(100 days)
Not Found
No
The description details a standard automated immunoassay technique (ELFA) with automated result analysis based on fluorescence intensity, not AI/ML. The "results are analyzed automatically by the instrument" refers to the calculation of a test value based on the measured fluorescence, which is a deterministic process, not an AI/ML algorithm.
No.
Explanation: This device is an in-vitro diagnostic test designed to detect a C. difficile antigen in fecal specimens, aiding in the diagnosis of C. difficile infection. It does not treat or cure any condition, which is the definition of a therapeutic device.
Yes
The "Intended Use / Indications for Use" section explicitly states that the test is to be used "as an aid in the diagnosis of C. difficile infection."
No
The device description clearly outlines a physical assay technique (ELFA) utilizing a Solid Phase Receptacle (SPR) and reagent strips, which are hardware components. The instrument performs automated steps, indicating a physical device is involved in the testing process.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it is a test for use on the VIDAS family instruments to detect the C. difficile antigen in fecal specimens from persons suspected of having C. difficile infection. This is a diagnostic test performed in vitro (outside the body) on a biological sample.
- Device Description: The description details a laboratory-based assay using reagents and an instrument to analyze a fecal specimen. This is characteristic of an in vitro diagnostic device.
- Anatomical Site: The test is performed on "Fecal specimens," which are biological samples collected from the body for analysis.
- Performance Studies: The document describes clinical testing and method comparisons using stool samples, which are standard practices for evaluating the performance of IVD devices.
- Predicate Device: The mention of a "Predicate Device" with a K number (K053572) is a strong indicator that this device is being submitted for regulatory clearance as an IVD, as predicate devices are used for comparison in the regulatory process for IVDs.
N/A
Intended Use / Indications for Use
VIDAS® C. difficile GDH (GDH) is an automated test based on the Enzyme Linked Fluorescent Assay technique (ELFA), for use on the VIDAS family instruments. The VIDAS C. difficile GDH (glutamate dehydrogenase) assay is a qualitative test that detects the C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile in fecal specimens from persons suspected of having C. difficile infection (CDI). The test does not distinguish toxigenic from non-toxigenic strains of C. difficile. With the use of additional tests that detect C. difficile toxins, the test is to be used as an aid in the diagnosis of C. difficile infection. As with other C. difficile tests, results should be considered in conjunction with the patient history.
Product codes (comma separated list FDA assigned to the subject device)
MCB
Device Description
The VIDAS® C. difficile GDH assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA).
The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and are pre-dispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components.
- Specific binding of GDH present in the sample with mouse monoclonal anti-GDH antibody coated on the interior of the SPR.
- Binding between GDH and mouse monoclonal anti-GDH antibody conjugated with alkaline phosphatase (ALP).
- Detection: alkaline phosphatase catalyzes the hydrolysis of the substrate (4-Methylumbellifery! phosphate) into a fluorescent product (4-Methy-umbelliferone) the fluorescence of which is measured at 450 nm.
The intensity of the fluorescence increases according to the quantity of GDH in the sample.
When the VIDAS C. difficile GDH test is completed, the results are analyzed automatically by the instrument, a test value is generated, and a result is printed for each sample.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
1 year to 100 years
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
1904 (1891 prospective and 13 retrospective) stool samples collected from patients suspected of having C. difficile infection (CDI) were tested at three sites (USA and Europe). A single replicate of each sample was tested using VIDAS C. difficile GDH on a VIDAS instrument. A bacterial culture test was performed for each sample on a CCFA medium according to the instructions for use. Thirteen (13) retrospectively collected samples from pediatric patients submitted for routine C. difficile testing (2-12 years) were assayed for C. difficile according to the same protocol.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Nonclinical Tests:
- Sample stability:
- Specimens storage after collection: Stool specimens may be stored at 2-8℃ for 3 days. For longer storage, freeze at -70°C+/- 10°C up to one month.
- Specimens storage after pretreatment: Specimen supernatants may be stored up to 8 hours at 18-25°C or 48 hours at 2-8°C.
- Precision:
- Within-laboratory precision: Estimated at one site based on CLSI® EP5-A2. Three human samples (1 high negative, 1 low positive, 1 moderate positive) were tested in triplicate in 2 runs per day with 2 operators, using 2 reagent lots over 12 testing days (N=72 test values for each sample). All replicates resulted in the expected interpretation.
- Reproducibility: Estimated at three sites based on CLSI® EP5-A2. Three human samples (1 high negative, 1 low positive, 1 moderate positive) were tested in triplicate in 2 runs per day with 2 operators, using 2 reagent lots over 6 testing days (N=108 test values for each sample). Percentage of interpretation changes were 0.9% for high negative, 3.7% for low positive, and 0% for moderate positive. These were considered normal for samples close to the decision threshold.
- Strain reactivity: Evaluated using several strains of C. difficile grown on Columbia agar + 5% sheep blood. The VIDAS C. difficile GDH detects various toxinogenic and non-toxinogenic C. difficile strains, including those from Cardiff ECDC collection and bioMerieux collection ribotypes, at concentrations of 9x10° CFU/mL (3 McFarland) and 3x10° CFU/mL for general strains, and 9x10^8 CFU/mL for specific collections.
- Analytical sensitivity - Limit of detection: Evaluated using dilutions of purified native C. difficile GDH and recombinant C. difficile GDH in C. difficile-negative stool samples based on CLSI EP17-A. The limit of detection is 3.0 ng/mL for purified native GDH.
- Hook effect: No hook effect observed up to purified native GDH concentrations of 2 µg/Ml.
- Interferences: Study of drug interferences and other potentially interfering substances based on CLSI® EP7-A2, at 2 levels of GDH (low positive and high positive). Most tested compounds showed no significant interference. Potential interference was observed for Calcium carbonate (at 13.06 mg/mL), Mineral oil (at 0.27 v/v), and Tergitol (at 0.5 v/v); however, at lower concentrations, they did not cause interference.
- Cross-reactivity and microbial interference: Tested by diluting microorganisms in C. difficile-negative and C. difficile-positive stool samples, respectively. Tested at a concentration of 3x10^8 CFU/mL for bacteria and 1x10^4 PFU/mL for viruses. None of the tested microorganisms reacted with the assay.
Clinical Testing:
- Clinical sensitivity and specificity: 1904 (1891 prospective and 13 retrospective) stool samples from patients suspected of CDI were tested at three sites (USA and Europe) against a CCFA bacterial culture test.
- Performance of VIDAS C. difficile GDH assay versus CCFA bacterial culture on prospective samples:
- Sensitivity: 95.6% [92.6 - 97.6]%
- Specificity: 90.1% [88.5 - 91.5]%
- Negative Predictive Value (NPV): 99.1% [98.5 - 99.5]%
- 158 samples were GDH positive/CCFA negative; 13 samples were GDH negative/CCFA positive.
- 21 (1.0%) out of 2038 patient samples were invalid.
- Testing on retrospective samples (pediatric patients 2-12 years): (n=13)
- Sensitivity: 100.0% (10/10)
- Specificity: 33.3% (1/3)
- Performance of VIDAS C. difficile GDH assay versus CCFA bacterial culture on all prospective and retrospective samples: (n=1904)
- Sensitivity: 95.8% (293/306) [92.8 - 97.7]%
- Specificity: 90.0% (1438/1598) [88.4 - 91.4]%
- Negative Predictive Value: 99.1% [98.5 - 99.5]%
- Sensitivity and Specificity performances versus CCFA medium by age group on prospective samples:
*
- Performance of VIDAS C. difficile GDH assay versus CCFA bacterial culture on prospective samples:
§ 866.2660 Microorganism differentiation and identification device.
(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.
0
VIDAS®C. difficile GDH
510(k) SUMMARY
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of Safe Medical Devices Act of 1990 and 21 CFR 807.92.
VIDAS® C. difficile GDH
A. Submitter Information
| Submitter's Name: | bioMérieux SA |
|---|---|
| Address: | Chemin de l'Orme |
| 69280 Marcy-l'Etoile - France | |
| Contact Person: | Caroline KOCH-MATHIAN |
| Phone Number: | +33 4 78 87 70 32 |
| Fax Number: | +33 4 78 87 20 75 |
| Date of Preparation: | May 2013 |
OCT 0 9 2013
B. Device Name
| Trade Name: | VIDAS® C. difficile GDH |
|---|---|
| Common Name: | VIDAS C. difficile GDH Assay |
| Classification Name: | 21 CFR 866.2660 – Microorganism Differentiation and Identification Device |
| MCB - Antigen, Clostridium difficile |
C. Predicate Device Name
Trade Name: C. DIFF QUIK CHEK® (TECHLAB, INC.), K053572
D. Device Description
The VIDAS® C. difficile GDH assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA).
The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and are pre-dispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components.
- · Specific binding of GDH present in the sample with mouse monoclonal anti-GDH antibody coated on the interior of the SPR.
- · Binding between GDH and mouse monoclonal anti-GDH antibody conjugated with alkaline phosphatase (ALP).
- · Detection: alkaline phosphatase catalyzes the hydrolysis of the substrate (4-Methylumbellifery! phosphate) into a fluorescent product (4-Methy-umbelliferone) the fluorescence of which is measured at 450 nm.
The intensity of the fluorescence increases according to the quantity of GDH in the sample.
1
1
When the VIDAS C. difficile GDH test is completed, the results are analyzed automatically by the instrument, a test value is generated, and a result is printed for each sample.
E. Intended Use
VIDAS® C. difficile GDH (GDH) is an automated test based on the Enzyme Linked Fluorescent Assay technique (ELFA), for use on the VIDAS family instruments. The VIDAS C. difficile GDH (glutamate dehydrogenase) assay is a qualitative test that
detects the C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile in fecal specimens from persons suspected of having C. difficile infection (CDI). The test does not distinguish toxigenic from non-toxigenic strains of C. difficile. With the use of additional tests that detect C. difficile toxins, the test is to be used as an aid in the diagnosis of C. difficile infection. As with other C. difficile tests, results should be considered in conjunction with the patient history.
F. Technological Characteristics Summary
A general comparison of the similarities and differences of the assays is presented in the table below.
| Item | VIDAS® C. difficile GDH Assay | C. DIFF QUIK CHEK® Assay
(K053572) |
|--------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | VIDAS® C. difficile GDH (GDH) is an
automated test based on the Enzyme
Linked Fluorescent Assay technique
(ELFA), for use on the VIDAS family
instruments.
The VIDAS C. difficile GDH
(glutamate dehydrogenase) assay is
a qualitative test that detects the C.
difficile antigen, glutamate
dehydrogenase, as a screen for the
presence of C. difficile in fecal
specimens from persons suspected
of having C. difficile infection (CDI).
The test does not distinguish
toxigenic from non-toxigenic strains
of C. difficile. With the use of
additional tests that detect C. difficile
toxins, the test is to be used as an
aid in the diagnosis of C. difficile
infection. As with other C. difficile
tests, results should be considered in
conjunction with the patient history. | The C. DIFF QUIK CHEK® test is a
rapid membrane enzyme
immunoassay for use as a
screening test to detect
Clostridium difficile antigen,
glutamate dehydrogenase, in fecal
specimens from persons
suspected of having C. difficile
disease. The test does not
distinguish toxigenic from non
toxigenic strains of C. difficile. With
the use of additional tests that
detect C. difficile toxins, the test is
to be used as an aid in the
diagnosis of C. difficile disease. As
with other C. difficile tests, results
should be considered in
conjunction with the patient
history. |
| Specimen | Fecal | Fecal |
| Analyte | Clostridium difficile glutamate
dehydrogenase | Clostridium difficile glutamate
dehydrogenase |
| Automated | Yes | No |
| Assay
Technique | Enzyme-linked fluorescent assay
(ELFA) | Rapid Membrane Enzyme
immunoassay |
2
All nonclinical and clinical tests were performed following the recommendations of the FDA draft guidance from November 29th 2010.
G. Nonclinical Tests
A summary of the non-clinical results is presented below.
Sample stability
Specimens storage after collection
Stool specimens may be stored at 2-8℃ for 3 days (from time of collection) prior to processing. If longer storage is required, freeze the specimens at -70°C+/- 10°C up to one month. Avoid repeated freezing and thawing cycles and storage at -19/-31℃
Specimens storage after pretreatment
Specimen supernatants may be stored up to 8 hours at 18-25°C or 48 hours at 2-8°C before being tested with the VIDAS C. difficile GDH assay. Specimen supernatants storage at -19/-31°C and -70°C +/-10°C was not validated and is therefore not recommended.
Precision
The within-laboratory precision was estimated at one site based on the recommendations of the CLSI® EP5-A2.
Three human samples, including 2 close to the clinical cut-off (1 high negative and 1 low positive) and 1 moderate positive, were tested in triplicate in 2 runs per day with 2 different operators, with 2 reagent lots for a total of 12 testing days (6 days of test per lot) on 1 VIDAS instrument (N=72 test values for each sample). Two calibrations were used for each reagent lot (3 days of test per calibration and lot) over the whole period of the study. Data from the study are summarized in the following table:
| Sample | N | Mean test value | Repeatability | | Total within-
laboratory precision
(total within-
instrument, between-
lot, between-
calibration) | |
|----------------------------------|----|-----------------|-----------------------|--------|------------------------------------------------------------------------------------------------------------------|--------|
| | | | Standard
deviation | CV (%) | Standard
deviation | CV (%) |
| Sample 1
High negative | 72 | 0.07 | 0.00 | 6.0 | 0.01 | 14.1 |
| Sample 2
Low positive | 72 | 0.12 | 0.01 | 5.2 | 0.01 | 11.9 |
| Sample 3
Moderate
positive | 72 | 0.27 | 0.02 | 5.7 | 0.03 | 11.2 |
3
The within-laboratory precision of each panel member was also analyzed by determining the percentage of agreement between the test interpretation and the expected outcome (negative/positive interpretation). There was no change of interpretation for the 3 panel samples tested: all replicates of each panel member resulted in the expected interpretation. Data from the qualitative analysis are summarized in the following table:
| Sample | Expected Result | N | Observed result
Lot 1 | | Observed result
Lot 2 | | Total
Agreement | [Cl95] % |
|----------------------------------|-----------------|----|--------------------------|----------|--------------------------|----------|--------------------|--------------------|
| | | | Negative | Positive | Negative | Positive | | |
| Sample 1
High
negative | Negative | 72 | 36 | 0 | 36 | 0 | 72/72
(100.0%) | [95.0 -
100.0]% |
| Sample 2
Low
positive | Positive | 72 | 0 | 36 | 0 | 36 | 72/72
(100.0%) | [95.0 -
100.0]% |
| Sample 3
Moderate
positive | Positive | 72 | 0 | 36 | 0 | 36 | 72/72
(100.0%) | [95.0 -
100.0]% |
The reproducibility was estimated at three sites based on the recommendations of the CLSI® EP5-A2.
Three human samples, including 2 close to the clinical cut-off (1 high negative and 1 low positive) and 1 moderate positive, were tested in triplicate in 2 runs per day with 2 different operators, using 2 reagent lots for a total of 6 testing days (3 days of test for each lot) on 3 VIDAS instruments at 3 different sites (N=108 test values for each sample). One calibration was used for each reagent lot over the whole period of the study. Data from the study are summarized in the following table:
| Sample | N | Mean test value | Reproducibility
(total between sample
preparation/operator/run/day/lot
instrument) | |
|----------------------------------|-----|-----------------|---------------------------------------------------------------------------------------------|--------|
| | | | Standard deviation | CV (%) |
| Sample 1
High negative | 108 | 0.06 | 0.01 | 19.1 |
| Sample 2
Low positive | 108 | 0.12 | 0.02 | 12.9 |
| Sample 3
Moderate
positive | 108 | 0.26 | 0.03 | 13.0 |
4
The reproducibility of each panel member was also analyzed by determining the percentage of agreement between the test interpretation and the expected outcome (negative/positive interpretation). Data from the qualitative analysis for all sites combined are summarized in the following table:
| Panol
Sample | Expected
Result | N | Observed result
Site 1 | | Observed result
Site 2 | | Observed result
Site 3 | | Total
Agreement | [CI₉₅] % |
|----------------------------------|--------------------|-----|---------------------------|----------|---------------------------|----------|---------------------------|----------|---------------------|--------------------|
| | | | Negative | Positive | Negative | Positive | Negative | Positive | | |
| Sample 1
High
negative | Negative | 108 | 36 | 0 | 36 | 0 | 35 | 1 | 107/108
(99.1%) | [94.9 -
99.9]% |
| Sample 2
Low
positive | Positive | 108 | 0 | 36 | 1 | 35 | 3 | 33 | 104/108
(96.3%) | [90.8 -
99.0]% |
| Sample 3
Moderate
positive | Positive | 108 | 0 | 36 | 0 | 36 | 0 | 36 | 108/108
(100.0%) | [96.6 -
100.0]% |
Out of the 108 results obtained for each precision sample, there were:
- 1 change of interpretation (0.9%) for the high negative sample (Sample 1), -
- 4 changes of interpretation (3.7%) for the low positive sample (Sample 2), "
- 0 change of interpretation (0%) for the moderate positive sample (Sample 3). -
The percentages of change of interpretation observed for Sample 1 and Sample 2 were less than 5%, which was considered as normal and expected for these types of samples very close to the assay decision threshold (average test value for Sample 1 = 0.06 and average test value for Sample 2 = 0.12 for a decision threshold at 0.10.
5
Strain reactivity
The VIDAS C. difficile GDH assay was evaluated using several strains of C. difficile. Strains were grown on Columbia agar + 5% sheep blood (bioMérieux ref. 43041).
The VIDAS C. difficile GDH detects the following C.difficile strains at the tested concentrations of 9x10° CFU/mL (3 McFarland) and 3x10° CFU/mL:
| Toxinogenic C.difficile strains: | Non toxinogenic C.difficile strains: | ||||
|---|---|---|---|---|---|
| ATCC® 43255TM | ATCC® 43600TM | ATCC® 700057TM | |||
| ATCC® 9689TM | ATCC® 43599TM | ATCC® 43593TM | |||
| ATCC® 700792TM | ATCC® 43596TM | X1a IS58 | |||
| ATCC® 17858TM | ATCC® 43594TM | X1b R1 1402 | |||
| ATCC® BAA-1805TM | ATCC® 17857TM | ATCC® 43601TM (3x108 CFU/mL only) | |||
| ATCC® BAA-1382TM | ATCC® 43598TM | ||||
| ATCC® 51695TM | CCUG 20309 |
The VIDAS C. difficile GDH detects the following C.difficile strains at the tested concentration of 9x108 CFU/mL (3 McFarland):
| Cardiff ECDC collection
including the following
ribotypes | 001 (7 strains); 002; 003; 012; 014; 015; 017; 020; 023; 027;
029; 046; 053; 056; 070; 075; 077; 078; 081; 087; 095; 106;
126; 131; VPI 10463; 005; 010; 045; 048; 156; 174. |
|-----------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| bioMerieux collection
including the following
ribotypes | 001 (6 strains); 002 (9 strains); 005 (2 strains); 010 (1 strain);
012 (4 strains); 014 (10 strains); 015 (1 strain); 017 (20 strains);
020 (5 strains); 023 (1 strain); 027 (24 strains); 047 (1 strain);
050 (1 strain); 053 (4 strains); 054 (2 strains); 056 (2 strains);
057 (1 strain); 058 (1 strain); 075 (1 strain); 078 (3 strains); 096
(1 strain); 097 (1 strain); 103 (2 strains); 106 (16 strains); 110 (2
strains); 118 (1 strain); 153 (1 strain); 177 (1 strain). |
Analytical sensitivity
Limit of detection
The limit of detection was evaluated using a range of dilutions of purified native C.difficile GDH and recombinant C. difficile GDH in a pool of C. difficile-negative stool samples based on the recommendations of the CLSI EP17-A.
The limit of detection of the VIDAS C. difficile GDH assay (95% detection rate for positive samples) is 3.0 ng/mL for purified native GDH.
Hook effect
No hook effect was observed up to purified native GDH concentrations of 2 µg/Ml.
6
Interferences
Study of drug interferences and other potentially interfering substances
Potential interferences by commonly used drugs and other substances was determined based on the recommendations of the CLSI® EP7-A2, at 2 levels of GDH (a low positive close to the clinical cut-off and a high positive).
| Tested compound | Highest
concentration
tested | Result |
|------------------------|------------------------------------|--------------------------------------|
| Hemoglobin | 3.2 mg/mL | No significant interference observed |
| Lipids | 20 mg/mL | No significant interference observed |
| Mucin | 3.33 mg/mL | No significant interference observed |
| Amoxicillin | 206 µmol/L | No significant interference observed |
| Bismuth salicylate | 8.2 mg/mL | No significant interference observed |
| Calcium carbonate | 13.06 mg/mL | Potential interference* |
| Ceftriaxone | 1.46 mmol/L | No significant interference observed |
| Benzalkonium chloride | 2 µg/mL | No significant interference observed |
| Ciprofloxacin | 30.2 µmol/L | No significant interference observed |
| Erythromycin | 81.6 µmol/L | No significant interference observed |
| Ethanol | 86.8 mmol/L | No significant interference observed |
| Fidaxomicin | 4 mg/mL | No significant interference observed |
| Gentamicin | 21 µmol/L | No significant interference observed |
| Mineral oil | 0.27 v/v | Potential interference* |
| Hydrocortisone | 0.6 mg/mL | No significant interference observed |
| Aluminium hydroxide | 15.3 mg/mL | No significant interference observed |
| Magnesium hydroxide | 6.2 mg/mL | No significant interference observed |
| Lidocaine | 0.12 mg/mL | No significant interference observed |
| Loperamide | 0.08 mg/mL | No significant interference observed |
| Mesalazine | 19.2 mg/mL | No significant interference observed |
| Metronidazole | 2 mg/mL | No significant interference observed |
| Naproxen | 2170 µmol/L | No significant interference observed |
| Nystatin | 600 UI/mL | No significant interference observed |
| Phenylephrine | 0.225 mg/mL | No significant interference observed |
| Sennosides | 0.24 mg/mL | No significant interference observed |
| Tergitol (nonoxynol-9) | 0.5 v/v | Potential interference* |
| Tetracycline | 34 µmol/L | No significant interference observed |
| Vancomycin | 5 mg/mL | No significant interference observed |
*Calcium carbonate at 9.80 mg/mL, Mineral oil at 0.20 v/v and Tergitol at 0.125 v/v did not cause interference.
7
Cross-reactivity and microbial interference:
To test for cross-reactivity, each micro-organism was diluted in a pool of C. difficile-negative stool samples, pretreated and a single replicate was tested using the VIDAS C. difficile GDH assav.
To test for microbial interference, each micro-organism was diluted in a pool of C. difficilepositive stool samples, pretreated and a single replicate was tested using the VIDAS C. difficile GDH assay.
For both cross-reactivity and microbial interference studies, the micro-organisms were tested at a concentration of 3x108 CFU/mL (1 McFarland) for bacteria and 1x10 PFU/mL for viruses.
None of the following micro-organisms, present in the stool samples, reacted with the VIDAS C. difficile GDH assay:
Abiotrophia defectiva, Acinetobacter baumannii, Acinetobacter Iwoffii, Aeromonas hydrophila ssp hydrophila, Alcaligenes faecalis, Anaerococcus tetradius, Bacillus cereus, Bacteroides caccae, Bacteroides merdae, Bacteroides stercoris, Bifidobacterium adolescentis, Bifidobacterium longum, Campylobacter ieiuni, Candida albicans, Candida catenulata, Cedecea davisae, Chlamydia trachomatis, Citrobacter amalonaticus, Citrobacter freundii. Citrobacter koseri. Citrobacter sedlakii. Clostridium nexile. Clostridium beijerinckii, Clostridium bifermentans, Clostridium bolteae, Clostridium butyricum, Clostridium chauvoei, Clostridium fallax, Clostridium haemolyticum, Clostridium histolyticum, Clostridium innocuum, Clostridium novyi, Clostridium paraputrificum, Clostridium perfringens, Clostridium ramosum, Clostridium scindens, Clostridium septicum, Clostridium sordellii. Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium symbosum, Clostridium tertium, Clostridium tetani, Collinsella aerofaciens, Corynebacterium genitalium, Desulfovibrio piger, Edwardsiella tarda, Eggerthella lenta, Enterobacter aerogenes, Enterobacter cloacae, Enteroccus casseliflavus, Enterococcus cecorum, Enterococcus dispar. Enterococcus faecalis, Enterococcus faecium, Enterococcus gallinarum, Enterococcus hirae, Enterococus raffinosus, Escherichia coli, Escherichia fergusonii, Escherichia hermannii, Flavonifractor plautii, Fusobacterium varium, Gardnerella vaginalis, Gemella morbillorum, Hafnia alvei, Helicobacter fenneliae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Lactobacillus acidophilus, Lactobacillus reuteri, Lactoccus lactis, Leminorella grimontii, Listeria grayi, Listeria innocua, Listeria monocytogenes, Peptoniphilus asaccharolyticus, Peptostreptococcus anaerobius, Plesiomonas shigelloides, Porphyromonas asaccharolytica, Prevotella melaninogenica, Proteus mirabilis, Proteus penneri, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas putida, Salmonella enterica ssp arizonae, Salmonella ser.Choleraesuis, Salmonella ser.Typhimurium Serratia liquefaciens, Serratia marcescens, Shigella boydii, Shigella dysenteriae, Shigella sonnei, Staphylococcus aureus ssp aureus, Staphylococcus epidermidis, Stenotrophomonas maltophilia, Streptococcus ---------------------------------------------------------------------------------------------------------------------------------------------------------------agalactiae, Streptococcus dysgalactiae SSD dysgalactiae, Streptococcus intermedius, Streptococcus uberis, Trabulsiella quamensis, Veillonella parvula, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia bercovieri. Yersinia rohdei, Adenovirus 40 et 41, Rotavirus RF, Norovirus, Enterovirus 70, Echovirus 12, Coxsackie virus, Cytomegalovirus AD169.
8
H. Clinical Testing
Clinical sensitivity and specificity
1904 (1891 prospective and 13 retrospective) stool samples collected from patients suspected of having C. difficile infection (CDI) were tested at three sites (USA and Europe). The age groups of the patients range from 1 year to 100 years. A single replicate of each sample was tested using VIDAS C. difficile GDH on a VIDAS instrument. A bacterial culture test was performed for each sample on a CCFA medium according to the instructions for use. Data from the study are summarized in the following tables:
| CCFA bacterial culture test | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site 1 (EU) | Site 2 (US) | Site 3 (US) | Total (All Sites) | ||||||
| Positive | Negative | Positive | Negative | Positive | Negative | Positive | Negative | ||
| VIDAS | |||||||||
| C. difficile | |||||||||
| GDH | Positive | 42 | 24 | 78 | 21 | 163 | 113 | 283 | 158* |
| Negative | 7 | 451 | 4 | 363 | 2 | 623 | 13** | 1437 | |
| Total | 49 | 475 | 82 | 384 | 165 | 736 | 296 | 1595 | |
| Performance | % | [CI95%] | % | [CI95%] | % | [CI95%] | % | [CI95%] | |
| Sensitivity | 85.7% | [72.8 - | |||||||
| 94.1]% | 95.1% | [88.0 - | |||||||
| 98.7]% | 98.8% | [95.7 - | |||||||
| 99.9]% | 95.6% | [92.6 - | |||||||
| 97.6]% | |||||||||
| Specificity | 94.9% | [92.6 - | |||||||
| 96.7]% | 94.5% | [91.8 - | |||||||
| 96.6]% | 84.6% | [81.8 - | |||||||
| 87.2]% | 90.1% | [88.5 - | |||||||
| 91.5]% | |||||||||
| Negative | |||||||||
| Predictive Value | |||||||||
| (NPV) | 98.5% | [96.9 - | |||||||
| 99.4]% | 98.9% | [97.2 - | |||||||
| 99.7]% | 99.7% | [98.8 - | |||||||
| 99.9]% | 99.1% | [98.5 - | |||||||
| 99.5]% |
Performance of the VIDAS C. difficile GDH assay versus CCFA bacterial culture on prospective samnles
- 158 samples were found positive with the VIDAS C. difficile GDH assay and negative with the CCFA bacterial culture test, 73 of which were found positive and 85 negative with the commercially available C. difficile GDH assay.
** 13 samples were found negative with the VIDAS C. difficile GDH assay and positive with the CCFA bacterial culture test. 9 of which were found negative and 4 positive with the commercially available C. difficile GDH assay.
Out of 2038 patient samples tested with the VIDAS C. difficile GDH assay, 21 (1,0%) were reported as invalid.
Testing on retrospective samples
Thirteen (13) retrospectively collected samples from pediatric patients submitted for routine C. difficile testing (2-12 years) were assayed for C. difficile according to the same protocol. For these 13 retrospective samples alone, the VIDAS C. difficile GDH assay demonstrated a sensitivity of 100.0% (10/10) and a specificity of 33.3% (1/3).
Performance of the VIDAS C. difficile GDH assay versus CCFA bacterial culture on all prospective and retrospective samples
For all 1904 specimens and all sites combined, the VIDAS C. difficile GDH assay demonstrated a sensitivity of 95.8% (293/306) with 95%C1: 92.8 - 97.7%, a specificity of 90.0% (1438/1598) with 95%Cl: 88.4 – 91.4%, and a negative predictive value of 99.1% with 95%Cl: 98.5 - 99.5%.
9
| Age Group | VIDAS Positive
/CCFA Positive | Sensitivity [Cl95] % | VIDAS
Negative
/CCFA
Negative | Specificity [Cl95] % |
|-------------|----------------------------------|------------------------|----------------------------------------|------------------------|
|