(35 days)
VITEK® 2 AST-Gram Negative Eravacycline 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 Eravacycline is a quantitative test. Eravacycline 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:
Citrobacter freundii
Enterobacter cloacae
Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
In vitro data are available, but clinical significance is unknown:
Citrobacter koseri
Klebsiella (Enterobacter) aerogenes
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 (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 Eravacycline has the following concentrations in the card: 0.25, 1, 2 and 4 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
This document describes the validation of the VITEK® 2 AST-Gram Negative Eravacycline system for antimicrobial susceptibility testing.
Here's an analysis based on the provided text, addressing the points requested:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems: Guidance for Industry and FDA (Issued August 28, 2009)". This guidance document sets benchmarks for essential agreement and category agreement.
| Acceptance Criteria (from FDA Guidance) | Reported Device Performance |
|---|---|
| Overall Essential Agreement: Acceptable performance | 97.0% |
| Overall Category Agreement: Acceptable performance | 99.1% |
Note: While the document states "acceptable performance" for these metrics, it does not provide explicit numerical thresholds for acceptance within the text. However, the reported values are presented as meeting this acceptability.
2. Sample Size Used for the Test Set and Data Provenance
The document states:
- Test Set Description: "An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains."
- Sample Size: The exact number of isolates/samples used in the external evaluation (test set) is not explicitly stated in the provided text.
- Data Provenance: The document does not specify the country of origin for the data (clinical isolates). It also doesn't explicitly state whether the study was retrospective or prospective, though the use of "fresh and stock clinical isolates" suggests a mix, potentially involving prospectively collected fresh isolates and retrospectively accessed stock isolates.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. The ground truth (reference method) for the VITEK® 2 system's performance is the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not reliant on expert interpretation in the same way clinical image analysis might be. Therefore, the concept of "number of experts" or "qualifications of experts" establishing ground truth is not directly applicable here.
4. Adjudication Method for the Test Set
The concept of an "adjudication method" (like 2+1 or 3+1 for discrepancies) is typically relevant for studies where human interpretation of data (e.g., radiology images) forms the ground truth, and discrepancies between readers need to be resolved.
In this context, the ground truth is established by a standardized laboratory method (CLSI broth microdilution). Therefore, an adjudication method in the human-in-the-loop sense is not applicable and not mentioned in the document.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Improvement with AI vs. without AI Assistance
This document describes the validation of an automated antimicrobial susceptibility testing (AST) system, not an AI-assisted diagnostic tool that humans use to interpret medical images or other complex data.
Therefore:
- An MRMC comparative effectiveness study was not done as it's not relevant for this type of automated diagnostic device.
- No effect size of human reader improvement with AI assistance is reported, as the system does not involve human readers interpreting AI outputs.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this study effectively represents a standalone performance evaluation of the VITEK® 2 AST-Gram Negative Eravacycline system. The device itself is an automated system that provides a direct result (MIC value and interpretive category). Its performance is compared directly against the reference standard (CLSI broth microdilution method), without human intervention in the interpretation of the device's output.
7. The Type of Ground Truth Used
The type of ground truth used is the CLSI broth microdilution reference method. This is considered a gold standard laboratory method for determining antimicrobial susceptibility, providing quantitative Minimum Inhibitory Concentration (MIC) values.
8. The Sample Size for the Training Set
The document describes the "external evaluation" as the performance (test) set. It does not explicitly mention or provide the sample size for a training set. Automated AST systems like VITEK® 2 are typically developed using established microbiological principles and algorithmic analysis of growth patterns, rather than a machine learning approach that requires a distinct "training set" in the common sense of deep learning models. The "analysis algorithms" are described as "Growth Pattern Analysis" which suggests rule-based or statistical algorithms rather than trainable neural networks.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" in the context of machine learning is not explicitly mentioned or implied to be used for a trainable algorithm, the method for establishing ground truth for such a set is not applicable/not provided. The system's underlying principles are based on established microbiology and the CLSI reference method serves as the benchmark for validation.
§ 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.”