(59 days)
VITEK® 2 AST-Gram Negative Imipenem/Relebactam is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative Imipenem/Relebactam is a quantitative test. Imipenem/Relebactam 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: Acinetobacter calcoaceticus-baumannii complex Klebsiella (Enterobacter) aerogenes Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Citrobacter freundii Klebsiella oxytoca
In vitro data are available, but clinical significance is unknown: Citrobacter koseri Enterobacter asburiae
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 bacili 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 (2). 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 cycle, 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 Imipenem/Relebactam has the following concentrations in the card: 0.25/4, 1/4, 4/4 and 16/4 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
The acceptance criteria, study details, and performance of the VITEK® 2 AST-Gram Negative Imipenem/Relebactam device are as follows:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (from FDA Class II Special Controls Guidance Document: AST Systems) | Reported Device Performance (for Acinetobacter calcoaceticus-baumannii complex) |
|---|---|---|
| Essential Agreement | Acceptable performance (details not specified in provided text) | 98.2% |
| Categorical Agreement | Acceptable performance (details not specified in provided text) | 98.2% |
2. Sample Size and Data Provenance for the Test Set:
- Sample Size: The document does not specify the exact total number of isolates used in the external evaluation. However, it mentions "fresh and stock clinical isolates, as well as a set of challenge strains." The reported performance specifically for Acinetobacter calcoaceticus-baumannii complex indicates a sample size for this specific organism.
- Data Provenance: The isolates included "fresh and stock clinical isolates" and "challenge strains." The document does not explicitly state the country of origin, but it implies clinical relevance. The study appears to be retrospective due to the use of "stock clinical isolates."
3. Number of Experts and Qualifications for Ground Truth:
- This information is not applicable as the device compares its performance against a reference method (CLSI broth microdilution), not against human expert interpretation.
4. Adjudication Method:
- This information is not applicable as the device's performance is compared against a defined reference methodology (CLSI broth microdilution), not against human expert consensus requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted as this device is an automated antimicrobial susceptibility test system, not an AI-assisted diagnostic tool for human readers. Therefore, there is no effect size reported for human readers with and without AI assistance.
6. Standalone Performance:
- Yes, a standalone performance evaluation was conducted. The VITEK® 2 AST-Gram Negative Imipenem/Relebactam system, without human intervention in the susceptibility interpretation, was directly compared to the CLSI broth microdilution reference method.
7. Type of Ground Truth Used:
- The ground truth used was the CLSI broth microdilution reference method, which is a widely accepted and standardized laboratory method for determining antimicrobial susceptibility.
8. Sample Size for the Training Set:
- The document does not explicitly mention a "training set" in the context of machine learning model development. For an AST system like VITEK® 2, the "training" would typically involve developing and validating the growth pattern analysis algorithms and the concentrations used in the cards, which rely on extensive laboratory data and established microbiological principles. The document describes 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 (2)."
9. How the Ground Truth for the Training Set Was Established:
- As mentioned above, for an AST system, the "ground truth" for developing the underlying methodology (which could be considered analogous to a training set in some contexts) is established through established microbiological principles and validated reference methods like the broth microdilution technique. The document references published works (MacLowry and Marsh, Gerlach, Barry) that describe the basis for the microdilution MIC technique on which the VITEK® 2 AST cards are based. This indicates that the core methodology is derived from well-documented and accepted scientific practices in microbiology.
§ 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.”