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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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.

Conditions
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Bacteremia Sepsis, Fungemia

Intervention / Treatment
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* Diagnostic Test: Multiplex PCR
* Diagnostic Test: Current strategy alone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized assignation. Half of the patients will be diagnosed by the rapid test in addition to current diagnosis strategy and the other half by current diagnosis strategy alone.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiplex PCR + Current strategy<br>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<br>* Quick adaptation of antibiotic treatment according to the species identified and to the results of the resistance markers present in the multiplex PCR<br>|
| Active Comparator: Current strategy alone<br>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<br>* 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<br>* Other names: MALDI-TOFF identification;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiplex PCR, blood culture, rapid diagnosis