(98 days)
VITEK® 2 AST-Gram Positive Daptomycin is designed for antimicrobial susceptibility testing of Gram positive microorganisms 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 Positive Daptomycin is a quantitative test. Daptomycin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active both in vitro and in clinical infections: Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus (including methicillin-resistant isolates)
In vitro data are available, but their clinical significance is unknown: Enterococcus faecalis (vancomycin-resistant isolates)
The VITEK® 2 Gram-positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae 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-GP Daptomycin has the following concentrations in the card: 0.5, 1, 2, 4, and 8 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
The provided document describes the VITEK® 2 AST-GP Daptomycin system, an antimicrobial susceptibility test, and its performance evaluation.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for antimicrobial susceptibility test (AST) systems in the US are generally defined by the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems. While specific numerical targets for Essential Agreement (EA) and Category Agreement (CA) are usually outlined in this guidance, the summary states the device demonstrated substantially equivalent performance when compared with the broth microdilution reference method, as defined in the FDA Class II Special Controls Guidance Document.
The reported performance of the VITEK® 2 AST-GP Daptomycin is provided in "Table 2: VITEK® 2 AST-GP Daptomycin Performance".
| Metric | Staphylococcus aureus | Enterococcus faecalis | Overall (implied from text) |
|---|---|---|---|
| Acceptance Criteria | (As per FDA Guidance, typical minimums for new ASTs are usually >90% for EA and >90% for CA with specific limits on VME/ME/mE) | ||
| Essential Agreement (%EA) | (183/194) 94.3% | (262/270) 97.0% | 95.9% |
| Very Major Errors (VME) | N/A | (1/8) 12.5% | |
| Major Errors (ME) | (2/185) 1.1% | (0/219) 0.0% | |
| Minor Errors (mE) | N/A | (41/270) 15.2% | |
| Category Agreement (%CA) | (192/194) 99.0% | (228/270) 84.4% | 90.5% |
Note on VME/ME/mE for Staphylococcus aureus: The document lists "N/A" for VME and mE for Staphylococcus aureus and "0.0%" for ME for Enterococcus faecalis. This might indicate that no specific VME/ME/mE were observed or reported in those categories, or that the formatting of the table in the document itself uses N/A for cases where a specific error type threshold wasn't relevant or wasn't met to be explicitly calculated. However, for a complete picture, the FDA guidance document would provide the specific acceptance thresholds for these error types. The (1/8) 12.5% VME for Enterococcus faecalis and (41/270) 15.2% mE for Enterococcus faecalis would likely be subject to specific acceptance criteria limits in the FDA guidance; for example, VMEs are typically expected to be ≤ 1.5% and MEs ≤ 3.0%, while mEs generally have a higher tolerance but still a limit. The document states a 90.5% overall Category Agreement, which for Enterococcus faecalis alone is 84.4%, falling below the typical 90% threshold for CA. This discrepancy might be addressed in a larger context within the full premarket notification, or perhaps the overall performance across all tested species met the required threshold despite one species being lower.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Staphylococcus aureus: 194 isolates
- Enterococcus faecalis: 270 isolates
- Total Clinical Isolates in Performance Study: 194 + 270 = 464 isolates.
- The study also used a "set of challenge strains" in addition to fresh and stock clinical isolates, but the exact number of challenge strains is not specified in this summary.
- Data Provenance:
- "An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a prospective or a mix of prospective and retrospective collection from external sources (likely clinical laboratories).
- The document does not specify the country of origin for the data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
- The ground truth was established by the CLSI broth microdilution reference method. This method is a standardized laboratory procedure, not reliant on human expert interpretation in the same way as, for example, image reading. Therefore, "number of experts" and "qualifications of experts" are not directly applicable in the context of establishing ground truth for this type of antimicrobial susceptibility testing.
4. Adjudication Method for the Test Set
- The reference method itself (CLSI broth microdilution) serves as the "ground truth" or "adjudication." No separate human adjudication process (e.g., 2+1, 3+1 consensus) is applicable or mentioned for this type of in vitro diagnostic device study. The device's results are directly compared to the results of the reference 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 type of study design is typically used for AI-powered diagnostic imaging devices where human readers interpret images with or without AI assistance. This device is an automated in vitro diagnostic system for antimicrobial susceptibility testing, not requiring human interpretation of complex visual data for its primary function.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, the performance study effectively evaluates the "standalone" performance of the VITEK® 2 AST-GP Daptomycin system. The system automatically processes the samples and generates MIC values and interpretive categories, which are then compared directly to the CLSI broth microdilution reference method. There is no human intervention in the device's determination of susceptibility.
7. The Type of Ground Truth Used
- The ground truth used was the CLSI broth microdilution reference method, which is a highly standardized and accepted laboratory method for determining antimicrobial susceptibility. This is essentially a "gold standard" laboratory method.
8. The Sample Size for the Training Set
- The document does not provide information on the training set size. This type of premarket notification summary focuses on the performance evaluation of the final device, not typically on the specific dataset used for algorithm development or training. The "Discriminant Analysis" mentioned under "Analysis Algorithms" implies a statistical model was used, which would have been developed/trained on a dataset, but details of this dataset are not included in this summary.
9. How the Ground Truth for the Training Set Was Established
- As the training set details are not provided, the method for establishing its ground truth is also not described in this summary. It would logically be established using a similar or identical reference method to the test set, but this is not confirmed.
§ 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.”