Clinical and Medico-economic Evaluation of a Rapid Test (ePlex-BCID®, GenMark) for the Diagnosis of Bacteremia and Fungemia. (HEMOFAST)

Clinical and Medico-economic Evaluation of a Rapid Test (ePlex-BCID®, GenMark) for the Diagnosis of Bacteremia or Fungemia From Positive Blood Culture Bottles, Combining Fast Identification of Bacteria and Fungi and Evaluation of Bacterial Resistance to First Line Antibiotics.

This study evaluates the clinical benefit of a rapid test for fast diagnosis of bacteremia and fungemia from positive blood cultures in case of sepsis. This assay enables rapid identification of bacteria and fungi and allows to evaluate bacterial resistance to first line antibiotics. The clinical and medico-economic impact of this assay used in addition to the current diagnosis strategy (half of the patients) will be compared to the current diagnostic strategy alone (other half of the patient).

Study Overview

• Status: Completed
• Conditions: Fungemia; Bacteremia Sepsis
• Intervention / Treatment: Diagnostic test: Multiplex PCR; Diagnostic test: Current strategy alone

Detailed Description

Bacteremia and fungemia are severe complications, sometimes life-threatening, of every sepsis. During septicemia, every hour matters to start an appropriate antibiotic or antifungal treatment as every hour of delay is associated to higher death rate.

The rapid multiplex PCR assay that is evaluated in this study allows to identify in 60 to 90 minutes, the bacteria or fungi that is present in the positive blood culture bottles and to identify resistance markers to first line antibiotics that are used to treat sepsis. This strategy allows quicker adaptation of antibacterial or antifungal treatment based on the species of the bacteria or fungi identified and on the results of the resistance markers compared to current diagnosis strategy of bacteremia or fungemia. This quicker adaptation could lead to improved survival rate, reduced complications of sepsis, reduced hospital stay length and could reduce the use of large spectrum antibiotics.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38043
    • Grenoble University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with bacteremia and/or fungemia defined by :

  1/ the presence of clinical signs of sepsis; AND 2/ a positive blood culture, i.e. the growth of at least one species of bacteria or micromyces in at least one blood culture vial

• Patient Hospitalized at Grenoble University Hospital (only North site) and seen by a physician from the antibiotic stewardship team
• First blood culture positive for the patient's sepsis episode
• Informed and written consent signed by the patient or his legal representative or the doctor in case of emergency.

Exclusion Criteria:

• Patients mentioned in the law articles L1121-5 to L1121-8 from French Health Code
• Patients hospitalized in palliative care unit
• Persons with an estimated survival of less than one month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Multiplex PCR + Current strategy; Results of the multiplex PCR will be send as soon as possible to the infectious disease phycian for quick adaptation of antibiotic treatment. Positive blood cultures will also undergo current diagnosis strategy for bacteremia and fungemia.	Diagnostic test: Multiplex PCR; Quick adaptation of antibiotic treatment according to the species identified and to the results of the resistance markers present in the multiplex PCR
ACTIVE_COMPARATOR: Current strategy alone; Current diagnostic strategy based on the identification of bacteria and micromyces isolated in blood cultures after subculture by mass spectrometry (MALDI-TOF) and determination of their sensitivity to antibiotics or antifungals by antibiotic susceptibility testing or antifungigram	Diagnostic test: Current strategy alone; Identification of bacteria and micromyces isolated in blood cultures after subculture by mass spectrometry (MALDI-TOF) and determination of their sensitivity to antibiotics or antifungals by antibiotic susceptibility testing or antifungigram; Other Names: MALDI-TOFF identification

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay from suspicion of sepsis to optimized antibiotic/antifungal treatment	Delay between first sampling of blood cultures for sepsis and optimized antibiotic/antifungal treatment. Treatment will be considered optimized if it is active on the bacteria/fungi responsible for sepsis and if it follows current treatment recommendations for the bacteria/fungi identified.	Follow up is set to hospital length stay with a maximum of 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical evaluation of the consequences of the innovative strategy compared to current strategy : 30-day mortality	The following clinical consequences will be measured and compared in each arm : 30-day mortality	Hospital length stay with a maximum of 30 days
Medical evaluation of the consequences of the innovative strategy compared to current strategy : complication rate	The following clinical consequences will be measured and compared in each arm : complication rate (ICU admission or length of stay, antibiotic/antifungal treatment toxicity rate, recurrence of sepsis within 30 days, re-admission to hospital within 30 days)	Hospital length stay with a maximum of 30 days
Medical evaluation of the consequences of the innovative strategy compared to current strategy : length of hospital stay	The following clinical consequences will be measured and compared in each arm : length of hospital stay	Hospital length stay with a maximum of 30 days
Medical evaluation of the consequences of the innovative strategy compared to current strategy : antibiotic treatment duration	The following clinical consequences will be measured and compared in each arm : treatment duration for antibiotics with high impact on the commensal flora (i.e. : carbapenems) or with high toxicity (i.e. : vancomycin)	Hospital length stay with a maximum of 30 days
Medical evaluation of the consequences of the innovative strategy compared to current strategy : delay of antibiotic/antifungal treatment modification at several time points	The following clinical consequences will be measured and compared in each arm : delay of antibiotic/antifungal treatment modification at several time points (after the result of the Gram stain, after the results of the multiplex PCR, after the results of the identification of the bacteria/fungi and after the results of antibiotic/antifungal treatment susceptibility).	Hospital length stay with a maximum of 30 days
Medical evaluation of the consequences of the innovative strategy compared to current strategy : rate of antibiotic/antifungal treatment modification at several time points	The following clinical consequences will be measured and compared in each arm : rate of antibiotic/antifungal treatment modification at several time points (after the result of the Gram stain, after the results of the multiplex PCR, after the results of the identification of the bacteria/fungi and after the results of antibiotic/antifungal treatment susceptibility).	Hospital length stay with a maximum of 30 days
Economic evaluation of the hospitalization costs of the innovative strategy compared to current strategy	Hospitalization costs will be measured	Hospital length stay with a maximum of 30 days
Economic evaluation of the treatments costs of the innovative strategy compared to current strategy	Anti-infectious treatment costs will be measured	Hospital length stay with a maximum of 30 days
Economic evaluation of the costs of the innovative compared to current strategy	Costs of the innovative assay (reagents and device) will be measured	Hospital length stay with a maximum of 30 days
Economic evaluation of the medical imaging costs of the innovative strategy compared to current strategy	Medical imaging costs will be measured	Hospital length stay with a maximum of 30 days
Economic impact of the introduction of the innovative strategy for Grenoble University Hospital	Measurement and evaluation of the economic impact of the innovative strategy on the budget of Grenoble University Hospital, on the target population, for a period of one year.	Extrapolation of the costs for a one year period

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: GenMark Diagnostics
• Investigators: Principal Investigator: Yvan CASPAR, MD, University Hospital, Grenoble

Publications and helpful links

General Publications

• Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
• Huang TD, Melnik E, Bogaerts P, Evrard S, Glupczynski Y. Evaluation of the ePlex Blood Culture Identification Panels for Detection of Pathogens in Bloodstream Infections. J Clin Microbiol. 2019 Jan 30;57(2):e01597-18. doi: 10.1128/JCM.01597-18. Print 2019 Feb.
• Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, Shah ND, Mandrekar JN, Patel R. Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing. Clin Infect Dis. 2015 Oct 1;61(7):1071-80. doi: 10.1093/cid/civ447. Epub 2015 Jul 20.
• Patel TS, Kaakeh R, Nagel JL, Newton DW, Stevenson JG. Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections. J Clin Microbiol. 2016 Dec 28;55(1):60-67. doi: 10.1128/JCM.01452-16. Print 2017 Jan.
• Maubon D, Dard C, Garnaud C, Cornet M. Profile of GenMark's ePlex(R) blood culture identification fungal pathogen panel. Expert Rev Mol Diagn. 2018 Feb;18(2):119-132. doi: 10.1080/14737159.2018.1420476. Epub 2017 Dec 28.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 20, 2019
• Primary Completion (ACTUAL): February 19, 2021
• Study Completion (ACTUAL): February 19, 2021

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (ACTUAL): March 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2021
• Last Update Submitted That Met QC Criteria: October 26, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: multiplex PCR; blood culture; rapid diagnosis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Bacteremia; Fungemia
• Other Study ID Numbers: 38RC15.091

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes