(39 days)
The MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive enterococci and staphylococci. After inoculation, panels are incubated for 4.5 - 18 hours at 35℃ +/- 1℃, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. Additionally, the panels may be incubated in a non-CO2 incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert.
This particular submission is for the addition of the antimicrobial linezolid, at concentrations of 0.5 to 16 ug/ml Long Dilution Sequence and 0.5 - 4 ug/ml 4-Dilution Breakpoint Sequence, for enterococci and staphylococci, to the test panel.
The Gram-positive organisms which may be used for linezolid susceptibility testing in this panel are:
Enterococcus faecium (vancomycin-resistant) Staphylococcus aureus (methicillin-susceptible and methicillin-resistant)
MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels, utilizing both the MicroScan® Rapid Fluorogenic Identification and Dried Overnight Antimicrobial Susceptibility Testing (AST) technologies, are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic Gram-positive enterococci and staphylococci.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in water and dehydrated. Various antimicrobial agents are diluted in water, buffer, or minute concentrations of broth, to concentrations bridging the range of clinical interest. Panels are rehydrated with Synergies plus™ Pos Broth, after inoculation with a standardized suspension of the organism. After incubation in the WalkAway® SI, or equivalent, System, or equivalent, for 4.5 - 18 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
Here's an analysis of the provided text regarding the acceptance criteria and study for the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels with linezolid:
1. Table of Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria (Implicit from Guidance) | Reported Device Performance (Linezolid) |
|---|---|---|
| Overall Essential Agreement (EA) | Not explicitly stated but expected to demonstrate "acceptable performance" as per FDA guidance for AST systems. | Demonstrated "acceptable performance with an overall Essential Agreement (EA) and 4-Dilution Agreement of 76.0% with the Long Dilution Sequence and 76.0% with the 4-Dilution Breakpoint Sequence" |
| Reproducibility | Acceptable reproducibility | Demonstrated "acceptable reproducibility" |
| Quality Control Testing | Acceptable results for linezolid | Demonstrated "acceptable results for linezolid" |
Note: The document refers to the FDA's "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA" dated February 5, 2003. This document would contain the explicit, quantitative acceptance criteria for Essential Agreement, Category Agreement, and reproducibility that the device must meet. The provided summary only states that the device "demonstrated acceptable performance" and met the criteria.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document does not explicitly state the total number of isolates (fresh, stock efficacy, and stock challenge strains combined) used for the external validation.
- It mentions that "external validation was conducted with fresh and stock Efficacy isolates and stock Challenge strains."
- For the reported performance of linezolid, it states "Essential Agreement (EA) and 4-Dilution Agreement of 76.0%," which implies a certain number of comparisons were made, but the exact count is not given.
- Data Provenance: The text does not specify the country of origin. The study was an "external validation." It involved both retrospective (stock isolates) and potentially prospective (fresh isolates) data, though the exact proportion is not mentioned.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not provide information on the number or qualifications of experts used to establish the ground truth for the test set.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method used for the test set. The ground truth appears to be established by comparison to a "frozen Reference Panel" and "Expected Results determined prior to the evaluation" for challenge strains, rather than expert consensus on individual cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility test system, not a diagnostic imaging device that typically involves human readers interpreting results.
6. Standalone Performance Study
Yes, a standalone study was done. The study specifically compared the performance of the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel with linezolid against a "frozen Reference Panel" and "Expected Results" for challenge strains. This evaluates the algorithm's (or system's) performance purely in terms of its output (MIC values and agreement) without direct human intervention in the interpretation phase beyond setting up the test and reading the final MIC.
7. Type of Ground Truth Used
The ground truth was established by:
- Comparison to a frozen Reference Panel for efficacy isolates. This suggests a pre-established, highly reliable method for determining antimicrobial susceptibility.
- "Expected Results determined prior to the evaluation" for stock Challenge strains. These are typically well-characterized strains with known susceptibility profiles.
8. Sample Size for the Training Set
The document does not provide any information about a discreet training set used for developing the device. This is typical for a microbiology susceptibility panel, where the "training" (if it can be called that) often comes from years of established methodology and the development of the panel's design, rather than a machine learning training phase on a specific dataset.
9. How Ground Truth for the Training Set Was Established
Since no explicit training set is mentioned, the method for establishing its ground truth is not applicable/not provided. The device's design and expected performance would be based on well-established microbiological principles and previous generations of AST systems, rather than a separate "training phase" and associated ground truth process as seen in AI algorithms.
§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.
(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”