(308 days)
VRESelect ™ is a selective and differential chromogenic medium, containing 8 µg/mL of vancomycin, for the qualitative detection of gastrointestion of vancomycin-resistant Enterococcus faecium (VREfm) and vancomycin-resistant Enterococcus faecalis (VREfs) and to aid in the prevention and control of vancomycin-resistant Enterococcus (VRE) in healthcare settings. The test is performed on rectal swabs from patients to be screened for VRE colonization. VRESelect ™ is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Results can be interpreted after 24 to 28 hours incubation. Subculture to non-selective media (e.g., trypticase soy agar with 5% sheep blood) is need for susceptibility testing and epidemiological typing.
VRESelect ™ is a selective medium for the detection of vancomyoin-resistant Enterococcus (VRE). The selectivity of this medium is based on the presence of an antifungal/antibiotic mixture that inhibits the growth of most yeast, Gram negative and Gram positive bacteria, with the exception of vancomycin-resistant Enterococci (VRE).
Detection is based on the cleavage of chromogenic substrates by specific enzymes of Enterococcus facium which produces pink colonies and Enterococcus faecalis which produces blue colonies.
Enterococcus gallinarum and Enterocccus casseliflavus are intrinsically resistant to vancomycin and may grow on the VRESelect™ medium as colories or white colonies because they do not metabolize the chromogenic substrates. Vancomycin susceptible enterococci are inhibited.
After 24 to 28 hours incubation pink colonies can be reported as VRESm. Blue colonies should be confirmed by a catalase test and susceptibility testing (refer to limitation 8 in package insert).
The provided text describes the performance of VRESelect™ Culture Media, which is a selective and differential chromogenic medium for the detection of vancomycin-resistant Enterococcus (VRE).
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a numerical target format (e.g., "sensitivity must be >90%"). However, the "Method Comparison" section and the subsequent tables present performance metrics (Positive Agreement and Negative Agreement) against established reference methods, which implicitly serve as the acceptance criteria for the device to be deemed "substantially equivalent."
| Performance Metric | Acceptance Criteria (Implied by Predicate Performance / Standard) | Reported Device Performance (VRESelect™) |
|---|---|---|
| Positive Agreement (VRESelect vs BEAV+Conf.) | Not explicitly stated, but high agreement expected with predicate. | 98% (24 hrs), 99% (28 hrs) |
| Negative Agreement (VRESelect vs BEAV+Conf.) | Not explicitly stated, but high agreement expected with predicate. | 97% (24 hrs), 96% (28 hrs) |
| Positive Agreement VREfm (VRESelect vs Vitek 2) | Not explicitly stated, but high agreement expected with Vitek 2. | 97% (24 hrs), 98% (28 hrs) |
| Negative Agreement VREfm (VRESelect vs Vitek 2) | Not explicitly stated, but high agreement expected with Vitek 2. | 97% (24 hrs), 97% (28 hrs) |
| Positive Agreement VREfs (VRESelect vs Vitek 2) | Not explicitly stated, but high agreement expected with Vitek 2. | 79% (24 hrs), 82% (28 hrs) |
| Negative Agreement VREfs (VRESelect vs Vitek 2) | Not explicitly stated, but high agreement expected with Vitek 2. | 97% (24 hrs), 97% (28 hrs) |
| Positive Agreement VREfm (VRESelect vs Vancomycin MIC) | Not explicitly stated, but high agreement expected with Vancomycin MIC. | 99% (24 hrs), 100% (28 hrs) |
| Negative Agreement VREfm (VRESelect vs Vancomycin MIC) | Not explicitly stated, but high agreement expected with Vancomycin MIC. | 98% (24 hrs), 98% (28 hrs) |
| Positive Agreement VREfs (VRESelect vs Vancomycin MIC) | Not explicitly stated, but high agreement expected with Vancomycin MIC. | 96% (24 hrs), 96% (28 hrs) |
| Negative Agreement VREfs (VRESelect vs Vancomycin MIC) | Not explicitly stated, but high agreement expected with Vancomycin MIC. | 98% (24 hrs), 97% (28 hrs) |
| Minimum Concentration of VRE Detected | Not explicitly stated as acceptance criteria, but 10³ CFU/mL is stated as detectable. | 10³ CFU/mL |
| Cross-Reactivity | No cross-reactivity with non-VRE strains. | No cross-reactivity observed with 119 strains. |
| Reproducibility | 100% expected results. | 100% of the time at 24 and 28 hours. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Method Comparison (BEAV + Confirmation): 757 specimens.
- Biochemical Identification (Vitek 2) & Vancomycin MIC: Based on the same 757 specimens, but stratified by VREfm (97 positive for VREfm, 660 negative) and VREfs (38 positive for VREfs, 719 negative) for Vitek 2, and VREfm (94 resistant, 637 susceptible) and VREfs (28 resistant, 637 susceptible) for Vancomycin MIC.
- Cross-Reactivity: 119 microorganisms.
- Recovery Study: Panel of eighteen vancomycin-resistant enterococci (8 VREfm and 10 VREfs).
- Reproducibility: 6 ATCC reference strains.
- Challenge Panel: 56 well-characterized strains.
- Interfering Substances: Multiple substances tested, but specific strain counts not given for each.
- Data Provenance: The document does not specify the country of origin. It is a 510(k) submission to the FDA, implying studies conducted to US regulatory standards, but the physical location of the patient sample collection is not mentioned. The data appears to be prospective as it involves testing specimens with the VRESelect™ media and comparing them to reference methods.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly mention "experts" in the context of establishing ground truth for the test set in the same way one might in imaging studies. Instead, the ground truth is established through standard microbiological laboratory procedures:
- "BEAV + Confirmation": The confirmation included "Gram stain, catalase, PYR, Vitek 2 identification and vancomycin (MIC E-Test)." These are objective laboratory tests. While trained microbiologists perform and interpret these tests, the ground truth is based on the results of these standardized methods rather than subjective expert consensus.
- "Biochemical identification (Vitek) vs. VRESelect™ results": Vitek 2 is an automated system for identification, which provides objective results.
- "Vancomycin minimal inhibitory concentration (MIC) demonstrated the following results": Vancomycin E-Test (MIC) provides an objective measure of antimicrobial resistance.
Therefore, the ground truth is established by a combination of conventional microbiological techniques and automated systems, interpreted by trained laboratory personnel, not by a panel of "experts" as in, for example, a radiology consensus read.
4. Adjudication Method for the Test Set
There's no mention of an "adjudication method" in the sense of multiple experts independently reviewing and then resolving discrepancies for the ground truth. The ground truth relies on objective laboratory tests ("BEAV + Confirmation," Vitek 2, Vancomycin MIC E-Test). Any discrepancies between VRESelect™ and these reference methods are presented as performance metrics (Positive/Negative Agreement) and sometimes further analyzed (e.g., false positives/negatives were sometimes confirmed by subculture to BAPs and further testing).
5. If a Multi_Reader Multi_Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
This document describes the performance of a culture medium, not an AI algorithm for diagnostic imaging. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The VRESelect™ media is itself a diagnostic tool that produces a visible result (colony color). The "standalone" performance is effectively what is reported in the tables, where the media's results are compared directly to the reference methods (BEAV+Confirmation, Vitek 2, Vancomycin MIC). The interpretation of the visible colonies (pink/blue) is part of the "system" performance. There is no "algorithm only" in the sense of a software-based AI system operating independently of human observation of the culture medium.
7. The Type of Ground Truth Used
The ground truth used is a combination of:
- Expert Consensus (Implicit/Procedural): The "BEAV + Confirmation" method, which includes Gram stain, catalase, PYR, Vitek 2 identification, and vancomycin (MIC E-Test), represents a gold standard of laboratory procedures for identifying and confirming VRE, interpreted by trained microbiologists following established protocols.
- Pathology/Laboratory Results: Vitek 2 biochemical identification and vancomycin MIC E-Test are objective laboratory tests providing definitive identification and resistance profiles.
8. The Sample Size for the Training Set
The document does not explicitly differentiate between "training" and "test" sets in the context of an algorithm. This product is a culture medium, not a machine learning model that undergoes a training phase. The described studies represent validation studies for the performance of the medium.
9. How the Ground Truth for the Training Set Was Established
As this is a culture medium, not an AI algorithm, there is no "training set" in the machine learning sense. The development of the medium would have involved internal R&D and testing, but the document focuses on the formal validation studies.
§ 866.1700 Culture medium for antimicrobial susceptibility tests.
(a)
Identification. A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.(b)
Classification. Class II (performance standards).