Search Results

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

Escherichia coli

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 sigmificant 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(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 Fosfomycin (≤4 - ≥256 ug/mL) has the following concentrations in the card: 2, 8, 16 and 64 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

The provided text describes the performance of the VITEK® 2 AST-GN Fosfomycin device for antimicrobial susceptibility testing. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document refers to the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)" for acceptance criteria. While the specific numerical acceptance criteria (e.g., minimum percentage for %EA and %CA, maximum percentage for VME, ME, mE) are not explicitly stated in the provided text, the reported device performance is given in Table 2.

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

• Test Sample Size: 380 isolates for Escherichia coli (Enterobacterales). The reported performance values (e.g., 377/380 for %EA, 379/380 for %CA) confirm this.
• Data Provenance: The study was an "external evaluation conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a prospective study using a mix of clinical and challenge strains. The country of origin is not specified.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

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

No MRMC study was done, as this is an antimicrobial susceptibility testing system, not a device that involves human readers interpreting cases.

6. Standalone Performance:

Yes, a standalone performance study was done. The VITEK® 2 AST-GN Fosfomycin demonstrated performance by comparing its results with the "CLSI agar dilution reference method." This indicates the algorithm (device) performed the susceptibility testing independently.

7. Type of Ground Truth Used:

The ground truth used was the CLSI agar dilution reference method. This is considered a gold standard for antimicrobial susceptibility testing.

8. Sample Size for the Training Set:

The document does not explicitly state the sample size for a training set. The study focuses on the "external evaluation" of the device's performance against a reference method. AST systems like VITEK 2 typically rely on established microbiological principles rather than machine learning models requiring large training sets in the same way an image analysis AI might.

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

As there's no mention of a separate training set in the context of machine learning, this information is not applicable/provided. If a "training set" were to be conceptualized for an AST system, it would relate to the initial development and calibration of the system's algorithms against established reference methods, which is part of the overall design and development process for such devices. The "CLSI agar dilution reference method" serves as the benchmark against which the device's accuracy is continually validated.

Ask a specific question about this device

ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Fosfomycin has been shown to be active against the Gram-positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® (FO) can be used to determine the MIC of Fosfomycin against the following microorganisms:

Active both in vitro and in clinical infections:

• Escherichia coli
• Enterococcus faecalis

ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in µg/mL on one side and a predefined antibiotic gradient on the other side.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Fosfomycin contains a range of fosfomycin from 0.032 to 512 ug/mL.

The provided document is a 510(k) premarket notification for a medical device called ETEST® Fosfomycin (FO) (0.032-512 ug/mL). This device is an Antimicrobial Susceptibility Test Powder used to determine the Minimum Inhibitory Concentration (MIC) of fosfomycin against certain bacteria.

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based only on the provided text. Please note that the document is a regulatory submission, not a detailed scientific paper, so some requested information may not be explicitly stated or might not be applicable to this type of device (e.g., "human readers" for an in-vitro diagnostic).

1. A table of acceptance criteria and the reported device performance

The acceptance criteria for this type of device are generally qualitative (e.g., "acceptable performance," "substantially equivalent," "meets guidance document performance requirements") and quantitative, primarily focusing on "Essential Agreement" and "Category Agreement" with a reference method. The document states that ETEST® Fosfomycin (FO) "demonstrated substantially equivalent performance when compared with the CLSI M07-A11 January 2018 agar microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009 and following specifications as defined in CLSI M100 30th Ed. (January 2020)."

While specific numerical acceptance thresholds are not explicitly listed in the document for Essential Agreement (EA) and Category Agreement (CA), the reported performance is presented as meeting acceptable levels. The predicate device also states "Meets Guidance Document Performance Requirements: Yes." This implies the acceptance criteria for EA and CA were those outlined in the referenced FDA Guidance Document and CLSI standards.

1 EA = % of MIC values within ± 1 dilution of the reference method.
2 CA = Correct determination of susceptibility category (e.g., Susceptible, Intermediate, Resistant)

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

• Test Set Sample Size:
  • Enterococcus faecalis: 191 strains
  • Escherichia coli: 238 strains
• Data Provenance: The document states "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates the data is retrospective (using existing clinical isolates and stock cultures) and likely prospective (fresh clinical isolates). The country of origin is not explicitly stated, but bioMérieux is a French company.

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

This information is not applicable to this type of device and study. The ground truth for antibiotic susceptibility testing (AST) devices is established by a standardized, laboratory-based reference method (CLSI agar microdilution method), not by human expert opinion or consensus.

4. Adjudication method for the test set

Not applicable. The ground truth is determined by a standardized laboratory method, not by human 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 in-vitro diagnostic for antimicrobial susceptibility testing. It does not involve human readers interpreting images, nor does it incorporate AI assistance in the way typically seen in radiology or ophthalmology devices. The comparison is between the test device (ETEST) and a laboratory reference method (CLSI agar microdilution).

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

This concept is also not directly applicable in the same way it would be for an AI algorithm interpreting images. The ETEST operates as a "standalone" laboratory test in that its result (the MIC value) is read directly from the strip after incubation. There isn't an "algorithm" in the typical AI sense; rather, it's a defined chemical gradient interaction with bacterial growth. The performance study evaluates the device's accuracy in determining MIC and category agreement compared to a reference method, which is essentially its "standalone" performance.

7. The type of ground truth used

The ground truth used was the CLSI (Clinical and Laboratory Standards Institute) M07-A11 January 2018 agar microdilution reference method. This is a laboratory-based reference method widely accepted as the gold standard for antimicrobial susceptibility testing. It's not expert consensus, pathology, or outcomes data in this context.

8. The sample size for the training set

The document does not explicitly state the sample size used for a "training set." This type of regulatory submission outlines the performance of the device against a reference method, which corresponds to what would typically be a "test set" in an AI/ML context. For a device like ETEST, which is a physical consumable strip with a pre-defined chemical gradient, there isn't a traditional "training" phase for an algorithm in the way a machine learning model would be trained. The development and optimization of the gradient would occur during product development, but this information is not part of the 510(k) submission.

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

As described in point 8, there isn't a "training set" in the machine learning sense for this device. The physical characteristics and performance of the ETEST strip are developed and characterized, and then validated against the CLSI reference method. The "ground truth" for evaluating the performance of the final device (the "test set") is consistently the CLSI agar microdilution reference method.

Ask a specific question about this device

ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Delafloxacin has been shown to be active against the aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® DFX can be used to determine the MIC of Delafloxacin against the following microorganisms:

Active both in vitro and in clinical infections:

Gram-positive bacteria:

• · Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible strains)
• Staphylococcus haemolyticus
• Staphylococcus lugdunensis
• Enterococcus faecalis

Gram-negative bacteria:

• Pseudomonas aeruginosa

ETEST® is a thin, inert and non-porous plastic strip carrying on one side the MIC reading scale in ug/mL, and on the other side a predefined antibiotic gradient.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Delafloxacin contains a range of delafloxacin from 0.002 to 32 u2/mL.

This document describes the performance of the ETEST® Delafloxacin (DFX) device, a manual, quantitative technique for determining antimicrobial susceptibility. The study aims to demonstrate that the device is substantially equivalent to a predicate device (ETEST® Telavancin (TLA)) and meets pre-defined acceptance criteria based on established guidance and standards.

Here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

The acceptance criteria are derived from the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009" and "CLSI M100-S29 January 2019". While specific numerical targets for Essential Agreement (EA) and Category Agreement (CA) are not explicitly stated as "acceptance criteria" percentages in the text, the performance data presented in the tables are implied to meet these criteria, as the conclusion states the device demonstrated "acceptable performance" and "substantially equivalent performance". The data strongly suggests typical FDA acceptance thresholds for AST devices, which often require high percentages.

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

The document mentions "fresh and stock clinical isolates, as well as a set of challenge strains" were used for external evaluations. However, the specific sample sizes (number of isolates) for the test set are not provided in the document.

The data provenance implies a multi-center study ("External evaluations were conducted") and the use of clinical and challenge strains, suggesting a mix of real-world (clinical) and engineered (challenge) samples. The country of origin for the data is not explicitly stated, but the submitter's address is in France. The study appears to be prospective in nature for data collection, as it describes conducting evaluations for the purpose of this submission.

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 document. The ground truth for antimicrobial susceptibility testing (AST) devices is typically established through a reference method.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not provided in the document. For AST devices, adjudication as typically understood for image-based diagnostic AI is not directly applicable. Instead, the "ground truth" is established by a well-defined and accepted 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 MRMC comparative effectiveness study was done or mentioned. This device is a manual, quantitative technique for antimicrobial susceptibility testing, not an AI-assisted diagnostic tool that would typically involve human reader performance improvement with AI.

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

This refers to the performance of the ETEST® Delafloxacin device itself. The data presented in Table 1 ("Performance Characteristics for ETEST® Delafloxacin") represents the standalone performance of the device compared to the reference method. There is no "human-in-the-loop" component in the sense of an AI interpreting results and a human reviewing them; rather, a human reads the MIC value directly from the ETEST strip.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for the performance study was established by the CLSI M07-A11 January 2018 broth microdilution reference method. This is considered the gold standard for determining Minimum Inhibitory Concentrations (MICs) in microbiology.

8. The sample size for the training set

The document does not specify a training set sample size. ETEST® products are physical diagnostic devices (strips), not machine learning algorithms that require a "training set" in the computational sense. The "training" for such devices would involve extensive research and development, and the performance is validated through studies like the one described.

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

As there is no "training set" in the context of an AI algorithm, this question is not applicable. The development and optimization of the ETEST® system itself would have relied on established microbiological principles and validated methods for determining antimicrobial concentrations and their effects on bacterial growth.

Ask a specific question about this device

ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minibitory Concentration (MC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media using overnight incubation.

Eravacycline has been shown to be active against most isolates of the microorganisms listed below according to this antimicrobial agent.

ETEST® ERV can be used to determine the MIC of Eravacycline against the following microorganisms:

Active both in vitro and in clinical infections:

Gram-negative:

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae

Gram-positive: Enterococcus faecalis Enterococcus faecium

In vitro data are available for the following microorganisms, but clinical significance is unknown:

Citrobacter koseri Klebsiella aerogenes

ETEST® is a thin, inert and non-porous plastic strip carrying on one side the MIC reading scale in ug/mL, and on the other side a predefined antibiotic gradient.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Eravacycline contains a range of eravacycline from 0.002 to 32 µg/mL.

The document describes the performance of the ETEST Eravacycline (ERV) (0.002-32 ug/mL) device for determining the minimum inhibitory concentration (MIC) of Eravacycline against various microorganisms.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for Antimicrobial Susceptibility Test (AST) Systems are typically defined by regulatory guidance documents, such as the FDA Class II Special Controls Guidance Document and CLSI standards. For this device, the performance is evaluated based on Essential Agreement (EA) and Category Agreement (CA) with a reference method. While explicit numerical acceptance criteria for EA and CA are not directly stated as pass/fail thresholds in the provided text, the document implies that the reported percentages of EA and CA demonstrate "acceptable performance" and "substantially equivalent performance" when compared to the CLSI reference method and predicate device.

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

The test set included both contemporary and stock clinical isolates, as well as challenge strains.

• Enterobacteriaceae (Total N = 552):
  • C. freundii (70 isolates)
  • C. koseri (30 isolates)
  • E. cloacae (72 isolates)
  • E. coli (191 isolates)
  • K. aerogenes (32 isolates)
  • K. oxytoca (43 isolates)
  • K. pneumoniae (104 isolates)
  • The overall categorical very major error rate for Eravacycline was evaluated on 92 Enterobacteriaceae clinical and challenge isolates for non-susceptible results. This suggests that at least 92 isolates were non-susceptible for this specific analysis.
• Enterococci (Total N = 137):
  • E. faecalis (74 isolates)
  • E. faecium (63 isolates)
  • The overall categorical major and very major error rates for Eravacycline were evaluated on 128 isolates (for major errors) and 9 isolates (for very major errors). This implies at least 128 isolates were included for major error evaluation and 9 for very major error evaluation for non-susceptible isolates.

Data Provenance: The document states that "External evaluations were conducted with contemporary and stock clinical isolates, as well as a set of challenge strains." The country of origin of the data is not specified in the provided text, but bioMérieux SA is based in France.

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

The document does not explicitly state the number of experts or their specific qualifications. However, it indicates that the device's performance was compared against the "CLSI M07-A11 January 2018 broth microdilution reference method" and "CLSI M100-S28 January 2018 specifications." This implies that the ground truth was established by laboratory personnel proficient in performing and interpreting these standard reference methods, which are widely accepted in microbiology for antimicrobial susceptibility testing.

4. Adjudication Method for the Test Set

The document does not mention an explicit adjudication method (e.g., 2+1, 3+1, none) for the test set. The ground truth was established by comparison to the CLSI broth microdilution reference method. Any discrepancies or "errors" (e.g., Major Errors, Very Major Errors) are noted, and for some cases (e.g., Klebsiella pneumoniae VME), it mentions that "When tests were repeated in triplicate, all the results were in category agreement," which could be considered a form of internal re-evaluation or confirmation rather than formal adjudication by independent experts.

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

No multi-reader multi-case (MRMC) comparative effectiveness study is mentioned. The device is a diagnostic test for antimicrobial susceptibility, not an AI-assisted diagnostic tool that directly influences human reader performance.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance evaluation was conducted. The ETEST® Eravacycline device itself is the "algorithm" in this context, as it's a physical strip with a predefined antibiotic gradient designed to produce a measurable MIC value. Its performance (Essential Agreement, Category Agreement, Reproducibility, Quality Control) was assessed independently by comparing its results directly to the CLSI broth microdilution reference method. No human-in-the-loop interaction for interpretation beyond reading the MIC from the strip itself is implied as part of the evaluated "device performance."

7. Type of Ground Truth Used

The ground truth used was the CLSI M07-A11 January 2018 broth microdilution reference method. This is considered the gold standard for determining minimum inhibitory concentrations (MICs) in microbiology and serves as the primary comparative method for new AST devices. Interpretive categories (susceptible, intermediate, resistant) are typically derived from MIC values based on breakpoints established by CLSI guidelines (e.g., CLSI M100-S28).

8. Sample Size for the Training Set

The document does not provide information about a separate "training set" or its sample size. This type of device (an ETEST strip) is a physical, pre-calibrated product based on a chemical gradient, not a machine learning algorithm that requires a training set in the conventional sense. Its design and manufacturing process would be informed by decades of antimicrobial susceptibility testing principles and prior ETEST product development, rather than a data-driven training phase as seen with AI/ML models.

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

As no training set is described for this type of device, this question is not applicable. The device's fundamental principle is based on established scientific principles of antibiotic diffusion and bacterial growth inhibition, rather than being "trained" on data.

Ask a specific question about this device

ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Imipenem/Relebactam has been shown to be active against the Gram-negative aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® IPR can be used to determine the MIC of Imipenem/Relebactam against the following microorganisms:

Active both in vitro and in clinical infections:

• Citrobacter freundii
• Enterobacter cloacae
• Escherichia coli
• Klebsiella aerogenes
• Klebsiella oxytoca
• Klebsiella pneumoniae
• Pseudomonas aeruginosa

ETEST® is a thin, inert and non-porous plastic strip carrying on one side the MIC reading scale in ug/mL, and on the other side a predefined antibiotic gradient.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Imipenem/Relebactam contains a range of imipenem from 0.002 to 32 µg/mL, overlaid with a fixed concentration of 4ug/mL of relebactam.

Here's a breakdown of the acceptance criteria and the study details for the ETEST® Imipenem/Relebactam (IPR) device, based on the provided text:

1. A table of acceptance criteria and the reported device performance

Note: The document refers to "substantially equivalent performance when compared with the CLSI M07-A10 January 2015 broth microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009 and following specifications as defined in CLSI M100-S28 January 2018." This implies that the acceptance criteria are based on the guidelines and specifications outlined in these documents for establishing substantial equivalence for AST systems. The specific numerical thresholds for EA, CA, and VME set by these guidelines are not explicitly detailed in the provided text but are the underlying acceptance criteria.

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

• Sample Size for Test Set:
  • Enterobacteriaceae:
    • Citrobacter freundii: 30 isolates
    • Klebsiella aerogenes: 30 isolates
    • Enterobacter cloacae: 33 isolates
    • Enterobacter cloacae complex: 70 isolates
    • Escherichia coli: 165 isolates
    • Klebsiella oxytoca: 32 isolates
    • Klebsiella pneumoniae: 117 isolates
    • Total Enterobacteriaceae: 30 + 30 + 33 + 70 + 165 + 32 + 117 = 477 isolates (Note: one error in the text is 1/44 resistant isolates for VME, but the total number tested for Enterobacteriaceae is 477. It indicates 44 resistant isolates were tested specifically for VME, not for the entire EA/CA.)
  • Pseudomonas aeruginosa: The exact number is not explicitly broken down but is part of the overall "Gram negative aerobic bacteria" and the 96.0% EA/CA. The document does not provide a specific number of P. aeruginosa isolates, only the performance result for that category.
• Data Provenance: "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates the data is from prospective and retrospective clinical samples that were then tested, likely across multiple sites (implied by "external evaluations"). The country of origin is not specified.

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

The document does not mention the number or qualifications of experts used to establish the ground truth. The ground truth method is the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not typically an expert consensus reading.

4. Adjudication method for the test set

The document does not describe an adjudication method involving experts for the test set. The comparison is made against a standardized laboratory reference method (CLSI broth microdilution).

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 MRMC comparative effectiveness study was done as this device is an in vitro diagnostic (IVD) for antimicrobial susceptibility testing, not an AI-assisted diagnostic for human interpretation. It directly determines MIC values.

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

Yes, this evaluates the standalone performance of the ETEST® system. While a human technician applies the strip and reads the ellipse, the interpretation of the MIC value from the scale is directly determined by the physical outcome (inhibition ellipse) on the strip, comparing it to the CLSI reference method. The "device" in this context refers to the ETEST® strip and its inherent gradient.

7. The type of ground truth used

The ground truth used is the CLSI M07-A10 January 2015 broth microdilution reference method. This is a laboratory reference method that is considered the gold standard for antimicrobial susceptibility testing.

8. The sample size for the training set

The document does not specify a separate "training set" for the ETEST® device. As an IVD, its performance is established against a reference method rather than through a machine learning training paradigm common in AI devices. The "test set" described above is used for performance evaluation, not training.

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

Not applicable, as no training set (in the machine learning sense) is described. The device's performance is established by direct comparison to the CLSI broth microdilution reference method.

Ask a specific question about this device

ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Piperacillin/Tazobactam has been shown to be active against the Gram-negative aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® P/T can be used to determine the MIC of Piperacillin/Tazobactam against the following microorganisms:

Active both in vitro and in clinical infections: Acinetobacter baumannii Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa

In vitro data are available for the following microorganisms, but clinical significance is unknown:

Citrobacter koseri Morganella morganii Proteus mirabilis Proteus vulgaris Serratia marcescens Providencia stuartii Providencia rettgeri Salmonella enterica

ETEST® is a thin, inert and non-porous plastic strip carrying on one side the MIC reading scale in ug/mL, and on the other side a predefined antibiotic gradient.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Piperacillin/Tazobactam contains a range of piperacillin from 0.016 to 256 ug/mL, overlaid with a fixed concentration of 4 ug/mL of tazobactam.

This document describes the performance of the ETEST® Piperacillin/Tazobactam (P/T) device in determining antimicrobial susceptibility.

1. Table of acceptance criteria and the reported device performance:

Note: The document references the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009" and "CLSI M100-S28 January 2018," which would contain the specific acceptance criteria for Essential Agreement and Category Agreement. The reported performance is directly quoted from Table 1.

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

• Sample Size (Test Set):
  • Enterobacteriaceae: The performance data for Enterobacteriaceae includes: E. coli (168), K. pneumoniae (190), C. koseri (46), M. morganii (41), P. mirabilis (41), P. vulgaris (31), S. marcescens (47), P. stuartii (36), P. rettgeri (28), and S. enterica (31). The total number of unique isolates for Enterobacteriaceae is the sum of these values: 168 + 190 + 46 + 41 + 41 + 31 + 47 + 36 + 28 + 31 = 659 isolates.
  • P. aeruginosa and Acinetobacter spp.: Specific numbers for these categories are not provided beyond the overall performance percentages.
  • The study utilized "fresh and stock clinical isolates, as well as a set of challenge strains." This implies a diverse collection of organisms.
• Data Provenance: The document does not explicitly state the country of origin. It indicates "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a retrospective and potentially prospective collection of real-world clinical isolates for the test set.

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 document. The ground truth method (CLSI broth microdilution) is a standardized laboratory procedure, not typically relying on expert interpretation in the same way an imaging study would.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

This information is not applicable for this type of device and study. The ground truth (broth microdilution) is a quantitative laboratory measurement, not subject to subjective expert 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:

A multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an Antimicrobial Susceptibility Test (AST) system, which provides quantitative MIC values and categorical interpretations (Susceptible, Intermediate, Resistant). It is not an AI-assisted diagnostic imaging or interpretation tool for human readers.

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

The study assessed the standalone performance of the ETEST® Piperacillin/Tazobactam device. The device itself (the strip and its resulting inhibition ellipse) generates the result, which is then read by a trained user to determine the MIC. While a human reads the strip, the performance metrics (Essential Agreement, Category Agreement) refer to the accuracy of the device's output compared to the reference method, essentially evaluating the "algorithm only" in generating the gradient and inhibition pattern. The document mentions optional inoculator and ETEST® strip applicator, but clarifies that "swabs were used for plate inoculation/streaking and forceps were used for ETEST® strip application" in the clinical studies, indicating manual procedures for the setup, but the core measurement is from the device.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth used was the CLSI M07-A11 January 2018 broth microdilution reference method. This is a recognized standard laboratory method for determining antimicrobial susceptibility.

8. The sample size for the training set:

The document does not explicitly mention a training set sample size. For AST devices, performance studies typically focus on an independent test set compared to a reference method. While there's a development process for the ETEST® strip formulation, the submitted data pertains to its validation against established standards, not a machine learning model's training.

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

As no explicit training set is mentioned in the context of machine learning, the question of how its ground truth was established is not applicable here. The "development" of the ETEST® device would have involved ensuring the stability and accuracy of the antibiotic gradient, but this is a manufacturing/chemistry process, not a data-driven model training process with ground truth labels.

Ask a specific question about this device

ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Meropenem/Vaborbactam has been shown to be active against the Gram-negative aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® MEV can be used to determine the MIC of Meropenem/Vaborbactam against the following microorganisms:

Active both in vitro and in clinical infections: Enterobacter cloacae complex Escherichia coli Klebsiella pneumoniae

In vitro data are available for the following microorganisms, but clinical significance is unknown:

• Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca Morganella morganii Providencia spp. Serratia marcescens

ETEST® is a thin, inert and non-porous plastic strip carrying on one side (A) the MIC reading scale in ug/mL, and on the other side (B) a predefined antibiotic gradient.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Meropenem/Vaborbactam contains a range of meropenem from 0.004 to 64 ug/mL, overlaid with a fixed concentration of 8 µg/mL of vaborbactam.

This document describes the performance study and acceptance criteria for the ETEST® Meropenem/Vaborbactam (MEV) device, an antimicrobial susceptibility test system.

1. Table of Acceptance Criteria and Reported Device Performance

The performance of the ETEST® Meropenem/Vaborbactam device was evaluated against the CLSI M07-A10 January 2015 broth microdilution reference method. The acceptance criteria and the device's reported performance are summarized below:

Notes:

• Essential Agreement (EA): Defined as the percentage of MIC values within ± 1 dilution of the reference method.
• Category Agreement (CA): Not explicitly defined in this document but generally refers to agreement in interpretation (Susceptible, Intermediate, Resistant) between the test method and the reference method.
• The document states that the performance met acceptable levels as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems and CLSI M100-S28 January 2018. The specific numerical acceptance thresholds are implied by the statement "acceptable performance" and the satisfactory agreement percentages reported.

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

• Sample Size for Test Set: The species and their counts that comprised the Enterobacteriaceae (excluding Proteus mirabilis) test isolates are provided:
  • C. freundii: 32
  • C. koseri: 32
  • K. aerogenes: 33
  • E. cloacae complex: 98
  • E. coli: 136
  • K. oxytoca: 31
  • K. pneumoniae: 128
  • M. morganii: 31
  • P. rettgeri: 21
  • P. stuartii: 21
  • S. marcescens: 31
  • Total number of isolates: 594
• Data Provenance: The document states that "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates that the data are from real-world clinical samples (retrospective or prospective collections) and likely representative of strains encountered in clinical settings, supplemented with challenge strains designed to test specific resistance mechanisms. The country of origin is not explicitly stated, but the submitter's address is France.

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

• This study evaluates an Antimicrobial Susceptibility Test (AST) system. The "ground truth" for ASTs is typically established by specific, standardized laboratory reference methods (e.g., CLSI broth microdilution), not by human expert interpretation of images or clinical data.
• Therefore, the concept of "number of experts" and their qualifications as applies to image-based AI studies (like those with radiologists) is not directly applicable here. The "experts" in this context would be the skilled laboratory personnel who meticulously performed the CLSI broth microdilution reference method, ensuring adherence to the standard protocol.

4. Adjudication Method for the Test Set

• Not applicable in the context of an AST device performance study where the ground truth is a standardized quantitative laboratory method (CLSI broth microdilution). The comparison is direct between the ETEST® results and the reference method results. There is no "adjudication" in the sense of resolving disagreements between human readers or between human readers and an AI.

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

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. MRMC studies are primarily relevant for imaging-based diagnostic aids where human readers interpret medical images with or without AI assistance. This submission pertains to a laboratory diagnostic device that determines quantitative antimicrobial susceptibility, not an imaging AI.

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

• Yes, the performance study effectively measures the "standalone" performance of the ETEST® system. The ETEST® device generates a MIC value, and this value is directly compared to the reference method's MIC value without human interpretation influencing the ETEST® result itself. The human component is involved in applying the ETEST® strip and reading the inhibition zone, but this is a direct measurement against a scale rather than a subjective interpretation. The agreement percentages (EA and CA) reflect the accuracy of the device in generating these values compared to the reference.

7. The Type of Ground Truth Used

• Gold Standard Ground Truth: The ground truth for this study was established using the CLSI (Clinical and Laboratory Standards Institute) M07-A10 January 2015 broth microdilution reference method. This is a widely accepted, standardized, and highly reproducible method considered the gold standard for determining Minimum Inhibitory Concentrations (MICs) of antimicrobial agents.

8. The Sample Size for the Training Set

• This device is not an AI model that undergoes a "training phase" in the conventional sense. The "training set" concept (data used to train a machine learning algorithm) does not apply here. ETEST® is a chemical-biological device with a physical mechanism of action (predefined antibiotic gradient diffusion), not a software algorithm that learns from data. Its performance is inherent to its design and manufacturing.
• Therefore, there is no "training set" in the context of machine learning. The studies described are for validation (performance evaluation) against a reference standard.

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

• As explained above, there is no "training set" for this type of device. The ground truth for the performance evaluation (test set) was established by the CLSI broth microdilution reference method (see point 7).

Ask a specific question about this device

CHROMID® CARBA agar is a selective and differential chromogenic medium that is intended for the qualitative detection and presumptive identification of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in rectal swab specimens from patients at risk of colonization. CHROMID® CARBA agar is intended as an aid in the detection, identification of colonization and control of these bacteria in a healthcare setting.

Rectal swabs are inoculated directly onto CHROMID® CARBA agar without enrichment and results can be interpreted after incubation for 18-24 hours. Presumptive carbapenemase-producing colonies of E. coli appear pink to burgundy and those of K. pneumoniae appear blue-green or blue-grey.

Other organisms besides carbapenemase-producing E. coli and K. pneumoniae can also grow on CHROMID® CARBA agar with colonies that appear pink to burgundy or blue-grey. Sub-culture to non-selective medium is required to confirm organism identity, for antimicrobial susceptibility testing, confirmation of carbapenemase production and epidemiological typing.

A lack of growth or the absence of pink to burgundy or blue-grey colonies does not preclude the carriage of carbapenemase producing organisms.

CHROMID® CARBA agar consists of a nutritive base combining different peptones, 3 chromogenic substrates and antibiotics. These components enable the screening and presumptive identification of E. coli: spontaneous coloration (pink to burgundy) of strains producing ß-glucuronidase (ß-GUR) and/or ß-galactosidase (ß-GAL) and K. pneumoniae: spontaneous blue-green to bluish-grey coloration of strains producing ß-glucosidase (ß-GLU) from rectal swabs.

The document describes the regulatory approval of CHROMID® CARBA agar, a chromogenic medium for detecting carbapenemase-producing Escherichia coli and Klebsiella pneumoniae. While it specifies the device's performance, it doesn't present "acceptance criteria" in a typical table format with specific target values like "sensitivity > X%" and "specificity > Y%." Instead, it details the results of analytical and clinical studies to demonstrate the device's acceptable performance and substantial equivalence to a predicate device.

Here's an attempt to structure the information based on your request, inferring acceptance criteria from the presented results:

1. Table of Acceptance Criteria (Inferred from Study Results) and Reported Device Performance

Since explicit numerical acceptance criteria were not directly stated, they are inferred based on the observed "acceptable results" and high agreement percentages across various studies.

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

• Analytical Studies (Overall): Specific sample sizes vary per analytical test:
  • Recovery Study (LOD): 2 well-characterized KPC strains.
  • Cross Reactivity: 59 target and non-target organisms.
  • Challenge Testing (Analytical Reactivity): 52 KPC-EK strains.
  • Mixed Infection: 4 carbapenemase-producing strains in various mixtures.
  • Incubation: 10 KPC-EK strains.
• Clinical Studies / Method Comparison:
  • Prospective Clinical Study: Total of 709 unique rectal swab specimens were included in the analysis.
    • Data Provenance: Prospectively collected rectal swabs from three external laboratories (2 in the US, 1 in Europe).
  • Challenge Study (Clinical Section): 50 well-characterized isolates (11 KPC negative, 39 KPC positive) tested in saline matrix.
    • Data Provenance: One external site.
  • Contrived Samples Study: Total of 210 contrived samples (simulated rectal swab matrix).
    • Data Provenance: Tested at four different sites.
  • Reproducibility: 10 well-characterized isolates tested in triplicate each day for five days at three sites.

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

• The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") for establishing the ground truth for the test sets.
• For the clinical studies, "ground truth" was established based on a combination of CDC enrichment culture method, followed by subculture, biochemical identification, carbapenem susceptibility testing, CARBA NP testing, and PCR for carbapenemase resistance markers (blaKPC, blaNDM, blaOXA-48, blaVIM, blaIMP). This indicates a highly technical and multi-faceted laboratory-based ground truth definition rather than expert visual interpretation. The performance of these reference methods themselves would implicitly rely on expert laboratory personnel and validated protocols.

4. Adjudication Method for the Test Set

• The document does not describe an explicit adjudication method (like 2+1 or 3+1 consensus) for the test set used in the context of human reviewers agreeing on an outcome.
• The determination of the "carbapenemase status" for ground truth in clinical studies followed a defined algorithm (Table 1), which relied on multiple laboratory tests (MIC, Carba NP, PCR). This is a rules-based, objective definition rather than an expert consensus interpretation.

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

• No, an MRMC comparative effectiveness study was not done.
• This device is a culture medium interpreted visually (colony color). The studies described are primarily analytical and clinical performance evaluations of the medium itself, not comparative studies of human reader performance with or without AI assistance. The "reader" in this context is a lab technician observing colony growth and color.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

• This question is not directly applicable to the device. CHROMID® CARBA agar is a manual culture medium that relies on visual interpretation by a human observer (a laboratory technician/microbiologist). It is not an AI algorithm. Its performance is inherently "human-in-the-loop," as the human observes the results.

7. Type of Ground Truth Used

• Expert Consensus / Reference Method based on Laboratory Techniques for Clinical Samples:
  • For the clinical studies, the "ground truth" (Carbapenemase Status) was highly robust, determined by a comprehensive CDC enrichment culture method combined with:
    • Biochemical identification
    • Carbapenem susceptibility testing
    • CARBA NP testing (a phenotypic test for carbapenemase activity)
    • PCR for specific carbapenemase resistance genes (blaKPC, blaNDM, blaOXA-48, blaVIM, blaIMP).
  • A specific algorithm (Table 1) was used to integrate these results to define a positive or negative carbapenemase status. This is a very strong, multi-modal, and objective form of ground truth for microbial resistance.

8. Sample Size for the Training Set

• The document does not explicitly mention a separate "training set" as is common in AI/machine learning contexts. This is because the device is a chemical culture medium, not a machine learning model that undergoes a training phase. Its formulation and development (analogous to "training") would be based on scientific principles of microbiology and chromogenic media development, validated through the analytical and clinical studies described.

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

• As there is no distinct "training set" for an AI model, this question is not applicable. The development of the medium's formula would have relied on known biochemical properties of target organisms and carbapenemase mechanisms discovered through extensive microbiological research, which form the scientific basis for its selective and differential properties.

Ask a specific question about this device

ETEST® is a quantitative technique for determination of antimicrobial susceptibility of non-fasticious Gram-negative and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC), in ug/mL, of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.

Telavancin has been shown to be active against the Gram positive aerobic microorganisms listed below, according to the FDA label for this antimicrobial agent.

Active both in vitro and in clinical infections: Staphylococcus aureus (including methicillin resistant isolates) Enterococcus faecalis (vancomycin susceptible isolates only)

ETEST® is a thin, inert and non-porous plastic strip carrying on one side (A) the MIC reading scale in ug/mL, and on the other side (B) a predefined antibiotic gradient.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

Here's an analysis of the acceptance criteria and study detailed in the provided document for the ETEST® Telavancin device:

Acceptance Criteria and Device Performance

Study Information:

1. Sample sizes used for the test set and the data provenance:
   The document does not specify the exact sample sizes for Staphylococcus aureus or Enterococcus faecalis isolates used in the test set. It mentions "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." The provenance of the data (country of origin) is not explicitly stated. The nature of the data (retrospective or prospective) is also not explicitly detailed, but the use of "fresh and stock clinical isolates" suggests a mix, potentially with retrospective elements for the stock isolates and prospective elements for the fresh isolates.

2. 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 document. The ground truth was established by comparing the device's performance to the CLSI M07-A10 January 2015 broth microdilution reference method, which is a standardized laboratory procedure, not typically relying on individual expert judgment for ground truth determination.

3. Adjudication method for the test set:
   This is not applicable as the ground truth was established by a standardized reference method (CLSI broth microdilution) rather than human adjudication.

4. 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. The ETEST® Telavancin is an antimicrobial susceptibility test system, not an AI-assisted diagnostic tool for human readers. Its performance is evaluated against a reference laboratory method.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
   Yes, a standalone performance evaluation was done. The ETEST® Telavancin device's performance was compared directly to the CLSI M07-A10 broth microdilution reference method, without human-in-the-loop assistance influencing the ETEST® results. The ETEST® strip itself is read visually by a laboratory technician to determine the MIC value, which is part of its intended "standalone" use.

6. The type of ground truth used:
   The ground truth used was a reference laboratory method: the CLSI M07-A10 January 2015 broth microdilution method. This method is considered the gold standard for antimicrobial susceptibility testing.

7. The sample size for the training set:
   The document does not provide information regarding a separate "training set" or its sample size. For medical devices like AST systems, the development often involves an iterative process of design and internal testing, but the document focuses on the validation against established reference methods, which is typically done on a distinct "test set."

8. How the ground truth for the training set was established:
   Since no information on a specific "training set" and its sample size is provided, the method for establishing its ground truth is also not described.

Ask a specific question about this device

RAPIDEC® CARBA NP is a phenotypic (colorimetric) in vitro diagnostic test for the qualitative detection of carbapenemase enzymes in Enterobacteriaceae and Pseudomonas aeruginosa colonies that have elevated MIC values to any carbapenem. RAPIDEC® CARBA NP is performed on pure colonies grown on non-selective sheep blood agar culture media.

RAPIDEC® CARBA NP is intended as an aid in the prevention and control of infection caused by carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa.

RAPIDEC® CARBA NP is not intended to guide or monitor the treatment for these bacterial infections. A negative result does not preclude the presence of carbapenemase enzymes. The ability of RAPIDEC® CARBA NP to detect carbapenemase enzymes encoded by genetic markers other than KPC, NDM, OXA-48, VIM, and IMP has not been established. RAPIDEC® CARBA NP testing should be used in conjunction with other laboratory tests including antimicrobial susceptibility testing.

The RAPIDEC® CARBA NP strip is composed of 5 wells prepared with premeasured portions of the necessary substrates for the reactions. In addition, the kit contains the necessary accessories for performing the test.

In order to rehydrate the dry reagents and initiate the reactions, wells a, b and c are filled with 100 uL of API Suspension Medium (purified water). The strip is left at room temperature for 4-10 minutes to allow the dry reagents to reconstitute in the wells. The bacterial inoculum suspension is prepared in well c until the turbidity equals well b. Well c contains the lysis buffer. In order to achieve lysis of the inoculum suspension, which enables the extraction of the enzyme, the strip is left at room temperature for additionally 30 minutes.

As the next step, 25 uL of the lysed inoculum suspension is transferred to wells d and e and 25 µL from well a (phenol red solution) is also transferred to wells d and e. The strip is incubated for 30 minutes at 33-38°C to allow for the hydrolysis to occur and change in color of the phenol red solution in case of presence of a carbapenemase enzyme. The initial reading is performed after 30 minutes of incubation. In case of a negative or doubtful reaction, the strip is re-incubated for an additional 1 hour and 30 minutes before performing the final reading.

The hydrolysis acidifies the medium which results in the change in color of the pH indicator. Reading is performed by comparing the colors in wells d and e. The test is positive when a significant variation in color is observed between the two wells. For example, the control well is red and the test well has changed to yellow.

The document provided describes the RAPIDEC® CARBA NP device, an in vitro diagnostic test for the qualitative detection of carbapenemase enzymes. This is a 510(k) submission, meaning the manufacturer is demonstrating that their new device is substantially equivalent to a legally marketed predicate device, rather than proving its safety and effectiveness de novo. Therefore, the study focuses on establishing performance characteristics compared to a reference method and demonstrating substantial equivalence.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document implicitly defines acceptance criteria through the reported analytical and clinical performance. While explicit numerical acceptance criteria (e.g., "sensitivity must be >X%") are not laid out in a dedicated table, the "Results of QC testing...met the pre-defined acceptance criteria (≥95% agreement)" suggests this was a criterion for analytical performance. For clinical performance, the reported agreement percentages themselves serve as the outcome against which an implicit set of criteria would have been measured.

Here’s a summary of the performance characteristics:

Acceptance Criteria (Implied) and Reported Device Performance for RAPIDEC® CARBA NP

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

• Test Set Sample Size:

  • Analytical Reactivity (Challenge testing): 43 carbapenemase producers.
  • Cross-reactivity: 93 non-carbapenemase producing strains (67 Enterobacteriaceae/P. aeruginosa, 26 other organisms).
  • Agar Culture Media Compatibility Studies: 106 strains (92 carbapenemase producers, 14 non-carbapenemase producers).
  • Clinical Studies: 457 strains (394 Enterobacteriaceae, 63 P. aeruginosa).
  • Reproducibility: A panel of 10 organisms (9 Enterobacteriaceae + 1 P. aeruginosa), tested in triplicates for 5 days at 3 sites (total 900 measurements per subculture procedure).

• Data Provenance: The document does not explicitly state the country of origin for the clinical or analytical data. It mentions "5 sites" for the clinical study and "each study site" for QC, implying a multi-site study, but locations are not specified. The study appears to be prospective as it involves the evaluation of the device on collected strains and controlled experiments (e.g., QC, challenge testing, clinical evaluation).

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

The document does not mention the number or qualifications of experts used to establish the ground truth. The ground truth for the clinical study was established by a composite reference method consisting of three laboratory tests: carbapenem MIC, CLSI® Carba NP, and PCR for carbapenemase genetic markers. The "final composite reference result based on agreement of at least two of the three tests" does not explicitly involve human expert review for establishing "ground truth," but rather relies on the combined results of established laboratory methods.

For the reproducibility study, results were interpreted by "2 operators" but their qualifications are not specified beyond being "operators."

4. Adjudication method for the test set

For the clinical study, the adjudication method for the composite reference ground truth was: agreement of at least two of the three tests (carbapenem MIC, CLSI® Carba NP, and PCR).

For the reproducibility study, the results were interpreted by "2 operators" and their interpretations were then compared ("blinded to each other"), suggesting a form of comparative adjudication for reproducibility but not for establishing primary ground truth.

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 for this device. This is an in vitro diagnostic device (a laboratory test kit), not an AI-assisted imaging device or a device that directly supports human reader interpretation in a complex diagnostic task like radiology. Therefore, questions regarding "human readers improve with AI vs without AI assistance" are not applicable to this device type. The device provides a direct result (positive/negative for carbapenemase) which then informs downstream clinical decisions.

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

This refers to an in vitro diagnostic device, not typically an "algorithm only" device in the context of imaging or clinical decision support AI. The device itself is a test kit where reactions occur and a visual color change is observed. The "performance" described is of the device as a whole. While human operators perform the test and interpret the "visual based on color change," the core "algorithm" is the biochemical reaction itself. The analytical and clinical studies assess the performance of this system (device + human interpretation). No separate "algorithm only" study is described because the "algorithm" here is the chemical reaction and visual readout, which inherently involves human observation.

7. The type of ground truth used

The ground truth used was a composite reference method comprised of:

• Carbapenem MIC (Imipenem, Meropenem, Ertapenem and/or Doripenem).
• CLSI® Carba NP (a standardized carbapenemase test).
• Carbapenemase genetic markers by Polymerase Chain Reaction (PCR).

This is a form of expert consensus based on the agreement of established laboratory tests, rather than, for example, pathology or outcomes data.

8. The sample size for the training set

The document does not explicitly describe a separate "training set". In the context of a 510(k) submission for an in vitro diagnostic device, often the manufacturer develops and refines the device, and then tests its performance on a "test set" (clinical and analytical studies) to demonstrate substantial equivalence. If any internal development/optimization data was used, it's not detailed or referred to as a "training set" in this regulatory submission. The reported studies are validation studies on a specific set of samples.

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

Since a distinct "training set" is not described, the method for establishing its ground truth is also not detailed. Any internal development ground truth would likely have been established using similar reference methods to the ones described for the validation set.

Ask a specific question about this device