Effect of Direct-from-blood Bacterial Testing on Antibiotic Administration and Clinical Outcomes

Bloodstream Infection Clinical Trial

Official title:

Effect of Direct-from-blood Bacterial Testing on Antibiotic Administration and Clinical Outcomes: A Learning Healthcare Pragmatic Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06069206
• Other study ID #: 231229
• Status: Recruiting
• Phase: N/A
• Start date: December 13, 2023
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: Matthew Semler, MD, MSc
• Phone: 615-835-9870
• Email: matthew.w.semler[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bacterial blood stream infections are common and life-threatening. Bloodstream infections have historically been identified using blood cultures, which often take 24-72 hours to result and are imperfectly sensitive. Early administration of antimicrobial therapy is a fundamental component of the management of adults presenting to the hospital with a suspected bloodstream infection and/or sepsis. But because blood cultures frequently take 24-72 hours to result, patients are typically treated with empiric, broad spectrum antibiotics. In a meta-analysis of sepsis studies, empirical antibiotic therapy was inappropriate for the organism that ultimately grew in culture in almost half of patients. Thus, patients are commonly exposed to unnecessary antibiotics without evidence of infection or with evidence of infection requiring narrow antibiotic selection. For example, current guidelines recommend the use of empiric intravenous vancomycin as coverage for a bloodstream infection caused by the bacterial pathogen methicillin-resistant S. aureus (MRSA). Vancomycin requires careful monitoring due to its narrow therapeutic range and high risk of toxicity. Administration of vancomycin to patients who do not have MRSA can lead to avoidable adverse drug events and costs, as well as drive antimicrobial resistance. There has been increasing interest in using rapid diagnostic tests that identify bacteria directly from whole blood samples without relying on growth in culture, referred to as "direct-from-blood" tests, to guide early therapeutic management of patients with suspected bloodstream infections in addition to standard blood cultures. One such FDA-approved, direct-from-blood test is the T2Bacteria® Panel. This panel's performance as a direct-from blood test for bacterial pathogens has been described in previous studies. A recent meta-analysis of largely observational studies reported a faster transition to targeted microbial therapy and de-escalation of empirical microbial therapy, as well as a shorter duration of intensive care unit stay and hospital stay for patients who received this direct-from-blood test. We will conduct a pragmatic, randomized clinical trial examining the effect of using the T2Bacteria® Panel direct from-blood testing, compared to using blood cultures alone (standard of care), on antimicrobial receipt and clinical outcomes for adults presenting to the hospital with suspected infection and who have been initiated on empiric therapy with intravenous vancomycin.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: November 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient is located in the Emergency Department at Vanderbilt University Hospital
• = 12 hours from patient presentation to the Emergency Department at Vanderbilt University Hospital
• Age = 18 years
• Clinician has ordered blood cultures
• Clinician has ordered intravenous vancomycin

Exclusion Criteria:

• Patient is known to be a prisoner
• Patient is known to be pregnant
• Patient is known to have received 2 or more doses of vancomycin since presentation to the Vanderbilt ED
• Patient is known to have a positive bacterial culture in the previous 7 days
• Patient is known to have an infection for which at least 7 days of intravenous vancomycin would routinely be administered regardless of bacterial testing results (e.g., skin and soft tissue infection, etc.)

Related Conditions & MeSH terms

• Bacteremia
• Bloodstream Infection
• MRSA Bacteremia
• Sepsis
• Sepsis Bacterial
• Vancomycin

Intervention

Other:
• T2Bacteria® Panel (direct-from-blood testing)
Providers will be prompted to order the T2Bacteria® Panel (direct-from-blood testing) and accompanying communications regarding panel results will be delivered.
• Usual Care
Standard blood cultures.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (17)

De Angelis G, Posteraro B, De Carolis E, Menchinelli G, Franceschi F, Tumbarello M, De Pascale G, Spanu T, Sanguinetti M. T2Bacteria magnetic resonance assay for the rapid detection of ESKAPEc pathogens directly in whole blood. J Antimicrob Chemother. 2018 Mar 1;73(suppl_4):iv20-iv26. doi: 10.1093/jac/dky049. — View Citation

Drevinek P, Hurych J, Antuskova M, Tkadlec J, Berousek J, Prikrylova Z, Bures J, Vajter J, Soucek M, Masopust J, Martinkova V, Adamkova J, Hysperska V, Bebrova E. Direct detection of ESKAPEc pathogens from whole blood using the T2Bacteria Panel allows early antimicrobial stewardship intervention in patients with sepsis. Microbiologyopen. 2021 Jun;10(3):e1210. doi: 10.1002/mbo3.1210. — View Citation

Giannella M, Pankey GA, Pascale R, Miller VM, Miller LE, Seitz T. Antimicrobial and resource utilization with T2 magnetic resonance for rapid diagnosis of bloodstream infections: systematic review with meta-analysis of controlled studies. Expert Rev Med Devices. 2021 May;18(5):473-482. doi: 10.1080/17434440.2021.1919508. Epub 2021 Jun 7. — View Citation

Leggieri N, Rida A, Francois P, Schrenzel J. Molecular diagnosis of bloodstream infections: planning to (physically) reach the bedside. Curr Opin Infect Dis. 2010 Aug;23(4):311-9. doi: 10.1097/QCO.0b013e32833bfc44. — View Citation

Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011 Feb 1;52(3):285-92. doi: 10.1093/cid/cir034. — View Citation

Nguyen MH, Clancy CJ, Pasculle AW, Pappas PG, Alangaden G, Pankey GA, Schmitt BH, Rasool A, Weinstein MP, Widen R, Hernandez DR, Wolk DM, Walsh TJ, Perfect JR, Wilson MN, Mylonakis E. Performance of the T2Bacteria Panel for Diagnosing Bloodstream Infections: A Diagnostic Accuracy Study. Ann Intern Med. 2019 Jun 18;170(12):845-852. doi: 10.7326/M18-2772. Epub 2019 May 14. — View Citation

Opota O, Croxatto A, Prod'hom G, Greub G. Blood culture-based diagnosis of bacteraemia: state of the art. Clin Microbiol Infect. 2015 Apr;21(4):313-22. doi: 10.1016/j.cmi.2015.01.003. Epub 2015 Jan 16. — View Citation

Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010 Nov;54(11):4851-63. doi: 10.1128/AAC.00627-10. Epub 2010 Aug 23. — View Citation

Peralta G, Rodriguez-Lera MJ, Garrido JC, Ansorena L, Roiz MP. Time to positivity in blood cultures of adults with Streptococcus pneumoniae bacteremia. BMC Infect Dis. 2006 Apr 27;6:79. doi: 10.1186/1471-2334-6-79. — View Citation

Peri AM, Stewart A, Hume A, Irwin A, Harris PNA. New Microbiological Techniques for the Diagnosis of Bacterial Infections and Sepsis in ICU Including Point of Care. Curr Infect Dis Rep. 2021;23(8):12. doi: 10.1007/s11908-021-00755-0. Epub 2021 Jun 16. — View Citation

Pliakos EE, Andreatos N, Shehadeh F, Ziakas PD, Mylonakis E. The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship. Clin Microbiol Rev. 2018 May 30;31(3):e00095-17. doi: 10.1128/CMR.00095-17. Print 2018 Jul. — View Citation

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18. — View Citation

Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro BM. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020 May 19;77(11):835-864. doi: 10.1093/ajhp/zxaa036. No abstract available. — View Citation

Shah SS, Downes KJ, Elliott MR, Bell LM, McGowan KL, Metlay JP. How long does it take to "rule out" bacteremia in children with central venous catheters? Pediatrics. 2008 Jan;121(1):135-41. doi: 10.1542/peds.2007-1387. — View Citation

Tabak YP, Vankeepuram L, Ye G, Jeffers K, Gupta V, Murray PR. Blood Culture Turnaround Time in U.S. Acute Care Hospitals and Implications for Laboratory Process Optimization. J Clin Microbiol. 2018 Nov 27;56(12):e00500-18. doi: 10.1128/JCM.00500-18. Print 2018 Dec. — View Citation

Timbrook TT, Morton JB, McConeghy KW, Caffrey AR, Mylonakis E, LaPlante KL. The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review and Meta-analysis. Clin Infect Dis. 2017 Jan 1;64(1):15-23. doi: 10.1093/cid/ciw649. Epub 2016 Sep 26. — View Citation

Voigt C, Silbert S, Widen RH, Marturano JE, Lowery TJ, Ashcraft D, Pankey G. The T2Bacteria Assay Is a Sensitive and Rapid Detector of Bacteremia That Can Be Initiated in the Emergency Department and Has Potential to Favorably Influence Subsequent Therapy. J Emerg Med. 2020 May;58(5):785-796. doi: 10.1016/j.jemermed.2019.11.028. Epub 2020 Jan 23. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to last dose of intravenous vancomycin	The time between randomization and the start time for the last dose of intravenous vancomycin received by the patient within 14 days of randomization.	Baseline to 14 days
Secondary	Time to last dose of systemic anti-pseudomonal beta-lactam antibiotic	The time between randomization and start time of the last dose of systemic anti-pseudomonal beta-lactam antibiotic received by the patient within 14 days of randomization.	Baseline to 14 days