(50 days)
VITEK® 2 Gram Negative Trimethoprim/sulfamethoxazole is designed for antimicrobial susceptibility testing of gram-negative organisms 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 Gram Negative Trimethoprim/sulfamethoxazole is a quantitative test. Trimethoprim/sulfamethoxazole 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 (including susceptible enterotoxigenic strains implicated in traveler's diarrhea)
Klebsiella species Enterobacter species Morganella morganii Proteus vulgaris
Proteus mirabilis Shigella flexneri Shigella sonnei
The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 and VITEK® 2 Compact Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae.
The VITEK 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology.
The bacterial isolate to be tested is diluted to a standardized concentration in 0.45% 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 and sealing operation. The VITEK 2 monitors the growth of each well in the card over a defined period of time (up to 18 hours). 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.
Here's an analysis of the provided text regarding the VITEK® 2 Gram Negative Trimethoprim/sulfamethoxazole device, focusing on acceptance criteria and study details:
1. Table of 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 Feb. 5, 2003. The specific metric mentioned for performance is overall Category Agreement.
| Acceptance Criteria (from FDA Guidance) | Reported Device Performance |
|---|---|
| Acceptable performance as defined in the FDA Guidance Document for AST Systems | 100% Overall Category Agreement |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The document mentions "fresh and stock clinical isolates and stock challenge strains" for the external evaluation, but it does not specify the exact number (sample size) of isolates used in this test set.
- Data Provenance: The external evaluation was conducted. The country of origin is not explicitly stated, but it's likely primarily US-based given the FDA regulatory context. The isolates included "fresh and stock clinical isolates and stock challenge strains," indicating a mix of retrospective (stock isolates) and prospective (fresh clinical isolates) data.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not specify the number or qualifications of experts used to establish the ground truth. However, for antimicrobial susceptibility testing, the "gold standard" or reference method (CLSI broth microdilution) inherently involves expert-defined protocols and interpretation.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for the test set in the traditional sense of multiple readers reviewing results. The comparison is made directly against the CLSI broth microdilution reference method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was it done? No, an MRMC comparative effectiveness study was not conducted. This type of study is typically for evaluating human reader performance with and without AI assistance in diagnostic imaging, which is not applicable to an automated antimicrobial susceptibility test system.
- Effect size: Not applicable, as no such study was performed.
6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance
- Was it done? Yes, the performance described for the VITEK® 2 Gram Negative Trimethoprim/sulfamethoxazole is a standalone (algorithm only) performance. The device determines the MIC value and interpretive category automatically after incubation. The comparison is against the reference method, showing the device's inherent accuracy.
7. Type of Ground Truth Used
The ground truth used was the CLSI broth microdilution reference method. This is considered the gold standard for antimicrobial susceptibility testing, providing quantitative Minimum Inhibitory Concentration (MIC) values.
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" sample size or details about the development process that would typically involve a training phase for a machine learning model. For AST devices like VITEK, the "training" analogous to model development often involves extensive internal testing and refinement against reference methods during product development, prior to the external validation described. The current submission focuses on the validation of the finalized device.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" with established ground truth is not explicitly described, the method for establishing its ground truth is not provided. However, based on the nature of these devices, the development process would involve comparing device results against the CLSI broth microdilution reference method for a vast number of isolates during the initial design and optimization phases.
§ 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.”