(468 days)
No
The description mentions a "real-time algorithm" that detects sensor array responses, but it does not provide any details suggesting the use of AI or ML techniques for this algorithm or for interpreting the results. The interpretation is based on comparing growth to controls and applying breakpoints, which is a standard, non-AI/ML approach in AST.
No.
Explanation: This device is an in vitro diagnostic (IVD) system used for antimicrobial susceptibility testing, which provides information to aid clinicians in determining appropriate antimicrobial therapy, but it does not directly perform therapy or treatment on a patient.
Yes
The VITEK® REVEAL™ AST System is explicitly described as an "in vitro diagnostic (IVD) automated platform" and is used "for the in vitro quantitative determination of antimicrobial susceptibility," indicating its role in diagnosis within a clinical laboratory setting.
No
The device description explicitly states that the VITEK® REVEAL™ AST System includes hardware components such as a VITEK® REVEAL™ Sealer, a VITEK® REVEAL™ Instrument, and a master controller computer (MCC)/touch screen monitor. It also utilizes physical components like sensor panels and antibiotic panels.
Yes, the VITEK® REVEAL™ AST System is an IVD (In Vitro Diagnostic) device.
Here's why:
- Explicitly Stated: The "Device Description" section clearly states: "The VITEK® REVEAL™ AST System is an in vitro diagnostic (IVD) automated platform..."
- Intended Use: The "Intended Use / Indications for Use" describes the system as being used for "qualitative antimicrobial susceptibility testing (AST) of organisms direct from positive blood culture" and "for the in vitro quantitative determination of antimicrobial susceptibility." This aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for the diagnosis, treatment, or prevention of disease.
- Care Setting and User: The test is performed by "laboratory health professionals in a clinical diagnostic setting," which is typical for IVD devices.
- Purpose: The results are used as "an aid to clinicians in determining appropriate antimicrobial therapy," directly impacting patient treatment decisions based on in vitro testing.
- Mechanism: The system uses "broth microdilution (BMD) principles" and detects "volatile organic compounds emitted by growing bacteria," which are in vitro methods for analyzing biological samples.
N/A
Intended Use / Indications for Use
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 qualitative 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 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
Product codes
SAN, LON
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.
Mentions image processing
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Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
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Intended User / Care Setting
This test is performed by laboratory health professionals in a clinical diagnostic setting.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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. 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.
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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility Study:
Sample Size: Not explicitly stated as a single number, but involves testing Gram-negative isolates in triplicate at 3 sites on 3 days, leading to 27 results per sample.
Key Results: Overall best-case reproducibility (within +/-1 dilution of the mode) for each antimicrobial was ≥96%, meeting the acceptance criteria of ≥95%. Worst-case reproducibility for each antimicrobial was ≥91.7%, meeting the acceptance criteria of ≥89%.
Blood Culture Bottle Equivalency Study:
Sample Size: Nine (9) strains representing seven (7) species were contrived and tested, with six (6) bottle replicates per organism and bottle type.
Key Results: Overall Essential Agreement (EA) and Categorical Agreement (CA) for each bottle type across all antibiotics tested when compared to the reference MIC was >98%, meeting the acceptance criteria of >89.9%.
Sample Stability Study:
Sample Size: Twenty-five (25) strains representing nine (9) species were selected, tested in triplicate for each temperature condition and timepoint.
Key Results: 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, meeting the acceptance criteria. It was demonstrated that positive blood culture samples may be tested when samples are stored for up to 16 hours post positivity.
Interfering Substances Study:
Sample Size: Five (5) organisms (E. coli, P. aeruginosa, K. pneumoniae, E. cloacae, A. baumannii) tested in triplicate for each of 9 interfering substances.
Key Results: Overall EA and CA for each interferant tested across almost all organisms and antimicrobials were >95% when compared to the control samples (acceptance criteria: ≥95%). Eight antibiotic/interferent combinations did not meet EA acceptance criteria, but further testing determined these were not caused by interference.
Interfering Antibiotics Study:
Sample Size: A minimum of one (1) Gram-negative strain resistant to each of 9 interfering antimicrobials was tested in triplicate.
Key Results: Overall EA for each interfering antimicrobial tested was ≥97% and CA was >97% when compared to the control samples, meeting the overall acceptance criteria of >95%.
Carryover and Cross-talk Study:
Sample Size: Cross-talk: Five (5) species tested, alternating wells in 96-well plates, 4 total replicates per organism over 20 days. Carryover: Single replicate of a media-only panel over 20 days on 20 VITEK® REVEAL™ Instruments.
Key Results: Cross-talk: Overall rate of cross-talk was 0.1% (1/960), meeting acceptance criteria of 89.9%.
Method Comparison Study:
Study Type: Clinical Performance Evaluation.
Sample Size: Total of 1239 samples enrolled (480 fresh prospective, 106 clinical stock contrived, 653 challenge contrived). 1115 samples included in final performance analyses (424 fresh prospective, 101 clinical stock contrived, 590 challenge contrived).
AUC: Not mentioned.
MRMC: Not mentioned.
Standalone performance: Not explicitly stated, performance is compared to a reference BMD method.
Key Results (Overall performance by breakpoint group, all species combined):
- Amikacin: Enterobacterales (EA 98.1%, CA 99.4%), A. baumannii-calcoaceticus complex (EA 90.0%, CA 88.3%), P. aeruginosa (EA 95.4%, CA 95.4%).
- Amoxicillin/clavulanate: Enterobacterales (EA 95.0%, CA 90.8%).
- Ampicillin/sulbactam: Enterobacterales (EA 97.8%, CA 77.2%).
- Aztreonam: Enterobacterales (EA 97.4%, CA 96.0%), P. aeruginosa (EA 96.9%, CA 86.2%).
- Cefepime: Enterobacterales (EA 96.0%, CA 95.9%), P. aeruginosa (EA 97.0%, CA 97.0%).
- Cefotaxime: Enterobacterales (EA 97.3%, CA 99.1%), A. baumannii-calcoaceticus complex (EA 100.0%, CA 100.0%).
- Ceftazidime: Enterobacterales (EA 95.3%, CA 97.1%), A. baumannii-calcoaceticus complex (EA 97.4%, CA 94.9%).
- Ceftazidime/avibactam: Enterobacterales (EA 95.7%, CA 99.7%), P. aeruginosa (EA 97.8%, CA 97.8%).
- Ceftolozane/tazobactam: Enterobacterales (EA 92.9%, CA 97.6%), P. aeruginosa (EA 100.0%, CA 98.5%).
- Ceftriaxone: Enterobacterales (EA 97.1%, CA 96.6%).
- Cefuroxime: Enterobacterales (EA 95.8%, CA 97.3%).
- Ciprofloxacin: Enterobacterales (EA 99.0%, CA 95.6%), P. aeruginosa (EA 92.9%, CA 97.1%).
- Ertapenem: Enterobacterales (EA 97.8%, CA 98.8%).
- Gentamicin: Enterobacterales (EA 96.6%, CA 98.2%), P. aeruginosa (EA 96.9%, CA 95.4%).
- Imipenem: Enterobacterales (EA 98.1%, CA 97.7%), A. baumannii-calcoaceticus complex (EA 97.8%, CA 93.3%), P. aeruginosa (EA 93.8%, CA 93.8%).
- Levofloxacin: Enterobacterales (EA 99.2%, CA 96.3%), P. aeruginosa (EA 97.3%, CA 94.6%).
- Meropenem: Enterobacterales (EA 97.2%, CA 98.5%), A. baumannii-calcoaceticus complex (EA 90.2%, CA 96.7%), P. aeruginosa (EA 96.9%, CA 92.3%).
- Meropenem/vaborbactam: Enterobacterales (EA 97.1%, CA 98.0%).
- Piperacillin/tazobactam: Enterobacterales (EA 94.7%, CA 94.9%).
- Tetracycline: Enterobacterales (EA 98.4%, CA 97.1%), A. baumannii-calcoaceticus complex (EA 100.0%, CA 100.0%).
- Tobramycin: Enterobacterales (EA 96.5%, CA 94.8%), P. aeruginosa (EA 100.0%, CA 100.0%).
- Trimethoprim/sulfamethoxazole: Enterobacterales (EA 95.0%, CA 96.5%).
- ESBL Confirmation: Enterobacterales (CA 98.5%). EA not calculated as it is a qualitative test.
Trending analysis for various species and antimicrobials showing the percentage of MIC values that were lower, exact, or higher than the reference method.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Essential Agreement (EA), Categorical Agreement (CA), Very Major Errors (vmj), Major Errors (maj), Minor Errors (min). Specific values for each antibiotic and organism group are detailed in the "Summary of Performance Studies" section.
Predicate Device(s)
Accelerate Pheno System, Accelerate PhenoTest BC Kit, DEN160032
Reference Device(s)
No reference devices were used in this submission.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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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:
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
3
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 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 |
|---|---|
| ------------------------- | ------------------------------------------------------------------- |
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.
4
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5
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, LLC
130 Baytech Drive
San Jose, CA 95134 |
|----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Correspondent: | MDC Associates, Inc.
Katie Hahnemann, Ph.D.
48 Dunham Ridge Road
Beverly, MA 01915
Phone: (978) 927 3808
Specific@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 susceptibility
testing in a multiplex qualitative and/or quantitative in vitro 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. |
| 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 |
6
No reference devices were used in this submission.
Device Description Summary
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.
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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.
| | Reportable range on
VITEK® 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.
8
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
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 baumannii-calcoaceticus complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group
9
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
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 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
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
10
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
11
| Description | Specific Diagnostics
Subject Device | Accelerate Diagnostics, Inc.
Predicate Device |
|-----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | VITEK® REVEAL™ AST System and
VITEK® REVEAL™ GN AST Assay | Accelerate Pheno System and
PhenoTest BC Kit
K192665 |
| 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 hours
from positive blood cultures) | |
| Results | Report results as minimum inhibitory
concentration (MIC) and categorical
interpretation (SIR) for antimicrobials
and Positive/Negative (POS/NEG) for
the ESBL Confirmation screen test | Report results as minimum inhibitory
concentration (MIC) and categorical
interpretation (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
12
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.
13
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 +/-1
dilution / Total
tests | 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
14
| Antibiotic | Best case #
within +/-1
dilution / Total
tests | 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% when compared to the BMD modal MIC,
16
meeting the acceptance criteria (Table 4). For antibiotics that showed 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 | Normal
Concentrations | Concentration
Tested | 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 |
| Endogenous
| Interferent | 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) |
21
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) |
| Overall
performance | 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 Overall
performance | 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 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 combination
agents | 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 Synthesis
Inhibitor | 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)
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.
26
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
27
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 | Total | |||||||||
| Eval | # EA | ||||||||||||
| Eval | % 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 |
| Ceftazidime | |||||||||||||
| Enterobacterales | |||||||||||||
| 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/avibactam | |||||||||||||
| Enterobacterales | |||||||||||||
| 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
28
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.
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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
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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
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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 | Total
Evaluable
for Trending | ≥ 1
Dilution
lower # (%) | Exact #
(%) | ≥ 1 Dilution
Higher # (%) | Percent Difference
(95% CI) | Trending
Noted |
|------------------------------------------------------|------------------------------------|--------------------------------|----------------|------------------------------|--------------------------------|-------------------|
| 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 | Total
Evaluable
for Trending | ≥ 1
Dilution
lower # (%) | Exact #
(%) | ≥ 1 Dilution
Higher # (%) | Percent Difference
(95% CI) | Trending
Noted |
| 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 | Total
Evaluable
for Trending | ≥ 1
Dilution
lower # (%) | Exact #
(%) | ≥ 1 Dilution
Higher # (%) | Percent Difference
(95% CI) | Trending
Noted |
| 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.