(262 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.
chromID™ MRSA agar consists of a rich nutritive base combining different peptones. It also contains a chromogenic substrate of α-glucosidase and a combination of several antibiotics (cefoxitin, etc.) that favor the growth and direct detection of MRSA, including hetero-resistant strains, by revealing orglucosidase activity (patent registered) through the appearance of green colonies. The α-glucosidase produced by S. aureus cleaves the chromogenic substrate, which gives a green color to the S. aureus colonies growing on the medium. The MRSA strains are identified by the presence of green colonies that result from the chromogen incorporated in the medium. The selective mixture of antibiotics inhibits most bacteria not belonging to the genus Staphylococcus, as well as yeasts.
Here's an analysis of the acceptance criteria and study findings for the chromID™ MRSA device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the clinical study's sensitivity and specificity. However, the reported performance metrics can be considered the demonstrated performance of the device.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Preamble/General Acceptability | Adequate analytical and clinical performance to be substantially equivalent to the predicate device and aid in MRSA detection. | Demonstrated substantial equivalence to predicate device based on analytical and clinical studies. |
| Reproducibility | 100% reproducibility rate for mecA-positive/negative S. aureus isolates over 5 days across 3 sites. | 100% (450/450) |
| Quality Control | ≥95% agreement with expected results for QC organisms (ATCC 29213, ATCC 43300) when compared to oxacillin MIC and mecA PCR. | Met pre-defined acceptance criteria. |
| Analytical Reactivity (mecA MRSA) | N/A (Challenge set of 80 mecA-MRSA) | 58/80 (72.5%) detected |
| Analytical Reactivity (mecC MRSA) | N/A (Challenge set of 5 mecC-MRSA) | 4/5 (80%) detected |
| Expression of Resistance (Low & High-level MRSA) | All low and high-level methicillin-resistant S. aureus strains detected at >10² CFU/mL. | All detected at an inoculum of >10² CFU/mL. |
| Expression of Resistance (Borderline Oxacillin-Resistant & Methicillin-Susceptible S. aureus) | No growth at high inoculum concentrations. | No growth at inoculum concentrations as high as 10⁸ CFU/mL. |
| Mixed Infection Study | Performance not negatively impacted by presence of non-MRSA organisms. | Presence of non-MRSA organisms did not negatively impact chromID™ MRSA performance. |
| Recovery Study (ATCC® 43300™) | N/A (Lowest detection limit) | 10³ CFU/mL at 24 hours |
| Recovery Study (CDC Mu3-8R) | N/A (Lowest detection limit) | 10² CFU/mL at 24 hours |
| Cross Reactivity (Non-MRSA strains) | N/A (Expected limited cross-reactivity for specific non-MRSA strains, and green colonies for specific resistance mechanisms) | 44 strains did not grow. 20 strains grew without green pigment. 3 Klebsiella pneumoniae (KPC), 1 Enterobacter cloacae (KPC), 1 S. pseudintermedius (oxacillin-resistant), 2 S. sciuri (oxacillin-resistant) showed green colonies. |
| Interference | No interference from physiologically/biologically relevant concentrations of common substances; acknowledges potential inhibition from certain topical antibiotics/antiseptics. | No interference from human blood, mucin, anticoagulants, plasma, buffy coat. Specific topical antibiotics/antiseptics listed as inhibitory. |
| Incubation Time (ATCC 43300, S. aureus 0611169) | N/A (Time to positive) | 20 hours |
| Incubation Time (CDC Mu3-8R) | N/A (Time to positive) | 27 hours |
| Clinical Study Sensitivity | Not explicitly stated, but high sensitivity would be expected for a screening/diagnostic aid. | 93.8% (95% CI: [89.2-96.5]) |
| Clinical Study Specificity | Not explicitly stated, but high specificity would be expected for a screening/diagnostic aid. | 97.4% (95% CI: [95.6-98.5]) |
Note: The document does not explicitly state numerical "acceptance criteria" for sensitivity and specificity. The reported values are the observed performance. The FDA's substantial equivalence determination implies these values were deemed acceptable.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 680 specimens (valid for comparison after exclusions)
- Data Provenance: Clinical study data from four geographically diverse clinical sites. This suggests prospective collection within the United States, given it's an FDA submission. The specific country is not explicitly stated beyond "geographically diverse clinical sites" in relation to the US FDA. The nature of the study (collection of specimens for device evaluation) indicates it's prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the "number of experts" or their "qualifications" involved in establishing the ground truth. Ground truth was established using standard microbiological laboratory methods (Reference Culture Method) which would be performed by trained laboratory personnel.
4. Adjudication Method for the Test Set
The document describes a clear reference method for ground truth determination, which inherently serves as the "adjudication" (or gold standard). It does not mention a separate, independent adjudication panel or specific method like "2+1" or "3+1" for resolving discrepancies between the new device and the reference method. Discordant results were analyzed and described.
- Reference Culture Method:
- Specimens enriched in Tryptic Soy broth with 6.5% NaCl (TSB) for 24 hours (negative broths incubated an additional 24 hours).
- Positive broth cultures subcultured to Tryptic Soy agar with 5% sheep blood (BAP).
- Colonies suggestive of Staphylococcus species tested by Gram stain, catalase, and latex agglutination.
- Staphylococcus aureus isolates tested for resistance to oxacillin by the Cefoxitin Screen test (30µg).
- All oxacillin-resistant colonies by Cefoxitin Screen test were tested for the presence of the mecA gene by PCR and by VITEK® MS for species confirmation.
- Definition of Positive Ground Truth: Recovery of cefoxitin-resistant Staphylococcus aureus from the specimen.
- Definition of Negative Ground Truth: All other results (growth of cefoxitin-susceptible Staphylococcus aureus, growth of other species, or no growth).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is a culture medium, and its performance is assessed by direct comparison to a laboratory reference method, not by comparing human reader interpretations with and without AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
This is a standalone microbiological culture medium. Its performance (presence/absence of green colonies indicating MRSA) is interpreted directly by laboratory personnel based on the visual result of the culture. There is no separate "algorithm" being evaluated beyond the efficacy of the chromogenic medium itself. The clinical study evaluates this standalone culture medium's ability to detect MRSA compared to a reference lab method.
7. The Type of Ground Truth Used
The ground truth used was a composite reference standard based on:
- Standard microbiological culture methods (TSB enrichment, BAP subculture)
- Phenotypic tests (Gram stain, catalase, latex agglutination, Cefoxitin Screen test for oxacillin resistance)
- Molecular confirmation (mecA gene PCR)
- Species confirmation (VITEK® MS)
This detailed approach combines multiple laboratory techniques to confirm the presence and methicillin-resistance of Staphylococcus aureus.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of an algorithm or machine learning. As a diagnostic culture medium, it would have been developed and optimized through in vitro studies and experiments, but the concept of a "training set" for an algorithm's development, distinct from analytical validation, is not applicable here. The analytical performance data (e.g., reactivity, reproducibility, cross-reactivity) serves to demonstrate the medium's inherent characteristics.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for an algorithm in the traditional sense. The ground truth for the analytical studies (e.g., for determining mecA status for reactivity studies) would have been established using established molecular and phenotypic methods, similar to those used for the clinical ground truth. For instance, the QC organisms were compared to oxacillin MIC and mecA PCR.
§ 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).