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VITEK 2 AST-Gram Negative Cefazolin is designed for antimicrobial susceptibility testing of Gram-negative bacilli and is intended for use with the VITEK 2 Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.

VITEK 2 AST-Gram Negative Cefazolin (≤1-≥32 µg/mL) is a quantitative test. Testing is indicated for Enterobacterales (from infections other than uncomplicated UTI) as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).

VITEK 2 AST-Gram Negative Cefazolin (≤1-≥32 µg/mL) has demonstrated acceptable performance with the following organisms:

Enterobacterales (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri)

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 Cefazolin has the following concentrations in the card: 1, 2, and 8 (equivalent standard method concentration by efficacy in µg/mL).

The provided text describes the acceptance criteria and a study proving the device meets these criteria for the VITEK 2 AST-Gram Negative Cefazolin antimicrobial susceptibility testing system.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Note on Acceptance Criteria: The document references the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)" for defining acceptable performance. While specific numerical acceptance criteria (e.g., for EA, CA, VME, ME) are not explicitly listed in the provided text, they are implied by the reported performance metrics and the statement that the device "demonstrated substantially equivalent performance." For AST systems, the FDA typically looks for high Essential and Category Agreement, with very low rates of Major and Very Major Errors. The low Category Agreement (86.8%) is acknowledged and attributed mainly to minor errors.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set:
  • Total isolates tested: 862 (derived from the denominator for EA and CA calculations).
  • The study included "fresh and stock clinical isolates" as well as "a set of challenge strains."
• Data Provenance:
  • The study was an "external evaluation." This typically implies data collected from multiple sites outside of the manufacturer's primary lab.
  • The document does not specify the country of origin for the data.
  • The study included both "fresh" and "stock" clinical isolates, suggesting a mix of prospective (fresh isolates) and retrospective (stock isolates) data collection.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number or qualifications of experts used to establish the ground truth.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set. For AST devices, the "ground truth" is typically established by a reference method (broth microdilution in this case), not by expert consensus or adjudication in the way it might be for an imaging AI device.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Improvement

No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not performed. This type of study (human readers assisting vs. not assisting) is typically relevant for interpretative diagnostic devices, especially in imaging, where human interpretation is a key part of the workflow. The VITEK 2 AST system is an automated device for determining antimicrobial susceptibility, not directly for human interpretation or image reading.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the primary performance study presented is a standalone (algorithm only) performance study. The device's performance (VITEK 2 AST-GN Cefazolin) was compared directly against the CLSI broth microdilution reference method. There is no mention of human-in-the-loop performance evaluation, as the VITEK 2 system is automated.

7. The Type of Ground Truth Used

The type of ground truth used was: Reference Method Comparison.
Specifically, the performance of the VITEK 2 AST-GN Cefazolin was compared to the CLSI broth microdilution reference method, incubated for 16-20 hours. This is the gold standard for antimicrobial susceptibility testing.

8. The Sample Size for the Training Set

The document does not specify the sample size for the training set. This submission is for a 510(k) clearance, which typically focuses on the performance of the final device rather than the specifics of its development (like training data for AI/ML models). The VITEK 2 system relies on growth pattern analysis algorithms rather than deep learning models that require large, labeled training datasets in the conventional sense. Its "training" would likely involve optimizing these algorithms based on extensive internal validation.

9. How the Ground Truth for the Training Set Was Established

The document does not describe how the ground truth for the training set was established, as details on the development of the device's analysis algorithms (likely proprietary) are not typically included in a 510(k) summary. Given the nature of AST systems, any "ground truth" used during development would also likely stem from comparisons to established reference methods like broth microdilution, similar to the test set's ground truth.

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VITEK 2 AST-Yeast Voriconazole is designed for antifungal susceptibility testing of Candida species 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 antifungal agents. VITEK 2 AST-Yeast Voriconazole is a quantitative test. Voriconazole has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections: Candida krusei Candida parapsilosis Candida tropicalis

The VITEK 2 Fungal 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 yeasts to antifungal agents when used as instructed.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique. The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique. 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-YS Voriconazole has the following concentrations in the card: 0.03125, 0.125, 0.25, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

The provided FDA 510(k) summary describes the VITEK® 2 AST-Yeast Voriconazole device, which is an antimicrobial susceptibility test system.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance:

The acceptance criteria are implicitly derived from the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems and are presented through "Essential Agreement" (EA) and "Category Agreement" (CA) performance metrics, along with error rates. The table below summarizes the reported performance for each microorganism. The specific acceptance thresholds for EA and CA are not explicitly stated as numerical percentages (e.g., >90% EA, >90% CA) with the exception of the individual error types (VME, ME, mE) having specified maximum allowable percentages. However, it is implied that the presented results were deemed acceptable by the FDA.

Key Definitions:

• Essential Agreement (EA): Agreement between the MIC results of the test device and the reference method within plus or minus one doubling dilution.
• Category Agreement (CA): Agreement between the interpretive categories (Susceptible, Intermediate, Resistant) of the test device and the reference method.
• Very Major Error (VME): The test device reports susceptible, but the reference method reports resistant.
• Major Error (ME): The test device reports resistant, but the reference method reports susceptible.
• Minor Error (mE): Any other disagreement in interpretive category (e.g., susceptible vs. intermediate, resistant vs. intermediate).

2. Sample Size Used for the Test Set and Data Provenance:

The sample sizes for the test set (external evaluation) are provided for each microorganism:

• C. albicans: 257 isolates
• C. krusei: 76 isolates
• C. parapsilosis: 74 isolates
• C. tropicalis: 87 isolates

Data Provenance: The study conducted an "external evaluation" with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin of the data nor explicitly state if it was retrospective or prospective. However, "fresh clinical isolates" typically implies a prospective collection, while "stock clinical isolates" could be either.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:

The ground truth was established by the "CLSI broth microdilution reference method." This is a standardized laboratory method, not reliant on human expert adjudication in the same way an imaging study would be. Therefore, the concept of "experts" and their qualifications as typically applied to visual diagnostic tasks (e.g., radiologists) is not directly applicable here. The ground truth method itself (CLSI broth microdilution) is the expert-defined standard.

4. Adjudication Method for the Test Set:

Not applicable in the human expert sense. The "adjudication method" for determining the ground truth in this context is the CLSI broth microdilution reference method, which serves as the gold standard for antimicrobial susceptibility testing. The device's results are compared directly against this established reference.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret results, often in conjunction with AI. The VITEK® 2 AST-Yeast Voriconazole is an automated in vitro diagnostic device for antimicrobial susceptibility testing; its performance is evaluated by comparing its automated output to a gold standard laboratory method, not by how it assists human readers.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-Yeast Voriconazole system is an automated device designed to determine antimicrobial susceptibility without human interpretation of the primary data once the sample is loaded. The performance metrics (Essential Agreement, Category Agreement, error rates) directly reflect the device's standalone capability compared to the reference method.

7. The Type of Ground Truth Used:

The ground truth used was the CLSI broth microdilution reference method, incubated for 24 hours (up to 48 hours for slowly growing isolates). This is a well-established and scientifically accepted standard in microbiology for determining minimum inhibitory concentrations (MICs) of antifungal agents.

8. The Sample Size for the Training Set:

The document does not explicitly state the sample size for the training set. The descriptions focus on the "external evaluation" (test set). For IVD devices like this, the 'training set' often corresponds to historical data, internal studies, and method development efforts that lead to the final algorithm and concentration ranges. Without further information, the exact size of the training set used to develop the VITEK® 2 AST-Yeast Voriconazole algorithm is not provided in this 510(k) summary.

9. How the Ground Truth for the Training Set Was Established:

Similar to the answer for point 8, the document does not explicitly describe how the ground truth for any potential training set was established. However, given that the final performance is benchmarked against the CLSI broth microdilution reference method, it is highly probable that any internal development or training data would also have used this or a similar established reference method to determine the true susceptibility of isolates.

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VITEK 2 AST-Yeast Anidulafungin is designed for antifungal susceptibility testing of Candida species 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 antifungal agents. VITEK 2 AST-Yeast Anidulafungin is a quantitative test. Anidulafungin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections: Candida albicans Candida glabrata Candida parapsilosis Candida tropicalis

In vitro data are available, but clinical significance is unknown: Candida guillermondii Candida krusei

The VITEK 2 Fungal 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 yeasts to antifungal 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-YS Anidulafungin has the following concentrations in the card: 0.0625, 0.125, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based on the provided text.

Device: VITEK 2 AST-Yeast Anidulafungin

Indications for Use: Antifungal susceptibility testing of Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii, C. krusei) as a laboratory aid in determining in vitro susceptibility to antifungal agents.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state the acceptance criteria in a separate table directly defining thresholds for Essential Agreement (EA), Category Agreement (CA), or error rates (VME, ME, mE) that the device must meet for approval. Instead, it presents the results of the performance study and implies that these results were deemed "acceptable" by the FDA. The performance is compared to the "CLSI broth microdilution reference method, as defined in 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 would contain the specific acceptance criteria.

However, based on the presented "Performance Overview" (Page 7) and the overall context of AST device approvals, typical acceptance criteria for Essential Agreement and Category Agreement are usually in the range of 90-95% or higher, with Very Major Error (VME) and Major Error (ME) rates usually being low (e.g., <3% or <1.5%).

Here's the reported device performance:

Note on C. tropicalis VME: The document specifically highlights: "When evaluating VITEK 2 AST-YS Anidulafungin, there was a single very major error (VMJ) that resulted in an unacceptable VMJ rate of 33.3% (1/3) with C. tropicalis." Despite this, the overall conclusion states "VITEK® 2 AST-YS Anidulafungin demonstrated acceptable performance." This suggests that either the unacceptably high VME for C. tropicalis was mitigated by other factors (e.g., small sample size for VME calculation, or specific post-market surveillance requirements), or it points to a known limitation that the FDA found acceptable for clearance under the stated conditions.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set:

  • C. albicans: 206 isolates
  • C. glabrata: 116 isolates
  • C. guilliermondii: 21 isolates
  • C. krusei: 69 isolates
  • C. parapsilosis: 72 isolates
  • C. tropicalis: 81 isolates
  • Total Isolates: 565 isolates across the specified Candida species.

• 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 of the data or whether it was retrospective or prospective. Typically, "clinical isolates" imply prospective collection from real patient samples, and "stock isolates" could be reference strains or previously collected clinical isolates. "External evaluation" implies data was collected from multiple sites, which is standard for clinical trials of this nature.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

This information is not provided in the document. For antimicrobial susceptibility testing (AST) devices, the ground truth is established by a reference method (here, the CLSI broth microdilution reference method), not by human expert interpretation of images or data in a consensus setting.

4. Adjudication Method for the Test Set

Not applicable. The ground truth for AST devices is established by a standardized laboratory reference method (CLSI broth microdilution), not through expert adjudication of ambiguous cases like in imaging studies.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not performed. This type of study (comparing human readers with and without AI assistance on diagnostic tasks) is not relevant for an automated antimicrobial susceptibility testing device like the VITEK 2 AST-Yeast Anidulafungin. This device provides quantitative MIC values and interpretive categories, not an interpretation of a medical image or clinical data that would involve human readers.

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-Yeast Anidulafungin system. The device automatically reads and interprets the growth patterns in the microdilution wells to generate MIC values and interpretive categories (Susceptible, Intermediate, Resistant). This automated result is then compared directly to the established ground truth (CLSI broth microdilution reference method). While human operators physically load the cards, the core performance being evaluated is the device's automated analysis.

7. The Type of Ground Truth Used

The type of ground truth used was the CLSI broth microdilution reference method (Clinical and Laboratory Standards Institute). This is a well-established, standardized, and validated laboratory method for determining the minimum inhibitory concentration (MIC) of an antimicrobial agent against a microorganism. The reference method results serve as the "gold standard" for accuracy in AST device performance studies.

8. The Sample Size for the Training Set

The document does not provide specific details about the training set size. The device uses "Discriminant Analysis" algorithms. Typically, for a device like this, the algorithms would be developed and refined using a large dataset of isolates with known reference MICs to optimize the mapping between the device's optical measurements and the true MICs. However, the exact size of this internal development/training set is not disclosed in this summary. The provided performance data (the "test set") is for validation purposes, distinct from the training set.

9. How the Ground Truth for the Training Set Was Established

While not explicitly stated for a "training set" in this document, it is highly probable that the ground truth for any isolates used during the development and training of the VITEK 2 system's algorithms would also have been established using the CLSI broth microdilution reference method or similar highly standardized and validated laboratory methods, consistent with industry best practices for AST device development. This ensures that the algorithm learns from accurate data.

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VITEK® 2 AST-Gram Positive Lefamulin is designed for antimicrobial susceptibility testing of Gram positive microorganisms 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 Positive Lefamulin is a quantitative test. Lefamulin 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: Staphylococcus aureus (methicillin-susceptible 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., and S. agalactive 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 (0).

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 Lefamulin (≤ 0.03 –>4 µg/mL) has the following concentrations in the card: 0.125, 0.5, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

The VITEK® 2 AST-Gram Positive Lefamulin (≤ 0.03 - ≥4 µg/mL) device is an antimicrobial susceptibility testing system designed for Gram-positive microorganisms. The acceptance criteria and performance of the device are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance

The test set included:

• 404 isolates for Essential Agreement reporting and 404 isolates for Category Agreement reporting (derived from the numerators/denominators in Table 2).
• 3 resistant isolates were tested for VME (Very Major Error)
• 401 susceptible isolates were tested for ME (Major Error)

The data provenance is described as 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 of the data or explicitly state whether the study was retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the given text.

4. Adjudication method for the test set

This information is not provided in the given text.

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

A multi-reader multi-case (MRMC) comparative effectiveness study with human readers assisted by AI is not applicable to this device. This device is an automated antimicrobial susceptibility test system, not an AI-assisted diagnostic tool interpreted by human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-GP Lefamulin system's performance was compared directly to the CLSI broth microdilution reference method (the ground truth), without human intervention in the interpretation of the VITEK® 2 results. The system automatically generates MIC values and interpretive categories.

7. The type of ground truth used

The ground truth used was the CLSI broth microdilution reference method, incubated at 16-20 hours.

8. The sample size for the training set

The document does not explicitly mention a separate "training set" or its sample size. The description focuses on the external evaluation data used for performance assessment. As an AST system, the device's "training" for MIC determination is inherent in its design based on established microdilution principles and may not involve a distinct, large-scale machine learning training set in the way an AI algorithm might.

9. How the ground truth for the training set was established

Since a distinct training set is not explicitly mentioned as per the prompt's context (e.g., for an AI algorithm), details on how its ground truth was established are not provided. The device's operation is based on established microbiological principles, and its performance is validated against the CLSI broth microdilution reference method.

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VITEK® 2 AST-Gram Negative Levolloxacin 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 vito susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative Levofloxacin is a quantitative test. Levolloxacin 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: Enterchacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Active in vitro but clinical significance unknown: Citrobacter freundii, Enterobacter aerogenes, Klebsiella oxytoca, Morganii, Pantoea agglomerans, Proteus vulgaris, Providencia rettgeri, Providencia stuartii

VITEK® 2 AST-Gram Negative Levofloxacin also reports the susceptibility for the following additional organism as listed on the FDA Susceptibility Test Interpretive Criteria website: Salmonella 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 (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 Levofloxacin has the following concentrations in the card: 0.25, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

Here's a breakdown of the acceptance criteria and the study details for the VITEK® 2 AST-Gram Negative Levofloxacin device, based on the provided FDA 510(k) summary:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the FDA Class II Special Controls Guidance Document for Antimicrobial Susceptibility Test (AST) Systems. The performance metrics reported are Essential Agreement (EA), Category Agreement (CA), Very Major Errors (VME), Major Errors (ME), and minor Errors (mE). Reproducibility and Quality Control also demonstrated acceptable results, although specific percentage thresholds for these are not provided in this summary.

Here's the table of reported device performance:

Notes on Interpretation from the document:

• VITEK 2 Levofloxacin MIC values for Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa tended to be in exact agreement or at least one doubling dilution higher when compared to the reference agar dilution method.
• VITEK 2 Levofloxacin MIC values for Serratia marcescens tended to be in exact agreement or at least one doubling dilution lower when compared to the reference agar dilution method.

2. Sample Size and Data Provenance

The sample sizes for the test set are embedded within the performance data (e.g., 346 for Enterobacterales, 225 for Pseudomonas aeruginosa, 48 for Salmonella spp.). These numbers represent the total number of isolates tested for each organism group.

The data provenance is described as 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 "external" implies outside of the manufacturer's immediate control. The use of "fresh and stock clinical isolates" indicates a mix of prospective (fresh) and retrospective (stock) data, augmented by specific challenge strains.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts used or their specific qualifications (e.g., "radiologist with 10 years of experience"). However, the ground truth is established by the "CLSI agar dilution reference method incubated between 16-20 hours." This method is a standardized laboratory procedure, and implicitly requires trained laboratory professionals to perform and interpret, but it's not based on expert consensus in the typical sense of diagnostic imaging or clinical interpretation.

4. Adjudication Method

The concept of "adjudication" in the sense of multiple experts reviewing and reaching a consensus on a case (like 2+1 or 3+1) is not applicable here. The ground truth is determined by a single, standardized reference laboratory method (CLSI agar dilution). Any discrepancies would be between the VITEK 2 device's result and this reference method, leading to the error rates (VME, ME, mE) reported.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted as described. This type of study typically involves human readers or clinicians making diagnoses with and without AI assistance to measure improvement in human performance. The VITEK 2 device is a fully automated laboratory device, and the study compares its performance directly against a reference laboratory method, not against human interpretation of the images/data it produces.

6. Standalone Performance Study

Yes, a standalone (algorithm only without human-in-the-loop performance) study was done. The entire performance evaluation reported in the 510(k) summary is of the VITEK 2 device's output (MIC values and interpretive categories) compared directly to the CLSI agar dilution reference method. The device is intended to be automated, and its performance is assessed independently.

7. Type of Ground Truth Used

The ground truth used is the CLSI agar dilution reference method results. This is a recognized standard laboratory method for determining antimicrobial susceptibility, considered the gold standard for this type of in vitro diagnostic test. It is not based on expert consensus, pathology, or outcomes data in the usual clinical sense, but rather a robust, objective laboratory measurement.

8. Sample Size for the Training Set

The document does not specify the sample size for the training set. It describes the data used for the "external evaluation" (test set) but provides no information about the isolates used to develop or train the VITEK® 2 AST-GN Levofloxacin system's algorithms (Discriminant Analysis).

9. How the Ground Truth for the Training Set Was Established

The document does not provide details on how the ground truth for the training set was established. However, given the nature of AST systems, it is highly probable that the training set's ground truth would have also been established using a similar, if not identical, reference method like the CLSI agar dilution method. The device's "Discriminant Analysis" algorithms would have been developed and optimized to correlate its readings with these reference standard results.

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VITEK® 2 AST-Yeast Caspofungin is designed for antifungal susceptibility testing of Candida species 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 antifungal agents. VITEK® 2 AST-Yeast Caspofungin is a quantitative test. Caspofungin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections:
Candida albicans
Candida guilliermondii
Candida krusei
Candida parapsilosis
Candida tropicalis

The VITEK® 2 Fungal 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 yeasts to antifungal 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-YS Caspofungin has the following concentrations in the card: 0.125, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

The VITEK 2 AST-Yeast Caspofungin device is designed for antifungal susceptibility testing of Candida species. The study provided demonstrates its performance against the CLSI broth microdilution reference method.

Here's a breakdown of the information requested:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document doesn't explicitly state numerical acceptance criteria for EA, CA, VME, ME, and mE. The reported values are compared against what is generally considered acceptable in the field of antimicrobial susceptibility testing, often guided by FDA Class II Special Controls Guidance Document for AST Systems. The comment regarding VME indicates that despite the 100% (2/2) reported, the detailed analysis for specific Candida species outlines individual VMEs, suggesting these were analyzed within broader acceptability limits.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set: The number of isolates tested is derived from the agreement percentages.
  • Essential Agreement: 680 (Denominator for 679/680)
  • Category Agreement: 680 (Denominator for 663/680)
  • This indicates a total of 680 isolates were used in the external evaluation.
• Data Provenance: The external evaluation was conducted with:
  • "fresh and stock clinical isolates"
  • "a set of challenge strains"
  • Country of Origin: Not specified in the provided text.
  • Retrospective or Prospective: Not explicitly stated, however, the use of "fresh and stock clinical isolates" suggests a mix of potentially both, but the term "external evaluation" often implies collecting new data for the evaluation.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

This type of device (Antimicrobial Susceptibility Test System) does not typically rely on human expert interpretation for establishing ground truth in the same way an imaging AI device would. Instead, the ground truth is established by a reference laboratory method.

• Ground Truth Method: CLSI broth microdilution reference method, incubated at 24 hours (or up to 48 hours for isolates with insufficient growth).
• Therefore, the concept of "experts" to establish ground truth with qualifications like "radiologist with 10 years of experience" is not applicable here. The ground truth accuracy relies on the validated performance of the CLSI method itself.

4. Adjudication Method for the Test Set

Not applicable. As the ground truth is established by a standardized laboratory reference method (CLSI broth microdilution), there is no human adjudication process involved in comparing different interpretations. The device's result is directly compared to the reference method result.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret data, often with and without AI assistance. The VITEK 2 is an automated system for measuring antimicrobial susceptibility and does not involve human readers interpreting results in the same context.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the performance study conducted for the VITEK 2 AST-Yeast Caspofungin is a standalone performance study. The device, an automated system, generates results directly which are then compared to the reference method without human intervention in the device's determination process for the purpose of the study.

7. The Type of Ground Truth Used

The ground truth used was the CLSI broth microdilution reference method. This is a well-established and standardized laboratory method for determining the minimum inhibitory concentration (MIC) of antifungal agents against microorganisms.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for the training set. This is typical for an AST system such as VITEK 2, where the underlying "algorithm" (discriminant analysis) is based on established principles of microbial growth detection and concentration determination, rather than a machine learning model that requires explicit "training data" in the common AI sense. The development of such systems often involves internal validation and optimization data that are not typically disclosed as a "training set" in regulatory summaries.

9. How the Ground Truth for the Training Set was Established

Given that explicit "training data" and "training set ground truth" are not mentioned, it can be inferred that the fundamental principles and thresholds used by the VITEK 2 system are based on:

• Established microbiological methods for microdilution (e.g., MacLowry and Marsh, Gerlach references provided).
• Optimization and validation using a variety of isolates during product development.
• Correlation with established breakpoints and guidelines from organizations like CLSI and FDA, which are derived from extensive expert analysis, clinical outcomes data, and epidemiological cut-off values.

Therefore, the ground truth for any hypothetical "training" or development phase would likely have been established using reference laboratory methods (similar to the CLSI broth microdilution used for the test set) in conjunction with expert consensus on interpretive breakpoints.

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VITEK® 2 AST-Gram Negative Omadacycline 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 Omadacycline in is a quantitative test. Omadacycline 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:
For Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Enterobacter cloacae Klebsiella pneumoniae For Community Acquired Bacterial Pneumonia (CABP): Klebsiella pneumoniae

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() 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 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 Omadacycline (≤0.25 - >16 µg/mL) has the following concentrations in the card: 0.5, 2. 8 and 16 ug/mL (equivalent standard method concentration by efficacy in us/mL).

This document describes the VITEK® 2 AST-Gram Negative Omadacycline device, an automated antimicrobial susceptibility testing system. The information provided outlines the device's performance against established acceptance criteria, focusing on its ability to accurately determine the susceptibility of Gram-negative bacilli to Omadacycline.

Here's an analysis of the provided information concerning acceptance criteria and supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance:

   The provided document presents the performance of the VITEK® 2 AST-GN Omadacycline against specific criteria. Based on the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems," the key performance metrics are Essential Agreement (EA) and Category Agreement (CA), along with Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).

   Metric	Acceptance Criteria (as per FDA Guidance for AST Systems)	Reported Device Performance (Omadacycline) - ABSSSI (E. cloacae, K. pneumoniae)	Reported Device Performance (Omadacycline) - CABP (K. pneumoniae)
   Essential Agreement (EA) %	≥ 90% for drug/organism combinations	97.9% (410/419)	98.0% (342/349)
   Category Agreement (CA) %	≥ 90% for drug/organism combinations	94.3% (395/419)	93.7% (327/349)
   Very Major Errors (VME) %	≤ 1.5% and ≤ 3 VMEs	2.0% (1/51)	2.7% (1/37)
   Major Errors (ME) %	≤ 3.0% and ≤ 3 MEs	0.0% (0/343)	0.0% (0/290)
   Minor Errors (mE) %	≤ 10.0%	5.5% (23/419)	6.0% (21/349)

   Note: The VME percentages of 2.0% and 2.7% are above the typical acceptance criterion of ≤ 1.5%. However, the absolute number of VMEs is 1 in both cases, which might be considered acceptable depending on the specific interpretation of "and ≤ 3 VMEs" in the guidance document for small sample sizes of resistant isolates. The document explicitly states the device "demonstrated acceptable performance."

2. Sample Size Used for the Test Set and Data Provenance:

   • Test Set Sample Size:
     • For E. cloacae and K. pneumoniae (ABSSSI): 419 isolates.
     • For K. pneumoniae (CABP): 349 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 implies a clinical laboratory setting. It is likely a retrospective collection of isolates from clinical settings.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

   The document describes the "CLSI broth microdilution reference method" as the ground truth. This is a standardized laboratory method, not reliant on individual expert interpretation. Therefore, there were no "experts" in the sense of human readers establishing ground truth for this device; rather, a consensus reference method was used.

4. Adjudication Method for the Test Set:

   Not applicable. The ground truth was established by the CLSI broth microdilution reference method, which is a quantitative laboratory procedure, not a subjective interpretation requiring adjudication.

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:

   Not applicable. This device is an automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic imaging or interpretation system requiring human-in-the-loop performance measurement or MRMC studies. Its performance is compared to a reference laboratory method, not human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

   Yes, this was a standalone performance study. The VITEK® 2 AST-GN Omadacycline system's performance (an automated device/algorithm) was evaluated against the CLSI broth microdilution reference method without human interpretation as part of the primary outcome. The system generates an MIC value and interpretive category automatically.

7. The Type of Ground Truth Used:

   The ground truth used was the CLSI broth microdilution reference method, which is a standardized laboratory procedure for determining minimum inhibitory concentrations (MICs) of antimicrobials. This is considered a highly reliable and accepted reference standard in microbiology.

8. The Sample Size for the Training Set:

   The document describes a "Premarket Notification (510[k])" which "presents data in support of VITEK® 2 AST-GN Omadacycline." It mentions "external evaluation" with "fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a validation study, but it does not specify a separate "training set" or its size for the development of the VITEK 2 system's algorithms for omadacycline. The VITEK® 2 system itself is a pre-existing platform, and this submission is for a new antimicrobial agent card. The algorithms for interpreting growth patterns for MIC determination are inherent to the VITEK 2 system's design. The data presented are for validation, not explicit "training."

9. How the Ground Truth for the Training Set Was Established:

   As noted in point 8, a specific "training set" for the Omadacycline card and its ground truth establishment is not explicitly detailed in the provided document. The VITEK® 2 system's underlying interpretive algorithms would have been developed and validated previously using reference methods (like broth microdilution) for various antimicrobials and organisms during the initial development of the VITEK® 2 platform. For new antimicrobial cards, the focus is on validating the new agent's performance against the established reference method as outlined in the provided study.

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VITEK® MS PRIME is a mass spectrometry system using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for the identification of microorganisms cultured from human specimens.

The VITEK® MS PRIME system is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.

This 510(k) submission introduces the VITEK®MS PRIME System. The VITEK® MS PRIME is intended for laboratory use by professional users who are trained in microbiology and good laboratory practices.

The VITEK® MS PRIME makes microorganism identifications via matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS) technology, which includes the three basic principles of ionization, separation, and detection,

As a first step, a VITEK® MS-DS Target Slide is prepared in accordance with the instructions for use.

NOTE: Depending on the culture, the analyte sample (i.e. microorganism from cultured media) may be directly spotted to a target slide, or for Mycobacterium. Nocardia and mould it must be processed/inactivated before adding to the target slide.

Once the specimen (cultured from the appropriate media) is spotted to the target slide, a matrix is added for the purpose of easy sublimation and strong absorbance in the laser wavelength employed by theinstrument.

NOTE: The VITEK® MS PRIME is a Class 1 laser product, containing a Class 4 Neodymium-doped yttrium lithium fluoride (Nd:YLF) laser – the laser operates at a wavelength of 349 nm.

The prepared slide is then loaded onto the VITEK®MS PRIME instrument. where a laser targets the sample spot and pulses the isolate spot, resulting in vibrational excitation of matrix and analyte molecules. The matrix transfer protons to the analyte resulting in a positive charge. So as part of the first basic principle, the ionized molecules are then accelerated in an electromagnetic field and a grid electrode in the ionization chamber.

The acceleration in the electromagnetic field is the beginning of the second basic principle (i.e. the separation process that is based of the time-of-flight principle). The velocity of the molecules depends on the mass-to-charge (m/z) ratio of the analyte, with heavier molecules having a higher moment of inertia resulting in a lower velocity.

As a final step in the basic principle of MALDI-ToF technology (i.e. detection) the time of flight is measured precisely by the ions arrival at a particle detector. This speed of the ions in flight depends on their mass - with heavier molecules having a higher moment of inertia resulting in a lower velocity. The time of transit is measured precisely by the ions' arrival at a particle detector. Based on the time of flight, the m/z ratio of each particle can be determined, and a mass spectrum of the analyte sample mixture is generated. The recorded signal is processed and presented as a spectrum of intensity versus mass in Daltons (Da). The mass spectrum displays results as a series of peaks (spectrum) which correspond to the ionized proteins derived from the analyte sample. And for identification of an unknown organism, the resulting mass spectra are sufficiently distinctive to allow taxonomic characterization at the genus and species when compared against the VITEK® MS Knowledge Base.

Here's a breakdown of the acceptance criteria and study information for the VITEK® MS PRIME, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

2. Sample Sizes Used for the Test Set and Data Provenance:

• Biological Equivalency Study:

  • Sample Size: 1461 samples (representing 487 unique tests in triplicate).
  • Data Provenance: Not explicitly stated, but the strains tested included "critical pathogens" for the 479 claimed species. It is likely a combination of well-characterized laboratory strains and potentially some clinical isolates, given the reference to "clinically validated isolates." retrospective or prospective is not mentioned.

• Clinical Performance Evaluation:

  • Sample Size: 500 clinical isolates (from 100 species with five strains each).
  • Data Provenance: "clinical isolates tested from all sites combined." The specific countries of origin are not specified, but the data is explicitly from "clinical isolates," suggesting data from human specimens. The study design of using "clinical isolates" usually implies retrospective or prospectively collected samples from clinical settings. It refers to "reference identification obtained during previous clinical studies," suggesting a retrospective use of previously characterized clinical data.

• Challenge Isolate Results:

  • Sample Size: 100 challenge strains.
  • Data Provenance: Not specified, but "challenge strains" often refers to a curated set of difficult-to-identify or representative strains used for rigorous testing.

• Quality Control Results:

  • Sample Size: Not explicitly stated, but refers to "all quality control strains tested at all sites."

• Reproducibility Results:

  • Sample Size: Not explicitly stated, but refers to "Reproducibility strains."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:

• The document does not directly state the number of experts or their qualifications.
• For the Clinical Performance Evaluation, the ground truth was established by "a one choice or multiple choice (more than one species) reference identification obtained during previous clinical studies." This implies that the reference identifications were well-established and accepted, likely through conventional microbiological methods and expert interpretation from those previous studies. The nature of these "previous clinical studies" (e.g., whether they involved expert consensus or a gold standard method) is not detailed.

4. Adjudication Method for the Test Set:

• The document does not explicitly describe an adjudication method for the test set results. The ground truth for the clinical performance evaluation was "reference identification obtained during previous clinical studies," implying that disagreements with a single reference standard were likely noted as discordant results rather than undergoing a separate adjudication process within this specific study.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

• No MRMC comparative effectiveness study is mentioned. This device (VITEK® MS PRIME) is an automated system for microorganism identification using MALDI-TOF MS technology, which does not involve human readers interpreting results in the same way an imaging AI algorithm would. Its performance is compared to a reference method, not to human readers' performance with and without AI assistance.

6. Standalone Performance:

• Yes, a standalone performance study was done. Both the "Biological Equivalency study" and "Clinical Performance Evaluation" describe the performance of the VITEK® MS PRIME system alone (algorithm only) in identifying microorganisms, comparing its results to a ground truth or reference identification. The stated agreement rates (e.g., 98.4% clinical agreement) are measures of this standalone performance. The device is described as "a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings," but the performance metrics provided are for the device's identification capability itself.

7. Type of Ground Truth Used:

• The ground truth used appears to be reference identification by accepted microbiological methods (which implicitly includes expert consensus in their establishment).
  • For the Biological Equivalency study, performance was measured "in comparison with the reference method."
  • For the Clinical Performance Evaluation, performance was determined by comparing the VITEK® MS PRIME identification to "a one choice or multiple choice (more than one species) reference identification obtained during previous clinical studies." This "reference identification" would be established through a combination of traditional culture-based methods, molecular methods, and expert interpretation/consensus over time, serving as the gold standard for organism identification. "Outcomes data" or "pathology" as the direct ground truth are not mentioned for identifying the microorganisms themselves, though the device aids in diagnosis of infections.

8. Sample Size for the Training Set:

• The document does not explicitly state the sample size for the training set. It refers to a "VITEK® MS Knowledge Base" (KB v3.2) against which the mass spectra are compared. This knowledge base is the "training set" or reference library. The complexity and size of this knowledge base are not detailed in terms of number of samples/isolates used to build it.

9. How the Ground Truth for the Training Set Was Established:

• The document states that identifications are made "when compared against the VITEK® MS Knowledge Base." While it doesn't describe the exact process for building this KB, such knowledge bases for MALDI-TOF MS systems are typically built by:
  • Acquisition of mass spectra from a large collection of well-characterized and phenotypically/genetically confirmed (often by sequencing, biochemical tests, or other gold-standard methods) reference strains across various species.
  • Each reference strain's identity is verified by expert microbiologists using established methods before being added to the database.
  • The collection process ensures reproducibility and representation of intra-species variability.
  • Thus, the ground truth for the training set (Knowledge Base) is established through a rigorous process of expert-validated identification using traditional and molecular microbiological gold standards.

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VITEK® 2 AST-Yeast Fluconazole is designed for antifungal susceptibility testing of Candida species 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 antifungal agents. VITEK® 2 AST-Yeast Fluconazole is a quantitative test. Fluconazole has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections: Candida albicans Candida parapsilosis Candida tropicalis

The VITEK® 2 Fungal 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 yeasts to antifungal 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-YS Fluconazole has the following concentrations in the card: 2, 4, 8, 16, 32, and 64 (equivalent standard method concentration by efficacy in us/mL).

Here's a breakdown of the acceptance criteria and study details for the VITEK® 2 AST-Yeast Fluconazole device, based on the provided document:

Acceptance Criteria and Device Performance

                                                                                                                                                                                                                                                                                                                              |

| Major Errors (ME) | Not explicitly stated as a numerical threshold, but ME are generally expected to be low, typically < 3%. | 3.0% (12/398) for Fluconazole overall. |
| Minor Errors (mE) | Not explicitly stated as a numerical threshold, but mE are generally expected to be low, typically < 10%. | 3.2% (14/442) for Fluconazole overall. |
| Reproducibility | "Acceptable results" | 100% Reproducibility reported for Fluconazole. (The table shows "%Reproducibility" column with "100" for Fluconazole, though the full context of this 100% isn't detailed in what "reproducibility" exactly refers to within this specific table line item). The text also states "Reproducibility and Quality Control demonstrated acceptable results." |

Note on Acceptance Criteria: While explicit numerical thresholds for EA, CA, VME, ME, and mE are not directly listed as "acceptance criteria" in the provided text, these metrics are standard for evaluating AST systems. The statement "VITEK® 2 AST-YS Fluconazole demonstrated acceptable performance" in conjunction with the reported percentages implies that these percentages met the required performance standards for substantial equivalence. The document references the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)," which would contain the specific performance criteria.

Study Details

1. Sample Size Used for the Test Set and Data Provenance:

   • Sample Size: The device performance table indicates a total of 442 isolates tested (denominator for EA and CA percentages). For VME analysis, 26 susceptible reference results (total) and for ME analysis, 398 instances (total, meaning the total population excluding those susceptible) were used. The number of Candida parapsilosis specific results cited are 14.
   • Data Provenance: The external evaluation was 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 implies clinical relevance. The study appears to be prospective or designed to simulate prospective use for evaluation, as it uses clinical and challenge strains. It is an "external evaluation," which typically means the testing was done at multiple sites.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

   • Not Applicable. This is an in vitro diagnostic device for antimicrobial susceptibility testing. The ground truth is established by a reference laboratory method (CLSI broth microdilution), not by human experts. The "experts" in this context would be laboratory personnel meticulously performing the reference method.

3. Adjudication Method for the Test Set:

   • Not Applicable. As the ground truth is established by a quantitative laboratory method (CLSI broth microdilution), there is no human adjudication process involved for ambiguous interpretations. The comparison is directly between the MIC values and categorical interpretations (S, I, R) from the device and the reference method. Errors (VME, ME, mE) are calculated based on discrepancies from the reference method.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

   • No. This is an in vitro diagnostic device, not an imaging or interpretive device that relies on human readers. Therefore, an MRMC study is not relevant or performed for this type of product. The "readers" are the automated VITEK® 2 systems themselves.

5. Standalone (Algorithm-Only) Performance:

   • Yes. The study evaluates the performance of the VITEK® 2 AST-YS Fluconazole device in conjunction with the VITEK® 2 and VITEK® 2 Compact Systems. This is a standalone evaluation of the integrated system (test card + instrument + embedded analysis algorithms) against the CLSI reference method, without a human in the loop for interpretation of the raw data generated by the system. The system automatically generates the MIC value and interpretive category.

6. Type of Ground Truth Used:

   • CLSI broth microdilution reference method. This is a universally accepted, gold standard laboratory method for determining minimum inhibitory concentrations (MICs) of antifungal agents. The reference method was incubated at 24 hours (or up to 48 hours for isolates with slow growth).

7. Sample Size for the Training Set:

   • Not explicitly stated in the provided document. The document details the "Premarket Notification (Special 510[k]) presents data in support of VITEK® 2 AST-YS Fluconazole." This implies that the data presented here is for the validation or test set, used to demonstrate substantial equivalence. The VITEK® 2 system's "Discriminant Analysis" algorithms would have been developed and refined (trained) on prior datasets, but the size and nature of those training sets are not part of this 510(k) summary. These types of devices often use extensive historical isolate collections for algorithm development.

8. How the Ground Truth for the Training Set Was Established:

   • Not explicitly stated in the provided document for the training set. However, given the nature of the device and the reference method used for the test set, it is highly probable that the ground truth for any training sets used for the "Discriminant Analysis" algorithms would also have been established via the CLSI broth microdilution reference method or similar established laboratory methods.

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VITEK® 2 AST-Gram Positive Fosfomycin is designed for antimicrobial susceptibility testing of Gram positive microorganisms 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 Positive Fosfomycin is a quantitative test. Fosfomycin 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:
Enterococcus faecalis

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 clinically significant aerobic Gram-positive microorganisms 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 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 Fosfomycin (<8 - ≥256 µg/mL) has the following concentrations in the card: 8, 16, 32 and 128 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

The medical device is the VITEK® 2 AST-Gram Positive Fosfomycin (≤8 - ≥256 µg/mL).

Here's the detailed information regarding its acceptance criteria and the study proving it meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for antimicrobial susceptibility test (AST) systems are typically defined by the FDA Class II Special Controls Guidance Document. For the VITEK® 2 AST-GP Fosfomycin, the key performance metrics are Essential Agreement (EA) and Category Agreement (CA), along with the rates of Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).

Note: The document explicitly states "VITEK® 2 AST-GP Fosfomycin demonstrated substantially equivalent performance when compared with the CLSI agar dilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)." While specific numerical acceptance thresholds are not explicitly listed in this document, the reported performance clearly meets the general expectations for substantial equivalence based on FDA guidance for AST systems.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Test Set: 399 isolates.
• Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a combination of prospective clinical samples (fresh isolates) and retrospective/archived samples (stock clinical isolates and challenge strains). The country of origin is not specified but is implicitly within the scope of where such FDA-regulated clinical trials are conducted.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of study (Antimicrobial Susceptibility Testing) does not typically involve human experts establishing a "ground truth" in the way, for example, a radiology AI study would. The ground truth is established by a reference laboratory method. In this case, the CLSI agar dilution reference method was used. This is a standardized laboratory procedure, not reliant on expert subjective interpretation.

4. Adjudication Method for the Test Set

Not applicable. As noted above, the ground truth is established by a standardized laboratory reference method (CLSI agar dilution), not by human expert consensus or adjudication. Discrepancies would be resolved through re-testing or investigation of methods, rather than expert adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

Not applicable. This is an antimicrobial susceptibility test system, not an AI-assisted diagnostic imaging system that involves human readers. The VITEK® 2 system is essentially an automated laboratory test.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this study represents a standalone (algorithm only) performance evaluation. The VITEK® 2 system performs the antimicrobial susceptibility testing automatically. Its results are compared directly against the CLSI agar dilution reference method.

7. The Type of Ground Truth Used

The ground truth used was the CLSI agar dilution reference method. This is a well-established, standardized laboratory method for determining the minimum inhibitory concentration (MIC) of an antimicrobial agent against a microorganism, which then translates into interpretive categories (susceptible, intermediate, resistant).

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for the training set. It describes the performance evaluation conducted with "fresh and stock clinical isolates, as well as a set of challenge strains" which refers to the test set. For an AST system like VITEK® 2, the "training" (development and calibration) would involve a substantial, diverse collection of bacterial strains with known resistance profiles, but the specific number used to initially develop the "growth pattern analysis" algorithm is not provided in this summary.

9. How the Ground Truth for the Training Set Was Established

The ground truth for the development/training of microbial AST systems, including the VITEK® 2, is typically established using established reference laboratory methods, primarily agar dilution or broth microdilution, in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. These methods define the true minimum inhibitory concentration (MIC) for various microorganisms against specific antimicrobial agents. This extensive dataset of MICs across a wide range of strains would be used to develop and fine-tune the "Growth Pattern Analysis" algorithm of the VITEK® 2 system to accurately determine MICs and interpretive categories.

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