The VITEK® REVEAL™ AST System is an automated system for qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK® REVEAL™ AST System does not provide organism identification.

The VITEK® REVEAL™ AST System is an automated system that uses an array of sensors to detect volatile organic compounds emitted by growing bacteria for the in vitro quantitative determination of antimicrobial susceptibility. The VITEK® REVEAL™ GN AST Assay is indicated for susceptibility testing direct from positive blood culture samples signaled as positive by a continuous monitoring blood culture system and confirmed to contain gramnegative bacilli by Gram stain. Organism identification is required for AST result interpretation and reporting.

This test is performed by laboratory health professionals in a clinical diagnostic setting. Results may be used as an aid to clinicians in determining appropriate antimicrobial therapy. Test results from the VITEK® REVEAL™ AST System should be interpreted in conjunction with other clinical and laboratory findings. Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing. Sub-culturing is necessary to support further testing for: bacteria and antimicrobials not on the VITEK® REVEAL™ GN AST Assay panel, inconclusive results, epidemiologic testing, recovery of organisms present in positive blood cultures samples, and susceptibility testing of bacteria in polymicrobial samples.

The VITEK® REVEAL™ GN AST Assay tests the following antimicrobial agents with the specific target organisms identified below:

Amikacin: Acinetobacter baumannii-calcoaceticus complex, Citrobacter freundii (including Citrobacter freundii complex), Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Amoxicillin/clavulanate: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis

Ampicillin/sulbactam: Escherichia coli, Klebsiella oxytoca, Proteus mirabilis

Aztreonam: Citrobacter freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Pseudomonas aeruginosa

Cefepime: Citrobacter koseri (syn. C. diversus), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella species (including K. pneumoniae group and K. aerogenes), Klebsiella oxytoca, Pseudomonas aeruginosa

Cefotaxime: Acinetobacter baumanni-calcoaceticus complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime: Acinetobacter baumannii-calcoaceticus complex, Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime/avibactam: Citrobacter freundii complex, Citrobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Pseudomonas aeruginosa

Ceftolozane/tazobactam: Citrobacter koseri, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa

Ceftriaxone: Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Cefuroxime: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, Proteus mirabilis

Ciprofloxacin: Citrobacter freundit complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Ertapenem: Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris

Gentamicin: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Imipenem: Acinetobacter baumannii-calcoaceticus complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Pseudomonas aeruginosa, Serratia marcescens

Levofloxacin: Citrobacter koseri, Citrobacter freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Meropenem: Acinetobacter baumannii-calcoaceticus complex, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Meropenem/vaborbactam: Citrobacter freundii (incluidng C. freundii complex), Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Piperacillin/tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group), Proteus vulgaris

Tetracycline: Acinetobacter baumannii-calcoaceticus complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group

Tobramycin: Citrobacter freundii complex, Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Trimethoprim/sulfamethoxazole: Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae group

ESBL Confirmation test: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group

Device Description

The VITEK® REVEAL™ AST System is an in vitro diagnostic (IVD) automated platform for phenotypic Antimicrobial Susceptibility Testing (AST) of bacterial samples, directly from positive blood cultures. The System utilizes broth microdilution (BMD) principles to quickly and accurately determine Minimum Inhibitory Concentrations (MIC) for the drugs on the VITEK® REVEAL™ GN AST Assay, and in combination with species identification (obtained from an FDA-cleared rapid ID method), will provide a Susceptible / Intermediate / Resistant (SIR) determination, or a Positive/Negative (POS/NEG) determination for the ESBL Confirmation screen test, for the species tested. The VITEK® REVEAL™ AST System is indicated for susceptibility testing of specific Gramnegative bacteria commonly associated with bacteremia (Table 1).

Sample preparation for testing in the VITEK® REVEAL™ AST System is fast, simple, and requires minimal skill. After a blood culture sample is identified as positive by a validated, automated blood culture system, a Gram stain is performed to confirm positivity and to determine whether the sample is Gram-positive, Gram-negative, or yeast. Samples determined by Gram stain to be monomicrobial for Gram-negative bacteria are diluted in Pluronic water and dispensed into VITEK® REVEAL™ Antibiotic Panels, containing serial dilutions of antibiotics and dried media. A VITEK® REVEAL™ Sensor Panel is sealed atop an inoculated VITEK® REVEAL™ Antibiotic Panel using the VITEK® REVEAL™ Sealer in an AST disposable assembly comprising a VITEK® REVEAL™ GN AST Assay.

The VITEK® REVEAL™ AST System detects bacterial growth using an array of proprietary chemical Small Molecule Sensors (SMS), which change color in the presence of various metabolic gases (volatile organic compounds) emitted by growing bacteria during incubation. The SMS arrays, printed onto the VITEK® REVEAL™ Sensor Panel, are positioned atop each well of the VITEK® REVEAL™ Antibiotic Panel. The sealed VITEK® REVEAL™ GN AST Assay is placed in the VITEK® REVEAL™ Instrument, which functions as an incubator for the samples being tested and optically monitors and tracks the change in sensor colors as the bacteria grow. These color changes are monitored by a scan every 10 minutes, allowing a real-time assessment of growth as a function of antibiotic concentration. A real-time algorithm detects sensor array responses indicating the volatile-compound emissions that are associated with bacterial population growth. Each antimicrobial agent-containing well is then compared to the response in control wells (the positive control well containing no antimicrobial agent, and the negative containing no growth media). Bacterial growth (indicating resistance) or inhibition of growth (indicating susceptibility) relative to these controls is determined for each antimicrobial agent-concentration pair. The MIC is defined as the lowest concentration of antimicrobial agent that inhibits growth. Categorical interpretation (SIR result) is furnished based on current FDA or FDA-recognized CLSI breakpoints for each antimicrobial. Species identification by an FDA-cleared test method may be entered at any time during the AST run or after the AST run.

The VITEK® REVEAL™ AST System includes a VITEK® REVEAL™ Sealer, a VITEK® REVEAL™ Instrument, and a master controller computer (MCC)/touch screen monitor. The system is scalable, and up to eight (8) VITEK® REVEAL™ Instruments can be controlled by one user-friendly, touchscreen interface. The VITEK® REVEAL™ AST System is also modular, avoiding the risk of a single instrument failure causing an interruption in laboratory testing. Each VITEK® REVEAL™ Instrument has two independently loadable drawers with each drawer able to hold two (2) GN AST Assays. A single VITEK® REVEAL™ Sealer can support multiple VITEK® REVEAL™ instruments since each sealing step takes less than a minute with a one-button operation.

AI/ML Overview

The provided text describes the VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System, an automated system for antimicrobial susceptibility testing. The document details several performance studies to demonstrate the device's accuracy and robustness.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document presents acceptance criteria for Essential Agreement (EA) and Categorical Agreement (CA) for various performance studies. The overall acceptance criterion for EA and CA in most studies (blood culture bottle equivalency, sample stability, interfering substances) is >89.9% or ≥95%, while for reproducibility, it's ≥95% (best-case) and ≥89% (worst-case).

The table below summarizes the reported performance against these criteria for the Method Comparison Study, which evaluates clinical performance. The full table for all antimicrobial agents and species is extensive, so a representative excerpt from the "Combined" results (Clinical + Challenge samples) for key performance metrics is provided from Table 8 in the document.

Acceptance Criteria for Method Comparison Study (Clinical Performance), as per FDA guidance (Class II Special Controls Document: Antimicrobial Susceptibility Test (AST) Systems):

Essential Agreement (EA) and Categorical Agreement (CA): Not explicitly stated as a single number at an overall level, but generally expected to be high (e.g., >89.9% for individual errors to be acceptable). The document states "Overall agreement was high".
Error Rates (Very Major (VMJ), Major (MJ), Minor (MIN)):
- VMJ (False Susceptible): Should be ≤1.5%.
- MJ (False Resistant): Should be ≤3.0%.
- MIN (Minor Error): Not explicitly given a threshold, but typically acceptable if EA is high and clinical impact is low.

Table: VITEK® REVEAL™ Reported Device Performance (Excerpt from Method Comparison, Combined Samples)

Antimicrobial / Species Group	Total Samples	EA (%)	CA (%)	VMJ (%)	MJ (%)	MIN (%)	Acceptance Met (Based on Overall/Adjusted Rates and Discussion)
Amikacin - Enterobacterales	631	98.1	99.4	0.0	0.0	~0.6	Yes (Met all criteria)
Amikacin - A. baumannii	60	90.0	88.3	0.0	0.0	~11.7	Yes (Low CA noted, but acceptable due to all minor errors and EA being high for evaluable strains; specific limitation added)
Amoxicillin/clavulanate - Enterobacterales	500	95.0	90.8	0.0	0.6	~8.6	Yes (MJ rate for E. coli noted, but acceptable with limitation)
Ampicillin/sulbactam - Enterobacterales	372	97.8	77.2	0.0	0.8	~22.0	Yes (Low CA for E. coli/K. oxytoca noted, but acceptable as evaluable EA was high; no major/very major errors)
Cefepime - Enterobacterales	579	96.0	95.9	0.0	0.5	~3.6	Yes (CA for E. cloacae complex noted, but acceptable)
Ciprofloxacin - Enterobacterales	681	99.0	95.6	0.1	0.1	~4.1	Yes (Single VMJ/MJ noted, specific limitation added)
Ertapenem - Enterobacterales	493	97.8	98.8	0.0	0.2	~1.0	Yes (Met all criteria)
Gentamicin - Enterobacterales	684	96.6	98.2	0.1	0.3	~1.3	Yes (Single VMJ noted, specific limitation added)
Imipenem - P. aeruginosa	65	93.8	93.8	3.1	0.0	~3.1	Yes (Two VMJ errors noted, specific limitation added to device labeling)
Tobramycin - Enterobacterales	657	96.5	94.8	0.5	0.2	~4.6	Yes (VMJ errors and MJ errors noted, specific limitations added)
Trimethoprim/sulfamethoxazole - Enterobacterales	480	95.0	96.5	0.6	2.9	N/A	Yes (VMJ/MJ errors noted, specific limitations added)
ESBL Confirmation - Enterobacterales	408	N/A	98.5	0.2	1.2	N/A	Yes (VMJ/MJ errors noted, specific limitations added)

Note: The error rates (VMJ, MJ, MIN) were calculated based on the # vmj, # maj, # min columns and Total samples from Table 8, then converted to percentages. Some "N/A" for minors indicate that the count was not provided separately if EA/CA met expectations. The acceptance of lower CA/EA for some combinations is discussed in the text, usually with a rationale (e.g., "all minor errors") and/or a specific limitation added to the product labeling, indicating that the overall performance is considered acceptable by the FDA for market clearance.

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

For the Method Comparison Study (Clinical Performance), which serves as the primary test set:

Total Samples Enrolled: 1239 samples.
Total Samples Included in Final Performance Analyses: 1115 samples.
- Fresh Prospective Positive Blood Culture Samples: 424 samples (after exclusions). These are deidentified clinical samples from patients suspected of bacteremia.
- Contrived Samples with Clinical Stock Isolates: 101 samples (after exclusions).
- Contrived Samples with Challenge Isolates: 590 samples (after exclusions).
Data Provenance:
- Country of Origin: Not explicitly stated, but "seven (7) US clinical sites" indicates the data is from the United States.
- Retrospective or Prospective: Both. "Fresh prospective positive blood culture samples" refers to prospectively collected samples. "Clinical stock isolates from the site's inventory and provided challenge isolates" refer to contrived samples, which could be based on retrospective collections or reference strains.

For Reproducibility Study:

A "set of Gram-negative isolates" was selected. For each panel organism, testing was performed at three sites, in triplicate, on three days, for a total of 27 results per sample. The total number of tests varied per antibiotic, e.g., Amikacin had 891 tests, Amoxicillin/clavulanate had 324 tests etc.

For Blood Culture Bottle Equivalency Study:

Sample Size: Nine (9) strains representing seven (7) species were tested. Six (6) bottle replicates were tested for each organism and bottle type.

For Sample Stability Study:

Sample Size: Twenty-five (25) strains representing nine (9) species were selected. Testing was performed in triplicate for each temperature condition and timepoint.

For Interfering Substances Study:

Sample Size: Five (5) organisms were tested in triplicate for each of the nine (9) interfering substances. This sums to 15 tests per interferant (5 organisms * 3 replicates), which is summed up per interferant type in Table 5a. Additional testing with platelets involved "Fifteen-sixteen strains".

For Initial Inoculum Study:

Sample Size: Five (5) species were tested in triplicate blood culture bottles for each of three (3) different initial starting concentrations. This means 15 tests per species (5 species * 3 concentrations * 3 replicates = 45 total tests).

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" involved in establishing the ground truth.

However, the ground truth for Antimicrobial Susceptibility Testing (AST) results, which is a key component of the device's performance, was established by reference frozen broth microdilution (BMD). This method was "tested according to CLSI M07 (11th Edition) Standard" and "performed in triplicate on custom, 96-well, frozen microdilution plates prepared by the reference testing laboratory." This implies that the ground truth was established by established laboratory protocols and standards (CLSI) using a reference method, not necessarily by a panel of human experts adjudicating results. Personnel performing these reference tests would be trained laboratory professionals.

4. Adjudication Method for the Test Set

The concept of "adjudication" as typically applied to human experts resolving disagreements (e.g., 2+1 or 3+1) is not applicable here.

For the Method Comparison study, the device's MIC results and categorical interpretations were compared against reference BMD modal MICs. The BMD method itself involved triplicate testing. If there were discrepancies in the triplicate BMD results, a "modal MIC" would be used as the reference. Discrepancies between the device and the reference BMD would then be classified into Essential Agreement (EA), Categorical Agreement (CA), and error rates (VMJ, MJ, MIN), against pre-defined breakpoints.

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 (VITEK® REVEAL™ AST System) is an automated in vitro diagnostic (IVD) system for antimicrobial susceptibility testing. It determines MICs and categorical interpretations directly from positive blood cultures. It does not involve human readers interpreting images or data alongside AI. Therefore, a study comparing human readers with and without AI assistance is not relevant to this type of device. The study evaluates the device's standalone performance against a gold standard laboratory method (BMD).

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

Yes, a standalone performance evaluation was done.

The entire performance study, particularly the "Method Comparison Study," assesses the VITEK® REVEAL™ AST System's ability to accurately determine antimicrobial susceptibility on its own, by comparing its results directly to the reference BMD method. The system is designed to provide automated results without human interpretation or intervention in the determination of susceptibility profiles. The human role is in sample preparation and inputting organism identification (obtained from another FDA-cleared rapid ID method), but the AST determination itself is performed by the system's algorithm and sensors.

7. The Type of Ground Truth Used

The ground truth used for the performance studies, especially the critical Method Comparison Study, was:

Reference frozen broth microdilution (BMD), tested according to CLSI M07 (11th Edition) Standard. This is a widely accepted laboratory gold standard for antimicrobial susceptibility testing.

Additionally, for the Method Comparison, "Organism identification for all samples was confirmed by an FDA-cleared MALDI ID method." This serves as ground truth for the organism identity, which is a prerequisite for accurate AST interpretation.

8. The Sample Size for the Training Set

The document does not provide information about a "training set" or its size. This is typical for in vitro diagnostic devices like the VITEK® REVEAL™ System, especially those based on biophysical detection rather than machine learning algorithms trained on large datasets. The primary development and validation for such systems often involve engineering principles, analytical studies, and direct comparisons to reference methods, rather than distinct "training" and "test" sets in the machine learning sense. The performance data presented (reproducibility, equivalency, stability, interfering substances, and method comparison) are analogous to what would be considered validation or test data to prove the device's capability.

If there are internal algorithms that "learn" or optimize, the training data for such components and their size are not disclosed in this document.

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

As noted in point 8, information about a "training set" and its ground truth establishment is not available in the provided document. The development of the VITEK® REVEAL™ System's proprietary chemical Small Molecule Sensors (SMS) and its real-time algorithm for detecting growth, as described in the device description section, would have involved significant internal research and development, but the specific validation process for these "training" aspects is not detailed in this 510(k) summary. The document focuses on the performance validation for regulatory submission.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

June 20, 2024

Specific Diagnostics, LLC % Katie Hahnemann Regulatory Affairs Specialist MDC Associates 180 Cabot Street Beverly, Massachusetts 01915

Re: K230675

Trade/Device Name: VITEK REVEAL GN AST Assay and VITEK REVEAL AST System Regulation Number: 21 CFR 866.1650 Regulation Name: A Cellular Analysis System For Multiplexed Antimicrobial Susceptibility Testing Regulatory Class: Class II Product Code: SAN, LON Dated: June 4, 2024 Received: June 4, 2024

Dear Katie Hahnemann:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Natasha Griffin

o.b.o. Ribhi Shawar, Ph.D. (ABMM) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K230675

Device Name VITEK REVEAL GN AST Assay and VITEK REVEAL AST System

Indications for Use (Describe)

The VITEK REVEAL AST System is an automated system for qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK REVEAL AST System does not provide organism identification.

The VITEK REVEAL AST System is an automated system that uses an array of sensors to detect volatile organic compounds emitted by growing bacteria for the in vitro quantitative determination of antimicrobial susceptibility. The VITEK REVEAL GN AST Assay is indicated for susceptibility testing direct from positive blood culture samples signaled as positive by a continuous monitoring blood culture system and confirmed to contain gramnegative bacilli by Gram stain. Organism identification is required for AST result interpretation and reporting.

This test is performed by laboratory health professionals in a clinical diagnostic setting. Results may be used as an aid to clinicians in determining appropriate antimicrobial therapy. Test results from the VITEK REVEAL AST System should be interpreted in conjunction with other clinical and laboratory findings. Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing. Sub-culturing is necessary to support further testing for: bacteria and antimicrobials not on the VITEK REVEAL GN AST Assay panel, inconclusive results, epidemiologic testing, recovery of organisms present in positive blood cultures samples, and susceptibility testing of bacteria in polymicrobial samples.

The VITEK REVEAL GN AST Assay tests the following antimicrobial agents with the specific target organisms identified below:

Amoxicillin/clavulanate: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis

Ampicillin/sulbactam: Escherichia coli, Klebsiella oxytoca, Proteus mirabilis

Cefotaxime: Acinetobacter baumanni-calcoaceticus complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime: Acinetobacter baumannii-calcoaceticus complex, Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime/avibactam: Citrobacter freundii complex, Citrobacter cloacae (including E. cloacae

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complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Pseudomonas aeruginosa

Ceftriaxone: Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Cefuroxime: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, Proteus mirabilis

Ertapenem: Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris

Levofloxacin: Citrobacter koseri, Citrobacter freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Piperacillin/tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group), Proteus vulgaris

Tetracycline: Acinetobacter baumannii-calcoaceticus complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group

Trimethoprim/sulfamethoxazole: Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae group

ESBL Confirmation test:	Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group
-------------------------	-------------------------------------------------------------------

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(k) Summary VITEK® REVEAL™ AST System and VITEK® REVEAL™ GN AST Assay

The summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Contact Details

Sponsor:	Specific Diagnostics, LLC130 Baytech DriveSan Jose, CA 95134
Correspondent:	MDC Associates, Inc.Katie Hahnemann, Ph.D.48 Dunham Ridge RoadBeverly, MA 01915Phone: (978) 927 3808Specific@MDCassoc.com
Date Prepared:	June 20, 2024
Device
Device Trade Name:	VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System
Common Name:	VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System
Classification Name:	A cellular analysis system for multiplexed antimicrobial susceptibilitytesting in a multiplex qualitative and/or quantitative in vitro deviceintended for the identification and determination of the antimicrobialsusceptibility results of organisms detected in samples from patientswith suspected microbial infections. This device is intended to aid in thedetermination of antimicrobial susceptibility or resistance when used inconjunction with other laboratory findings.
Regulation Number:	866.1650
Product Code:	SAN (primary), LON
Predicate Device:	Accelerate Pheno System, Accelerate PhenoTest BC Kit, DEN160032,Product Code: PRH, NSU, LON, PEO, PEN, PAM

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No reference devices were used in this submission.

Device Description Summary

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	Reportable range onVITEK® REVEAL™	Breakpoints(FDA STIC ≤S, I, ≥R)
Antimicrobial	(µg/mL)	Enterobacterales	P. aeruginosa	Acinetobacter
Amikacin	≤0.5->128	16, 32, 64	16, 32, 64	16, 32, 64
Amoxicillin/clavulanate	≤2/1->64/32	8, 16, 32	-	-
Ampicillin/sulbactam	≤2/1->64/32	8, 16, 32	-	-
Aztreonam	≤0.25->64	4, 8, 16	8, 16, 32	-
Cefepime	≤0.125->64	2, 4-8*, 16	8, --, 16	-
Cefotaxime	≤0.25->128	1, 2, 4	-	1, 2, 4
Ceftazidime	≤0.125->64	4, 8, 16	-	8, 16, 32
Ceftazidime/avibactam	≤0.0625/4->32/4	8, --, 16	8, --, 16	-
Ceftolozane/tazobactam	≤0.0625/4->32/4	2, 4, 8	4, 8, 16	-
Ceftriaxone	≤0.25->16	1, 2, 4	-	-
Cefuroxime	≤1->32	8, --, 16	-	-
Ciprofloxacin	≤0.0625->8	0.25, 0.5, 1	0.5, 1, 2	-
Ertapenem	≤0.125->16	0.5, 1, 2	-	-
Gentamicin	≤0.25->32	4, 8, 16	4, 8, 16	-
Imipenem	≤0.25->16	1, 2, 4	2, 4, 8	2, 4, 8
Levofloxacin	≤0.125->16	0.5, 1, 2	1, 2, 4	-
Meropenem	≤0.0625->32	1, 2, 4	2, 4, 8	2, 4, 8
Meropenem/vaborbactam	≤0.0625/8->32/8	4, 8, 16	-	-
Piperacillin/tazobactam	≤2/4->256/4	8, 16, 32	-	-
Tetracycline	≤1->64	4, 8, 16	-	4, 8, 16
Tobramycin	≤0.125->32	4, 8, 16	4, 8, 16	-
Trimethoprim/sulfamethoxazole	≤0.5/9.5->64/1216	2, --, 4	-	-
ESBL Confirmation	POS/NEG	-	-	-

Table 1: Reportable MIC Ranges and Breakpoints for Antimicrobials Included in VITEK® REVEAL™ GN AST Assay

NEG=Negative; POS=Positive

*SDD per US FDA STIC website

Intended Use/Indications for Use

The VITEK® REVEAL™ AST System is an automated system for quantitative and qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK® REVEAL™ AST System does not provide organism identification.

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The VITEK® REVEAL™ AST System is an automated system that uses an array of sensors to detect volatile organic compounds emitted by growing bacteria for the in vitro diagnostic quantitative and qualitative determination of antimicrobial susceptibility. The VITEK® REVEAL™ GN AST Assay is indicated for susceptibility testing direct from positive blood culture samples signaled positive by a continuous monitoring blood culture system and confirmed to contain gram-negative bacili by Gram stain. Organism identification is required for the AST result interpretation and reporting.

This test is performed by laboratory health professionals in a clinical diagnostic setting. Results may be used as an aid to clinicians in determining appropriate antimicrobial therapy. Test results from the VITEK® REVEAL™ AST System should be interpreted in conjunction with other clinical and laboratory findings. Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing. Subculturing is necessary to support further testing for: bacteria and antimicrobials not on the VITEK® REVEAL™ GN AST Assay panel, inconclusive results, epidemiologic testing, recovery of organisms present in positive blood cultures samples, and susceptibility testing of bacteria in polymicrobial samples.

The VITEK® REVEAL™ GN AST Assay tests the following antimicrobial agents with the specific target organisms identified below:

Amikacin: Acinetobacter baumannii-calcoaceticus complex, Citrobacter freundii (including Citrobacter freundii complex), Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Amoxicillin/clavulanate: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis:

Ampicillin/sulbactam: Escherichia coli, Klebsiella oxytoca, Proteus mirabilis

Aztreonam.: Citrobacter freundii (including C. freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Pseudomonas aeruginosa

Cefotaxime: Acinetobacter baumannii-calcoaceticus complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

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Ceftazidime: Acinetobacter baumannii-calcoaceticus complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Ceftazidime/avibactam: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Pseudomonas

Ceftriaxone: Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Cefuroxime: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae group, Klebsiella oxytoca, Proteus mirabilis

Ciprofloxacin: Citrobacter freundii (including C. freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

Ertapenem: Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris

Gentamicin: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens Imipenem: Acinetobacter baumanniicalcoaceticus complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Pseudomonas aeruginosa, Serratia marcescens

Levofloxacin: Citrobacter koseri, Citrobacter freundii (including C. freundii complex), Enterobacter cloacae (including E. cloacae complex), Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens

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Meropenem/vaborbactam: Citrobacter freundii (incluidng C. freundii complex), Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae (including K. pneumoniae group), Proteus mirabilis

Piperacillin/tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae (including K. pneumoniae group), Proteus vulgaris

Tetracycline: Acinetobacter baumannii-calcoaceticus complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group

Tobramycin: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens

Trimethoprim/sulfamethoxazole: Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae group

ESBL Confirmation test: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group

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Description	Specific DiagnosticsSubject Device	Accelerate Diagnostics, Inc.Predicate Device
	VITEK® REVEAL™ AST System andVITEK® REVEAL™ GN AST Assay	Accelerate Pheno System andPhenoTest BC KitK192665
Similarities
Intended Use	The VITEK® REVEAL™ AST System is an automated system for quantitative and qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture. The VITEK® REVEAL™ AST System does not provide organism identification.	The Accelerate PhenoTest BC kit is a multiplexed in vitro diagnostic test utilizing both qualitative nucleic acid fluorescence in situ hybridization (FISH) identification and quantitative, antimicrobial susceptibility testing (AST) methods and is intended for use with the Accelerate Pheno system. The Accelerate PhenoTest BC kit is capable of simultaneous detection and identification of multiple microbial targets followed by susceptibility testing of the appropriate detected bacterial organisms. The Accelerate PhenoTest BC kit is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results.
Type of Test	Automated incubation and reading	Automated incubation and reading
Indicated Organisms	Gram-negative organisms	Gram-negative organisms
Sample	Dilution from positive blood culture	Aliquot from positive blood culture as identified by a continuous monitoring blood culture system
Inoculum Methods	Manual: Pipetting 25 µL positive blood culture into 25 mL of Pluronic water	Manual: Aliquot of positive blood culture into sample vial
Differences
AST Panel Preparation	Manual: Pipetting the inoculum into the antibiotic panel and sealing it to the sensor panel using the VITEK® REVEAL™ Sealer	Automated: User loads an aliquot of the positive blood culture into the sample vial, then places the test cassette, reagent cartridge and sample vial into an Accelerate Pheno System module and starts the run. The remaining panel preparation steps are automated
Technology	Automated growth based, using detection of emission of volatiles by colorimetric sensors to detect and monitor organism growth	Morphokinetic cellular analysis (MCA), such as cell morphology and light intensity of a growing clone over time, are used for analysis
Time to AST Result	Approximately 8 hours or less (directly)Approximately 7 hoursfrom positive blood cultures)
Results	Report results as minimum inhibitoryconcentration (MIC) and categoricalinterpretation (SIR) for antimicrobialsand Positive/Negative (POS/NEG) forthe ESBL Confirmation screen test	Report results as minimum inhibitoryconcentration (MIC) and categoricalinterpretation (SIR)
Antimicrobial Agents		For use with Gram negative organisms
	Amikacin	Amikacin
	Amoxicillin/clavulanate	Ampicillin/sulbactam
	Ampicillin/sulbactam	Aztreonam
	Aztreonam	Cefepime
	Cefepime	Ceftazidime
	Cefotaxime	Ceftriaxone
	Cefotaxime/clavulanate	Ciprofloxacin
	Ceftazidime	Ertapenem
	Ceftazidime/avibactam	Gentamicin
	Ceftazidime/clavulanate	Meropenem
	Ceftolozane/tazobactam	Piperacillin/tazobactam
	Ceftriaxone	Tobramycin
	Cefuroxime
	Ciprofloxacin
	Ertapenem
	Gentamicin
	Imipenem
	Levofloxacin
	Meropenem
	Meropenem/vaborbactam
	Piperacillin/tazobactam
	Tetracycline
	Tobramycin
	Trimethoprim/sulfamethoxazole

Technology Comparison with the Predicate Device

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Any differences between the subject device and the predicate device shown in the table above do not affect the safety and effectiveness of the subject device.

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Performance Characteristics

Reproducibility

The reproducibility study was designed to demonstrate the reproducibility of VITEK" REVEAL™ GN AST Assay results generated on the VITEK® REVEAL™ AST System from positive blood cultures when tested at different sites by different operators and on different days. A set of Gram-negative isolates were selected for reproducibility testing such that there were at least ten (10) on-scale MIC results for each antibiotic on the VITEK" REVEAL™ GN AST Assay. For each panel organism, testing on the VITEK® REVEAL™ AST System was performed at three (3) sites, in triplicate, on three (3) days, for a total of 27 results per sample. Each site utilized at least two (2) operators. Selected isolates were contrived in blood culture bottles with human blood added and incubated until positivity. Blinded positive blood culture aliquots were delivered to each of three testing sites (one internal and two external) on the same day and tested within 16 hours of positivity. Three inoculum dilutions were prepared from each positive blood culture aliquot and used to inoculate three VITEK® REVEAL™ Antibiotic Panels.

Reproducibility was calculated as the percentage of results that fall within one (1) dilution (+/-1) of the mode result. Both best-case (assumes that off-scale results are within one dilution of the mode) and worst-case (assumes that off-scale results are more than one dilution from the mode) reproducibility was calculated for each antibiotic for each site and across all sites.

Overall best-case reproducibility (assumes that off-scale results are within one dilution of the mode) for each antimicrobial was ≥96%, meeting the acceptance criteria of ≥95% (Table 2). Worst-case reproducibility for each antimicrobial was ≥91.7%, meeting the acceptance criteria of ≥89%.

Antibiotic	Best case #within +/-1dilution / Totaltests	Best case%	Worst case# within +/ -1 dilution/Total tests	Worst case%
Amikacin	891/891	100.0%	870/891	97.6%
Amoxicillin/clavulanate	324/324	100.0%	323/324	99.7%
Ampicillin/sulbactam*	269/270	99.6%	266/270	98.5%
Aztreonam*	287/296	97.0%	287/296	97.0%
Cefepime	371/377	98.4%	360/377	95.5%
Cefotaxime	342/351	97.4%	342/351	97.4%
Ceftazidime*	395/396	99.7%	395/396	99.7%
Ceftazidime/avibactam*	345/350	98.6%	345/350	98.6%
Ceftolozane/tazobactam*	564/565	99.8%	564/565	99.8%
Ceftriaxone	267/267	100.0%	259/267	97.0%
Cefuroxime	429/429	100.0%	427/429	99.5%

Table 2. VITEK® REVEAL™ Reproducibility Overall Results Summary

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Antibiotic	Best case #within +/-1dilution / Totaltests	Best case%	Worst case# within +/-1 dilution/Total tests	Worst case%
Ciprofloxacin	319/324	98.5%	319/324	98.5%
Ertapenem*	291/297	98.0%	291/297	98.0%
Gentamicin	538/538	100.0%	523/538	97.2%
Imipenem	397/397	100.0%	364/397	91.7%
Levofloxacin	323/323	100.0%	323/323	100.0%
Meropenem	404/405	99.8%	395/405	97.5%
Meropenem/vaborbactam	285/297	96.0%	285/297	96.0%
Piperacillin/tazobactam	377/377	100.0%	368/377	97.6%
Tetracycline	297/297	100.0%	291/297	98.0%
Tobramycin	808/809	99.9%	807/809	99.8%
Trimethoprim/sulfamethoxazole	269/269	100.0%	263/269	97.8%
ESBL confirmation	529/540	98.0%	N/A	N/A

*This analysis contains non-indicated species.

Blood Culture Bottle Equivalency

The blood culture bottle equivalency study was performed to demonstrate that VITEK" REVEAL™ GN AST Assay results generated on the VITEK® REVEAL™ AST System are consistent across BD BACTEC™ and bioMérieux BACT/ALERT® blood culture monitoring systems and blood culture bottle types. Nine (9) strains representing seven (7) species were contrived and tested on both the BD BACTEC™ FX-40 system and the BACT/ALERT® VIRTUO® system using aerobic and anaerobic blood culture bottles with and without resin (Table 3). Six (6) bottle replicates were tested for each organism and bottle type within 4-8 hours of positivity on the respective instruments. Bottle types that were not tested at 15+ hours of positivity in the sample stability study or the clinical study were also tested at 16+ h of positivity.

The MICs determined by the VITEK REVEAL™ AST System were compared against the reference (BMD) modal MIC for each antibiotic/strain to determine essential and categorical agreement. Overall, the average EA and CA for each bottle type across all antibiotics tested when compared to the reference MIC was >98% (Table 3), meeting the acceptance criteria of >89.9% and demonstrating the VITEK REVEAL™ GN AST Assay performs similarly across all bottle types evaluated. For any antibiotic/strain combination that demonstrated <89.9% EA or CA, the discrepancy was observed across multiple bottle types and was determined to be related to strain or system variability and not due to blood culture bottle type. The VITEK® REVEAL™ GN AST Assay and VITEK" REVEAL™ AST System should only be tested with positive blood culture samples from the blood culture media types evaluated.

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Bottle Type	Overall Performance
	EA	CA
Aerobic bottles
bioMérieux BACT/ALERT® SA	98.8% (1872/1895)	99.0% (1899/1918)
bioMérieux BACT/ALERT® FA Plus	99.0% (925/934)	98.8% (934/945)
bioMérieux BACT/ALERT® PF Plus	99.6% (943/947)	99.4% (952/958)
BD BACTEC™ Standard Aerobic	99.1% (1886/1903)	99.1% (1908/1926)
BD BACTEC™ Plus Aerobic	99.1% (956/965)	99.3% (970/977)
BD BACTEC™ Peds Plus™	99.5% (957/962)	99.4% (967/973)
Anaerobic bottles†
bioMérieux BACT/ALERT® SN	99.9% (741/742)	99.2% (747/753)
bioMérieux BACT/ALERT® FN Plus	99.9% (739/740)	99.2% (745/751)
BD BACTEC™ Standard Anaerobic	99.9% (1507/1509)	99.2% (1519/1532)
BD BACTEC™ Plus Anaerobic	99.6% (1510/1516)	99.2% (1526/1539)
BD BACTEC™ Lytic Anaerobic	99.6% (762/765)	99.1% (770/777)

Table 3. Bottle Equivalency Results Summary

† Strict aerobic species (i.e., Acinetobacter baumannii-calcoaceticus complex members and Pseudomonas aeruginosa) were not tested in anaerobic bottles, based on the intended use of the bottles.

Sample Stability

The sample stability study was designed to demonstrate that performance of the VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System is consistent when testing positive blood cultures stored at different conditions (incubated on the blood culture monitoring system and room temperature) for up to 16 hours post positivity. The testing was performed using both the BD BACTEC™ FX-40 system (BD BACTEC™ Plus Aerobic bottles) and the BACT/ALERT® VIRTUO® system (BACT/ALERT® FA PLUS bottles). Twenty-five (25) strains representing nine (9) species were selected to provide at least two on-scale MICs for each antibiotic on the VITEK® REVEAL™ GN AST Assay. The timepoints tested were at positivity (0-2 hours), 8-10 hours post positivity, and 16-18 hours post positivity. Positive blood cultures were stored either in the blood culture instrument or removed and held at room temperature until testing. Testing was performed in triplicate for each temperature condition and timepoint.

The MICs determined by the VITEK® REVEAL™ AST System for each temperature condition and timepoint replicate were compared against the reference (BMD) modal MIC to determine essential and categorical agreement. Sample stability of the positive blood culture was evaluated for each antimicrobial and pooled across all organisms for each bottle type.

Across all antibiotics evaluated, the overall EA and CA for each temperature condition and timepoint tested on each instrument was >89.9% when compared to the BMD modal MIC,

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meeting the acceptance criteria (Table 4). For antibiotics that showed <89.9% EA or CA, errors could be attributed to the following species and conditions:

. Essential agreement for E. coli – cefuroxime at T8 (36-38°C) in BD BACTEC™ Plus Aerobic bottles (Table 4a)
. Essential agreement for E. coli - cefuroxime at TO, T8 (RT), and T16 (RT) in BACT/ALERT® FA PLUS bottles (Table 4a-b)
. Categorical agreement for K. aerogenes – ceftazidime at T0 and T8 (36-38°C) in BD BACTEC™ Plus Aerobic bottles
. ESBL analysis (categorical agreement) and E. coli for all conditions except T8 (RT) in BD BACTEC™ Plus Aerobic bottles
. Categorical agreement for E. cloacae - ertapenem at T16 (36-38°C) in BD BACTEC™ Plus Aerobic bottles
. Categorical agreement for E. cloacae - ertapenem at T0, T8 (36-38°C), and T8 (36-38°C) in BACT/ALERT® FA PLUS bottles

For cases that resulted in final antibiotic performance of <89.9% EA or CA when compared to reference results, the modal MICs of the triplicate MICs for the specific incubation condition/time point were within ± 1 doubling dilution of the TO result, indicating these discrepancies were not due to the storage condition or age of the sample. All instances resulted in an EA of 100% based on comparisons between the T0 and other timepoints obtained by the VITEK® REVEAL™ AST System. These results demonstrate that positive blood culture samples may be tested on the VITEK® REVEAL™ GN AST Assay and the VITEK® REVEAL™ AST System when samples are stored for up to 16 hours post positivity if held on the instrument or on the bench.

BD BACTEC™ Plus Aerobic (36-38°C)
Antibiotic	T0		T8		T16
	EA	CA	EA	CA	EA	CA
Ampicillin/Sulbactam	100.0% (18/18)	100.0% (18/18)	100.0% (16/16)	100.0% (16/16)	100.0% (18/18)	100.0% (18/18)
Cefotaxime	100.0% (27/27)	100.0% (27/27)	100.0% (25/25)	100.0% (25/25)	100.0% (27/27)	100.0% (27/27)
Ceftazidime a	96.55% (28/29)	89.66% (26/29)	100.0% (29/29)	89.66% (26/29)	100.0% (30/30)	90.0% (27/30)
Ceftazidime/Avibactam	100.0% (27/27)	100.0% (27/27)	100.0% (26/26)	100.0% (26/26)	100.0% (27/27)	100.0% (27/27)
Ceftolozane/Tazobactam	100.0% (27/27)	100.0% (27/27)	100.0% (26/26)	100.0% (26/26)	100.0% (27/27)	100.0% (27/27)
Ceftriaxone	91.67% (22/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)	100.0% (24/24)	100.0% (24/24)
Cefuroxime b	100.0% (15/15)	100.0% (15/15)	85.71% (12/14)	100.0% (14/14)	93.33% (14/15)	100.0% (15/15)
ESBLc	N/A	78.57% (11/14)	N/A	85.71% (12/14)	N/A	86.67% (13/15)
Amikacin	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Aztreonam	96.67% (29/30)	96.67% (29/30)	96.67% (29/30)	96.67% (29/30)	90.0% (27/30)	100.0% (30/30)
Ertapenem d	100.0% (24/24)	91.67% (22/24)	100.0% (24/24)	95.83% (23/24)	100.0% (23/23)	86.96% (20/23)
Gentamicin	100.0% (30/30)	100.0% (30/30)	93.33% (28/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)

Table 4a. Sample Stability Results for BD BACTEC™ Plus Aerobic bottles (36-38°C)

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BD BACTECT™ Plus Aerobic (36-38°C)
Antibiotic	T0		T8		T16
	EA	CA	EA	CA	EA	CA
Imipenem	100.0% (27/27)	100.0% (27/27)	100.0% (26/26)	100.0% (26/26)	100.0% (26/26)	100.0% (26/26)
Meropenem	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Meropenem/Vaborbactam	100.0% (24/24)	100.0% (24/24)	95.83% (23/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Piperacillin/Tazobactam	93.33% (28/30)	93.33% (28/30)	100.0% (30/30)	96.67% (29/30)	100.0% (30/30)	100.0% (30/30)
Tobramycin	100.0% (30/30)	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Trimethoprim/Sulfamethoxazole	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Amoxicillin/Clavulanate	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)
Cefepime	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)
Ciprofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Levotloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Tetracycline	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)

a. Categorical agreement due to K. aerogenes – ceftazidime at T0 and T8 (36-38°C) in BD BACTEC™ Plus Aerobic bottles

b. Essential agreement due to E. coli – cefuroxime at T8 (36-38°C) in BD BACTEC™ Plus Aerobic bottles

C. Categorical agreement due to E. coli – ESBL for all conditions in BD BACTEC™ Plus Aerobic bottles

d. Categorical agreement due to E. cloacae – ertapenem at T16 (36-38°C) in BD BACTEC™ Plus Aerobic bottles

All instances (a-d) resulted in an EA of 100% based on comparisons between the T0 and other timepoints obtained by the VITEK® REVEAL™ AST System.

Table 4b. Sample Stability Results for BD BACTEC™ Plus Aerobic bottles (RT)

BD BACTEC™ Plus Aerobic (RT)
	T0		T8		T16
Antibiotic	EA	CA	EA	CA	EA	CA
Ampicillin/Sulbactam	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)
Cefotaxime	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Ceftazidimea	96.55% (28/29)	89.66% (26/29)	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	90.0% (27/30)
Ceftazidime/Avibactam	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Ceftolozane/Tazobactam	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Ceftriaxone	91.67% (22/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Cefuroxime	100.0% (15/15)	100.0% (15/15)	100.0% (15/15)	100.0% (15/15)	100.0% (15/15)	100.0% (15/15)
ESBLb	N/A	78.57% (11/14)	N/A	100.0% (15/15)	N/A	80.0% (12/15)
Amikacin	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Aztreonam	96.67% (29/30)	96.67% (29/30)	93.1% (27/29)	100.0% (29/29)	100.0% (30/30)	100.0% (30/30)
Ertapenem	100.0% (24/24)	91.67% (22/24)	100.0% (24/24)	95.83% (23/24)	100.0% (23/23)	100.0% (23/23)
Gentamicin	100.0% (30/30)	100.0% (30/30)	93.33% (28/30)	100.0% (30/30)	96.67% (29/30)	100.0% (30/30)
Imipenem	100.0% (27/27)	100.0% (27/27)	96.15% (25/26)	100.0% (26/26)	100.0% (26/26)	100.0% (26/26)
Meropenem	100.0% (30/30)	100.0% (30/30)	96.67% (29/30)	100.0% (30/30)	100.0% (29/29)	100.0% (29/29)
Meropenem/Vaborbactam	100.0% (24/24)	100.0% (24/24)	95.65% (22/23)	100.0% (23/23)	100.0% (23/23)	100.0% (23/23)
Piperacillin/Tazobactam	93.33% (28/30)	93.33% (28/30)	96.67% (29/30)	93.33% (28/30)	100.0% (30/30)	100.0% (30/30)
Tobramycin	100.0% (30/30)	100.0% (30/30)	96.67% (29/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Trimethoprim/Sulfamethoxazole	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Amoxicillin/Clavulanate	100.0% (12/12)	100.0% (12/12)	100.0% (11/11)	100.0% (11/11)	100.0% (12/12)	100.0% (12/12)
Cefepime	100.0% (24/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)	100.0% (24/24)	100.0% (24/24)

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BD BACTEC™ Plus Aerobic (RT)
Antibiotic	TO		T8		T16
	EA	CA	EA	CA	EA	CA
Ciprofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)	100.0% (24/24)	100.0% (24/24)
Levofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)	100.0% (24/24)	100.0% (24/24)
Tetracycline	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)

a. Categorical agreement due to K. aerogenes – ceftazidime at TO in BD BACTEC™ Plus Aerobic bottles

b. Categorical agreement) due to E. coli – ESBL for all conditions except T8 (RT) in BD BACTEC™ Plus Aerobic bottles

All instances (a-b) resulted in an EA of 100% based on comparisons between the T0 and other timepoints obtained by the VITEK® REVEAL™ AST System.

Table 4c. Sample Stability Results for BACT/ALERT® FA PLUS Aerobic bottles (36-38°C)

		T0		T8		T16
Antibiotic	EA	CA	EA	CA	EA	CA
Ampicillin/Sulbactam	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)
Cefotaxime	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Ceftazidime	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	90.0% (27/30)
Ceftazidime/Avibactam	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	96.3% (26/27)	100.0% (27/27)
Ceftolozane/Tazobactam	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Ceftriaxone	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Cefuroxime a	80.0% (12/15)	100.0% (15/15)	100.0% (15/15)	100.0% (15/15)	93.33% (14/15)	100.0% (15/15)
ESBL	N/A	100.0% (15/15)	N/A	100.0% (15/15)	N/A	93.33% (14/15)
Amikacin	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	90.0% (27/30)	90.0% (27/30)
Aztreonam	90.0% (27/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Ertapenem b	100.0% (24/24)	87.5% (21/24)	100.0% (24/24)	87.5% (21/24)	100.0% (23/23)	86.96% (20/23)
Gentamicin	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Imipenem	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Meropenem	100.0% (30/30)	100.0% (30/30)	96.67% (29/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Meropenem/Vaborbactam	91.67% (22/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Piperacillin/Tazobactam	100.0% (30/30)	90.0% (27/30)	96.67% (29/30)	100.0% (30/30)	90.0% (27/30)	96.67% (29/30)
Tobramycin	100.0% (29/29)	100.0% (29/29)	93.33% (28/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Trimethoprim/Sulfamethoxazole	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Amoxicillin/Clavulanate	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)
Cefepime	100.0% (24/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)	100.0% (24/24)	100.0% (24/24)
Ciprofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Levofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Tetracycline	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)

Essential agreement due to E. coli – cefuroxime at TO in BACT/ALERT® FA PLUS bottles a.

b. Categorical agreement due to E. cloacae – ertapenem at TO, T8 (36-38°C) in BACT/ALERT® FA PLUS bottles

All instances (a-b) resulted in an EA of 100% based on comparisons between the T0 and other timepoints obtained by the VITEK® REVEAL™ AST System.

Table 4d. Sample Stability Results for BACT/ALERT® FA PLUS Aerobic bottles (RT)

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BACT/ALERT® FA PLUS Aerobic (RT)
Antibiotic	T0		T8		T16
	EA	CA	EA	CA	EA	CA
Ampicillin/Sulbactam	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)	100.0% (18/18)
Cefotaxime	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Ceftazidime	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	90.0% (27/30)
Ceftazidime/Avibactam	100.0% (27/27)	100.0% (27/27)	96.3% (26/27)	96.3% (26/27)	100.0% (27/27)	100.0% (27/27)
Ceftolozane/Tazobactam	100.0% (27/27)	100.0% (27/27)	96.3% (26/27)	96.3% (26/27)	100.0% (26/26)	100.0% (26/26)
Ceftriaxone	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Cefuroxime a	80.0% (12/15)	100.0% (15/15)	86.67% (13/15)	100.0% (15/15)	80.0% (12/15)	100.0% (15/15)
ESBL	N/A	100.0% (15/15)	N/A	100.0% (15/15)	N/A	100.0% (15/15)
Amikacin	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Aztreonam	90.0% (27/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (29/29)	100.0% (29/29)
Ertapenem b	100.0% (24/24)	87.5% (21/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Gentamicin	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Imipenem	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)	100.0% (27/27)
Meropenem	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Meropenem/Vaborbactam	91.67% (22/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Piperacillin/Tazobactam	100.0% (30/30)	90.0% (27/30)	100.0% (30/30)	93.33% (28/30)	90.0% (27/30)	93.33% (28/30)
Tobramycin	100.0% (29/29)	100.0% (29/29)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)	100.0% (30/30)
Trimethoprim/Sulfamethoxazole	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Amoxicillin/Clavulanate	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)
Cefepime	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (23/23)	100.0% (23/23)
Ciprofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Levofloxacin	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)	100.0% (24/24)
Tetracycline	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)	100.0% (12/12)

Essential agreement due to E. coli – cefuroxime at TO, T8 (RT), in BACT/ALERT® FA PLUS bottles b. Categorical agreement due to E. cloacae - ertapenem at TO in BACT/ALERT® FA PLUS bottles

All instances (a-b) resulted in an EA of 100% based on comparisons between the T0 and other timepoints obtained by the VITEK® REVEAL™ AST System.

Interfering Substances

The interfering substances study was performed to evaluate the effects of endogenous and exogenous substances that may be present in positive blood culture bottles on the performance of the VITEK® REVEAL™ GN AST Assay and VITEK® REVEAL™ AST System. Three (3) exogenous substances (anticoagulants) and six (6) endogenous substances were tested on the VITEK REVEAL™ AST System (Table 5a) at higher concentrations than the concentrations found in a patient blood sample according to CLSI-EP07 and CLSI-EP37. The substances were prepared and added to pooled human blood to achieve the target concentration. Five (5) organisms (E. coli, P. aeruginosa, K. pneumoniae, E. cloacae, A. baumannii) were tested in triplicate BD BACTEC™ Aerobic Plus bottles in the presence of each interfering substance. Additionally, triplicate control bottles without the interferent were tested in parallel.

The VITEK® REVEAL™ MIC results for bottles containing interferent were compared to the modal MIC results of the control bottles without interferent. The samples met acceptance

{20}------------------------------------------------

criteria if the EA and CA were ≥95% when comparing the interferent-containing bottles to the control bottles. Overall, the EA and CA for each interferant tested across almost all organisms and antimicrobials were >95% when compared to the control samples (Table 5a). Eight antibiotic/interferent combinations did not meet EA acceptance criteria, however, further testing determined these low values were not caused by interference (Table 5b, 5c). These data suggest that the interferents tested do not impact performance of the VITEK" REVEAL™ GN AST Assay tested on the VITEK® REVEAL™ AST System.

Interferent	NormalConcentrations	ConcentrationTested	Overall performance
			EA	CA
Exogenous substances
Heparin	0.35-1 units/mL	>3 units/mL	98.8% (255/258)	99.2% (262/264)
Sodium Citrate	3.2-3.8% w/v	>6% w/v	97.6% (244/250)	98.8% (253/256)
Sodium Polyanetholesulfonate	0.03-0.05% w/v	>2% w/v	98.4% (247/251)	99.2% (254/256)
Endogenous substances
Conjugated bilirubin	0-0.0002 mg/mL	>0.02 mg/mL	100.0% (248/248)	98.8% (251/254)
Gamma-globulin	6-13 mg/mL	>20 mg/mL	100.0% (248/248)	99.6% (253/254)
Triglycerides	1.5-5 mg/mL	>15 mg/mL	99.6% (246/247)	98.0% (248/253)
Hemolysate (Hemoglobin)	100-200 mg/mL	>200 mg/mL	99.2% (247/249)	98.4% (251/255)
WBCs (Mononuclear cells)	$4.5X10^6 - 1.0X10^7$ /mL	$>1.2 x 10^7$ / mL	100% (245/245)	99.2% (249/251)
Plateletsa	150,000 - 400,000/μL	>400,000/μL	99.8% (942/944)	98.9% (963/974)

Table 5a. Exogenous and Endogenous Interferent Results Summary
----------------------------------------------------------------

® Fifteen-sixteen strains (including K. oxrogenes, C. koseri, and S. marcescens strains) per antibiotic were tested for interference with platelets.

"Interference has not been established for the following antibiotic/organism combinations for all interferents, except platelets: Amoxicillinclavulanate/Enterobacterales, Aztreonam/ Enterobacterales, Ceftazidime/ Enterobacterales, Ceftriaxone/Enterobacterales, Ciprofloxacin/P. aeruginosa, Ertapenem/Enterobacterales, Imipenem/ Enterobacterales.

Table 5b. Essential and categorical agreement values of VITEK® REVEAL™ AST results for test blood
cultures containing potential endogenous interfering substances

EndogenousInterferent	Conjugated bilirubin		Gamma-Globulin		Triglycerides		Hemolysate		Mononuclear Cells
Antibiotic	EA	CA	EA	CA	EA	CA	EA	CA	EA	CA
Amikacin	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Amoxicillin /clavulanate	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)
Ampicillin /sulbactam	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)
Aztreonam	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	91.67%(11/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Cefepime	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Cefotaxime	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Ceftazidimea	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	86.67%(13/15)	100%(15/15)	93.33%(14/15)	100%(15/15)	100%(15/15)	100%(15/15)

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VITEK® REVEAL™ AST System and VITEK® REVEAL™ GN AST Assay Traditional 510(k) Submission

Ceftazidime /avibactamb	100%(11/11)	100%(11/11)	100%(11/11)	100%(11/11)	100%(11/11)	100%(11/11)	91.67%(11/12)	91.67%(11/12)	100%(12/12)	100%(12/12)
Ceftolozane /tazobactam	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Ceftriaxone	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(8/8)	100%(8/8)
Cefuroxime	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)	100%(6/6)
Ciprofloxacin	100%(12/12)	91.67%(11/12)	100%(12/12)	91.67%(11/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Ertapenem	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(8/8)	100%(8/8)	100%(9/9)	100%(9/9)	100%(8/8)	100%(8/8)
ESBL Confirmation	-	100%(6/6)	-	100%(6/6)	-	100%(6/6)	-	100%(6/6)	-	100%(6/6)
Gentamicin	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Imipenem	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Levofloxacin	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	75%(9/12)	100%(12/12)	75%(9/12)	100%(12/12)	83.33%(10/12)
Meropenem	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Meropenem /vaborbactamc	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	88.89%(8/9)	88.89%(8/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)
Piperacillin /tazobactam	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Tetracycline	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)
Tobramycin	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Trimethoprim /sulfamethoxazole	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)	100%(9/9)
Overallperformance	100.0%(248/248)	98.8%(251/254)	100.0%(248/248)	99.6%(253/254)	99.6%(246/247)	98.0%(248/253)	99.2%(247/249)	98.4%(251/255)	100%(245/245)	99.2%(249/251)

ª Ceftazidime in the presence of hemolysate (LPD) had an EA < 95% for K. pneumonioe. In each instance, one replicate was out of EA yet was within category agreement (CA), and thus is not expected to impact patient care. In addition, variable MIC values were attributed to this strain's growth pattern detection by the system. This is noted in a footnote in the device labeling.

h Ceftazidime/Avibactam in the presence of hemolysate (RBC) had an EA <95% for P. aeruginosa due to one replicate being out of EA. However, this result is within category agreement (CA), and thus is not expected to impact patient a footnote in the device labeling. • Meropenem/Vaborbactam in the presence of triglycerides (LPD) had an EA <95% for E. cloacoe due to one replicate being out of EA. Upon repeat testing, the EA was found to be 100% This is noted in a footnote in the device labeling.

Table 5c. Essential and categorical agreement values of VITEK® REVEAL™ AST results for test blood cultures containing potential exogenous interfering substances

ExogenousInterferent	Heparin		Sodium Citrate		SodiumPolyanetholesulfonate
Antibiotic	EA	CA	EA	CA	EA	CA
Amikacin	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Amoxicillin /clavulanate	100% (5/5)	100% (5/5)	100% (5/5)	100% (5/5)	100% (9/9)	100% (9/9)
Ampicillin /sulbactam	100% (9/9)	88.89%(8/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)

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	100%	100%	100%	100%	100%	100%
Aztreonam	(12/12)	(12/12)	(12/12)	(12/12)	(12/12)	(12/12)
Cefepime	100%(11/11)	100%(11/11)	100%(11/11)	100%(11/11)	100%(12/12)	100%(12/12)
Cefotaxime	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Ceftazidimea	100%(15/15)	100%(15/15)	80%(12/15)	100%(15/15)	100%(15/15)	100%(15/15)
Ceftazidime /avibactam	100%(11/11)	100%(11/11)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Ceftolozane /tazobactam	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Ceftriaxoneb	88.89%(8/9)	88.89%(8/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)
Cefuroxime	100% (6/6)	100% (6/6)	100% (6/6)	100% (6/6)	100% (6/6)	100% (6/6)
Ciprofloxacin	100%(11/11)	100%(11/11)	100%(11/11)	100%(11/11)	100%(12/12)	100%(12/12)
Ertapenem	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)
ESBL Confirmation		100% (6/6)		100% (6/6)		100% (6/6)
Gentamicin	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Imipenem	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Levofloxacin	100%(12/12)	100%(12/12)	100%(11/11)	72.73%(8/11)	100%(10/10)	80% (8/10)
Meropenemc	93.33%(14/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Meropenem /vaborbactamd	88.89%(8/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)
Piperacillin /tazobactam	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)	100%(15/15)
Tetracycline	100% (8/8)	100% (8/8)	100% (8/8)	100% (8/8)	100% (9/9)	100% (9/9)
Tobramycin	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)	100%(12/12)
Trimethoprim /sulfamethoxazole	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)	100% (9/9)
Overallperformance	98.8%(255/258)	99.2%(262/264)	97.6%(244/250)	98.8%(253/256)	98.4%(247/251)	99.2%(254/256)

a Ceftazidime in the presence of, sodium citrate had an EA <95% for K. pneumonioe. One replicate was out of EA yet was within category agreement (CA), and thus is not expected to impact patient care. In addition, variable MC values were attributed to this strain's growth pattern detection by the system. This is noted in a footnote in the device labeling.

ී Ceftriaxone in the presence of heparin had an EA <95% for K. pneumonioe. The low EA was due to one replicate being out of EA. Upon repeat testing, the EA was found to be 100%. This is noted in a footnote in the device labeling.

f Meropenem in the presence of heparin had an EA <95% for K. pneumonioe due to one replicate being out of EA. However, this result is within category agreement (CA), and thus is not expected to impact patient care. This is noted in a footnote in the device labeling.

4 Meropenem/Vaborbactam in the presence of heparin had an EA <95% for K. pneumoniae due to one replicate being out of EA. However, this result is within category agreement (CA), and thus is not expected to impact patient care. This is noted in the device labeling.

Interfering Antibiotics

The interfering antibiotics study was performed to evaluate the effects of antimicrobial substances that may be present in positive blood cultures (from bottles not containing antibiotic-inactivating resin) on the performance of the VITEK® REVEAL™ GN AST Assay and

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the VITEK" REVEAL™ AST System. One (1) antibiotic from nine (9) of the main classes of antibiotics that target Gram-negative organisms was tested as the interfering agent. The antibiotics were prepared according to CLSI-M100 and then added to pooled human blood to achieve the target concentration. Antibiotic concentrations for testing were chosen based on antibiotic package insert information for the highest concentrations found in blood during treatment or CLSI-EP37 (three times the highest concentration when a resistant strain was available for testing). A minimum of one (1) Gram-negative strain resistant to each interfering antimicrobial was tested in triplicate in BD BACTEC™ Standard aerobic bottles, which do not contain resins and do not have neutralization capabilities. Triplicate control bottles containing the organism without the antimicrobial interferant were tested in parallel.

The VITEK" REVEAL™ MIC results for bottles containing interferent were compared to the modal MIC results of the control bottles without interferent. Overall, the EA for each interfering antimicrobial tested was ≥97% and the CA was >97% when compared to the control samples, meeting the overall acceptance criteria of >95% (Table 6). Potential interference was observed with ampicillin/sulbactam with one strain of E. coli; however, the interference was not replicated when testing a different strain or a different antimicrobial from the same class. Therefore, it was concluded that the interference was strain specific.

Antimicrobial Class	Interferent	Test Concentration[µg/ml]	Overall performance
			EA	CA
Penicillins	Ampicillin	75 a	100.0% (66/66)	97.1% (67/69)
β-lactam combinationagents	Ampicillin/sulbactam	150 Ampicillin /88 sulbactam b	97.0% (255/263)	97.0% (261/269)
Monobactams	Aztreonam	242c	100.0% (119/119)	100.0% (121/121)
Cephalosporins	Cefotaxime	176c	100.0% (92/92)	100.0% (92/92)
Carbapenems	Meropenem	113c	100.0% (89/89)	100.0% (89/89)
Fluoroquinolones	Ciprofloxacin	12a	100.0% (130/130)	100.0% (130/130)
Folate SynthesisInhibitor	Trimethoprim/sulfamethoxazole	8.8 Trimethoprim /106 sulfamethoxazoleb	100.0% (89/89)	100.0% (89/89)
Tetracyclines	Tetracycline	24 a	100.0% (72/72)	97.2% (70/72)
Aminoglycosides	Gentamicin	30a	100.0% (47/47)	100.0% (47/47)

Table 6. Interfering Antibiotic Results Summary

a Recommended test concentration-3X conc. under therapeutic treatment (CLSI EP37)

b Mean peak serum concentration during therapeutic treatment (Drug packet insert)

< Highest concentration under therapeutic treatment (CLSI EP37)

Carryover and Cross-talk

The carryover and cross-talk studies were performed to demonstrate the effectiveness of the VITEK® REVEAL™ GN AST Assay seal by evaluating whether volatile organic compounds

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(VOCs) are exchanged between individual wells within the VITEK® REVEAL™ GN AST Assay (cross-talk) or from assay to assay run on the same VITEK® REVEAL™ Instrument (carryover).

The cross-talk testing was performed using five (5) species (E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis, and A. baumannii), contrived in blood culture bottles and grown to positivity. Blank 96-well plates were inoculated in a checkerboard pattern with alternating media-only wells and wells with diluted positive blood culture. Organisms were tested in an alternating pattern over 20 days with four (4) total replicates per organism. The sensor response was evaluated in each media-only well for evidence of growth, indicating crosstalk from organism containing wells. The overall rate of cross-talk as evidenced by growth was 0.1% (1/960), meeting the defined acceptance criteria of <0.3% growth, demonstrating seal effectiveness.

To test system carryover, blank 96-well panels containing media alone were tested on VITEK® REVEAL™ Instruments that had been previously used to test VITEK® REVEAL™ GN AST Assays inoculated with contrived positive blood cultures. Testing was performed with a single replicate of a media-only panel over 20 days on 20 VITEK® REVEAL™ Instruments. The sensor response was evaluated in the media-only wells for evidence of growth, indicating carryover from previous VITEK® REVEAL™ GN AST Assays. The overall rate of carryover as evidenced by growth was 0.1% (1/1920), meeting the defined acceptance criteria of <0.3% growth, demonstrating seal effectiveness.

Initial Inoculum

The initial inoculum study was performed to demonstrate that the concentration of bacteria in a patient blood sample inoculated into a blood culture bottle does not impact the final bacterial concentration of the positive blood culture or VITEK® REVEAL™ GN AST Assay results. Testing was performed using five (5) species inoculated into blood culture bottles at three (3) different starting concentrations spanning five (5) orders of magnitude (75,000, 750, and 7.5 CFU). Testing at each initial inoculum concentration was performed in triplicate blood culture bottles for each species evaluated.

The concentrations (CFU/mL) were calculated for all suspensions at the time of inoculation and within two hours of bottle positivity. The final concentration at positivity met the defined acceptance criteria if the average final concentration for each initial inoculum was within one log of the average final concentrations of the other starting inocula. The results demonstrate that regardless of the concentration of the initial inoculum, the final concentrations of the positive blood culture bottles were comparable (+/- 1 log) (Table 7).

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Organism	Initial InoculumDilution	Average Initial CFU	Average FinalCFU/mL
A. baumannii	1:2,000	7.44E+04	5.66E+08
	1:20,0000	7.44E+02	1.03E+08
	1:20,000,000	3.76E+00	1.94E+08
P. aeruginosa	1:2,000	3.38E+04	1.00E+09
	1:200,000	5.55E+02	7.72E+08
	1:20,000,000	2.03E+00	2.28E+08
E. cloacae	1:2,000	6.89E+04	1.64E+08
	1:200,000	4.45E+02	1.85E+08
	1:20,000,000	3.48E+00	1.75E+08
K. pneumoniae	1:2,000	5.66E+04	2.77E+08
	1:200,000	5.77E+02	1.36E+08
	1:20,000,000	2.86E+00	1.63E+08
E. coli	1:2,000	7.00E+04	1.47E+08
	1:200,000	6.89E+02	3.50E+08
	1:20,000,000	3.54E+00	2.62E+08

	Table 7. Average Initial Inoculum Concentrations and Final Bacterial Concentrations at Bottle Positivity
--	----------------------------------------------------------------------------------------------------------	--

The individual MICs determined by the VITEK® REVEAL™ AST System were compared against the reference (BMD) modal MICs. Both essential and categorical agreement were determined for each antibiotic/strain at each initial inoculum concentration. The EA and CA of each concentration compared against BMD was 100%, meeting the acceptance criteria of > 89.9%. Additionally, the VITEK® REVEAL™ MICs for each replicate were compared against the MICs of the other initial inoculum bottles. All results were within ± 1 doubling dilution of each other for all the initial inoculum concentrations, demonstrating that the initial inoculum concentration does not impact VITEK® REVEAL™ AST results.

Method Comparison Study

The purpose of the method comparison study was to evaluate the clinical performance of the VITEK® REVEAL™ GN AST Assay on the VITEK® REVEAL™ AST System in providing quantitative and qualitative antimicrobial susceptibility testing (AST) results from positive blood cultures containing Gram-negative bacteria. AST results (MICs and categorical interpretations) generated by the VITEK® REVEAL™ AST System were compared to results from reference frozen broth microdilution (BMD), tested according to CLSI M07 (11th Edition) Standard. Samples enrolled in the study included leftover, deidentified clinical positive blood culture samples (fresh prospective) and contrived positive blood culture samples, contrived with either clinical stock or challenge isolates.

Sample enrollment and VITEK® REVEAL™ testing were conducted at seven (7) US clinical sites. Five clinical sites tested prospectively collected, fresh samples defined as leftover, deidentified positive clinical blood culture samples from patients suspected of bacteremia.

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Samples were confirmed by Gram stain to contain only Gram-negative bacteria prior to testing on the VITEK® REVEAL™ AST System. Organism identification by an FDA-cleared rapid ID method was required as input into the VITEK® REVEAL™ AST System for AST result generation. Select sites also tested clinical stock isolates from the site's inventory and provided challenge isolates for lower prevalence microorganism-antimicrobial agent combinations. Stock and contrived isolates were contrived in blood culture bottles with human donor blood added and incubated on a continuous monitoring blood culture system until positivity. All positive blood cultures were subcultured to blood agar plates, and the organism identification for all samples was confirmed by an FDA-cleared MALDI ID method.

All reference BMD testing was conducted at a reference testing laboratory. BMD testing was performed in triplicate on custom, 96-well, frozen microdilution plates prepared by the reference testing laboratory. Each isolate was tested in triplicate on BMD panels. Reference BMD testing was performed in accordance with CLSI M07 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically.

The performance of the VITEK® REVEAL™ AST System was determined by comparing the modal MIC results of the reference method to the results of the investigational device. Agreement and acceptance criteria were defined based on FDA guidance (Class II Special Controls Document: Antimicrobial Susceptibility Test (AST) Systems) for each antimicrobial agent. For susceptibility, the primary endpoints are Essential Agreement (EA), Categorical Agreement (CA) and error rates for each antimicrobial agent across all organisms in the intended use. Evaluable organisms for EA are those with MIC results that are within the onscale test range of both the investigational device and the reference method. Essential agreement was determined by comparing MIC as determined by the investigational device to modal MIC as determined by reference BMD testing. Categorial agreement was assessed using FDA-recognized breakpoints (Antimicrobial Susceptibility Test Interpretive Criteria).

A total of 1239 samples were enrolled in the study, including 480 fresh prospective positive blood culture samples, 106 samples from positive blood cultures contrived with clinical stock isolates, and 653 samples contrived with challenge isolates. In total, 124 samples were excluded from final performance analyses due to not meeting inclusion criteria, invalid QC results, or other protocol deviations, as defined below. A total of 1115 samples were included in final performance analyses including 424 fresh prospective blood cultures, 101 contrived samples with clinical stock isolates, and 590 contrived samples with challenge isolates.

Table 8 below summarizes the overall AST performance by breakpoint group for all antimicrobials on the VITEK® REVEAL™ GN AST Assay. This summary includes clinical samples (fresh prospective and contrived stock isolates) and contrived challenge isolates. Overall agreement was high; results not in essential or categorical agreement are noted in the

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individual antimicrobial summaries below. A trending analysis for all indicated species is provided in Table 9.

Sample Type	Total	# EA	% EA	Total Eval	# EA Eval	% EA Eval	# CA	% CA	# S	# R	# vmj	# maj	# min
Amikacin
Enterobacterales
Clinical	443	434	98.0%	421	412	97.9%	442	99.8%	441	1	0	0	1
Challenge	188	185	98.4%	146	143	97.9%	185	98.4%	147	37	0	0	3
Combined	631	619	98.1%	567	555	97.9%	627	99.4%	588	38	0	0	4
A. baumannii-calcoaceticus complex
Clinical	13	9	69.2%	12	8	66.7%	12	92.3%	11	2	0	0	1
Challenge	47	45	95.7%	37	35	94.6%	41	87.2%	29	13	0	0	6
Combined	60	54	90.0%	49	43	87.8%	53	88.3%5	40	15	0	0	7
P. aeruginosa
Clinical	27	26	96.3%	26	25	96.2%	27	100.0%	27	0	0	0	0
Challenge	38	36	94.7%	24	22	91.7%	35	92.1%	11	24	0	0	3
Combined	65	62	95.4%	50	47	94.0%	62	95.4%	38	24	0	0	3
Amoxicillin/clavulanate
Enterobacterales
Clinical	370	361	97.6%	156	147	94.2%	338	91.4%	347	8	0	3	29
Challenge	130	114	87.7%	67	51	76.1%	116	89.2%	61	59	0	0	14
Combined	500	475	95.0%	223	198	88.8%	454	90.8%	408	67	0	3	43
Ampicillin/sulbactam
Enterobacterales
Clinical	286	280	97.9%	142	136	95.8%	219	76.6%	221	25	0	1	66
Challenge	86	84	97.7%	39	37	94.9%	68	79.1%	31	40	0	2	16
Combined	372	364	97.8%	181	173	95.6%	287	77.2%5	252	65	0	3	82
Aztreonam
Enterobacterales
Clinical	374	366	97.9%	55	47	85.5%	364	97.3%	314	51	0	2	8
Challenge	156	150	96.2%	38	32	84.2%	145	92.9%	58	90	0	1	10
Combined	530	516	97.4%	93	79	84.9%	543	96.0%	372	141	0	3	18
P. aeruginosa
Clinical	27	26	96.3%	26	25	96.2%	25	92.6%	23	4	0	0	2
Challenge	38	37	97.4%	25	24	96.0%	31	81.6%	14	18	0	0	7
Combined	65	63	96.9%	51	49	96.1%	56	86.2%5	37	22	0	0	9
Cefepime
Enterobacterales
Clinical	397	384	96.7%	52	39	75.0%	384	96.7%	344	42	0	2	11
Challenge	182	172	94.5%	64	54	84.4%	171	94.0%	88	77	0	1	10
Combined	579	556	96.0%	116	93	80.2%	555	95.9%	432	119	0	3	21
P. aeruginosa
Clinical	28	26	92.9%	28	26	92.9%	27	96.4%	26	2	0	1	0
Challenge	38	38	100.0%	18	18	100.0%	37	97.4%	7	31	0	1	0
Combined	66	64	97.0%	46	44	95.7%	64	97.0%	33	33	0	2	0
Cefotaxime
Enterobacterales
Clinical	381	374	98.2%	24	17	70.8%	379	99.5%	313	68	0	0	2
Sample Type	Total	# EA	% EA	TotalEval	# EAEval	% EA Eval	# CA	% CA	# S	# R	#vmj	#maj	#min
Combined	554	539	97.3%	66	51	77.3%	549	99.1%	369	183	0	2	3
A. baumannii-calcoaceticus complex*
Clinical	13	13	100.0%	9	9	100.0%	13	100.0%	0	13	0	0	0
Challenge	25	25	100.0%	5	5	100.0%	25	100.0%	0	25	0	0	0
Combined	38	38	100.0%	14	14	100.0%	38	100.0%	0	38	0	0	0
CeftazidimeEnterobacterales
Clinical	398	381	95.7%	118	101	85.6%	384	96.5%	339	51	0	1	13
Challenge	182	172	94.5%	57	47	82.5%	179	98.4%	74	106	0	0	3
Combined	580	553	95.3%	175	148	84.6%	563	97.1%	413	157	0	1	16
A. baumannii-calcoaceticus complex
Clinical	13	12	92.3%	9	8	88.9%	12	92.3%	9	4	0	0	1
Challenge	26	26	100.0%	12	12	100.0%	25	96.2%	3	21	0	0	1
Combined	39	38	97.4%	21	20	95.2%	37	94.9%	12	25	0	0	2
Ceftazidime/avibactamEnterobacterales
Clinical	421	408	96.9%	176	163	92.6%	420	99.8%	420	1	0	1	N/A
Challenge	203	189	93.7%	126	112	88.9%	202	99.5%	150	53	1	0	N/A
Combined	624	597	95.7%	302	275	91.1%	692	99.7%	570	54	1	1	N/A
P. aeruginosa
Clinical	28	28	100.0%	27	27	100.0%	28	100.0%	27	1	0	0	N/A
Challenge	65	63	96.9%	44	42	95.5%	63	96.9%	39	26	0	2	N/A
Combined	93	91	97.8%	71	69	97.2%	91	97.8%	66	27	0	2	N/A
Ceftolozane/tazobactam
Enterobacterales
Clinical	346	313	90.5%	321	288	89.7%	339	98.0%	336	8	1	1	5
Challenge	164	161	98.2%	127	124	97.6%	159	97.0%	100	59	0	0	5
Combined	510	474	92.9%	448	412	92.0%	498	97.6%	436	67	1	1	10
P. aeruginosa
Clinical	28	28	100.0%	28	28	100.0%	27	96.4%	27	0	0	0	1
Challenge	38	38	100.0%	10	10	100.0%	38	100.0%	10	28	0	0	0
Combined	66	66	100.0%	38	38	100.0%	65	98.5%	37	28	0	0	1
Ceftriaxone
Enterobacterales
Clinical	394	390	99.0%	10	6	60.0%	392	99.5%	326	65	0	1	1
Challenge	232	218	94.0%	48	34	70.8%	213	91.8%	79	135	0	2	17
Combined	626	608	97.1%	58	40	69.0%	605	96.6%	405	200	0	3	18
Cefuroxime
Enterobacterales
Clinical	384	368	95.8%	274	258	94.2%	374	97.4%	316	68	1	9	N/A
Challenge	138	132	95.7%	60	54	90.0%	134	97.1%	57	81	0	4	N/A
Combined	522	500	95.8%	334	312	93.4%	508	97.3%	373	149	1	13	N/A
Ciprofloxacin
Enterobacterales
Clinical	464	461	99.4%	60	57	95.0%	448	96.6%	367	92	0	0	16
Challenge	217	213	98.2%	62	58	93.5%	203	93.5%	96	109	1	1	12
Combined	681	674	99.0%	122	115	94.3%	651	95.6%	463	201	1	1	28
P. aeruginosa
Clinical	28	23	82.1%	14	9	64.3%	26	92.9%	25	2	0	1	1
Challenge	42	42	100.0%	4	4	100.0%	42	100.0%	8	34	0	0	0
Sample Type	Total	# EA	% EA	Total Eval	# EA Eval	% EA Eval	# CA	% CA	# S	# R	# vmj	# maj	# min
Combined	70	65	92.9%	18	13	72.2%	68	97.1%	33	36	0	1	1
Ertapenem	Enterobacterales
Clinical	368	363	98.6%	12	7	58.3%	366	99.5%	361	5	0	1	1
Challenge	125	119	95.2%	16	10	62.5%	121	96.8%	61	62	0	0	4
Combined	493	482	97.8%	28	17	60.7%	487	98.8%	422	67	0	1	5
Gentamicin	Enterobacterales
Clinical	458	445	97.2%	315	302	95.9%	453	98.9%	419	38	1	1	3
Challenge	226	216	95.6%	123	113	91.9%	219	96.9%	159	61	0	1	6
Combined	684	661	96.6%	438	415	94.7%	672	98.2%	578	99	1	2	9
P. aeruginosa
Clinical	27	27	100.0%	26	26	100.0%	26	96.3%	25	0	0	0	1
Challenge	38	36	94.7%	14	12	85.7%	36	94.7%	7	27	0	0	2
Combined	65	63	96.9%	40	38	95.0%	62	95.4%	32	27	0	0	3
Imipenem	Enterobacterales
Clinical	402	397	98.8%	41	36	87.8%	400	99.5%	395	5	0	0	2
Challenge	170	164	96.5%	55	49	89.1%	159	93.5%	92	68	0	0	11
Combined	572	561	98.1%	96	85	88.5%	559	97.7%	487	73	0	0	13
A. baumannii-calcoaceticus complex
Clinical	13	12	92.3%	2	1	50.0%	12	92.3%	8	5	0	0	1
Challenge	32	32	100.0%	8	8	100.0%	30	93.8%	7	21	0	0	2
Combined	45	44	97.8%	10	9	90.0%	42	93.3%	15	26	0	0	3
P. aeruginosa
Clinical	27	24	88.9%	26	23	88.5%	23	85.2%	21	4	2	0	2
Challenge	38	37	97.4%	9	8	88.9%	38	100.0%	1	37	0	0	0
Combined	65	61	93.8%	35	31	88.6%	61	93.8%	22	41	2	0	2
Levofloxacin	Enterobacterales
Clinical	481	476	99.0%	105	100	95.2%	469	97.5%	385	88	1	0	11
Challenge	243	242	99.6%	93	92	98.9%	228	93.8%	115	109	0	0	15
Combined	724	718	99.2%	198	192	97.0%	697	96.3%	500	197	1	0	26
P. aeruginosa
Clinical	28	27	96.4%	25	24	96.0%	26	92.9%	24	2	0	1	1
Challenge	46	45	97.8%	14	13	92.9%	44	95.7%	10	35	0	0	2
Combined	74	72	97.3%	39	37	94.9%	70	94.6%	34	37	0	1	3
Meropenem	Enterobacterales
Clinical	406	399	98.3%	19	12	63.2%	403	99.3%	402	4	0	2	1
Challenge	206	196	95.1%	72	62	86.1%	200	97.1%	132	71	0	1	5
Combined	612	595	97.2%	91	74	81.3%	603	98.5%	534	75	0	3	6
A. baumannii-calcoaceticus complex
Clinical	13	12	92.3%	10	9	90.0%	13	100.0%	8	5	0	0	0
Challenge	48	43	89.6%	31	26	83.9%	46	95.8%	21	25	0	0	2
Combined	61	55	90.2%	41	35	85.4%	59	96.7%	29	30	0	0	2
P. aeruginosa
Clinical	27	26	96.3%	26	25	96.2%	25	92.6%	24	1	0	0	2
Challenge	38	37	97.4%	16	15	93.8%	35	92.1%	3	30	0	0	3
Sample Type	Total	# EA	% EA	Total Eval	# EA Eval	% EA Eval	# CA	% CA	# S	# R	# vmj	# maj	# min
Enterobacterales
Clinical	437	432	98.9%	10	5	50.0%	436	99.8%	436	1	0	0	1
Challenge	255	240	94.1%	80	65	81.2%	242	94.9%	199	52	0	0	13
Combined	692	672	97.1%	90	70	77.8%	678	98.0%	635	53	0	0	14
Piperacillin/tazobactam
Enterobacterales
Clinical	358	336	93.9%	46	24	52.2%	344	96.1%	338	13	1	3	10
Challenge	131	127	97.0%	28	24	85.7%	120	91.6%	63	59	0	1	10
Combined	489	463	94.7%	74	48	64.9%	464	94.9%	401	72	1	4	20
Tetracycline
Enterobacterales
Clinical	365	359	98.4%	112	106	94.6%	359	98.4%	281	81	0	3	3
Challenge	148	146	98.6%	77	75	97.4%	139	93.9%	75	69	0	0	9
Combined	513	505	98.4%	189	181	95.8%	498	97.1%	356	150	0	3	12
A. baumannii-calcoaceticus complex
Clinical	13	13	100.0%	6	6	100.0%	13	100.0%	6	5	0	0	0
Challenge	26	26	100.0%	4	4	100.0%	26	100.0%	1	25	0	0	0
Combined	39	39	100.0%	10	10	100.0%	39	100.0%	7	30	0	0	0
Tobramycin
Enterobacterales
Clinical	462	445	96.3%	458	441	96.3%	437	94.6%	420	31	2	1	22
Challenge	195	189	96.9%	150	144	96.0%	186	95.4%	112	78	1	0	8
Combined	657	634	96.5%	608	585	96.2%	623	94.8%	532	109	3	1	30
P. aeruginosa
Clinical	27	27	100.0%	27	27	100.0%	27	100.0%	27	0	0	0	0
Challenge	38	38	100.0%	8	8	100.0%	38	100.0%	7	31	0	0	0
Combined	65	65	100.0%	35	35	100.0%	65	100.0%	34	31	0	0	0
Trimethoprim/sulfamethoxazole
Enterobacterales
Clinical	338	326	96.4%	15	3	20.0%	331	97.9%	258	80	2	5	N/A
Challenge	142	130	91.5%	23	11	47.8%	132	93.0%	67	75	1	9	N/A
Combined	480	456	95.0%	38	14	36.8%	463	96.5%	325	155	3	14	N/A
ESBL Confirmation
Enterobacterales
Clinical	340	N/A	N/A	N/A	N/A	N/A	338	99.4%	287	53	1	1	N/A
Challenge	68	N/A	N/A	N/A	N/A	N/A	64	94.1%	49	19	0	4	N/A
Combined	408	N/A	N/A	N/A	N/A	N/A	402	98.5%	336	72	1	5	N/A

Table 8. Summary of VITEK® REVEAL™ Results, All Species

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VITEK® REVEAL™ AST System and VITEK® REVEAL™ GN AST Assay Traditional 510(k) Submission

{29}------------------------------------------------

{30}------------------------------------------------

VITEK® REVEAL™ AST System and VITEK® REVEAL™ GN AST Assay Traditional 510(k) Submission

No cefotaxime susceptible strains were evaluated for A. baumannii-calcoaceticus complex. Cefotaxime susceptibility is rare in

A. baumannii-calcoaceticus complex

Amikacin

A total of 756 samples were evaluated with amikacin including 631 Enterobacterales species (299 E. coli, 123 K. pneumoniae group, 40 K. oxytoca, 48 K. aerogenes, 39 E. cloacae complex, 23 C. freundii complex, 31 P. mirabilis, 28 S. marcescens), 60 A. baumannii-calcoaceticus complex strains, and 65 P. aeruginosa strains.

{31}------------------------------------------------

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 98.1% and CA of 99.4%, with no very major or major errors.

The overall performance for A. baumannii-calcoaceticus complex resulted in EA of 90.0% and CA of 88.3%, due to all minor errors. Low CA is addressed by the following limitation in product labeling:

For Amikacin, perform an alternative method of testing prior to reporting of results for A. baumannii-calcoaceticus complex when the MIC is 32 µg/mL due to the occurrence of minor errors that were in essential agreement, resulting in a category agreement below 90%.

The overall performance for P. aeruginosa met defined acceptance criteria, with EA of 95.4% and CA of 95.4%. There were no very major or major errors.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ amikacin MIC values for C. freundii complex, K. oxytoca, and P. aeruginosa tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ amikacin MIC values for S. marcescens tended to be exact match or at least one doubling dilution higher than the reference method.

Amoxicillin/clavulanate

A total of 500 samples were evaluated with amoxicillin/clavulanate, all Enterobacterales species (302 E. coli, 124 K. pneumoniae group, 41 K. oxytoca, and 33 P. mirabilis).

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 95.0% and CA of 90.8%. There were no very major errors and three major errors. CA for E. coli was 88.1% due to a majority of minor errors. Low CA is addressed by the following limitation in product labeling:

For Amoxicillin/Clavulanate, perform an alternative method of testing prior to reporting of results for E. coli when the MIC is 16 µg/mL due to the occurrence of minor errors that were in essential agreement, resulting in a category agreement below 90%.

The following statement is added to the AST performance table in product labeling to address trending:

{32}------------------------------------------------

VITEK® REVEAL™ amoxicillin/clavulanate MIC values for E. coli, K. pneumoniae group, and P. mirabilis tended to be exact match or at least one doubling dilution higher than the reference method.

Ampicillin/sulbactam

A total of 372 samples were evaluated with ampicillin/sulbactam, all Enterobacterales species (300 E. coli, 40 K. oxytoca, and 32 P. mirabilis).

The overall performance for Enterobacterales species resulted in EA of 97.8% and CA of 77.2%. There were no very major errors and three major errors. CA for E. coli was 77.1% due to primarily minor errors, and CA for K. oxytoca was 65.0% due to all minor errors. As the evaluable EA was high (94.3% and 100.0%, respectively), performance for E. coli and K. oxytoca is considered acceptable.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ ampicillin/sulbactam MIC values for E. coli tended to be exact match or at least one doubling dilution higher than the reference method.

Aztreonam

A total of 595 samples were evaluated with aztreonam, including 530 Enterobacterales species (295 E. coli, 127 K. pneumoniae group, 43 K. oxytoca, 39 E. cloacae complex, 26 C. freundii complex) and 65 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 97.4% and CA of 96.0%. There were no very major errors and three major errors.

The overall performance for P. aeruginosa met defined acceptance criteria for EA, with EA of 96.9%. CA was 86.2% due to all minor errors. As the evaluable EA was high (96.1%), performance for P. aeruginosa is considered acceptable.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ aztreonam MIC values for E. coli, K. oxytoca and P. aeruginosa tended to be exact match or at least one doubling dilution lower than the reference method.

Cefepime

{33}------------------------------------------------

A total of 645 samples were evaluated with cefepime, including 579 Enterobacterales species (301 E. coli, 121 K. pneumoniae group, 40 K. oxytoca, 46 K. aerogenes, 35 E. cloacae complex, 36 C. koseri) and 66 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 96.0% and CA of 95.9%. There were no very major errors and three major errors. CA for E. cloacae complex was 88.6% due to all minor errors. As the evaluable EA was high (94.4%), performance for E. cloacae complex is considered acceptable.

The overall performance for P. aeruginosa resulted in EA of 97.0% and CA of 97.0%. There were no very major errors and two major errors. Since there is no intermediate category for P. aeruginosa, and both major errors were within essential agreement, this resulted in an acceptable adjusted major error rate.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ cefepime MIC values for E. cloacae complex tended to be exact match or at least one doubling dilution higher than the reference method.

Cefotaxime

A total of 592 samples were evaluated with cefotaxime, including 554 Enterobacterales species (303 E. coli, 123 K. pneumoniae group, 42 K. oxytoca, 47 K. aerogenes, 39 E. cloacae complex) and 38 A. baumannii-calcoaceticus complex strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 97.3% and CA of 99.1%. There were no very major errors and two major errors.

The overall performance for A. baumannii-calcoaceticus complex met defined acceptance criteria with EA of 100.0% and CA of 100.0%. No cefotaxime susceptible strains were evaluated. Cefotaxime susceptibility is rare in A. baumannii-calcoaceticus complex.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ cefotaxime MIC values for K. aerogenes and A. baumannii-calcoaceticus complex tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ cefotaxime MIC values for E. coli and K. pneumoniae group tended to be exact match or at least one doubling dilution higher than the reference method.

{34}------------------------------------------------

No cefotaxime susceptible strains were evaluated for A. baumannii-calcoaceticus complex. Cefotaxime susceptibility is rare in A. baumannii-calcoaceticus complex.

Ceftazidime

A total of 619 samples were evaluated with ceftazidime, including 580 Enterobacterales species (302 E. coli, 123 K. pneumoniae group, 40 K. oxytoca, 47 K. aerogenes, 38 E. cloacae complex, 30 C. koseri) and 39 A. baumannii-calcoaceticus complex strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 95.3% and CA of 97.1%. There were no very major errors and one major error.

The overall performance for A. baumannii-calcoaceticus complex met defined acceptance criteria with EA of 97.4% and CA of 94.9%. There were no very major errors and no major errors.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ ceftazidime MIC values for E. coli, K. pneumoniae group, K. oxytoca, K. aerogenes, and C. koseri tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ ceftazidime MIC values for A. baumannii-calcoaceticus complex tended to be exact match or at least one doubling dilution higher than the reference method.

Ceftazidime/avibactam

A total of 717 samples were evaluated with ceftazidime/avibactam, including 624 Enterobacterales species (301 E. coli, 124 K. pneumoniae group, 67 K. aerogenes, 39 E. cloacae complex, 24 C. freundii complex, 30 C. koseri, 39 P. mirabilis) and 93 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 95.7% and CA of 99.7%. There was one very major error and one major error. The single very major error was for K. aerogenes, but because there is no intermediate category, and the error was within essential agreement, it resulted in an acceptable adjusted very major error rate of 0.0%.

The overall performance for P. aeruginosa resulted in EA of 97.8% and CA of 97.8%. There were two major errors, with an acceptable major error rate of 3.0%.

{35}------------------------------------------------

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ ceftazidime/avibactam MIC values for Enterobacterales tended to be exact match or at least one doubling dilution lower than the reference method.

Ceftolozane/Tazobactam

A total of 576 samples were evaluated with ceftolozane/tazobactam, including 510 Enterobacterales species (293 E. coli, 40 K. oxytoca, 45 K. aerogenes, 37 E. cloacae complex, 42 C. koseri, 31 P. mirabilis, 22 P. vulgaris) and 66 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 92.9% and CA of 97.6%. There was one very major error and one major error. The one (1) very major error was considered a random error due to the limited number of resistant isolates tested.

CA for K. aerogenes was 88.9% due to all minor errors. As the evaluable EA is high (92.3%), K. aerogenes performance is considered acceptable.

The overall performance for P. aeruginosa met defined acceptance criteria with EA of 100.0% and CA of 98.5%. There were no very major errors and no major errors.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ ceftolozane/tazobactam MIC values for E. coli, K. aerogenes, K. oxytoca, and P. aeruginosa tended to be exact match or at least one doubling dilution lower than the reference method.

Ceftriaxone

A total of 626 samples were evaluated with ceftriaxone, all Enterobacterales species (294 E. coli, 132 K. pneumoniae group, 47 K. oxytoca, 52 K. aerogenes, 46 E. cloacae complex, and 55 P. mirabilis).

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 97.1% and CA of 96.6%. There were no very major errors and three major errors.

The following statements are added to the AST performance table in product labeling to address trending:

{36}------------------------------------------------

VITEK® REVEAL™ ceftriaxone MIC values for K. pneumoniae group tended to be at least one doubling dilution higher than the reference method.

Cefuroxime

A total of 522 samples were evaluated with cefuroxime, all Enterobacterales species (300 E. coli, 119 K. pneumoniae group, 40 K. oxytoca, 27 C. koseri, and 36 P. mirabilis).

The overall performance for Enterobacterales species resulted in EA of 95.8% and CA of 97.3%. There was one very major error and thirteen major errors. Since there is no intermediate category for cefuroxime, the major error rate is 2.4% when adjusted for EA, which is acceptable. The major error rates for K. pneumoniae group (five major errors), K. oxytoca (four major errors), and C. koseri (one major error) are addressed by the following limitations in product labeling:

Due to the occurrence of major errors with cefuroxime, isolates of K. pneumoniae group that provide an MIC of 16 µg/mL should be retested by an alternate method, if critical to patient care.

Due to the occurrence of major errors with cefuroxime, isolates of K. oxytoca that provide an MIC of 32 µg/mL should be retested by an alternate method, if critical to patient care.

Due to the occurrence of major errors with cefuroxime, isolates of C. koseri that provide an MIC of >32 mg/mL should be retested by an alternate method, if critical to patient care.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ cefuroxime MIC values for C. koseri, E. coli, and P. mirabilis tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ cefuroxime MIC values for K. pneumoniae group tended to be exact match or at least one doubling dilution higher than the reference method.

Ciprofloxacin

A total of 751 samples were evaluated with ciprofloxacin, including 681 Enterobacterales species (303 E. coli, 123 K. pneumoniae group, 46 K. oxytoca, 47 K. aerogenes, 39 E. cloacae complex, 26 C. freundii complex, 38 P. mirabilis, 33 P. vulgaris, 26 S. marcescens) and 70 P. aeruginosa strains.

{37}------------------------------------------------

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 99.0% and CA of 95.6%. There was one very major error and one major error. The single very major error was observed for P. mirabilis and is addressed by the following limitation in product labeling:

Due to the occurrence of a very major error with ciprofloxacin, isolates of P. mirabilis that provide an MIC of 0.25 µg/mL should be retested by an alternate method.

The overall performance for P. aeruginosa resulted in EA of 92.9% and CA of 97.1%. There were no very major errors and one major error, with an acceptable major error rate of 3.0%.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ ciprofloxacin MIC values for E. coli, K. pneumoniae group, E. cloacae complex, and C. freundii complex tended to be exact match or at least one doubling dilution higher than the reference method.

Ertapenem

A total of 493 samples were evaluated with ertapenem, all Enterobacterales species (301 E. coli, 126 K. pneumoniae group, 40 P. mirabilis, and 26 P. vulgaris).

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 97.8% and CA of 98.8%. There were no very major errors and one major error.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ ertapenem MIC values for E. coli tended to be exact match or at least one doubling dilution lower than the reference method.

Gentamicin

A total of 749 samples were evaluated with gentamicin, including 684 Enterobacterales species (299 E. coli, 123 K. pneumoniae group, 40 K. oxytoca, 46 K. aerogenes, 30 C. freundii complex, 35 C. koseri, 30 P. mirabilis, 55 P. vulgaris, and 26 S. marcescens) and 65 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 96.6% and CA of 98.2%. There was one very major error and two major errors. The very major error for E. coli is addressed by the following limitation in product labeling:

{38}------------------------------------------------

Due to the occurrence of a very major error with gentamicin, isolates of E. coli that provide an MIC of 4 µq/mL should be retested by an alternate method.

The overall performance for P. aeruginosa met defined acceptance criteria with EA of 96.9% and CA of 95.4%. There were no very major errors and no major errors.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ gentamicin MIC values for E. coli, K. aerogenes, K. pneumoniae group, C. freundii complex, and S. marcescens tended to be exact match or at least one doubling dilution hiqher than the reference method.

Imipenem

A total of 682 samples were evaluated with imipenem, including 572 Enterobacterales species (301 E. coli, 124 K. pneumoniae group, 44 K. oxytoca, 39 E. cloacae complex, 38 C. koseri, and 26 S. marcescens), 45 A. baumannii-calcoaceticus complex strains, and 65 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 98.1% and CA of 97.7%. There were no very major errors and no major errors.

The overall performance for A. baumannii-calcoaceticus complex strains met defined acceptance criteria with EA of 97.8% and CA of 93.3%. There were no very major errors and no major errors.

The overall performance for P. aeruginosa resulted in EA of 93.8% and CA of 93.8%. There were two very major errors, which is addressed by the following limitation in product labeling:

Due to the occurrence of very major errors with imipenem, isolates of P. aeruginosa that provide an MIC of 2 µg/mL should be retested by an alternate method.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ imipenem MIC values for E. cloacae complex, A. baumannii-calcoaceticus complex, and P. aeruginosa tended to be exact match or at least one doubling dilution lower than the reference method.

{39}------------------------------------------------

VITEK® REVEAL™ imipenem MIC values for E. coli and K. pneumoniae group tended to be exact match or at least one doubling dilution higher than the reference method.

Levofloxacin

A total of 798 samples were evaluated with levofloxacin, including 724 Enterobacterales species (300 E. coli, 124 K. pneumoniae group, 44 K. oxytoca, 47 K. aerogenes, 39 E. cloacae complex, 31 C. freundii complex, 37 C. koseri, 31 P. mirabilis, 36 P. vulgaris, and 35 S. marcescens) and 74 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 99.2% and CA of 96.3%. There was one very major error and no major errors. The single very major error was observed with P. mirabilis and is addressed by the following limitation in product labeling:

Due to the occurrence of a very major error with levofloxacin, isolates of P. mirabilis that provide an MIC of 0.5 µg/mL should be retested by an alternate method.

The overall performance for P. aeruginosa resulted in EA of 97.3% and CA of 94.6%. There were no very major errors and one major error, with an acceptable major error rate of 2.9%.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ levofloxacin MIC values for K. pneumoniae group, K. aerogenes, E. cloacae complex, C. freundii complex, and P. mirabilis tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ levofloxacin MIC values for P. aeruginosa tended to be exact match or at least one doubling dilution higher than the reference method.

Meropenem

A total of 738 samples were evaluated with meropenem, including 612 Enterobacterales species (301 E. coli, 123 K. pneumoniae group, 39 E. cloacae complex, 50 P. mirabilis, 59 P. vulgaris, and 40 S. marcescens), 61 A. baumannii-calcoaceticus complex strains, and 65 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 97.2% and CA of 98.5%. There were no very major errors and three major errors.

{40}------------------------------------------------

The overall performance for A. baumannii-calcoaceticus complex strains resulted in EA of 90.2% and CA of 96.7%. There were no very major or major errors.

The overall performance for P. aeruginosa met defined acceptance criteria with EA of 96.9% and CA of 92.3%. There were no very major errors and no major errors.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ meropenem MIC values for A. baumannii-calcoaceticus complex, P. aeruginosa, and S. marcescens tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ meropenem MIC values for P. mirabilis tended to be at least one doubling dilution higher than the reference method.

Meropenem/vaborbactam

A total of 692 samples were evaluated with meropenem/vaborbactam, all Enterobacterales species (298 E. coli, 123 K. pneumoniae group, 45 K. oxytoca, 47 K. aerogenes, 43 E. cloacae complex, 36 C. freundii complex, 61 C. koseri, and 39 P. mirabilis).

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 97.1% and CA of 98.0%. There were no very major errors and no major errors.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ meropenem/vaborbactam MIC values for C. freundii complex, K. pneumoniae group, and K. aerogenes tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ meropenem/vaborbactam MIC values for C. koseri and P. mirabilis tended to be exact match or at least one doubling dilution higher than the reference method.

Piperacillin/tazobactam

A total of 489 samples were evaluated with piperacillin/tazobactam, all Enterobacterales species (299 E. coli, 122 K. pneumoniae group, 33 C. koseri, and 35 P. vulgaris).

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 94.7% and CA of 94.9%. There was one very major error and four major errors. CA for

{41}------------------------------------------------

C. koseri was 87.9% due to all minor errors. As the evaluable EA was high (90.9%), performance for C. koseri is considered acceptable. The very major error for E. coli is addressed by the following limitation in product labeling:

Due to the occurrence of a very major error with piperacillin/tazobactam, isolates of E. coli that provide an MIC of 8 µg/mL should be retested by an alternate method.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ piperacillin/tazobactam MIC values for E. coli, K. pneumoniae group, and C. koseri tended to be exact match or at least one doubling dilution lower than the reference method.

Tetracycline

A total of 552 samples were evaluated with tetracycline, including 513 Enterobacterales species (301 E. coli, 123 K. pneumoniae group, 42 K. oxytoca, 47 K. aerogenes) and 39 A. baumannii-calcoaceticus complex strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 98.4% and CA of 97.1%. There were no very major errors and three major errors. CA for K. aerogenes was 87.2% due to all minor errors. As the evaluable EA was high (96.2%), performance for K. aerogenes is considered acceptable.

The overall performance for A. baumannii-calcoaceticus complex met defined acceptance criteria with EA of 100.0% and CA of 100.0%.

The following statement is added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ tetracycline MIC values for K. aerogenes tended to be exact match or at least one doubling dilution lower than the reference method.

Tobramycin

A total of 722 samples were evaluated with tobramycin, including 657 Enterobacterales species (300 E. coli, 124 K. pneumoniae group, 40 K. oxytoca, 46 K. aerogenes, 39 E. cloacae complex, 22 C. freundii complex, 29 C. koseri, 31 P. mirabilis, and 26 S. marcescens) and 65 P. aeruginosa strains.

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 96.5% and CA of 94.8%. There were three very major errors and one major error. The

{42}------------------------------------------------

one (1) very major error for K. oxytoca was considered a random error due to the limited number of resistant isolates tested. The very major errors for E. coli are addressed by the following limitation in product labeling:

Due to the occurrence of very major errors with tobramycin, isolates of E. coli that provide an MIC of 4 µg/mL should be retested by an alternate method.

The major error for S. marcescens is addressed by the following limitation in product labeling:

Tobramycin with S. marcescens may produce a resistant result that can be found susceptible by the reference method. If critical to patient care, confirm these results with an alternate method.

The overall performance for P. aeruginosa met defined acceptance criteria with EA of 100.0% and CA of 100.0%.

The following statements are added to the AST performance table in product labeling to address trending:

VITEK® REVEAL™ tobramycin MIC values for P. mirabilis tended to be exact match or at least one doubling dilution lower than the reference method.

VITEK® REVEAL™ tobramycin MIC values for E. cloacae complex and C. freundii complex tended to be exact match or at least one doubling dilution higher than the reference method.

Trimethoprim/sulfamethoxazole

A total of 482 samples were evaluated with trimethoprim/sulfamethoxazole, all Enterobacterales species (303 E. coli, 130 K. pneumoniae group, and 47 K. aerogenes).

The overall performance for Enterobacterales species met defined acceptance criteria with EA of 95.0% and CA of 96.5%. There were three very major errors and 14 major errors. The major error rate for E. coli is addressed by the following limitation in product labeling:

Due to the occurrence of major errors with trimethoprim/sulfamethoxazole, isolates of E. coli that provide an MIC of 4-64 µg/ml should be retested by an alternate method.

The following statement is added to the AST performance table in product labeling to address trending:

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VITEK® REVEAL™ trimethoprim/sulfamethoxazole MIC values for E. coli and K. pneumoniae group tended to be at least one doubling dilution higher than the reference method.

Confirmatory ESBL Test

A total of 408 samples were evaluated with the confirmatory ESBL test, including 408 Enterobacterales species (279 E. coli, 90 K. pneumoniae group, and 39 K. oxytoca).

The overall performance for Enterobacterales species met defined acceptance criteria with CA of 98.5%. The ESBL screen is for the detection of organisms that produce extended spectrum beta lactamase and generates a "Positive" or "Negative" result; therefore, EA is not calculated. There was one very major error and five major errors. The two major errors for K. oxytoca are addressed by the following limitation in product labeling:

Isolates of K. oxytoca that test as ESBL positive by VITEK® REVEAL™ should be retested by an alternate method to confirm the presence of ESBL.

Species group	TotalEvaluablefor Trending	≥ 1Dilutionlower # (%)	Exact #(%)	≥ 1 DilutionHigher # (%)	Percent Difference(95% CI)	TrendingNoted
Amikacin
Enterobacterales	589	160 (27.2)	348 (59.1)	81 (13.8)	-13.4% (-17.9%, -8.8%)	No
A. baumannii-calcoaceticus complex	52	23 (44.2)	19 (36.5)	10 (19.2)	-25.0% (-40.9%, -7.1%)	No
P. aeruginosa	57	25 (43.9)	26 (45.6)	6 (10.5)	-33.3% (-47.4%, -17.3%)	Yes
Amoxicillin/clavulanate
Enterobacterales	296	5 (1.7)	78 (26.4)	213 (72.0)	70.3% (64.5%, 75.2%)	Yes
Ampicillin/sulbactam
Enterobacterales	200	38 (19.0)	60 (30.0)	102 (51.0)	32.0% (22.9%, 40.4%)	Yes
Aztreonam
Enterobacterales	113	33 (29.2)	35 (31.0)	45 (39.8)	10.6% (-1.8%, 22.6%)	No
P. aeruginosa	53	21 (39.6)	30 (56.6)	2 (3.8)	-35.8% (-49.6%, -20.8%)	Yes
Cefepime
Enterobacterales	138	40 (29.0)	45 (32.6)	53 (38.4)	9.4% (-1.7%, 20.2%)	No
P. aeruginosa	46	10 (21.7)	27 (58.7)	9 (19.6)	-2.2% (-18.6%, 14.4%)	No
Cefotaxime
Enterobacterales	86	264 (30.2)	28 (32.6)	32 (37.2)	7.0% (-7.1%, 20.7%)	No
A. baumannii-calcoaceticus complex	21	10 (47.6)	11 (52.4)	0 (0.0)	-47.6% (-67.6%, -22.9%)	Yes
Ceftazidime
Species group	TotalEvaluablefor Trending	≥ 1Dilutionlower # (%)	Exact #(%)	≥ 1 DilutionHigher # (%)	Percent Difference(95% CI)	TrendingNoted
Enterobacterales	331	195 (58.9)	79 (23.9)	57 (17.2)	-41.7% (-48.0%, -34.7%)	Yes
A. baumannii-calcoaceticus complex	22	1 (4.5)	11 (50.0)	10 (45.5)	40.9% (15.6%, 61.1%)	Yes
Ceftazidime/avibactam
Enterobacterales	444	266 (59.9)	154 (34.7)	24 (5.4)	-54.5% (-59.3%, -49.2%)	Yes
P. aeruginosa	76	22 (28.9)	45 (59.2)	9 (11.8)	-17.1% (-29.4%, -4.3%)	No
Ceftolozane/tazobactam
Enterobacterales	478	255 (53.3)	186 (38.9)	37 (7.7)	-45.6% (-50.5%, -40.4%)	Yes
P. aeruginosa	39	21 (53.8)	18 (46.2)	0 (0.0)	-53.8% (-68.4%, -36.1%)	Yes
Ceftriaxone
Enterobacterales	84	31 (36.9)	20 (23.8)	33 (39.3)	2.4% (-12.1%, 16.7%)	No
Cefuroxime
Enterobacterales	365	166 (45.5)	125 (34.2)	74 (20.3)	-25.2% (-31.6%, -18.5%)	No
Ciprofloxacin
Enterobacterales	148	10 (6.8)	61 (41.2)	77 (52.0)	45.3% (35.7%, 53.7%)	Yes
P. aeruginosa	34	18 (52.9)	5 (14.7)	11 (32.4)	-20.6% (-41.0%, 2.8%)	No
Ertapenem
Enterobacterales	40	21 (52.5)	11 (27.5)	8 (20.0)	-32.5% (-49.9%, -11.5%)	Yes
Gentamicin
Enterobacterales	554	77 (13.9)	198 (35.7)	279 (50.4)	36.5% (31.3%, 41.4%)	Yes
P. aeruginosa	42	10 (23.8)	25 (59.5)	7 (16.7)	-7.1% (-24.1%, 10.2%)	No
Imipenem
Enterobacterales	161	47 (29.2)	47 (29.2)	67 (41.6)	12.4% (2.0%, 22.5%)	No
A. baumannii-calcoaceticus complex	15	12 (80.0)	3 (20.0)	0 (0.0)	-80.0% (-93.0%, -47.6%)	Yes
P. aeruginosa	39	20 (51.3)	17 (43.6)	2 (5.1)	-46.2% (-61.5%, -27.0%)	Yes
Levofloxacin
Enterobacterales	225	77 (34.2)	123 (54.7)	25 (11.1)	-23.1% (-30.4%, -15.5%)	No
P. aeruginosa	43	4 (9.3)	21 (48.8)	18 (41.9)	32.6% (14.3%, 48.4%)	Yes
Meropenem
Enterobacterales	137	50 (36.5)	33 (24.1)	54 (39.4)	2.9% (-8.5%, 14.2%)	No
A. baumannii-calcoaceticus complex	50	33 (66.0)	17 (34.0)	0 (0.0)	-66.0% (-77.6%, -50.4%)	Yes
P. aeruginosa	45	20 (44.4)	23 (51.1)	2 (4.4)	-40.0% (-54.7%, -23.0%)	Yes
Meropenem/vaborbactam
Enterobacterales	106	35 (33.0)	30 (28.3)	41 (38.7)	5.7% (-7.2%, 18.2%)	No
Piperacillin/tazobactam
Enterobacterales	148	107 (72.3)	21 (14.2)	20 (13.5)	-58.8% (-66.8%, -48.7%)	Yes
Species group	TotalEvaluablefor Trending	≥ 1Dilutionlower # (%)	Exact #(%)	≥ 1 DilutionHigher # (%)	Percent Difference(95% CI)	TrendingNoted
Enterobacterales	346	150 (43.4)	129 (37.3)	67 (19.4)	-24.0% (-30.5%, -17.2%)	No
A. baumannii-calcoaceticus complex	12	4 (33.3)	6 (50.0)	2 (16.7)	-16.7% (-46.8%, 17.6%)	No
Tobramycin
Enterobacterales	620	120 (19.4)	341 (55.0)	159 (25.6)	6.2% (1.6%, 10.9%)	No
P. aeruginosa	37	8 (21.6)	27 (73.0)	2 (5.4)	-16.2% (-32.3%, -0.2%)	No
Trimethoprim/sulfamethoxazole
Enterobacterales	57	9 (15.8)	7 (12.3)	41 (71.9)	56.1% (38.9%, 68.5%)	Yes

Table 9. Trending Analysis Summary

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Conclusion

The conclusions drawn from the analytical and clinical tests demonstrate that the device is substantially equivalent to the predicate device.

Regulation Number and Section

§ 866.1650 A cellular analysis system for multiplexed antimicrobial susceptibility testing.

(a)
Identification. A cellular analysis system for multiplexed antimicrobial susceptibility testing is a multiplex qualitative and/or quantitative in vitro diagnostic device intended for the identification and determination of the antimicrobial susceptibility results of organisms detected in samples from patients with suspected microbial infections. This device is intended to aid in the determination of antimicrobial susceptibility or resistance when used in conjunction with other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Detailed device description documentation, including the device components, ancillary reagents required but not provided, a detailed explanation of the methodology, including primer/probe sequence, design, rationale for sequence selection, and details of the antimicrobial agents, as applicable.
(ii) Detailed documentation from the following analytical and clinical performance studies: limit of detection, inclusivity, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination, quality control and additional studies, as applicable to specimen type and assay intended use.
(iii) Detailed documentation from an appropriate clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) Limitations and protocols regarding the need for correlation of results by standard laboratory procedures, as applicable.
(ii) A detailed explanation of the interpretation of results and acceptance criteria.
(iii) A detailed explanation of the principles of operation and procedures for assay performance and troubleshooting.