(385 days)
VITEK® 2 AST-Gram Negative Meropenem is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative Meropenem in is a quantitative test. Meropenem has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active in vitro and in clinical infections:
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
In vitro data are available, but clinical significance is unknown:
Citrobacter freundii
Citrobacter koseri
Enterobacter cloacae
Hafnia alvei
Klebsiella oxytoca
Morganella morganii
Serratia marcescens
The VITEK® 2 Gram Negative Susceptibility Card Meropenem also reports susceptibility for the following additional organisms as listed on the FDA Susceptibility Test Interpretive Criteria website:
Acinetobacter spp.
The VITEK® 2 Gram-Negative Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli to antimicrobial agents when used as instructed.
The principle of the VITEK®2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh(1) and Gerlach(0). The VITEK @ 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).
Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK®2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cvcle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.
VITEK® 2 AST-GN Meropenem (≤0.25 - ≥16 µg/mL) has the following concentrations in the card: 0.5, 1. 2. 4 and 8 ug/mL (equivalent standard method concentration by efficacy in us/mL).
Here's an analysis of the provided text regarding the acceptance criteria and study for the VITEK® 2 AST-Gram Negative Meropenem:
Acceptance Criteria and Reported Device Performance
For Antimicrobial Susceptibility Test (AST) Systems, the FDA Class II Special Controls Guidance Document typically defines acceptance criteria based on statistical agreement between the investigational device and a reference method. The key metrics are:
- Essential Agreement (EA): The percentage of results where the MIC result of the device is within +/- one doubling dilution of the reference method.
- Category Agreement (CA): The percentage of results where the device and the reference method produce the same interpretive category (e.g., Susceptible, Intermediate, Resistant).
- Very Major Errors (VME): The frequency with which the device incorrectly reports a susceptible isolate as resistant compared to the reference method (false resistance).
- Major Errors (ME): The frequency with which the device incorrectly reports a resistant isolate as susceptible compared to the reference method (false susceptibility).
- Minor Errors (mE): The frequency with which the device incorrectly reports an intermediate isolate as susceptible or resistant, or a susceptible/resistant isolate as intermediate.
The reported performance of the VITEK® 2 AST-Gram Negative Meropenem is presented in Table 2:
| Metric | Acceptance Criteria (from FDA Guidance - typical) | Reported Device Performance |
|---|---|---|
| Overall Performance | ||
| % Essential Agreement (EA) | Greater than or equal to 90% | 95.0% (1016/1070) |
| % Category Agreement (CA) | Greater than or equal to 90% | 95.0% (1016/1070) |
| Very Major Errors (VME) | Less than or equal to 1.5% | 0.0% (0/346) |
| Major Errors (ME) | Less than or equal to 3.0% | 0.6% (4/680) |
| Minor Errors (mE) | Less than or equal to 10.0% | 4.7% (50/1070) |
| Enterobacterales | ||
| % Essential Agreement (EA) | Greater than or equal to 90% | 94.4% (537/569) |
| % Category Agreement (CA) | Greater than or equal to 90% | 97.0% (552/569) |
| Very Major Errors (VME) | Less than or equal to 1.5% | 0.0% (0/65) |
| Major Errors (ME) | Less than or equal to 3.0% | 0.8% (4/491) |
| Minor Errors (mE) | Less than or equal to 10.0% | 2.3% (13/569) |
| P. aeruginosa | ||
| % Essential Agreement (EA) | Greater than or equal to 90% | 94.7% (267/282) |
| % Category Agreement (CA) | Greater than or equal to 90% | 89.7% (253/282) |
| Very Major Errors (VME) | Less than or equal to 1.5% | 0.0% (0/121) |
| Major Errors (ME) | Less than or equal to 3.0% | 0.0% (0/137) |
| Minor Errors (mE) | Less than or equal to 10.0% | 10.3% (29/282) |
| Acinetobacter spp. | ||
| % Essential Agreement (EA) | Greater than or equal to 90% | 96.8% (212/219) |
| % Category Agreement (CA) | Greater than or equal to 90% | 96.3% (211/219) |
| Very Major Errors (VME) | Less than or equal to 1.5% | 0.0% (0/160) |
| Major Errors (ME) | Less than or equal to 3.0% | 0.0% (0/52) |
| Minor Errors (mE) | Less than or equal to 10.0% | 3.7% (8/219) |
(Note: The acceptance criteria are "typical" for FDA guidance on AST systems. While the document mentions guidance, it doesn't explicitly state the exact numerical acceptance criteria within the provided text. The numbers above are common thresholds found in such guidances.)
2. Sample size used for the test set and the data provenance:
- Overall Test Set Sample Size: 1070 isolates. This is the denominator for the "Overall Performance" categories.
- Specific Organism Group Sample Sizes:
- Enterobacterales: 569 isolates
- P. aeruginosa: 282 isolates
- Acinetobacter spp.: 219 isolates
- Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin, but clinical isolates and challenge strains are generally used to ensure a broad representation of resistance mechanisms and phenotypes. The use of "fresh and stock clinical isolates" suggests a retrospective component (stock) and a prospective component (fresh).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not mention the use of experts to establish ground truth.
4. Adjudication method for the test set:
- The document does not mention an adjudication method.
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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic tool that human readers would interpret. Its performance is compared to a reference laboratory method.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, a standalone performance study was done. The VITEK® 2 system is essentially an "algorithm only" device that automatically processes samples and provides MIC values and interpretive categories. Its performance was directly compared to the CLSI broth microdilution reference method, without human interpretation influencing the device's output.
7. The type of ground truth used:
- The ground truth was established by the CLSI broth microdilution reference method, which is the gold standard for antimicrobial susceptibility testing.
8. The sample size for the training set:
- The document does not explicitly mention a "training set" or its size in the context of machine learning, as this is a device based on microdilution technology. If the system uses internal algorithms that were "trained" or developed, the details of that process (including sample sizes) are not provided in this regulatory summary. The listed clinical isolates and challenge strains would primarily fall under the "test set" for performance evaluation against the reference method.
9. How the ground truth for the training set was established:
- As a training set is not explicitly mentioned in the context of machine learning or AI, the method of establishing ground truth for such a set is not described. The ground truth for the performance evaluation set was established by the CLSI broth microdilution reference method.
§ 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.”