(90 days)
chromID™ MRSA agar is a selective and differential chromogenic medium for :
A. The qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA), to aid in the prevention and control of MRSA in healthcare settings. The test is performed on anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. chromID™ MRSA when used to detect nasal colonization is not intended to diagnose, guide, or monitor therapy for MRSA infections, or provide results of susceptibility to methicillin.
B. The qualitative detection of MRSA from skin structure infections. chromID™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to aid in the identification and diagnosis of MRSA infections. Concomitant cultures for skin structure infections are necessary to recover organisms for further microbiological susceptibility testing or epidemiological typing. A negative result does not preclude MRSA infection. chromID™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin.
C. The qualitative detection of MRSA from positive blood cultures demonstrating Gram-positive cocci on Gram stain. chromID™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to aid in the identification and diagnosis of MRSA infections. Sub-culturing for positive blood cultures are necessary to recover organisms for further microbiological susceptibility testing or epidemiological typing. A negative result does not preclude, MRSA infection. chromID™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin.
chromID™ MRSA agar consists of a rich nutritive base combining different peptones. It also contains a chromogenic substrate of a-glucosidase and a combination of several antibiotics, including cefoxitin, which favor the growth of MRSA including heteroresistant strains and the direct detection of MRSA strains by revealing a-glucosidase activity (patent registered), green colonies. The selective mixture of antibiotics inhibits most bacteria not belonging to the genus Staphylococcus, as well as yeasts. The MRSA strains are identified by the presence of green colonies that result from the chromogen incorporated in the medium. The chromogen targets the a-glucosidase activity of S. aureus. The a-glucosidase produced by S. aureus cleaves the chromogenic substrate, which gives a green color to the S. aureus colonies growing on the medium.
The provide text describes the acceptance criteria and study results for chromID™ MRSA agar, a chromogenic medium for the qualitative detection of methicillin-resistant Staphylococcus aureus (MRSA).
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the reported performance data for sensitivity and specificity. The device is expected to perform accurately in detecting MRSA from various specimen types.
| Metric | Acceptance Criteria (Implied) | Reported Device Performance (Blood Culture) |
|---|---|---|
| Sensitivity | High (close to 100%) | 100.0% (215/215) [98.3% – 100]% |
| Specificity | High (close to 100%) | 98.9% (641/648) [97.8% – 99.5]% |
Note: The provided text primarily focuses on the clinical performance for blood cultures. While analytical studies are mentioned, specific numerical acceptance criteria for those were not explicitly stated beyond achieving "expected results" or specific growth/detection rates.
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Study Sample Size (Blood Culture): 863 positive blood culture specimens (demonstrating Gram-positive cocci) were initially analyzed. 187 cultures were removed due to low prevalence of the target or protocol deviations, resulting in a final evaluated sample size.
- Data Provenance: The study was conducted at four clinical sites. The geographical location of these sites (e.g., country of origin) is not specified. The clinical study is described as having "analyzed" specimens, suggesting a retrospective or prospective observational design where samples were collected and then tested. The phrase "clinical trial" is used, implying a prospective collection for evaluation. The "Analytical Studies" also mention the use of well-characterized strains, which would be laboratory-based rather than from clinical patients.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- The text does not explicitly state the number of experts used to establish the ground truth.
- It also does not specify the qualifications of these experts.
4. Adjudication Method for the Test Set
- The text describes a reference method for establishing ground truth, which involves:
- Growth on Tryptic Soy agar with 5% sheep blood (BAP).
- Testing of colonies suggestive of Staphylococcus species by Gram stain, catalase, and latex agglutination.
- Staphylococcus aureus isolates further tested for resistance to Oxacillin by the Cefoxitin Screen test.
- All Cefoxitin-resistant colonies tested for the presence of the mecA gene by PCR and by VITEK® MS for species confirmation.
- For discordant specimens in the blood culture clinical study, "Two false positives were confirmed as MRSA positive" and "Five false positives that grew green colonies were not identified as MRSA." This implies a form of adjudication or re-evaluation for discordant results, likely by further expert review or follow-up testing, though a formal "2+1" or "3+1" structure isn't explicitly detailed.
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
- No, an MRMC comparative effectiveness study was not done.
- This device (chromID™ MRSA agar) is a culture medium, not an AI-assisted diagnostic tool. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance was done, but it's important to clarify the context. The "device" here is the chromID™ MRSA agar medium itself. The performance evaluation measures the ability of this agar to correctly identify MRSA based on color change, which is then interpreted by a laboratory user (a manual interpretation of the agar plate).
- The clinical performance data for sensitivity and specificity (100.0% and 98.9% respectively for blood cultures) represent the standalone performance of the chromID™ MRSA agar in classifying samples as MRSA positive or negative, compared to the defined reference method.
7. The Type of Ground Truth Used
- The ground truth for the clinical studies was established using a multi-faceted reference method, which includes:
- Culture on Tryptic Soy agar with 5% sheep blood (BAP).
- Gram stain, catalase, and latex agglutination for presumptive identification.
- Oxacillin resistance testing by Cefoxitin Screen test.
- Molecular testing (PCR for mecA gene) for definitive confirmation of methicillin resistance.
- Species confirmation by VITEK® MS.
- This combination represents a robust "expert consensus" or "gold standard" laboratory method, incorporating phenotypic and genotypic characteristics.
8. The Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or AI development. Since this is a chromogenic culture medium, its development likely involved iterative formulation and testing, rather than a distinct machine learning training set as typically understood.
- The "Analytical Reactivity (Challenge)" and "Cross Reactivity (Analytical Specificity)" studies, using specific well-characterized strains (80 mecA MRSA strains, 5 mecC MRSA strains, and 71 non-MRSA strains), could be seen as part of the developmental testing that helps "train" the understanding of the medium's performance, but not in the AI sense.
9. How the Ground Truth for the Training Set Was Established
- As a "training set" for an AI algorithm is not applicable, the question of its ground truth establishment is also not directly applicable in the AI context.
- However, for the analytical studies involving known strains, the ground truth was established by prior characterization of these strains (e.g., they are known mecA MRSA strains, mecC MRSA strains, or specific non-MRSA species), likely through established microbiological and molecular methods.
§ 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).