(175 days)
Not Found
No
The summary describes an automated real-time PCR test for detecting specific gene sequences. The technology described is standard molecular diagnostics and does not mention any AI or ML components for analysis or interpretation.
No
The device is described as an in vitro diagnostic test for detecting gene sequences, intended as an aid for infection control and not for guiding or monitoring treatment.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that "The Xpert® Carba-R Assay... is a qualitative in vitro diagnostic test." It further clarifies that it is "intended as an aid for infection control in detecting and differentiating genetic markers of resistance." These phrases unequivocally indicate its diagnostic purpose.
No
The device description clearly states that the Xpert Carba-R Assay is performed on the GeneXpert Instrument Systems, which are hardware platforms. It also utilizes single-use, disposable cartridges containing reagents and hosting the PCR process. While software is involved in automating the process and generating results, the device is fundamentally a system comprising hardware (instrument, cartridges) and reagents, not software alone.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in the "Intended Use / Indications for Use" section: "The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test..."
It is also described as an "automated real-time polymerase chain reaction (PCR) in vitro diagnostic test" in the "Device Description" section.
Furthermore, the device is intended to be used in a laboratory setting (CLIA Moderate or High Complexity labs) to analyze biological samples (bacterial isolates from culture) to detect specific genetic markers, which is the definition of an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48 and blaIMP gene sequences associated with carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The test utilizes automated real-time polymerase chain reaction (PCR).
A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms. The Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The Xpert Carba-R Assay is intended as an aid for infection control in detecting and differentiating genetic markers of resistance to monitor the spread of carbapenem-non-susceptible organisms in healthcare settings. The Xpert Carba-R Assay is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections.
Product codes (comma separated list FDA assigned to the subject device)
PMY, OOI
Device Description
The Xpert Carba-R Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of the blaker, blaym, blaym, blagxa-a8, and blang gene sequences from isolates of pure cultures of carbapenem-non-susceptibility gram-negative bacteria. The Xpert Carba-R Assay is intended as an aid for infection control for monitoring the spread of carbapenem-non-susceptible organisms in healthcare settings.
The Xpert Carba-R Assay is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert Carba-R cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
The Xpert Carba-R Assay cartridges contain reagents for the detection of blaker, blayDM. blaym, blaoxa-as, and blansp gene sequences. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the real-time PCR reaction to reduce the possibility of false negative results. The PCC verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of the blakpc, blaNDM, blaviM, blaoxA-48, and blamp gene sequences from isolates of pure cultures of carbapenem-nonsusceptibility gram-negative bacteria in approximately 50 minutes. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample processing and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
The bacterial isolates from culture are placed into a sample reagent. The sample is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert Carba-R cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex PCR for detection of the blaker, bland, blaym, blagx,-48, and blange gene sequences. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Operators in CLIA Moderate or High Complexity labs
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical Study Sample Set:
A total of 489 isolates (431 clinical stock isolates and 58 fresh isolates) were initially enrolled in this clinical study, of which 485 were eligible for inclusion.
From the 485 eligible isolates, 467 isolates (410 clinical stock isolates and 57 fresh isolates) were included in the final dataset used for the analyses presented in this report; two isolates were excluded because reference testing was not performed; and sixteen isolates were excluded because they were not identified as Enterobacteriaceae, A. baumannii, or P. aeruginosa.
To be included in the study, isolates must have been previously identified as Enterobacteriaceae, Pseudomonas aeruginosa, or Acinetobacter baumannii. For determination of sensitivity, isolates must have been either intermediate or resistant to meropenem, ertapenem and/or imipenem per CLSI M100-S24. Isolates of Pseudomonas aeruginosa or Acinetobacter baumannii must have been intermediate or resistant to either imipenem or meropenem. These organisms are intrinsically resistant to ertapenem. For evaluation of specificity, isolates may have been susceptible or resistant to meropenem, ertapenem, and imipenem per CLSI M100-S24. Pseudomonas aeruginosa and Acinetobacter baumannii isolates should have been susceptible to both imipenem and meropenem. Isolates were tested only once in the study.
Reference Sequencing Protocol:
For reference sequencing, DNA from culture isolates was purified, quantified, and amplified using primers specific to all 5 target genes that amplify larger regions than the assay targets and include the Xpert Carba-R primer sequences. The production of the appropriate size of amplification product was confirmed on Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA).
If bands shown on the Bioanalyzer corresponded to the expected size of the amplicon from any of the five target genes detected by the Xpert Carba-R Assay, the amplicon for the isolate was sent to an independent laboratory for reference bi-directional sequencing analysis, validated for detection of the five targets in the Xpert Carba-R Assay. If no bands were shown on the Bioanalyzer for any of the five target genes, the isolate was not sent for sequence analysis and the reference method result was considered negative for the five target genes.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Non-Clinical Studies, Clinical Performance Study, Reproducibility Study
Non-Clinical Studies:
- Analytical Reactivity (Inclusivity):
- Sample Size: 71 samples (11 blaKPC, 13 blaNDM, 11 blaVIM, 8 blaOXA-48, 5 blaNDM/OXA-181, 5 blaOXA-181, 17 blaIMP, and one blaKPC/VIM well-characterized bacterial strains). Organisms were tested in replicates of four.
- Key Results: Xpert Carba-R Assay target genes were detected in 68 of 71 bacterial strains from both blood agar and MacConkey plates. IMP-13, IMP-7, and IMP-14 genes were not detected in three bacterial strains.
- Analytical Specificity (Cross-reactivity):
- Sample Size: 62 well-characterized bacterial strains of carbapenem-susceptible bacteria or bacteria with carbapenem non-susceptibility due to non-target genes/mechanisms. Twenty-four commensal bacterial strains and other enteric microorganisms were also evaluated.
- Key Results: The Xpert Carba-R Assay did not cross-react with any of the organisms tested. The analytical specificity of the assay was 100%.
- Carry-Over Contamination:
- Sample Size: 50 high positive samples and 52 negative samples.
- Key Results: All 50 positive samples correctly reported all Xpert Carba-R targets as DETECTED. All 52 negative samples correctly reported all Xpert Carba-R targets as NOT DETECTED.
Clinical Performance Study:
- Study Type: Multi-site investigational study comparing Xpert Carba-R Assay to reference bi-directional sequencing.
- Sample Size: 467 eligible isolates (410 clinical stock isolates and 57 fresh isolates).
- Standalone Performance (Blood Agar):
- Overall Sensitivity: 100.0% (95% CI: 99.0-100)
- Overall Specificity: 98.1% (95% CI: 93.2-99.5)
- Sensitivity per target: IMP (100%), VIM (100%), NDM (100%), KPC (100%), OXA-48 (100%)
- Specificity per target: IMP (99.8%), VIM (99.7%), NDM (100%), KPC (99.7%), OXA-48 (100%)
- Standalone Performance (MacConkey Agar):
- Overall Sensitivity: 100% (95% CI: 99.0-100)
- Overall Specificity: 97.1% (95% CI: 91.8-99.0)
- Sensitivity per target: IMP (100%), VIM (100%), NDM (100%), KPC (100%), OXA-48 (100%)
- Specificity per target: IMP (99.8%), VIM (99.7%), NDM (99.7%), KPC (100%), OXA-48 (100%)
- Phenotypic Comparison:
- Blood Agar: 356 (Gene Detected)/95 (Gene Not Detected) for Non-susceptible phenotype; 10 (Gene Detected)/6 (Gene Not Detected) for Susceptible phenotype.
- MacConkey Agar: 357 (Gene Detected)/94 (Gene Not Detected) for Non-susceptible phenotype; 10 (Gene Detected)/6 (Gene Not Detected) for Susceptible phenotype.
- Valid reporting rate: 100% (934/934 tests).
Reproducibility Study:
- Study Type: Panel of 13 bacterial samples tested by two operators at three study sites over six days, with three lots of cartridges.
- Sample Size: 13 samples x 2 times/day x 6 days x 2 operators x 3 sites = 936 expected tests. After exclusions, 1847 samples were included in the analyses (this number appears inconsistent with the previous calculation, but is quoted directly).
- Key Results (Total Agreement by Sample):
- KPC (1): 100%
- KPC (2): 99.3%
- VIM (1): 100%
- VIM (2): 100%
- IMP (1): 100%
- IMP (2): 100%
- OXA (1): 98.6%
- OXA (2): 100%
- NDM (1): 100%
- NDM (2): 98.6%
- OXA,NDM (1): 100%
- OXA,NDM (2): 100%
- NEG: 100%
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
From Clinical Performance Study (Against Reference Sequencing - Blood Agar Culture)
- Overall Sensitivity: 100.0% (95% CI: 99.0-100)
- Overall Specificity: 98.1% (95% CI: 93.2-99.5)
- IMP Sensitivity: 100% (91.2-100)
- IMP Specificity: 99.8% (98.7-100)
- VIM Sensitivity: 100% (95.5-100)
- VIM Specificity: 99.7% (98.5-100)
- NDM Sensitivity: 100% (95.3-100)
- NDM Specificity: 100% (99.0-100)
- KPC Sensitivity: 100% (95.6-100)
- KPC Specificity: 99.7% (98.5-100)
- OXA-48 Sensitivity: 100% (95.9-100)
- OXA-48 Specificity: 100% (99.0-100)
From Clinical Performance Study (Against Reference Sequencing - MacConkey Agar Culture)
- Overall Sensitivity: 100% (95% CI: 99.0-100)
- Overall Specificity: 97.1% (95% CI: 91.8-99.0)
- IMP Sensitivity: 100% (91.2-100)
- IMP Specificity: 99.8% (98.7-100)
- VIM Sensitivity: 100% (95.5-100)
- VIM Specificity: 99.7% (98.5-100)
- NDM Sensitivity: 100% (95.3-100)
- NDM Specificity: 99.7% (98.6-100)
- KPC Sensitivity: 100% (95.6-100)
- KPC Specificity: 100% (99.0-100)
- OXA-48 Sensitivity: 100% (95.9-100)
- OXA-48 Specificity: 100% (99.0-100)
Valid Reporting Rate: 100% (934/934).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Cepheid Xpert® vanA [510(k) #K092953]
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
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
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name encircling a stylized symbol. The symbol consists of three human profiles facing right, stacked on top of each other. Below the profiles are three curved lines.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
March 7, 2016
CEPHEID JIM KELLY, Ph.D. EXECUTIVE DIRECTOR, REGULATORY AFFAIRS 904 CARIBBEAN DRIVE SUNNYVALE CA 94089-1189
Re: K152614
Trade/Device Name: Xpert® Carba-R Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: PMY, OOI Dated: February 5, 2016 Received: February 8, 2016
Dear Dr. Kelly:
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 (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. 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.
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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Ribhi Shawar -S
For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
K152614
Device Name
Xpert Carba-R
Indications for Use (Describe)
The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection and differentiation of the blaχρι, blaკγι blaკγൂ and blânup gene sequences associated with carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The test utilizes automated real-time polymerase chain reaction (PCR).
A negative Xpert Carba-R Assay result does not presence of other resistance mechanisms. The Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The Xpert Carba-R Assay is intended as an aid for infection control in detecting and differentiating genetic markers of resistance to monitor the spread of carbapenem-non-susceptible organisms in healthcare settings. The Xpert Carba-R Assay is not intended to quide or monitor treatment for carbapenem-non-susceptible bacterial infections.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (847) 228-3299
Fax number: (847) 890-6589 |
|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Scott A. Campbell, PhD, MBA |
| Date of Preparation: | March 2, 2016 |
| Device: | |
| 510(k) Number: | K152614 |
| Trade name: | Xpert® Carba-R |
| Common name: | Xpert Carba-R Assay |
| Type of Test: | Qualitative nucleic acid amplification test of the blaKPC, blaNDM,
blaVIM, blaOXA-48, and blaIMP gene sequences from isolates of
pure cultures of carbapenem-non-susceptibility gram-negative
bacteria |
| Classification: | II |
| Regulation number | 866.1640 |
| Classification name:
Product code: | Antimicrobial susceptibility test powder
PMY, OOI |
| Classification
Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device
Assay: | Cepheid Xpert® vanA
[510(k) #K092953] |
4
Device Description:
The Xpert Carba-R Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of the blaker, blaym, blaym, blagxa-a8, and blang gene sequences from isolates of pure cultures of carbapenem-non-susceptibility gram-negative bacteria. The Xpert Carba-R Assay is intended as an aid for infection control for monitoring the spread of carbapenem-non-susceptible organisms in healthcare settings.
The Xpert Carba-R Assay is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert Carba-R cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
The Xpert Carba-R Assay cartridges contain reagents for the detection of blaker, blayDM. blaym, blaoxa-as, and blansp gene sequences. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the real-time PCR reaction to reduce the possibility of false negative results. The PCC verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of the blakpc, blaNDM, blaviM, blaoxA-48, and blamp gene sequences from isolates of pure cultures of carbapenem-nonsusceptibility gram-negative bacteria in approximately 50 minutes. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample processing and real-time PCR and RT-PCR tests. Each module contains a svringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
The bacterial isolates from culture are placed into a sample reagent. The sample is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert Carba-R cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex PCR for detection of the blaker, bland, blaym, blagx,-48, and blange gene sequences. The results are automatically generated at the end of the process in a report that can be viewed and printed.
5
Device Intended Use:
The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection and differentiation of the blakpor blands blayms blacks and bland gene sequences associated with carbapenem-nonsusceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The test utilizes automated real-time polymerase chain reaction (PCR).
A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms. The Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The Xpert Carba-R Assay is intended as an aid for infection control in detecting and differentiating genetic markers of resistance to monitor the spread of carbapenem-nonsusceptible organisms in healthcare settings. The Xpert Carba-R Assay is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections.
Substantial Equivalence:
The Cepheid Xpert Carba-R Assay is substantially equivalent to the Xpert® vanA, 510(k) #K092953. The Xpert Carba-R Assay and the Xpert vanA Assay both detect target gene sequences from antibiotic-resistant bacteria and use real-time PCR amplification and fluorogenic target-specific hybridization detection. The performance of the Xpert Carba-R Assay was determined in a multi-site clinical study in which the performance of the Xpert Carba-R Assay was evaluated relative to reference DNA sequence analysis. The results of the study demonstrated that the performance of the Xpert Carba-R Assay is substantially equivalent to the predicate device.
Table 5-1 shows the similarities and differences between the Xpert Carba-R Assay and the predicate device.
6
| Similarities | ||
|---|---|---|
| Item | Device | Predicate Device |
| Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay | |
| K092953 | ||
| General Intended | ||
| Use | The Xpert® Carba-R Assay, | |
| performed on the GeneXpert® | ||
| Instrument Systems, is a | ||
| qualitative in vitro diagnostic | ||
| test for the detection and | ||
| differentiation of the bla KPC, | ||
| bla NDM, bla VIM, bla OXA-48, and | ||
| bla IMP gene sequences | ||
| associated with carbapenem- | ||
| non-susceptible pure colonies of | ||
| Enterobacteriaceae , | ||
| Acinetobacter baumannii , or | ||
| Pseudomonas aeruginosa | ||
| grown on blood agar or | ||
| MacConkey agar. The test | ||
| utilizes automated real-time | ||
| polymerase chain reaction | ||
| (PCR) . |
A negative Xpert Carba-R
Assay result does not preclude
the presence of other resistance
mechanisms. The Xpert®
Carba-R Assay should be used
in conjunction with other
laboratory tests including
phenotypic antimicrobial
susceptibility testing. The Xpert
Carba-R Assay is intended as
an aid for infection control in
detecting and differentiating
genetic markers of resistance
to monitor the spread of
carbapenem-non-susceptible
organisms in healthcare
settings. The Xpert Carba-R
Assay is not intended to guide
or monitor treatment for
carbapenem-non-susceptible
bacterial infections. | The Cepheid Xpert® vanA Assay
performed in the GeneXpert® Dx
System is a qualitative in vitro
diagnostic test designed for rapid
detection of the vanA gene
sequence associated with
vancomycin resistance in
bacteria obtained from rectal
swab specimens from patients at
risk for intestinal colonization
with vancomycin-resistant
bacteria . The test utilizes
automated real-time
polymerase chain reaction
(PCR) to detect the vanA gene
that is frequently associated with
vancomycin-resistant enterococci
(VRE). The Xpert vanA Assay is
intended to aid in the recognition,
prevention, and control of
vancomycin resistant organisms
that colonize patients in
healthcare settings. The Xpert
vanA Assay is not intended to
diagnose infections caused by
vancomycin-resistant bacteria
nor to guide or monitor treatment
for vancomycin-resistant
bacterial infections. Concomitant
cultures are necessary to recover
organisms for confirmatory
identification of vancomycin-
resistant bacteria, antimicrobial
susceptibility testing, and for
epidemiological typing. |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay
K092953 |
| Type of test | Same | Qualitative |
| Technological
Principles | Same | Fully-automated nucleic acid
amplification (DNA); real-time
PCR |
| Test Cartridge | Same | Disposable single-use, multi-
chambered fluidic cartridge |
| Probes | Same | TaqMan® Probes |
| Controls | Same | Internal sample processing
control (SPC) and probe
check control (PCC)
External controls available |
| Instrument
System | GeneXpert Instrument System
(includes GeneXpert Dx,
Infinity-48, Infinity-48s, and
Infinity-80) | GeneXpert Dx |
| Time to obtain
test results | Approximately 50 minutes to
results | Approximately 45 minutes to
results |
| Interpretation of
test results | Diagnostic software of the
GeneXpert Instrument System | Diagnostic software of the
GeneXpert Dx |
| Laboratory Users | Operators in CLIA Moderate or
High Complexity labs | Operators in CLIA Moderate or
High Complexity labs |
| Differences | | |
| Item | New Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay
K092953 |
| Sample Type | Bacterial isolates from culture | Rectal swabs |
| Assay Targets | Detects blaKPC, blaNDM, blaVIM,
blaOXA-48, and blaIMP gene
sequences | Detects gene sequences for the
vanA encoded resistance to
vancomycin/teicoplanin |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay
K092953 |
| Instrument
System | GeneXpert Instrument System
(includes GeneXpert Dx,
Infinity-48, Infinity-48s, and
Infinity-80) | GeneXpert Dx |
Table 5-1: Comparison of Similarities and Differences of the
7
8
The Xpert Carba-R Assay has the same general intended use as the predicate device and has the same technological characteristics as the predicate device. The differences between the Xpert Carba-R Assay and the predicate device do not raise questions of safety and effectiveness. The clinical study demonstrates that the Xpert Carba-R Assay is acceptable for its intended use with inexperienced laboratory users and is substantially equivalent to the predicate device described above.
Non-Clinical Studies:
Analytical Reactivity (Inclusivity)
The analytical sensitivity of the Xpert Carba-R Assay was evaluated by testing a panel of 71 samples consisting of 11 blakec (KPC), 13 blandy (NDM), 11 blavm (VIM), 8 blaoxa-48 (OXA-48), 5 blaNDM/OXA-181 (NDM/OXA-181), 5 blaoxA-181 (OXA-181), 17 blann (IMP), and one blakecym (KPC/VIM) well-characterized bacterial strains (Table 5-2). Organisms were tested in replicates of four that were prepared by diluting 10 µL of 0.5 McFarland cell suspension for each bacterial strain in 5 mL of Xpert Carba-R Sample Reagent. Testing was performed using both blood agar and MacConkey plates. Xpert Carba-R Assay target genes were detected in 68 of 71 bacterial strains from both plates (Table 5-2). Xpert Carba-R Assay target DNA sequences were not detected in three bacterial strains as shown in Table 5-2. In one of the three bacterial strains, the IMP-13 gene was not detected by the assay, although it was predicted to be detected by in silico analysis. In two of the three bacterial strains, theIMP-7 and IMP-14 genes that were not detected by the assay were also not predicted to be detected by in silico analysis. See the Limitations section in the package insert.
The variants detected, and predictions for detecting other subtypes of each resistance gene based on in silico analysis, are presented in Table 5-3.
9
| Strain ID | Organism | Resistance Marker
with variant
information |
|-------------------|-------------------------|--------------------------------------------------|
| NCTC 13438 | Klebsiella pneumoniae | KPC-3 |
| 31551 | Klebsiella pneumoniae | KPC-4 |
| ATCC BAA-
1705 | Klebsiella pneumoniae | KPC-2 |
| CFVL | Enterobacter cloacae | KPC-2 |
| KBM18 | Enterobacter aerogenes | KPC-2 |
| COL | Escherichia coli | KPC-2 |
| BM9 | Klebsiella pneumoniae | KPC-3 |
| CGNC | Serratia marcescens | KPC-2 |
| PA3 | Pseudomonas aeruginosa | KPC-2 |
| COL | Pseudomonas aeruginosa | KPC-2 |
| GR-04/KP-69 | Klebsiella pneumoniae | KPC-2, VIM |
| 164-3 | Klebsiella oxytoca | KPC |
| NCTC 13437 | Pseudomonas aeruginosa | VIM-10 |
| NCTC 13439 | Klebsiella pneumoniae | VIM-1 |
| NCTC 13440 | Klebsiella pneumoniae | VIM-1 |
| 758 | Pseudomonas aeruginosa | VIM |
| N/A | Klebsiella pneumoniae | VIM |
| N/A | Pseudomonas aeruginosa | VIM |
| Col 1 | Pseudomonas aeruginosa | VIM-2 |
| BM19 | Serratia marcescens | VIM-2 |
| KOW7 | Escherichia coli | VIM-4 |
| DIH | Klebsiella pneumoniae | VIM-19 |
| MSH2014-3 | Enterobacter cloacae | VIM |
| NCTC 13443 | Klebsiella pneumoniae | NDM-1 |
| ATCC BAA-
2146 | Klebsiella pneumoniae | NDM-1 |
| 34262 | Klebsiella pneumoniae | NDM |
| GEN | Acinetobacter baumannii | NDM-1 |
| 3047 | Enterobacter cloacae | NDM-1 |
| 7892 | Proteus mirabilis | NDM-1 |
| CAN | Salmonella spp. | NDM-1 |
| EGY | Acinetobacter baumannii | NDM-2 |
| I5 | Escherichia coli | NDM-4 |
| 405 | Escherichia coli | NDM-5 |
| CF-ABE | Citrobacter freundii | NDM |
| 73999 | Pseudomonas aeruginosa | NDM |
| 39365 | Providencia rettgeri | NDM-1 |
Table 5-2: Analytical Reactivity of the Xpert Carba-R Assay
10
| Strain ID | Organism | Resistance Marker with variant information |
|---|---|---|
| NCTC 13442 | Klebsiella pneumoniae | OXA-48 |
| OM11 | Klebsiella pneumoniae | OXA-48 |
| 501 | Enterobacter cloacae | OXA-48 |
| DUW | Klebsiella pneumoniae | OXA-48 |
| OM22 | Escherichia coli | OXA-48 |
| BOU | Enterobacter cloacae | OXA-48 |
| TUR | Enterobacter cloacae | OXA-48 |
| 11670 | Escherichia coli | OXA-48 |
| MSH2014-64 | Klebsiella pneumoniae | OXA-181 |
| MSH2014-72 | Escherichia coli | OXA-181 |
| B108A | Klebsiella pneumoniae | NDM, OXA-181 |
| C10192- | ||
| DISCS | Enterobacter aerogenes | NDM, OXA-181 |
| KP-OMA3 | Klebsiella pneumoniae | NDM-1, OXA-181 |
| 166643 | Klebsiella pneumoniae | OXA-181 |
| 42194 | Klebsiella pneumoniae | OXA-181 |
| 1300920 | Klebsiella pneumoniae | NDM, OXA-181 |
| MSH2014-69 | Klebsiella pneumoniae | NDM, OXA-181 |
| 74 | Escherichia coli | OXA-181 |
| NCTC 13476 | Escherichia coli | IMP-1 |
| 695 | Acinetobacter baumannii | IMP-1 |
| 2340 | Enterobacter cloacae | IMP-1 |
| IMPBMI | Klebsiella pneumoniae | IMP-1 |
| 6852 | Klebsiella pneumoniae | IMP-1 |
| Yonsei_1 | Acinetobacter baumannii | IMP-1 |
| Yonsei_2 | Acinetobacter baumannii | IMP-1 |
| 70450-1 | Pseudomonas aeruginosa | IMP-1 |
| 3994 | Pseudomonas | IMP-10 |
| MKAM | Pseudomonas aeruginosa | IMP-1 |
| 5344 | Pseudomonas aeruginosa | IMP-2 |
| G029 | Salmonella spp | IMP-4 |
| 3985 | Pseudomonas aeruginosa | IMP-11 |
| 4032 | Pseudomonas aeruginosa | IMP-6 |
| 3424 | Pseudomonas aeruginosa | IMP-7 a,b |
| 32443 | Klebsiella pneumoniae | IMP-13 a |
| 92 | Pseudomonas aeruginosa | IMP-14 a, b |
a. Not detected by Xpert Carba-R (see Limitations in package insert).
b. IMP-7 and IMP-14 genes were not detected by the assay and were not predicted to be
detected by in silico analysis (see Limitations in package insert).
11
| Marker | | Wet testing | | | Not tested but predicted to
be detected based on |
|------------------------------|-------------------|-----------------------------------------------|-------------------------|--------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------|
| (or Traditional
Subgroup) | No. of
Samples | Type(s)
Detected | Type(s) not
Detected | | in silico analysis |
| KPC | 12 | KPC-2, 3, 4 | -- | KPC-5, 6, 7, 8, 9, 10, 11, 12,
13, 14, 15, 16 | |
| NDM | 18 | NDM-1, 2, 4,
5 | -- | NDM-3, 6, 7, 8, 9 | |
| VIM | 12 | VIM-1, 2, 4,
10, 19 | -- | VIM-5, 6, 7, 8, 9, 11, 12, 13,
14, 15, 16, 17, 18, 20, 23, 24,
25, 26, 27, 28, 29, 30, 31, 32,
33, 34, 35, 36, 37, 38 | |
| OXA-48 | 18 | OXA-48,
181(OXA-48
variant) | -- | OXA-162, 163, 204, 232, 244,
245, 247 | |
| IMP | 17 | IMP-1 (9
strains), IMP-
2, 4, 6, 10, 11 | IMP-7a,
13b, 14a | IMP-3, 8, 9, 13b, 19, 20, 21,
22, 24, 25, 27, 28, 30, 31, 33,
37, 40, 42 | |
Table 5-3: Summary of Variants Detected by Wet Testing or Predicted to be Detected Based on In Silico Analysis
a. IMP-7 and IMP-14 genes (Pseudomonas aeruginosa) were not detected by the assay and were not predicted to be detected by in silico analysis (see Limitations in package insert).
b. IMP-13 gene (Klebsiella pneumoniae): although predicted to be detected by in silico analysis, the IMP-13 gene was not detected by the assay (see Limitations in package insert).
Analytical Specificity (Cross-reactivity)
The analytical specificity of the Xpert Carba-R Assay was evaluated by testing a panel of 62 well-characterized bacterial strains of carbapenem-susceptible bacteria or bacteria with carbapenem non-susceptibility due to genes or mechanisms other than the Xpert Carba-R target genes (Table 5-4 and Table 5-5). Twenty-four commensal bacterial strains and other enteric microorganisms were also evaluated in the study (Table 5-6). Resistance mechanisms were determined by individual PCR assays, DNA sequence analysis, or Check-Points array version CT102.
Organisms were grown aerobically on blood agar and MacConkey agar plates or chocolate agar plates. Two cell suspensions equivalent to a 0.5 McFarland cell suspension were prepared from isolated colonies on each type of agar plate. Each organism was tested a total of four times (two replicates from each of two 0.5 McFarland cell suspensions per organism) from each plate.
12
The Xpert Carba-R Assay did not cross react with any of the organisms tested (Table 5-5, and Table 5-6). The analytical specificity of the assay was 100%.
| Ertapenem | Imipenem | Meropenem | |
|---|---|---|---|
| Susceptible | 19 | 30 | 24 |
| Intermediate | 0 | 8 | 4 |
| Resistant | 43 | 24 | 34 |
Table 5-4: Number of Carbapenem-susceptible and Non-susceptible Organisms for each Antibiotic
| Organism | Strain ID | Confirmed Resistance
Mechanisms | Carbapenem
susceptibility (S/I/R)a | | |
|---------------------------------|------------------|----------------------------------------------|---------------------------------------|------|------|
| | | | ETPa | IMPa | MEMa |
| Escherichia coli | NCTC 13441 | CTX-M (15) | S | S | S |
| Klebsiella pneumoniae | NCTC 13465 | CTX-M (25) | S | S | S |
| Enterobacter cloacae | Clinical isolate | OmpC/OmpF deficient | R | R | R |
| Citrobacter freundii | Clinical isolate | TEM (WT+164S) | S | S | S |
| Enterobacter cloacae | Clinical isolate | AmpC (ACT/MIR) | R | R | R |
| Klebsiella pneumoniae | kpn5 | CTX-M-2 | R | S | R |
| Klebsiella pneumoniae | kpn12 | TEM; SHV; CTX-M | R | R | R |
| Escherichia coli | eco1 | TEM; CTX-M-2 | R | R | R |
| Escherichia coli | Clinical isolate | CTX-M (2); TEM | R | S | S |
| Enterobacter cloacae | Clinical isolate | CTX-M (2); TEM | R | R | R |
| Serratia marcescens | Clinical isolate | CTX-M (2); TEM | S | S | S |
| Morganella morganii | fer29 | CTX-M (2); TEM | S | R | S |
| Proteus mirabilis | gut25 | CTX-M (2); TEM | S | R | S |
| Salmonella spp. | Clinical isolate | CTX-M (2); TEM | S | S | S |
| Shigella flexnerii | Clinical isolate | CTX-M (2); TEM | S | S | S |
| Enterobacter cloacae | PA_3 | AmpC; CTX-M-15; TEM | S | S | S |
| Klebsiella pneumoniae | Clinical isolate | SHV | S | S | S |
| Klebsiella pneumoniae | Clinical isolate | CTX-M (1, -type 15
like); SHV | S | S | S |
| Klebsiella pneumoniae | 32598 | CTX-M (-1, -type 15
like); SHV; TEM | R | I | R |
| Klebsiella pneumoniae | 33560 | CTX-M (15); SHV-11;
TEM-1 | S | S | S |
| Organism | Strain ID | Confirmed Resistance
Mechanisms | Carbapenem
susceptibility (S/I/R)a | | |
| | | | ETPa | IMPa | MEMa |
| Klebsiella pneumoniae | 33603 | SHV-2 | R | I | R |
| Klebsiella pneumoniae | Clinical isolate | SHV-27 | S | S | S |
| Klebsiella pneumoniae | Clinical isolate | SHV (-5, -55); TEM | S | S | S |
| Klebsiella pneumoniae | 34430 | SHV; TEM; CTX-M-15 | S | S | S |
| Klebsiella pneumoniae | 34680 | TEM; CTX-M-2 | R | S | R |
| Klebsiella pneumoniae | 34732 | CTX-M (15); SHV; TEM | R | S | S |
| Enterobacter cloacae | PA_174 | GX-/Culture+; SHV; TEM | S | S | S |
| Enterobacter aerogenes | Clinical isolate | SHV (WT+238S+240K) | R | S | R |
| Enterobacter aerogenes | STU 669 | SHV (WT+238S+240K) | R | R | R |
| Escherichia coli | C3015 | AmpC (CMY II); TEM | R | R | R |
| Enterobacter aerogenes | RI_100 | AmpC (DHA); SHV | R | R | R |
| Klebsiella pneumoniae | B4A | SHV (WT + 238S +240K) | R | R | R |
| Klebsiella pneumoniae | B13A | SHV (WT + 238S +240K) | R | S | S |
| Enterobacter cloacae | RI_474 | AmpC (ACT/MIR) | R | I | I |
| Enterobacter amnigenus | B71 | AmpC (ACT/MIR) | R | R | R |
| Klebsiella pneumoniae | DD82A | SHV (WT + 238S + 240K) | R | S | R |
| Klebsiella pneumoniae | B100 | CTX-M (-1, type-15 like); SHV (WT+238S); TEM | R | S | R |
| Enterobacter cloacae | 135B | TEM | S | S | S |
| Klebsiella pneumoniae | B157 | SHV; TEM | R | R | R |
| Escherichia coli | T2914280 | CTX-M (-1, -15); TEM | R | S | R |
| Providencia stuartii | DD188 | TEM (104K + 164S) | R | I | I |
| Enterobacter cloacae | DD189 | AmpC (ACT/MIR) | R | S | S |
| Escherichia coli | B198B | CTX-M (-1, type -15 like); TEM | R | S | R |
| Klebsiella pneumoniae | T3019989-1 | CTX-M (-1, type-15 like); SHV | R | I | R |
| Klebsiella pneumoniae | T3019989-2 | CTX-M (-1, type-15 like); SHV | R | S | R |
| Enterobacter cloacae | ENC-THAI14 | VEB-1, TEM | S | S | S |
| Escherichia coli | CB154006 | CTX-M (9); TEM | R | I | I |
| Enterobacter cloacae | S35766 | AmpC(ACT/MIR) | S | S | S |
| Enterobacter cloacae | X1856910 | AmpC (ACT/MIR); TEM | R | I | I |
| Organism | Strain ID | Confirmed Resistance | Carbapenem
susceptibility (S/I/R)ª | | |
| | | Mechanisms | ETPa | IMPa | MEMª |
| Klebsiella pneumoniae | W3758164 | CTX-M (-1, -15 like);
SHV; TEM. | R | I | R |
| Klebsiella pneumoniae | X2135758 | CTX-M (-1, -15 like);
SHV | R | S | S |
| Klebsiella pneumoniae | W3809535 | CTX-M (-1, -15 like);
SHV | R | R | R |
| Pseudomonas aeruginosa | CDC0064 | SPM | R | R | R |
| Serratia marcescens | CDC0099 | SME | R | R | R |
| Serratia marcescens | CDC0121 | SME | R | R | R |
| Serratia marcescens | CDC0122 | SME | R | R | R |
| Serratia marcescens | CDC0123 | SME | R | R | R |
| Serratia marcescens | CDC0124 | SME | R | R | R |
| Serratia marcescens | CDC0130 | SME | R | R | R |
| Serratia marcescens | CDC0131 | SME | R | R | R |
| Enterobacter cloacae
group | CDC0132 | IMI | R | R | R |
| Enterobacter cloacae
complex | CDC0164 | IMI | R | R | R |
Table 5-5: Cross-Reactivity Panel
13
14
S/I/R = Susceptible/Intermediate/Resistant, ETP = Ertapenem, IMP = Imipenem, MEM = Meropenem a.
| Organism | Strain ID |
|---|---|
| Escherichia coli | ATCC 25922 |
| Enterococcus faecalis | ATCC 29212 |
| Klebsiella pneumoniae | ATCC 700603 |
| Escherichia coli | ATCC 35218 |
| Staphylococcus aureus | ATCC 25923 |
| Pseudomonas aeruginosa | ATCC 27853 |
| Enterobacter cloacae | ATCC 700621 |
| Enterococcus faecium | ATCC 9756 |
| Klebsiella oxytoca | ATCC 13182 |
| Acinetobacter baumannii | ATCC BAA-747 |
| Citrobacter freundii | ATCC 33128 |
| Morganella morganii | ATCC 49948 |
| Stenotrophomonas maltophilia | ATCC 51331 |
| Citrobacter koseri | ATCC 27028 |
| Providencia stuartii | ATCC 49809 |
| Streptococcus agalactiae | CCUG 29780 / ATCC |
| 12401 |
15
| Organism | Strain ID |
|---|---|
| Enterobacter aerogenes | ATCC 51697 |
| Proteus mirabilis | ATCC 43071 |
| Acinetobacter spp. | CCUG 34787 |
| Citrobacter freundii | CCUG 418 |
| Corynebacterium diphtheriae | CCUG 33629 |
| Helicobacter pylori | CCUG 17874 |
| Listeria monocytogenes | CCUG 33548 |
| Providencia alcalifaciens | CCUG 6325 |
Carry-Over Contamination
A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent carry-over contamination in negative samples run following very high positive samples. The study consisted of a negative sample processed in the same GeneXpert module immediately following a very high positive sample. The high positive sample is composed of inactivated E. coli cells containing a plasmid with an insert consisting of a synthetic oligonucleotide of the amplicon sequences from the five Xpert Carba-R target analyte genes (KPC, NDM, VIM, IMP and OXA-48 targets). Positive cells were diluted in Sample Reagent to a concentration of 1 x 100 CFU/mL. The testing scheme was repeated 50 times on two GeneXpert modules for a total of 102 tests (25 high positive samples per module and 26 negative samples per module). All 50 positive samples correctly reported all Xpert Carba-R targets as DETECTED. All 52 negative samples correctly reported all Xpert Carba-R targets as NOT DETECTED.
Clinical Studies
Clinical Performance
Performance characteristics of the Xpert Carba-R Assay with bacterial isolates were determined in a multi-site investigational study by comparing the Xpert Carba-R Assay to reference bi-directionalsequencing of the amplified DNA target. Study sampless included bacterial isolates grown from both blood agar and MacConkey agar.
To be included in the study, isolates must have been previously identified as Enterobacteriaceae, Pseudomonas aeruginosa, or Acinetobacter baumannii. For determination of sensitivity, isolates must have been either intermediate or resistant to meropenem, ertapenem and/or imipenem per CLSI M100-S24. Isolates of Pseudomonas aeruginosa or Acinetobacter baumannii must have been intermediate or resistant to either imipenem or meropenem. These organisms are intrinsically resistant to ertapenem. For evaluation of specificity, isolates may have been susceptible or resistant to meropenem, ertapenem, and imipenem per CLSI M100-S24. Pseudomonas aeruginosa and Acinetobacter baumannii isolates should have been susceptible to both imipenem and meropenem. Isolates were tested only once in the study.
A total of 489 isolates (431 clinical stock isolates and 58 fresh isolates) were initially enrolled in this clinical study, of which 485 were eligible for inclusion. The ineligible isolates included four isolates previously enrolled in the study.
16
From the 485 eligible isolates, 467 isolates (410 clinical stock isolates and 57 fresh isolates) were included in the final dataset used for the analyses presented in this report; two isolates were excluded because reference testing was not performed; and sixteen isolates were excluded because they were not identified as Enterobacteriaceae, A. baumannii, or P. aeruginosa.
For Xpert Carba-R Assay testing, well-isolated colonies that grew on each of the agar types were diluted to a 0.5 McFarland standard equivalent suspension using the direct colony suspension method per CLSI M07-A9.
For reference sequencing, DNA from culture isolates was purified, quantified, and amplified using primers specific to all 5 target genes that amplify larger regions than the assay targets and include the Xpert Carba-R primer sequences. The production of the appropriate size of amplification product was confirmed on Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA).
If bands shown on the Bioanalyzer corresponded to the expected size of the amplicon from any of the five target genes detected by the Xpert Carba-R Assay, the amplicon for the isolate was sent to an independent laboratory for reference bi-directional sequencing analysis, validated for detection of the five targets in the Xpert Carba-R Assay. If no bands were shown on the Bioanalyzer for any of the five target genes, the isolate was not sent for sequence analysis and the reference method result was considered negative for the five target genes.
Multiple targets were detected by the Xpert Carba-R Assay in samples from ten isolates. The details are provided in Table 5-7, along with the reference sequencing result.
| Table 5-7. Isolates with Multiple Targets Detected | |||
|---|---|---|---|
| Isolate | Agar | ||
| Typea | Targets Detected by | ||
| Xpert Carba-R Assay | Targets Detected by | ||
| Reference Sequencing | |||
| 1 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 2 | BA | VIM, KPC | VIM |
| 3 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 4 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 5 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 6 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 7 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 8 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 9 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
| 10 | BA, MC | NDM, OXA-48 | NDM, OXA-48 |
Table 5-7 Isolates with Multiple Targets Detected
a. BA=blood agar, MC=MacConkey agar
When tested with isolates from blood agar, the Xpert Carba-R Assay demonstrated an overall sensitivity and specificity of 100.0% (95% CI: 99.0-100) and 98.1% (95% CI: 93.2-99.5), respectively, relative to reference sequencing performed from the blood agar isolates (Table 5-8). The combined result was defined as positive for the Xpert Carba-R Assay if any of the targets were positive, and negative for the Xpert Carba-R Assay if all of the targets were negative.
17
Table 5-8: Xpert Carba-R (blood agar) vs. Reference Sequencing (isolate grown on blood agar) - Combined
| Target | N | TP | FP | TN | FN | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
|---------|-----|------|----|-----|----|--------------------------|--------------------------|
| Overall | 467 | 364a | 2a | 101 | 0 | 100.0%
(99.0-100) | 98.1%
(93.2-99.5) |
a. Combined results represent results by isolate. Multiple target results were observed for some isolates.
When tested with isolates from blood agar, the Xpert Carba-R Assay demonstrated a sensitivity and specificity of >99% for each of the five assay targets, relative to reference sequencing performed from the blood agar isolates (Table 5-9).
For isolates with discordant results between the Xpert Carba-R Assay and reference sequencing, discrepant testing was performed using bi-directional sequencing on isolates from MacConkey agar plates. Discrepant testing results are footnoted in Table 5-9 and Table 5-11.
Table 5-9: Xpert Carba-R (blood agar) vs. Reference Sequencing (isolate grown on blood agar) -
| Target | N | TP | FP | TN | FN | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
|--------|-----|----|-----|-----|----|--------------------------|--------------------------|
| IMP | 467 | 40 | 1 a | 426 | 0 | 100%
(91.2-100) | 99.8%
(98.7-100) |
| VIM | 467 | 82 | 1 b | 384 | 0 | 100%
(95.5-100) | 99.7%
(98.5-100) |
| NDM | 467 | 78 | 0 | 389 | 0 | 100%
(95.3-100) | 100%
(99.0-100) |
| KPC | 467 | 84 | 1 c | 382 | 0 | 100%
(95.6-100) | 99.7%
(98.5-100) |
| OXA-48 | 467 | 89 | 0 | 378 | 0 | 100%
(95.9-100) | 100%
(99.0-100) |
By Target
a. The bi-directional DNA sequencing result for this false positive IMP isolate exhibited 92.95% sequence homology which was slightly below the 95% cutoff criteria. Discrepant testing was not performed.
b. Discrepant testing results: 1 of 1 was VIM positive.
c. This false positive isolate is likely due to KPC cross-contamination at the level of sample preparation. Discrepant testing did not produce a sequence match with the KPC target. Discrepant testing produced a sequence match for the VIM target, therefore this isolate is classified as a TP in the Combined" assessment presented in Table 5-8, above.
When tested with isolates from MacConkey agar, the Xpert Carba-R Assay demonstrated an overall sensitivity and specificity of 100% (95% CI: 99.0-100) and 97.1% (95% CI: 91.8-99.0), respectively, relative to reference sequencing performed from the blood agar isolates (Table 5-10). The combined result was defined as positive for the Xpert Carba-R Assay if any of the targets were positive, and negative for the Xpert Carba-R Assay if all of the targets were negative.
18
| Target | N | TP | FP | TN | FN | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
|----------|-----|------|----|-----|----|--------------------------|--------------------------|
| Combined | 467 | 364a | 3 | 100 | 0 | 100%
(99.0-100) | 97.1%
(91.8-99.0) |
Table 5-10. Xpert Carba-R (MacConkey agar) vs. Reference Sequencing (isolate grown on blood agar) - Combined
Combined results represent results by isolate. Multiple target results were observed for some a. isolates.
When tested with isolates from MacConkey agar, the Xpert Carba-R Assay demonstrated a sensitivity and specificity of >99% for each of the five assay targets, relative to reference sequencing performed from the blood agar isolates (Table 5-11).
Table 5-11. Xpert Carba-R (MacConkey agar) vs. Reference Sequencing (isolate grown on blood agar) - By Target
| Target | N | TP | FP | TN | FN | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
|--------|-----|----|-----|-----|----|--------------------------|--------------------------|
| IMP | 467 | 40 | 1 a | 426 | 0 | 100%
(91.2-100) | 99.8%
(98.7-100) |
| VIM | 467 | 82 | 1 b | 384 | 0 | 100%
(95.5-100) | 99.7%
(98.5-100) |
| NDM | 467 | 78 | 1 c | 388 | 0 | 100%
(95.3-100) | 99.7%
(98.6-100) |
| KPC | 467 | 84 | 0 | 383 | 0 | 100%
(95.6-100) | 100%
(99.0-100) |
| OXA-48 | 467 | 89 | 0 | 378 | 0 | 100%
(95.9-100) | 100%
(99.0-100) |
The bi-directional DNA sequencing result for this false positive IMP isolate exhibited 92.95% a. sequence homology which was slightly below the 95% cutoff criteria. Discrepant testing was not performed.
Discrepant testing results: 1 of 1 was VIM positive. b.
The clinical site reported that in-house characterization of this false positive isolate prior to study C. testing resulted in a positive NDM gene target. Discrepant testing did not produce a sequence match for any of the 5 gene targets.
The Xpert Carba-R Assay performance by specific organism group is shown in Table 5-12 for both blood agar and MacConkey Agar medium. The overall result was defined as positive for the Xpert Carba-R Assay if any of the targets were positive, and negative for the Xpert Carba-R Assay if all of the targets were negative.
19
| Medium | Organisms | Target | N | TP | FP | TN | FN | Sensitivity %
(95 CI) | Specificity%
(95 CI) |
|-------------------|----------------------------|---------|-----|------|----|-----|----|--------------------------|--------------------------|
| Blood Agar | Enterobacteriaceae | IMP | 343 | 4 | 0 | 339 | 0 | 100%
(51.0-100) | 100%
(98.9-100) |
| | | VIM | 343 | 51 | 1 | 291 | 0 | 100%
(93.0-100) | 99.7%
(98.1-99.9) |
| | | NDM | 343 | 73 | 0 | 270 | 0 | 100%
(95.0-100) | 100%
(98.6-100) |
| | | KPC | 343 | 83 | 1 | 259 | 0 | 100%
(95.6-100) | 99.6%
(97.9-99.9) |
| | | OXA-48 | 343 | 89 | 0 | 254 | 0 | 100%
(95.9-100) | 100%
(98.5-100) |
| | | Overall | 343 | 291a | 1a | 51 | 0 | 0 | 100%
(98.7-100) |
| | Pseudomonas
aeruginosa | IMP | 80 | 16 | 1 | 63 | 0 | 100%
(80.6-100) | 98.4%
(91.7-99.7) |
| | | VIM | 80 | 31 | 0 | 49 | 0 | 100%
(89.0-100) | 100%
(92.7-100) |
| | | NDM | 80 | 0 | 0 | 80 | 0 | NA | 100%
(95.4-100) |
| | | KPC | 80 | 1 | 0 | 79 | 0 | 100%
(20.7-100) | 100%
(95.4-100) |
| | | OXA-48 | 80 | 0 | 0 | 80 | 0 | NA | 100%
(95.4-100) |
| | | Overall | 80 | 48 | 1 | 31 | 0 | 100%
(92.6-100) | 96.9%
(84.3-99.5) |
| | Acinetobacter
baumannii | IMP | 44 | 20 | 0 | 24 | 0 | 100%
(83.9-100) | 100%
(86.2-100) |
| | | VIM | 44 | 0 | 0 | 44 | 0 | NA | 100%
(92.0-100) |
| | | NDM | 44 | 5 | 0 | 39 | 0 | 100%
(56.6-100) | 100%
(91.0-100) |
| | | KPC | 44 | 0 | 0 | 44 | 0 | NA | 100%
(92.0-100) |
| | | OXA-48 | 44 | 0 | 0 | 44 | 0 | NA | 100%
(92.0-100) |
| | | Overall | 44 | 25 | 0 | 19 | 0 | 100%
(86.7-100) | 100%
(83.2-100) |
| MacConkey
Agar | Enterobacteriaceae | IMP | 343 | 4 | 0 | 339 | 0 | 100%
(51.0-100) | 100%
(98.9-100) |
| | | VIM | 343 | 51 | 1 | 291 | 0 | 100%
(93.0-100) | 99.7%
(98.1-99.9) |
| | | NDM | 343 | 73 | 1 | 269 | 0 | 100%
(95.0-100) | 99.6%
(97.9-99.9) |
| | | KPC | 343 | 83 | 0 | 260 | 0 | 100%
(95.6-100) | 100%
(98.5-100) |
| | | OXA-48 | 343 | 89 | 0 | 254 | 0 | 100%
(95.9-100) | 100%
(98.5-100) |
| | | Overall | 343 | 291a | 2 | 50 | 0 | 0 | 100%
(98.7-100) |
| | Pseudomonas
aeruginosa | IMP | 80 | 16 | 1 | 63 | 0 | 100%
(80.6-100) | 98.4%
(91.7-99.7) |
| | | VIM | 80 | 31 | 0 | 49 | 0 | 100%
(89.0-100) | 100%
(92.7-100) |
| Medium | Organisms | Target | N | TP | FP | TN | FN | Sensitivity %
(95 CI) | Specificity %
(95 CI) |
| | | NDM | 80 | 0 | 0 | 80 | 0 | NA | 100%
(95.4-100) |
| | | KPC | 80 | 1 | 0 | 79 | 0 | 100%
(20.7-100) | 100%
(95.4-100) |
| | | OXA-48 | 80 | 0 | 0 | 80 | 0 | NA | 100%
(95.4-100) |
| | | Overall | 80 | 48 | 1 | 31 | 0 | 100%
(92.6-100) | 96.9%
(84.3-99.5) |
| | Acinetobacter
baumannii | IMP | 44 | 20 | 0 | 24 | 0 | 100%
(83.9-100) | 100%
(86.2-100) |
| | | VIM | 44 | 0 | 0 | 44 | 0 | NA | 100%
(92.0-100) |
| | | NDM | 44 | 5 | 0 | 39 | 0 | 100%
(56.6-100) | 100%
(91.0-100) |
| | | КРС | 44 | 0 | 0 | 44 | 0 | NA | 100%
(92.0-100) |
| | | OXA-48 | 44 | 0 | 0 | 44 | 0 | NA | 100%
(92.0-100) |
| | | Overall | 44 | 25 | 0 | 19 | 0 | 100%
(86.7-100) | 100%
(83.2-100) |
Table 5-12: Xpert Carba-R vs. Reference Sequencing
20
a.Overall results represent results by isolate. Multiple target results were observed for some isolates.
Xpert Carba-R Assay results by phenotype are presented in Table 5-13 and Table 5-14 below. Phenotypic results were based on the organism identification and susceptibility results for each of the isolates. The combined result was defined as positive for the Xpert Carba-R Assay if any of the five assay targets were positive, and negative for the Xpert Carba-R Assay if all five of the assay targets were negative. A non-susceptible phenotype means the isolate was intermediate or resistant to at least one carbapenem. A susceptible phenotype means the isolate was susceptible to imipenem, meropenem, and ertapenem.
| Phenotypic Results | ||||
|---|---|---|---|---|
| Non-susceptible | Susceptible | Total | ||
| Xpert Carba-R | Gene Detected | 356 | 10 | 366 |
| Gene Not Detected | 95 | 6 | 101 | |
| Total | 451 | 16 | 467 |
Table 5-13. Xpert Carba-R (blood agar) vs. Phenotype – Combined
21
| Phenotypic Results | ||||
|---|---|---|---|---|
| Non-susceptible | Susceptible | Total | ||
| Xpert Carba-R | Gene Detected | 357 | 10b | 367 |
| Gene Not Detected | 94a | 6 | 100 | |
| Total | 451 | 16 | 467 |
Table 5-14. Xpert Carba-R (MacConkey agar) vs. Phenotype - Combined
a. The 94 isolates that are phenotypically carbapenem non-susceptible but negative by the Xpert Carba-R Assay may contain other mechamisms of carbapenem resistance, such as AmpC betalactamases or extended spectrum beta-lactamases in combination with porin mutations, or potentially other carbapenem resistance genes that are not detected by the Xpert Carba-R Assay.
b. The 10 isolates that are phenotypically carbapenem susceptible but positive by the Xpert Carba-R assay may contain mutations that inactivate or down regulate expression of the carbapenem resistance gene detected by the Xpert Carba-R Assay.
Among the 934 tests performed (467 isolates x 2 agar types), one had an initial NO RESULT outcome (0.10%, 95% CI 0.00-0.58). The isolate vielded valid results upon repeat assay. The overall valid reporting rate of the assay was 100% (934/934).
Reproducibility Study
Reproducibility of the Xpert Carba-R Assay was evaluated using a panel of 13 bacterial samples that included: two different organisms per each of the five resistance gene targets detected by the Xpert Carba-R Assay; two stock samples that included two gene targets; and one stock sample negative for all five gene targets. Two operators at each of the three study sites tested one panel of 13 samples in replicates of four per day. Each sample was used to make two 0.5 McFarland equivalent suspensions from which two replicates were tested over six testing days (13 samples x 2 times/day x 6 days x 2 operators x 3 sites). Three lots of Xpert Carba-R Assay cartridges were used at each of the 3 testing sites. The Xpert Carba-R Assay was performed according to the Xpert Carba-R Assay procedure. Upon completion of the testing, 25 tests run on one instrument module were excluded resulting in a total of 1847 samples included in the analyses. Results are summarized in Table 5-15.
22
| Resistance
Gene | | Site 1 | | | Site 2 | | | Site 3 | % Total
Agreement | |
|--------------------|---------|---------|---------|---------|---------|---------|---------|---------|----------------------|-----------|
| (Sample #) | Op 1 | Op 2 | Site | Op 1 | Op 2 | Site | Op 1 | Op 2 | Site | by Sample |
| KPC (1) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (144/144) |
| KPC (2) | 100% | 100% | 100% | 95.8% | 100% | 97.9% | 100% | 100% | 100% | 99.3% |
| | (23/23) | (22/22) | (45/45) | (23/24) | (24/24) | (47/48) | (24/24) | (24/24) | (48/48) | (140/141) |
| VIM (1) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (22/22) | (23/23) | (45/45) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (141/141) |
| VIM (2) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (22/22) | (24/24) | (46/46) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (142/142) |
| IMP (1) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (23/23) | (24/24) | (47/47) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (143/143) |
| IMP (2) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (23/23) | (23/23) | (46/46) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (142/142) |
| OXA (1) | 100% | 100% | 100% | 100% | 91.7% | 95.8% | 100% | 100% | 100% | 98.6% |
| | (23/23) | (23/23) | (46/46) | (24/24) | (22/24) | (46/48) | (24/24) | (24/24) | (48/48) | (140/142) |
| OXA (2) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (23/23) | (22/22) | (45/45) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (141/141) |
| NDM (1) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (22/22) | (21/21) | (43/43) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (139/139) |
| NDM (2) | 100% | 100% | 100% | 91.7% | 100% | 95.8% | 100% | 100% | 100% | 98.6% |
| | (23/23) | (23/23) | (46/46) | (22/24) | (24/24) | (46/48) | (24/24) | (24/24) | (48/48) | (140/142) |
| OXA,NDM (1) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (24/24) | (23/23) | (47/47) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (143/143) |
| OXA,NDM (2) | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (23/23) | (24/24) | (47/47) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (143/143) |
| NEG | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (24/24) | (24/24) | (48/48) | (144/144) |
Table 5-15: Summary of Reproducibility Results
The reproducibility of the Xpert Carba-R Assay was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-sites, between-lots, betweendays, between-operators, and within-assays for each panel member are presented in Table 5-16.
23
| Resistance
Gene
(Sample #) | Assay
Channel
(Analyte) | Na | Between-
Site | | Between-Lot | | Between-
Day | | Between-
Operator | | Within-
Assay | | Total | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
|----------------------------------|-------------------------------|-----|------------------|-----|-------------|-----|-----------------|-----|----------------------|-----|------------------|-----|-------|-----|-------------|-----|-----|-----|-----|-----|-----|---|---|-----|-----|-----|-----|-----|-----|-------|-----|-----|-----|-----|-----|---|---|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|-----|---|---|-----|-----|-----|-----|
| | | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| KPC (1) | KPC | 144 | 1.1 | 4.4 | 0 | 0 | 0 | 0 | 0.6 | 2.6 | 0.6 | 2.6 | 1.4 | 5.8 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| KPC (2) | KPC | 143 | 0.8 | 3.1 | 0.1 | 0.2 | 0.2 | 0.9 | 0.5 | 2.0 | 0.8 | 3.1 | 1.2 | 4.9 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| VIM (1) | VIM | 141 | 1.1 | 5.1 | 0 | 0 | 0 | 0 | 0.5 | 2.3 | 0.8 | 3.7 | 1.5 | 6.7 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| VIM (2) | VIM | 142 | 0.3 | 1.3 | 0.2 | 0.8 | 0 | 0 | 0.8 | 3.8 | 0.7 | 3.1 | 1.1 | 5.1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| IMP (1) | IMP1 | 143 | 0.3 | 1.0 | 0 | 0 | 0.3 | 1.2 | 0.6 | 2.3 | 0.8 | 3.1 | 1.0 | 4.2 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| IMP (2) | IMP1 | 142 | 1.4 | 6.3 | 0.1 | 0.5 | 0 | 0 | 0.6 | 2.8 | 0.7 | 3.2 | 1.7 | 7.6 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| OXA (1) | OXA48 | 140 | 0.6 | 2.6 | 0 | 0 | 0 | 0 | 0.7 | 2.8 | 0.8 | 3.5 | 1.2 | 5.2 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| OXA (2) | OXA48 | 141 | 1.1 | 4.9 | 0.3 | 1.5 | 0 | 0 | 0.5 | 2.0 | 0.7 | 3.3 | 1.5 | 6.4 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| NDM (1) | NDM | 139 | 1.2 | 5.3 | 0 | 0 | 0 | 0 | 0.6 | 2.4 | 0.7 | 3.1 | 1.5 | 6.6 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| NDM (2) | NDM | 140 | 0.9 | 4.0 | 0.3 | 1.4 | 0 | 0 | 0.8 | 3.3 | 0.8 | 3.3 | 1.5 | 6.3 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| NDM/OXA (1) | NDM | 143 | 1.3 | 5.4 | 0.2 | 0.8 | 0 | 0 | 0.6 | 2.5 | 0.7 | 3.1 | 1.6 | 6.8 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | OXA48 | 143 | 1.2 | 6.2 | 0.3 | 1.4 | 0 | 0 | 0.5 | 2.4 | 0.7 | 3.7 | 1.5 | 7.7 | NDM/OXA (2) | NDM | 143 | 1.2 | 5.3 | 0.2 | 1.1 | 0 | 0 | 0.5 | 2.4 | 0.8 | 3.5 | 1.6 | 6.9 | OXA48 | 143 | 1.2 | 6.0 | 0.2 | 1.2 | 0 | 0 | 0.5 | 2.5 | 0.7 | 3.8 | 1.5 | 7.6 | NEG | SPC | 144 | 0.1 | 0.3 | 0.1 | 0.3 | 0 | 0 | 0.2 | 0.5 | 0.4 | 1.3 |
| OXA48 | 143 | 1.2 | 6.2 | 0.3 | 1.4 | 0 | 0 | 0.5 | 2.4 | 0.7 | 3.7 | 1.5 | 7.7 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| NDM/OXA (2) | NDM | 143 | 1.2 | 5.3 | 0.2 | 1.1 | 0 | 0 | 0.5 | 2.4 | 0.8 | 3.5 | 1.6 | 6.9 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | OXA48 | 143 | 1.2 | 6.0 | 0.2 | 1.2 | 0 | 0 | 0.5 | 2.5 | 0.7 | 3.8 | 1.5 | 7.6 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| NEG | SPC | 144 | 0.1 | 0.3 | 0.1 | 0.3 | 0 | 0 | 0.2 | 0.5 | 0.4 | 1.3 | 0.5 | 1.5 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Table 5-16. Summary of Reproducibility Data
a. Results with non-zero Ct values out of 144.
Conclusions
The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert Carba-R Assay is safe and effective for its intended use and is substantially equivalent to the predicate device.