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
,
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
Affiliations
Li Wang
1 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
Wesley H Self
Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Todd W Rice
professor of medicine
Matthew W Semler
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Karen F Miller
1 Department of Emergency Medicine, Vanderbilt University, Nashville, Tennessee, USA
Cheryl L Gatto
Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA
Andrea Fletcher
Romney M Humphries
2Department of Laboratory Medicine, University of California Los Angeles, Los Angeles, USA
Joanna L Stollings
Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Adrienne Baughman
Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Jakea Johnson
Edward T Qian
clinical fellow of pulmonary and critical care
Mary Lynn Dear
Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA
David C Gaston
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Ariel A Lewis
Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA
George E Nelson
Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Benjamin J Ereshefsky
Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Matthew A Christensen
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Ritu Banerjee
Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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.
