
| title_fullStr | Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial |
| title_full_unstemmed | Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial |
| title_short | Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial |
| title_sort | examining the effect of direct from blood bacterial testing on antibiotic administration and clinical outcomes a protocol and statistical analysis plan for a pragmatic randomised trial |
| url | https://bmjopen.bmj.com/content/15/1/e090263.full |
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