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HardyCHROM™ CRE is a selective and differential chromogenic agar medium intended for the qualitative and presumptive detection from stool specimens of Escherichia coli that are non- susceptible to carbapenems as pink colonies and KES (Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter cloacae complex, and Serratia marcescens) that are non-susceptible to carbapenems as blue colonies.

HardyCHROM CRE is intended as an aid in the detection, identification of colonization and control of these bacteria in a healthcare setting. HardyCHROM™ CRE is not intended to diagnose infection or guide therapy. Results can be interpreted after incubation for 18-24 hours. Subculture to non-selective medium is required for confirming identification, antimicrobial susceptibility testing and epidemiological typing.

A lack of growth or the absence of pink or blue colonies on HardyCHROM™ CRE does not preclude the presence of Escherichia coli and KES that are non-susceptible to carbapenems.

HardyCHROM™ CRE is a selective and differential chromogenic medium designed to screen for carbapenem non-susceptible Escherichia coli and KES (Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter cloacae complex, and Serratia marcescens.) from fecal specimens. The selective components in HardyCHROM™ CRE inhibit the growth of yeast, Gram-positive bacteria, and Gram-negative bacteria sensitive to ertapenem. HardyCHROM™ CRE differentiates Escherichia coli (pink colonies) from KES (blue colonies).

The CLSI guidelines recommend screening for CREs with an MIC greater than or equal to an established limit to one of several selected agents. Phenotypic confirmation of non-susceptibility to carbapenems is done by demonstrating non-susceptibility to one of the selected agents using MIC or disk diffusion. Further biochemical analysis is required to confirm the production of carbapenemase or any other mechanism of resistance.

Here's a summary of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in discrete numerical targets. Instead, it presents performance data (Sensitivity, Specificity, PPV, NPV) and concludes with a statement that the data "support the safety of the device verification and validation" and "demonstrate that the HardyCHROM™ CRE device is substantially equivalent to the predicate device." Therefore, the reported performance metrics serve as the de facto demonstration of meeting the required standards for substantial equivalence.

Performance of HardyCHROM™ CRE for detection of Carbapenem non-susceptible E. coli (Pink Colonies)

Performance of HardyCHROM™ CRE for detection of Carbapenem non-susceptible KES (Blue Colonies)

Agreement of Carbapenem NS Target Species with color on HardyCHROM CRE (at 24 hours)

Performance on Contrived Specimens (E. coli Pink Morphology)

Performance on Contrived Specimens (KES Blue Morphology)

Analytical Sensitivity (LoD) and Reactivity:

• LoD: 1.5x10^2 CFU/mL in stool specimen (for all 10 target strains evaluated)
• Analytical Reactivity: Recovered 72 of 77 (93.5%) carbapenem non-susceptible strains at 1.5x10^2 CFU/mL.

Analytical Specificity:

• Majority of organisms tested did not produce target morphology or were inhibited.
• Certain non-target organisms developed blue pigmentation after 24-48 hours or had distinct morphology, allowing differentiation. None developed pink color.

Microbial Interference:

• HardyCHROM™ CRE was able to recover all target organisms from mixed suspensions in the presence of high concentrations of non-target organisms.

Incubation Study:

• All organisms recovered with expected color by 18 hours.

Stool Specimen Stability:

• 100% recovery from raw stool and stool in Cary Blair at room temperature for up to 24 hours.
• 100% recovery from raw stool and stool in Cary Blair at 2-8℃ for up to 7 days.

Reproducibility:

• 95% agreement with known test results. All CRE-positive isolates (100%) detected.

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

• Test Set Sample Size (Clinical Study): A total of 1,628 samples were tested. 144 specimens were excluded, resulting in 1,484 valid samples for analysis.
• Contrived Test Set Sample Size: A total of 203 contrived specimens were evaluated.
• Data Provenance: The clinical study used freshly collected stool specimens from "three geographically diverse hospitals." This indicates a prospective study collected from clinical settings in the United States (implied by FDA submission).

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

The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologist with 10 years of experience). However, it mentions:

• "Identity and susceptibility of organisms that grew on both HardyCHROM™ CRE and MacConkey Agar were confirmed using FDA-cleared ID and AST systems."
• For the reproducibility study: "The testing was done with at least one operator and two readers, blinded to each other's results, per site."
  This implies that trained laboratory personnel and validated laboratory methods were used for ground truth determination, which is standard for in vitro diagnostic devices.

4. Adjudication method for the test set

• Clinical Study: The "routine culture" method served as the reference method, followed by confirmation using "FDA-cleared ID and AST systems." This acts as the primary ground truth. There is no explicit mention of an adjudication process (e.g., 2+1, 3+1) involving multiple human readers reviewing results for initial discrepancies to establish a ground truth. Rather, the "reference method" and "FDA-cleared systems" for confirmation established the ground truth.
• Reproducibility Study: "at least one operator and two readers, blinded to each other's results, per site" suggests a form of consensus or independent reading for the reproducibility of the device's visual interpretation, but not for establishing the ultimate ground truth of the organisms' identity and susceptibility, which was pre-determined.

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 document describes the performance of a culture medium (HardyCHROM™ CRE), which is a device for bacterial detection and differentiation based on colony color. It is not an AI-assisted diagnostic tool. Therefore, an MRMC study comparing human readers with and without AI assistance was not conducted and is not relevant to this type of device.

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

• Yes, in essence. The HardyCHROM™ CRE functions as a standalone diagnostic medium. Its performance metrics (Sensitivity, Specificity, PPV, NPV) were calculated based on the observable color reaction on the agar medium compared to the reference method (culture with confirmed ID and AST). While human observation is required to read the colony color, the "performance" as presented (e.g., "Pink (Positive)" vs. "Negative 1") reflects the intrinsic capability of the medium itself to produce the correct visual signal for Carbapenem non-susceptible E.coli or KES. The study directly evaluates the medium's performance in identifying target organisms based on their chromogenic reaction.

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

The ground truth for the clinical study was established by a reference culture method (selective enrichment in Tryptic Soy Broth with meropenem and vancomycin, followed by subculture to MacConkey Agar), with subsequent identification (ID) and antimicrobial susceptibility testing (AST) using FDA-cleared systems. This is considered a laboratory-based reference standard, which is highly objective for microbiological assays.

8. The sample size for the training set

The document does not explicitly mention a "training set" in the context of machine learning or AI, as the device is a chromogenic culture medium. The studies described are for performance evaluation, not for training an algorithm.

However, if "training set" is broadly interpreted as any data used to refine or develop the product before final validation, then:

• The "Analytical Reactivity" study used 77 well-characterized carbapenem non-susceptible strains.
• The "Analytical Specificity" study used 110 strains (carbapenem-susceptible target species and non-target species).
• The "Microbial Interference" study used the organisms from the Analytical Specificity study plus target organisms.
• The "Reproducibility" study used a panel of 10 blinded isolates (5 positive, 5 negative) at three sites.

These analytical studies and reproducibility tests likely serve as internal development and verification steps before the large-scale clinical validation.

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

As noted above, there isn't a "training set" in the common AI sense. For the analytical studies, the ground truth was established by:

• Known strains and concentrations: For LoD and Analytical Reactivity, "well-characterized carbapenem non-susceptible strains" at known concentrations were used.
• Known strains (susceptible/non-susceptible) and non-target species: For Analytical Specificity and Microbial Interference, the identity and susceptibility of the tested strains were pre-determined and "well-characterized."
• Known test results: For the Reproducibility study, the panel of 10 isolates had "known test results," meaning their identity and carbapenem resistance status were previously confirmed by standard laboratory methods.

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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.

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MRSASelect™II is a selective and differential chromogenic medium for:

A) The qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA infections in healthcare settings. The test can be performed on anterior nares specimens from patients to screen for MRSA colonization. MRSASelect™II is not intended to diagnose MRSA infection nor to guide or monitor treatment of infection. A negative result does not preclude MRSA nasal colonization. Concomitant cultures are necessary to recover organisms for identification, antimicrobial susceptibility testing, or epidemiological typing. Results can be interpreted after 18 to 28 hours incubation.

B) The qualitative detection of methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue wound specimens. The MRSASelect™II is indicated for use in conjunction with other laboratory tests and clinical data available to aid in the identification and diagnosis of MRSA from patients with skin and soft-tissue infections. Concomitant cultures and antimicrobial susceptibility testing are necessary for all skin and soft-tissue wound specimens. MRSASelect™I is not intended to guide, or monitor treatment for MRSA infection, or provide results of susceptibility to methicillin. Results can be interpreted after 18 to 28 hours incubation.

MRSASelect™I is a selective medium for the detection and direct identification of MRSA. The selectivity of this medium is based on the presence of an antibiotic/antifungal mixture and an optimized salt concentration that inhibits the growth of yeasts and the majority of Gram negative and Gram positive bacteria, with the exception of methicillin-resistant staphylococci. Identification is based on the cleavage of a chromogenic substrate by a specific enzymatic activity of Staphylococcus aureus, leading to a strong pink coloration of the Staphylococcus aureus colonies. Plates may be read within 18-28 hours incubation:

• Methicillin-resistant Staphylococcus aureus produces pink colonies on MRSASelect™II;
• . Coagulase negative methicillin-resistant staphylococci may not grow or may grow as colorless or white colonies;
• Methicillin-susceptible staphylococci (MSS) are inhibited.

Here's an analysis of the provided text, focusing on the acceptance criteria and the study proving the device meets them, presented in the requested format.

This document describes the premarket notification (510(k)) for the MRSASelect™II device, a culture medium for detecting methicillin-resistant Staphylococcus aureus (MRSA). The information provided is for a diagnostic device (culture medium) and not an AI device. Therefore, some of the requested categories (e.g., number of experts for ground truth, MRMC study, training set information) are not directly applicable or are not detailed in the same way they would be for an AI/ML medical device submission. However, an effort will be made to extract comparable information where possible.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for a diagnostic culture medium are typically established as performance targets for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) against a reference method. These are not explicitly stated as "acceptance criteria" with numerical thresholds to be met, but the clinical performance data provided demonstrates the device's accuracy.

Table 1: Acceptance Criteria (Implied Performance Targets) and Reported Device Performance

Note on "Acceptance Criteria": For traditional in vitro diagnostic devices like culture media, the "acceptance criteria" are typically defined internally by the manufacturer during product development and validation, often based on predicate device performance or clinical utility. The FDA then evaluates whether the provided performance data supports the claim of substantial equivalence. The tables above reflect the achieved performance which the FDA deemed acceptable for substantial equivalence.

Study Details

Given that this is a 510(k) for a culture medium (not an AI device), some of the requested information directly pertaining to AI/ML device studies will not be present in the document.

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

   • Total Clinical Samples: 3,252 prospective valid wound and anterior nares specimens.
   • Wound Samples (Test Set): 842 specimens.
   • Anterior Nares Samples (Test Set): 2,410 specimens.
   • Data Provenance:
     • Country of Origin: United States.
     • Retrospective or Prospective: Prospective. Specimens were collected from 2013 to 2016.

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

   • This information is not directly stated in the document as it would be for an AI imaging study involving human readers. For diagnostic culture media, ground truth is established by specific, well-defined laboratory reference methods. The document describes a multi-step microbiological process for establishing ground truth, involving culture enrichment, subculturing, Gram stain, agglutination tests, tube coagulase, and for MRSA confirmation PBP2a testing and mecA-mediated oxacillin resistance testing. The execution of these laboratory methods implies the involvement of qualified laboratory personnel (e.g., clinical microbiologists, medical technologists), but specific numbers or qualifications are not specified in the document in the format relevant to expert readers of AI output.

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

   • Not applicable in the context of human reader adjudication for an AI device. For discordant results between the device and the reference method, "Discordant analysis" was performed (e.g., for wound samples, PBP2a test was used; for anterior nares, specific non-S. aureus and MSSA determinations were made). This is a laboratory-based adjudication of the samples themselves, not an adjudication of human interpretations.

4. If a multi-reader, multi-case (MRMC) comparative effectiveness study was done:

   • No. An MRMC study is relevant for comparing human reader performance with and without an AI device. This submission is for a culture medium, not an AI device.

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

   • Yes, effectively. The performance of the MRSASelect™II device itself, without human interpretation beyond reading the chromogenic results, was assessed against the established reference methods. This "standalone" performance is what the sensitivity, specificity, PPV, and NPV data represent.

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

   • Laboratory Reference Method / Microbiological Culture Confirmation: The ground truth was established by using standard microbiological culture enrichment broth methods (Tryptic Soy Broth with 6.5% NaCl) followed by definitive identification tests for Staphylococcus aureus (Gram stain, slide agglutination, tube coagulase) and confirmation of methicillin resistance (PBP2a testing for anterior nares; mecA-mediated oxacillin resistance testing using cefoxitin disk for wound samples, with PBP2a for discordant wound samples). This is a gold standard for bacterial identification and resistance.

7. The sample size for the training set:

   • This document describes a clinical performance study (test set) for device validation, not an AI/ML model. Therefore, there's no explicitly defined "training set" in the context of machine learning. The device design and refinement would have been based on internal R&D, potentially involving earlier, smaller studies or characterization data, but these are not disclosed as a "training set" in this document.

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

   • Not applicable as there is no specific "training set" described for an AI/ML model. The design and analytical validation of the culture medium (e.g., Analytical Sensitivity (Inclusivity) testing with 54 characterized MRSA strains, Analytical Specificity (Cross Reactivity) with 109 strains, Precision/Reproducibility using ATCC® strains) demonstrate how the device's fundamental properties were confirmed against known bacterial strains/isolates, which serve as an equivalent to a "ground truth" for analytical performance.

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Remel Spectra™ ESBL is a selective and differential growth medium for use in primary isolation and presumptive identification of Extended Spectrum β Lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis to aid in prevention and control of these bacteria in a healthcare setting. Testing may be performed from either perirectal swabs or fresh stool specimens. Remel Spectra™ ESBL is not intended to diagnose ESBL infection, or to guide or monitor treatment.

Do not report Spectra™ ESBL positive screening results. Subculture of presumptive positive colonies to non-selective medium (e.g. Tryptic Soy Agar with 5% sheep blood) is required for organism identification, confirmatory testing for ESBL, susceptibility testing and epidemiological typing.

A lack of growth or the absence of pink, blue-turquoise-green or tan colonies on Spectra™ ESBL does not preclude the presence of ESBL producing organisms.

Spectra™ ESBL contains a combination of antibacterial agents which aid in inhibiting non-ESBL Enterobacteriaceae and suppress the growth of some AmpC organisms and other non-ESBL flora. Peptones supply amino acids and essential nutrients which promote the growth of enteric gram-negative bacilli. Sodium chloride is a source of essential electrolytes and maintains osmotic equilibrium. Phosphate buffers are added to maintain the pH.

A mixture of chromogens forms a substrate for two enzymes: βgalactosidase and glucuronidase that are differentially expressed in different species of bacteria resulting in blue/turquoise-green or pink colonies. Other ESBL-producing organisms that do not utilize the chromogenic substrates may produce tan colonies through deamination of tryptophan. Non-target organisms generally appear cream colored or are naturally pigmented green or brown.

The provided text describes the performance evaluation of the Remel Spectra™ ESBL device. The following information details the acceptance criteria and study findings:

1. Table of Acceptance Criteria and Reported Device Performance:

Note: The document implicitly defines "high agreement" as the acceptance criterion for sensitivity, specificity, PPA, and NPA, demonstrated by the reported percentages and confidence intervals. Reproducibility, reactivity, and cross-reactivity have explicit criteria.

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

• Sample Size: A total of 1176 prospective rectal swab (439) and fecal (737) surveillance specimens.
• Data Provenance: Clinical data collected prospectively from three different clinical hospitals in the United States.

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 qualifications for establishing the ground truth. It mentions that the ground truth was "obtained from growth on MacConkey agar with a 10μg cefpodoxime disk […], followed by biochemical identification and disk diffusion phenotypic confirmatory antimicrobial susceptibility testing for ESBLs as outlined in the Clinical and Laboratory Standards Institute document M100-S23." This implies adherence to a standardized protocol rather than individual expert consensus for each case.

4. Adjudication Method for the Test Set:

The document does not describe an adjudication method involving multiple human readers for the test set. The reference method (ground truth) appears to be based on a standardized laboratory protocol.

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 explicitly mentioned or performed. The study evaluates the performance of the Remel Spectra™ ESBL device against a laboratory-based reference method, not against human readers with or without AI assistance.

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

This study directly assesses the standalone performance of the Remel Spectra™ ESBL agar medium as a diagnostic tool. The interpretation of results ("Manual, visual") is performed by laboratory personnel, but the "device" itself (the culture medium) provides the observable outcome (colony color and growth) which is then interpreted. So, in essence, it's a standalone diagnostic performance assessment of the medium.

7. The Type of Ground Truth Used:

The ground truth was established by a laboratory-based reference method, which included:

• Growth on MacConkey agar with a 10µg cefpodoxime disk.
• Selection of colonies from within the zone of inhibition.
• Biochemical identification.
• Disk diffusion phenotypic confirmatory antimicrobial susceptibility testing for ESBLs as outlined in the Clinical and Laboratory Standards Institute document M100-S23.

8. The Sample Size for the Training Set:

The document does not mention a specific "training set" in the context of machine learning or AI models. This device is a culture medium, and its development (which would be analogous to a training phase) involves formulation and empirical testing, rather than a data-driven training set in the AI sense. The "Reactivity" and "Reproducibility" studies involve a limited number of isolates (48 confirmed ESBL-producing strains for reactivity; 9 blinded ESBL and Non-ESBL isolates for reproducibility) that could be considered part of the development/validation process.

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

As there is no "training set" in the AI sense, this question is not directly applicable. For the isolates used in "Reactivity" and "Reproducibility" studies, their ESBL status was "confirmed" (for reactivity) and "expected" (for reproducibility), implying that a definitive laboratory method was used to classify them prior to testing with the Spectra™ ESBL. This would likely follow similar gold standard methods as the clinical study's ground truth.

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HardyCHROM ESBL is a selective and differential chromogenic medium which is intended for the qualitative and presumptive detection from stool specimens of: 1) Enterobacteriaceae that are potentially non-susceptible to ceftazidime and cefpodoxime; and 2) Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca.

The test is performed on stool specimens from patients at risk of harboring Enterobacteriaceae that are non-susceptible to 3rd generation cephalosporins or ESBL-producing E. coli, K. pneumoniae and K. oxytoca, and is intended as an aid in the detection, identification of colonization and control of these bacteria in a healthcare setting. HardyCHROM ESBL is not intended to diagnose infection or to guide or monitor treatment for infections. Results can be interpreted after incubation for 18-24 hours. Subculture to non-selective medium is required for confirming identification, susceptibility testing and epidemiological typing.

A lack of growth or the absence of pink, blue or yellow/gold colonies on HardyCHROM ESBL does not preclude the presence of Enterobacteriaceae that are non-susceptible to 3rd generation cephalosporins or ESBL producing organisms.

HardyCHROM™ ESBL is a selective and differential chromogenic medium containing a broad-spectrum beta-lactam intended for detection and isolation of Enterobacteriaceae non-susceptible to 3rd generation cephalosporins. HardyCHROM™ ESBL can also be used as a screening medium for K. pneumoniae, K. oxytoca, and E. coli that produce an extended-spectrum beta-lactamase (ESBL).

The selective components in HardyCHROM™ ESBL are designed to inhibit the growth of yeast, Grampositive bacteria, and Gram-negative bacteria sensitive to broad spectrum beta-lactams (3rd generation cephalosporins). Chromogenic substrates in the medium allow for differentiation of Enterobacteriaceae non-susceptible to 3rd generation cephalosporins or that are ESBL-producing, as bacteria that can grow and utilize the chromogens produce a colored colony. ESBL-producing Klebsiella spp. produce large, dark blue colonies. ESBL-producing Escherichia coli produce colonies that are rose to magenta in color, with darker pink centers. Other Enterobacteriaceae not susceptible to 3rd generation cephalosporins will produce colonies of varying size that are pink, blue, with pink halos, and yellow/gold.

The provided document is a 510(k) Premarket Notification for the HardyCHROM ESBL device. It details the device's indications for use, its comparison to a predicate device, and performance data from various studies.

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

Device: HardyCHROM™ ESBL
Intended Use: Qualitative and presumptive detection from stool specimens of:

1. Enterobacteriaceae potentially non-susceptible to ceftazidime and cefpodoxime.
2. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a separate, pre-defined set of thresholds. Instead, it presents performance metrics from various studies (clinical, contrived, analytical reactivity, analytical specificity, microbial interference, specimen stability, and reproducibility). The results are presented as the device's performance, implying these values met the internal requirements for substantial equivalence.

Here's a table summarizing key performance metrics observed in the studies:

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

Clinical Study (Prospective):

• Sample Size: 1,559 valid clinical stool specimens (out of 1,687 initially tested).
• Data Provenance: Fresh stool specimens collected prospectively at three geographically diverse hospitals. The specific countries are not mentioned, but the context implies US given the FDA submission.

Contrived Specimen Study:

• Sample Size: 50 contrived specimens.
• Data Provenance: Patient specimens inoculated with known resistant organisms (ESBL producing or non-susceptible to third-generation cephalosporins) at the Limit of Detection (LoD).

Reproducibility Study:

• Sample Size:
  • For 3rd gen. cephalosporin non-susceptible Enterobacteriaceae: 272 positive samples (N) and 280 negative samples (N) overall across 5 days of testing and 3 sites.
  • For ESBL-producing organisms: 216 positive samples (N) and 336 negative samples (N) overall across 5 days of testing and 3 sites.
• Data Provenance: Blinded panels of bacterial suspensions in transport medium. Tested at three different sites.

Analytical Reactivity & Specificity Studies:

• Analytical Reactivity (ESBL): 54 characterized ESBL-producing strains of E. coli, K. pneumoniae, and K. oxytoca.
• Analytical Reactivity (Non-ESBL non-susceptible): 21 strains representative of various Enterobacteriaceae that were non-susceptible to at least one 3rd generation cephalosporin.
• Analytical Specificity: 99 strains (52 Enterobacteriaceae and 47 non-Enterobacteriaceae, including ESBL non-producing and 3rd gen. cephalosporin susceptible species).
• Data Provenance: Internal testing using characterized bacterial strains.

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

For the Clinical Study:

• Ground Truth Establishment: "Routine culture, defined as the selective enrichment of microorganisms in Tryptic Soy Broth (TSB) containing either 1ug/mL ceftazidime or 1ug/mL cefotaxime, followed by subculture to MacConkey Agar. Organisms that grew on MacConkey Agar were identified using an FDA-cleared ID system. Confirmation of ESBL production and 3rd generation cephalosporin non-susceptibility was performed using traditional Kirby-Bauer AST following the device manufacturer's instructions. ID of organisms that grew on HardyCHROM™ ESBL was confirmed using an FDA-cleared ID system."
• Number/Qualifications of Experts: The document does not specify the number or qualifications of experts involved in performing the "routine culture" or interpreting the Kirby-Bauer AST and FDA-cleared ID system results. This would typically be performed by trained laboratory personnel (e.g., medical technologists, clinical microbiologists).

For the Reproducibility Study:

• Ground Truth Establishment: Not applicable as it's a test of reproducibility using known positive and negative controls.
• Number/Qualifications of Experts: Readings were performed by 2 independent operators at each of the three sites (total 6 operators). Their specific qualifications beyond "operator" are not detailed.

4. Adjudication Method for the Test Set

For the Clinical Study:

• The ground truth seems to be established by a defined laboratory methodology (selective enrichment, subculture, FDA-cleared ID, Kirby-Bauer AST). There is no explicit mention of expert adjudication of the ground truth in the clinical study beyond the standard laboratory procedures. It's a method-based ground truth comparison.

For the Reproducibility Study:

• Readings were done by "2 independent operators." There is no explicit mention of an adjudication process if their readings differed. However, for a reproducibility study with known controls, discrepancies might lead to re-testing or investigation rather than adjudication of the "truth."

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

• No, a MRMC comparative effectiveness study was not done in the context of comparing human readers with and without AI assistance, as this device is a culture medium, not an AI or imaging diagnostic tool. The performance is compared against a "traditional culture" method.
• The reproducibility study involved multiple readers (operators) across multiple sites, but it was for assessing inter-operator and inter-site variability of the device itself, not a comparative effectiveness study involving AI assistance for human readers.

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

• Yes, in essence, standalone performance was evaluated. The device (HardyCHROM™ ESBL) is a culture medium, and its "standalone" performance is measured by its ability to recover and differentiate target organisms based on colony growth and color from the specimen. Human observation is then used to interpret these results.
• The sensitivity and specificity data presented for the clinical and analytical studies reflect the performance of the medium itself to appropriately grow and present the target organisms, which is then visually interpreted. There is no "algorithm" separate from the biological reaction on the medium.

7. The Type of Ground Truth Used

• Clinical Study: The ground truth for the clinical study was established by conventional microbiological methods, including selective enrichment, subculture, identification using FDA-cleared ID systems, and confirmation of non-susceptibility/ESBL production using traditional Kirby-Bauer Antimicrobial Susceptibility Testing (AST). This is a method-based ground truth derived from established laboratory practices.
• Contrived Specimen Study: The ground truth was based on known resistant organisms (ESBL-producing or non-susceptible) used to inoculate patient specimens. This is a "spiked" study design where the ground truth is precisely controlled.
• Analytical Reactivity/Specificity: The ground truth for these studies was based on characterized bacterial strains with known ESBL production, non-susceptibility, or other relevant characteristics (e.g., non-ESBL, susceptible, non-Enterobacteriaceae).

8. The Sample Size for the Training Set

• The document does not mention a "training set" in the context of machine learning or AI models. This device is a culture medium relying on biological and chemical reactions, not an AI algorithm that requires training data.
• The studies described are primarily for performance validation/verification of the manufactured product (culture medium).

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

• As there is no AI algorithm training set, this question is not applicable to this device.

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chromID™ MRSA agar is a selective and differential chromogenic medium for :

A. The qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA), to aid in the prevention and control of MRSA in healthcare settings. The test is performed on anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. chromID™ MRSA when used to detect nasal colonization is not intended to diagnose, guide, or monitor therapy for MRSA infections, or provide results of susceptibility to methicillin.

B. The qualitative detection of MRSA from skin structure infections. chromID™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to aid in the identification and diagnosis of MRSA infections. Concomitant cultures for skin structure infections are necessary to recover organisms for further microbiological susceptibility testing or epidemiological typing. A negative result does not preclude MRSA infection. chromID™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin.

C. The qualitative detection of MRSA from positive blood cultures demonstrating Gram-positive cocci on Gram stain. chromID™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to aid in the identification and diagnosis of MRSA infections. Sub-culturing for positive blood cultures are necessary to recover organisms for further microbiological susceptibility testing or epidemiological typing. A negative result does not preclude, MRSA infection. chromID™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin.

chromID™ MRSA agar consists of a rich nutritive base combining different peptones. It also contains a chromogenic substrate of a-glucosidase and a combination of several antibiotics, including cefoxitin, which favor the growth of MRSA including heteroresistant strains and the direct detection of MRSA strains by revealing a-glucosidase activity (patent registered), green colonies. The selective mixture of antibiotics inhibits most bacteria not belonging to the genus Staphylococcus, as well as yeasts. The MRSA strains are identified by the presence of green colonies that result from the chromogen incorporated in the medium. The chromogen targets the a-glucosidase activity of S. aureus. The a-glucosidase produced by S. aureus cleaves the chromogenic substrate, which gives a green color to the S. aureus colonies growing on the medium.

The provide text describes the acceptance criteria and study results for chromID™ MRSA agar, a chromogenic medium for the qualitative detection of methicillin-resistant Staphylococcus aureus (MRSA).

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the reported performance data for sensitivity and specificity. The device is expected to perform accurately in detecting MRSA from various specimen types.

Note: The provided text primarily focuses on the clinical performance for blood cultures. While analytical studies are mentioned, specific numerical acceptance criteria for those were not explicitly stated beyond achieving "expected results" or specific growth/detection rates.

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

• Clinical Study Sample Size (Blood Culture): 863 positive blood culture specimens (demonstrating Gram-positive cocci) were initially analyzed. 187 cultures were removed due to low prevalence of the target or protocol deviations, resulting in a final evaluated sample size.
• Data Provenance: The study was conducted at four clinical sites. The geographical location of these sites (e.g., country of origin) is not specified. The clinical study is described as having "analyzed" specimens, suggesting a retrospective or prospective observational design where samples were collected and then tested. The phrase "clinical trial" is used, implying a prospective collection for evaluation. The "Analytical Studies" also mention the use of well-characterized strains, which would be laboratory-based rather than from clinical patients.

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

• The text does not explicitly state the number of experts used to establish the ground truth.
• It also does not specify the qualifications of these experts.

4. Adjudication Method for the Test Set

• The text describes a reference method for establishing ground truth, which involves:
  • Growth on Tryptic Soy agar with 5% sheep blood (BAP).
  • Testing of colonies suggestive of Staphylococcus species by Gram stain, catalase, and latex agglutination.
  • Staphylococcus aureus isolates further tested for resistance to Oxacillin by the Cefoxitin Screen test.
  • All Cefoxitin-resistant colonies tested for the presence of the mecA gene by PCR and by VITEK® MS for species confirmation.
• For discordant specimens in the blood culture clinical study, "Two false positives were confirmed as MRSA positive" and "Five false positives that grew green colonies were not identified as MRSA." This implies a form of adjudication or re-evaluation for discordant results, likely by further expert review or follow-up testing, though a formal "2+1" or "3+1" structure isn't explicitly detailed.

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, an MRMC comparative effectiveness study was not done.
• This device (chromID™ MRSA agar) is a culture medium, not an AI-assisted diagnostic tool. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply.

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

• Yes, a standalone performance was done, but it's important to clarify the context. The "device" here is the chromID™ MRSA agar medium itself. The performance evaluation measures the ability of this agar to correctly identify MRSA based on color change, which is then interpreted by a laboratory user (a manual interpretation of the agar plate).
• The clinical performance data for sensitivity and specificity (100.0% and 98.9% respectively for blood cultures) represent the standalone performance of the chromID™ MRSA agar in classifying samples as MRSA positive or negative, compared to the defined reference method.

7. The Type of Ground Truth Used

• The ground truth for the clinical studies was established using a multi-faceted reference method, which includes:
  • Culture on Tryptic Soy agar with 5% sheep blood (BAP).
  • Gram stain, catalase, and latex agglutination for presumptive identification.
  • Oxacillin resistance testing by Cefoxitin Screen test.
  • Molecular testing (PCR for mecA gene) for definitive confirmation of methicillin resistance.
  • Species confirmation by VITEK® MS.
  • This combination represents a robust "expert consensus" or "gold standard" laboratory method, incorporating phenotypic and genotypic characteristics.

8. The Sample Size for the Training Set

• The document does not explicitly mention a "training set" in the context of machine learning or AI development. Since this is a chromogenic culture medium, its development likely involved iterative formulation and testing, rather than a distinct machine learning training set as typically understood.
• The "Analytical Reactivity (Challenge)" and "Cross Reactivity (Analytical Specificity)" studies, using specific well-characterized strains (80 mecA MRSA strains, 5 mecC MRSA strains, and 71 non-MRSA strains), could be seen as part of the developmental testing that helps "train" the understanding of the medium's performance, but not in the AI sense.

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

• As a "training set" for an AI algorithm is not applicable, the question of its ground truth establishment is also not directly applicable in the AI context.
• However, for the analytical studies involving known strains, the ground truth was established by prior characterization of these strains (e.g., they are known mecA MRSA strains, mecC MRSA strains, or specific non-MRSA species), likely through established microbiological and molecular methods.

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chromID™ MRSA agar is a selective and differential chromogenic medium for :

A. The qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA), to aid in the prevention and control of MRSA in healthcare settings.

The test is performed on anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. chromID™MRSA when used to detect nasal colonization is not intended to diagnose, guide, or monitor therapy for MRSA infections, or provide results of susceptibility to methicillin.

B. The qualitative detection of MRSA from skin structure infections.

chromID™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to aid in the identification and diagnosis of MRSA infections. Concomitant cultures for skin structure infections are necessary to recover organisms for further microbiological susceptibility testing or epidemiological typing.

A negative result does not preclude MRSA infection. chromID™MRSA is not intended to monitor treatment for MRSA · infections, or provide results of susceptibility to methicillin.

chromID™ MRSA agar consists of a rich nutritive base combining different peptones. It also contains a chromogenic substrate of α-glucosidase and a combination of several antibiotics (cefoxitin, etc.) that favor the growth and direct detection of MRSA, including hetero-resistant strains, by revealing orglucosidase activity (patent registered) through the appearance of green colonies. The α-glucosidase produced by S. aureus cleaves the chromogenic substrate, which gives a green color to the S. aureus colonies growing on the medium. The MRSA strains are identified by the presence of green colonies that result from the chromogen incorporated in the medium. The selective mixture of antibiotics inhibits most bacteria not belonging to the genus Staphylococcus, as well as yeasts.

Here's an analysis of the acceptance criteria and study findings for the chromID™ MRSA device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for the clinical study's sensitivity and specificity. However, the reported performance metrics can be considered the demonstrated performance of the device.

Note: The document does not explicitly state numerical "acceptance criteria" for sensitivity and specificity. The reported values are the observed performance. The FDA's substantial equivalence determination implies these values were deemed acceptable.

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

• Test Set Sample Size: 680 specimens (valid for comparison after exclusions)
• Data Provenance: Clinical study data from four geographically diverse clinical sites. This suggests prospective collection within the United States, given it's an FDA submission. The specific country is not explicitly stated beyond "geographically diverse clinical sites" in relation to the US FDA. The nature of the study (collection of specimens for device evaluation) indicates it's prospective.

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

The document does not specify the "number of experts" or their "qualifications" involved in establishing the ground truth. Ground truth was established using standard microbiological laboratory methods (Reference Culture Method) which would be performed by trained laboratory personnel.

4. Adjudication Method for the Test Set

The document describes a clear reference method for ground truth determination, which inherently serves as the "adjudication" (or gold standard). It does not mention a separate, independent adjudication panel or specific method like "2+1" or "3+1" for resolving discrepancies between the new device and the reference method. Discordant results were analyzed and described.

• Reference Culture Method:
  • Specimens enriched in Tryptic Soy broth with 6.5% NaCl (TSB) for 24 hours (negative broths incubated an additional 24 hours).
  • Positive broth cultures subcultured to Tryptic Soy agar with 5% sheep blood (BAP).
  • Colonies suggestive of Staphylococcus species tested by Gram stain, catalase, and latex agglutination.
  • Staphylococcus aureus isolates tested for resistance to oxacillin by the Cefoxitin Screen test (30µg).
  • All oxacillin-resistant colonies by Cefoxitin Screen test were tested for the presence of the mecA gene by PCR and by VITEK® MS for species confirmation.
• Definition of Positive Ground Truth: Recovery of cefoxitin-resistant Staphylococcus aureus from the specimen.
• Definition of Negative Ground Truth: All other results (growth of cefoxitin-susceptible Staphylococcus aureus, growth of other species, or no growth).

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 done. This device is a culture medium, and its performance is assessed by direct comparison to a laboratory reference method, not by comparing human reader interpretations with and without AI assistance.

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

This is a standalone microbiological culture medium. Its performance (presence/absence of green colonies indicating MRSA) is interpreted directly by laboratory personnel based on the visual result of the culture. There is no separate "algorithm" being evaluated beyond the efficacy of the chromogenic medium itself. The clinical study evaluates this standalone culture medium's ability to detect MRSA compared to a reference lab method.

7. The Type of Ground Truth Used

The ground truth used was a composite reference standard based on:

• Standard microbiological culture methods (TSB enrichment, BAP subculture)
• Phenotypic tests (Gram stain, catalase, latex agglutination, Cefoxitin Screen test for oxacillin resistance)
• Molecular confirmation (mecA gene PCR)
• Species confirmation (VITEK® MS)

This detailed approach combines multiple laboratory techniques to confirm the presence and methicillin-resistance of Staphylococcus aureus.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of an algorithm or machine learning. As a diagnostic culture medium, it would have been developed and optimized through in vitro studies and experiments, but the concept of a "training set" for an algorithm's development, distinct from analytical validation, is not applicable here. The analytical performance data (e.g., reactivity, reproducibility, cross-reactivity) serves to demonstrate the medium's inherent characteristics.

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

Not applicable, as there is no "training set" for an algorithm in the traditional sense. The ground truth for the analytical studies (e.g., for determining mecA status for reactivity studies) would have been established using established molecular and phenotypic methods, similar to those used for the clinical ground truth. For instance, the QC organisms were compared to oxacillin MIC and mecA PCR.

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Mueller Hinton Agar is a standard basal medium intended for in vitro antimicrobial disk diffusion susceptibility testing of isolated colonies of common, rapidly growing bacteria by the Bauer-Kirby method as standardized by the Clinical and Laboratory Standards Institute (CLSI). This product has not been evaluated for gradient diffusion testing.

Mueller Hinton Agar is a standard basal medium intended for in vitro antimicrobial disk diffusion susceptibility testing of isolated colonies of common, rapidly growing bacteria by the Bauer-Kirby method standardized by the Clinical and Laboratory Standards Institute (CLSI). This product has not been evaluated for gradient diffusion testing.

The Bauer-Kirby procedure is based on the diffusion through an agar gel of antimicrobial substances which are impregnated on sterile paper disks. This method employs disks with a sinqle concentration of antimicrobial agent and zone sizes are correlated with minimum inhibitory concentrations. In the test procedure, a standardized suspension of the organism is swabbed over the entire surface of the agar medium. Sterile paper disks impregnated with specified amounts of antibiotic or other antimicrobial agents are then placed on the surface of the inoculated agar medium. The agar medium is incubated at 35+ 2°C for 16-18 hours. The organism will grow as a solid "lawn". The antimicrobial will diffuse outward (in a circle). If the antimicrobial agent has activity against the organism, a circular zone of growth inhibition will result. The zone of inhibition around the paper disk is measured. A determination as to whether the organism is susceptible, intermediate or resistant to the antimicrobial agent is determined by comparing the size of the zone of inhibition to the zone diameter interpretive criteria in the CLSI M100 Standard.

Here's an analysis of the provided information regarding the Mueller Hinton Agar device, structured according to your request:

Acceptance Criteria and Device Performance Study

1. Table of Acceptance Criteria and Reported Device Performance

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

• Test Set Sample Size: The sample size varies per organism-antimicrobial combination.
  • For most organism-antimicrobial combinations, a total of 72 results were generated (3 sites x 3 separate days x 2 duplicate tests x 2 lots of Mueller Hinton Agar x 2 different manufacturers of antimicrobial disks).
  • For Ceftaroline, High Level Gentamicin, and High Level Streptomycin, a total of 36 results were generated (only one manufacturer of antimicrobial disks available).
  • The total number of individual test results presented are:
    • Escherichia coli ATCC 25922: 972
    • Staphylococcus aureus ATCC 25923: 648
    • Pseudomonas aeruginosa ATCC 27853: 468
    • Enterococcus faecalis ATCC 29212: 72
    • Enterococcus faecalis ATCC 51299: 144
    • Escherichia coli ATCC 35218: 360
• Data Provenance: The study was a "multi-site reproducibility study" conducted with "CLSI recommended quality control organisms from American Type Culture Collection (ATCC)". The document implies it was a prospective study specifically designed for the 510(k) submission. The country of origin for the data is not explicitly stated, but given the submission to the FDA and reference to CLSI standards, it is highly likely to be the USA.

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

This type of study (in vitro diagnostic for microbial susceptibility) does not typically involve human experts establishing a "ground truth" for each individual test result in the same way an imaging study would. The ground truth (acceptable range) is established by:

• Antimicrobial-specific FDA drug label: These labels are based on extensive clinical trials and regulatory review, involving many experts in microbiology, pharmacology, and clinical medicine.
• CLSI Standards M100-S24 or M02-A11: These standards are developed by consensus of numerous international experts in clinical microbiology, including microbiologists, infectious disease physicians, and laboratory scientists.
• Therefore, the "ground truth" is derived from a consensus of a large, unnamed group of highly qualified experts in the field of clinical microbiology and infectious diseases, codified in widely accepted standards.

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

Not applicable. This study measures the zone of inhibition, which is a quantitative measurement compared against predefined interpretive criteria (acceptable range). There is no subjective interpretation requiring adjudication by multiple readers for individual test results.

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 is an in vitro diagnostic device for antimicrobial susceptibility testing, not an AI-based diagnostic platform for 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 of the Mueller Hinton Agar medium itself. The performance was evaluated based on the quantitative measurement of inhibition zones, with the interpretation of these zones determined by established CLSI standards and FDA drug labels, not by a human interpreting a visual output from an AI algorithm.

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

The ground truth used is expert consensus and regulatory/scientific standards. Specifically, the acceptable ranges for zone of inhibition measurements are derived from:

• Antimicrobial-specific FDA drug labels.
• CLSI Standards M100-S24 (Performance Standards for Antimicrobial Susceptibility Testing) or M02-A11 (Performance Standards for Antimicrobial Disk Susceptibility Tests). These standards represent the consensus of experts in clinical microbiology.

8. The sample size for the training set

Not applicable. This is not an AI/machine learning device that requires a training set. The study evaluated the intrinsic performance of the agar medium itself.

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

Not applicable, as there is no training set for this type of device.

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VRESelect ™ is a selective and differential chromogenic medium, containing 8 µg/mL of vancomycin, for the qualitative detection of gastrointestinal colonization of vancomycin-resistant Enterococcus faecium (VREfm) and vancomycin-resistant Enterococcus faecalis (VREfs) and to aid in the prevention and control of vancomycin-resistant Enterococcus (VRE) in healthcare settings. The test is performed on rectal swabs or fecal specimens from patients to be screened for VRE colonization. VRESelect ™ is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Results can be interpreted after 24 to 28 hours incubation. Subculture to non-selective media (e.g., trypticase soy agar with 5% sheep blood) is needed for susceptibility testing and epidemiological typing.

VRESelect ™ is a selective medium for the detection of vancomycin-resistant Enterococcus (VRE). The selectivity of this medium is based on the presence of an antifungal/antibiotic mixture that inhibits the growth of most yeast, Gram negative and Gram positive bacteria, with the exception of vancomycin-resistant Enterococci (VRE).

Detection is based on the cleavage of chromogenic substrates by specific enzymes of Enterococcus faecium which produces pink colonies and Enterococcus faecalis which produces blue colonies.

Enterococcus gallinarum and Enterococcus casseliflavus are intrinsically resistant to vancomycin and may grow on the VRESelect™ medium as colorless or white colonies because they do not metabolize the chromogenic substrates. Vancomycin susceptible enterococci are inhibited.

After 24 to 28 hours incubation pink colonies can be reported as VREfm. Blue colonies should be confirmed by a catalase test and susceptibility (refer to limitation 9 in package insert).

K122187: VRESelect™ Media Acceptance Criteria and Performance Study

The VRESelect™ Media is a selective and differential chromogenic medium intended for the qualitative detection of gastrointestinal colonization of vancomycin-resistant Enterococcus faecium (VREfm) and Enterococcus faecalis (VREfs).

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for VRESelect™ Media are not explicitly stated as numerical thresholds in this document. However, performance is assessed through comparison with a predicate device (BEAV + Confirmation) and established laboratory methods (Biochemical identification (Vitek) and Vancomycin minimal inhibitory concentration (MIC) by E-Test). The implicit acceptance criteria appear to be high levels of positive and negative agreement with these reference methods.

The conclusion states that "The VRESelect™ showed high diagnostic sensitivity and accuracy in this study," indicating that the reported performance met the sponsor's internal acceptance criteria.

2. Sample Size and Data Provenance for the Test Set

• Sample Size: 946 stool samples were used for the method comparison study.
• Data Provenance: The document does not explicitly state the country of origin for the samples. It also doesn't specify if the samples were retrospective or prospective, though the nature of a method comparison study often implies prospectively collected samples or a mixed approach.

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

The document does not specify the number of individual experts involved in establishing the ground truth for the test set. However, it indicates these processes:

• For the Method Comparison Study (vs. BEAV + Confirmation): It states "confirmatory testing (Gram stain, catalase, PYR, Vitek 2 identification and vancomycin (MIC E-Test))." This implies established laboratory protocols and potentially certified laboratory personnel rather than individual "experts" in the sense of clinical specialists.
• For Biochemical identification (Vitek) and Vancomycin minimal inhibitory concentration (MIC) (E-Test): These are standard laboratory methods with established protocols.

No specific qualifications (e.g., "radiologist with 10 years of experience") are mentioned for these individuals, as the ground truth relies on recognized laboratory tests rather than expert interpretation of images or clinical findings.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method in the context of multiple human readers or interpretations. The ground truth for the test set was established through a combination of a predicate device (BEAV) and a series of confirmatory laboratory tests (Gram stain, catalase, PYR, Vitek 2 identification, and vancomycin (MIC E-Test)). These are objective laboratory procedures, which typically do not involve an "adjudication" process in the same way clinical interpretations might.

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

No, an MRMC comparative effectiveness study was not performed. The study evaluates the performance of the VRESelect™ medium itself against established laboratory methods, not how human readers improve with or without AI assistance. The device is a culture medium, not an AI or human-assisted diagnostic tool in the typical sense of an MRMC study.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire document describes the performance of the VRESelect™ media (the algorithm/device only, without human interpretation beyond reading the colonies) against established ground truth methods. The results are presented as agreement percentages.

7. Type of Ground Truth Used

The ground truth used was a combination of:

• Predicate Device Performance: The results from the current standard, "BEAV plus Confirmation."
• Laboratory Diagnostic Tests: This includes Gram stain, catalase, PYR, Vitek 2 identification, and vancomycin (MIC E-Test) for bacterial identification and resistance determination. This aligns with what can be considered definitive laboratory methods/gold standard diagnostic tests.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or "training data" in the context of machine learning model development. This is because VRESelect™ is a chromogenic culture medium, not an AI/machine learning algorithm that requires training. Its performance is based on biochemical reactions and enzymatic activity, which are inherent properties of the medium. The studies described are validation or verification studies, not training for an adaptive algorithm.

However, if we interpret "training" in a broader sense of product development and optimization, the "limit of detection study" involving a panel of 18 vancomycin-resistant enterococci and the "challenge panel" of 56 well-characterized strains could be considered part of the development and refinement process, though not a "training set" for a learning algorithm.

9. How the Ground Truth for the Training Set (if applicable) was Established

As noted above, there is no explicit "training set" as understood in machine learning. For the studies that involved characterized strains (e.g., Limit of Detection, Challenge Panel), the ground truth for these strains would have been established through well-defined microbiological methods, including identification to species level and vancomycin susceptibility testing using standard laboratory techniques (e.g., AST methods like MIC E-Test or broth microdilution). The "ATCC reference strains" mentioned in the reproducibility study also serve as a form of "ground truth" with known characteristics.

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VRESelect ™ is a selective and differential chromogenic medium, containing 8 µg/mL of vancomycin, for the qualitative detection of gastrointestion of vancomycin-resistant Enterococcus faecium (VREfm) and vancomycin-resistant Enterococcus faecalis (VREfs) and to aid in the prevention and control of vancomycin-resistant Enterococcus (VRE) in healthcare settings. The test is performed on rectal swabs from patients to be screened for VRE colonization. VRESelect ™ is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Results can be interpreted after 24 to 28 hours incubation. Subculture to non-selective media (e.g., trypticase soy agar with 5% sheep blood) is need for susceptibility testing and epidemiological typing.

VRESelect ™ is a selective medium for the detection of vancomyoin-resistant Enterococcus (VRE). The selectivity of this medium is based on the presence of an antifungal/antibiotic mixture that inhibits the growth of most yeast, Gram negative and Gram positive bacteria, with the exception of vancomycin-resistant Enterococci (VRE).

Detection is based on the cleavage of chromogenic substrates by specific enzymes of Enterococcus facium which produces pink colonies and Enterococcus faecalis which produces blue colonies.

Enterococcus gallinarum and Enterocccus casseliflavus are intrinsically resistant to vancomycin and may grow on the VRESelect™ medium as colories or white colonies because they do not metabolize the chromogenic substrates. Vancomycin susceptible enterococci are inhibited.

After 24 to 28 hours incubation pink colonies can be reported as VRESm. Blue colonies should be confirmed by a catalase test and susceptibility testing (refer to limitation 8 in package insert).

The provided text describes the performance of VRESelect™ Culture Media, which is a selective and differential chromogenic medium for the detection of vancomycin-resistant Enterococcus (VRE).

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 document doesn't explicitly state "acceptance criteria" in a numerical target format (e.g., "sensitivity must be >90%"). However, the "Method Comparison" section and the subsequent tables present performance metrics (Positive Agreement and Negative Agreement) against established reference methods, which implicitly serve as the acceptance criteria for the device to be deemed "substantially equivalent."

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

• Sample Size:
  • Method Comparison (BEAV + Confirmation): 757 specimens.
  • Biochemical Identification (Vitek 2) & Vancomycin MIC: Based on the same 757 specimens, but stratified by VREfm (97 positive for VREfm, 660 negative) and VREfs (38 positive for VREfs, 719 negative) for Vitek 2, and VREfm (94 resistant, 637 susceptible) and VREfs (28 resistant, 637 susceptible) for Vancomycin MIC.
  • Cross-Reactivity: 119 microorganisms.
  • Recovery Study: Panel of eighteen vancomycin-resistant enterococci (8 VREfm and 10 VREfs).
  • Reproducibility: 6 ATCC reference strains.
  • Challenge Panel: 56 well-characterized strains.
  • Interfering Substances: Multiple substances tested, but specific strain counts not given for each.
• Data Provenance: The document does not specify the country of origin. It is a 510(k) submission to the FDA, implying studies conducted to US regulatory standards, but the physical location of the patient sample collection is not mentioned. The data appears to be prospective as it involves testing specimens with the VRESelect™ media and comparing them to reference methods.

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

The document does not explicitly mention "experts" in the context of establishing ground truth for the test set in the same way one might in imaging studies. Instead, the ground truth is established through standard microbiological laboratory procedures:

• "BEAV + Confirmation": The confirmation included "Gram stain, catalase, PYR, Vitek 2 identification and vancomycin (MIC E-Test)." These are objective laboratory tests. While trained microbiologists perform and interpret these tests, the ground truth is based on the results of these standardized methods rather than subjective expert consensus.
• "Biochemical identification (Vitek) vs. VRESelect™ results": Vitek 2 is an automated system for identification, which provides objective results.
• "Vancomycin minimal inhibitory concentration (MIC) demonstrated the following results": Vancomycin E-Test (MIC) provides an objective measure of antimicrobial resistance.

Therefore, the ground truth is established by a combination of conventional microbiological techniques and automated systems, interpreted by trained laboratory personnel, not by a panel of "experts" as in, for example, a radiology consensus read.

4. Adjudication Method for the Test Set

There's no mention of an "adjudication method" in the sense of multiple experts independently reviewing and then resolving discrepancies for the ground truth. The ground truth relies on objective laboratory tests ("BEAV + Confirmation," Vitek 2, Vancomycin MIC E-Test). Any discrepancies between VRESelect™ and these reference methods are presented as performance metrics (Positive/Negative Agreement) and sometimes further analyzed (e.g., false positives/negatives were sometimes confirmed by subculture to BAPs and further testing).

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

This document describes the performance of a culture medium, not an AI algorithm for diagnostic imaging. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

The VRESelect™ media is itself a diagnostic tool that produces a visible result (colony color). The "standalone" performance is effectively what is reported in the tables, where the media's results are compared directly to the reference methods (BEAV+Confirmation, Vitek 2, Vancomycin MIC). The interpretation of the visible colonies (pink/blue) is part of the "system" performance. There is no "algorithm only" in the sense of a software-based AI system operating independently of human observation of the culture medium.

7. The Type of Ground Truth Used

The ground truth used is a combination of:

• Expert Consensus (Implicit/Procedural): The "BEAV + Confirmation" method, which includes Gram stain, catalase, PYR, Vitek 2 identification, and vancomycin (MIC E-Test), represents a gold standard of laboratory procedures for identifying and confirming VRE, interpreted by trained microbiologists following established protocols.
• Pathology/Laboratory Results: Vitek 2 biochemical identification and vancomycin MIC E-Test are objective laboratory tests providing definitive identification and resistance profiles.

8. The Sample Size for the Training Set

The document does not explicitly differentiate between "training" and "test" sets in the context of an algorithm. This product is a culture medium, not a machine learning model that undergoes a training phase. The described studies represent validation studies for the performance of the medium.

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

As this is a culture medium, not an AI algorithm, there is no "training set" in the machine learning sense. The development of the medium would have involved internal R&D and testing, but the document focuses on the formal validation studies.

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