Xpert Carba-R
Device Facts
| Record ID | K173263 |
|---|---|
| Device Name | Xpert Carba-R |
| Applicant | Cepheid |
| Product Code | POC · Microbiology |
| Decision Date | Jan 9, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.1640 |
| Device Class | Class 2 |
Intended Use
The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test designed for the detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP gene sequences associated with carbapenem-non-susceptibility. The test utilizes automated real-time polymerase chain reaction (PCR). The Xpert Carba-R Assay is intended as an aid to infection control in the detection of carbapenem-non-susceptible bacteria that colonize patients in healthcare settings. A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms. The Xpert Carba R-Assay is for use with the following sample types: Pure Colonies The assay is performed on carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa, when grown on blood agar or MacConkey agar. For testing pure colonies, the Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The identification of a blaIMP, blaNDM, or blaVIM metallo-beta-lactamase gene (i.e., the genes that encode the IMP, NDM, and VIM metallo-beta-lactamases, respectively) may be used as an aid to clinicians in determining appropriate therapeutic strategies for patients with known or suspected carbapenem-non-susceptible bacterial infections. Rectal and Perirectal Swab Specimens The assay is performed on rectal and perirectal swab specimens from patients at risk for intestinal colonization with carbapenem-non-susceptible bacteria. Concomitant cultures are necessary to recover organisms for epidemiological typing, antimicrobial susceptibility testing, and for further confirmatory bacterial identification. The Xpert Carba-R Assay, when performed on rectal and perirectal swab specimens, is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections or to determine infection from carbapenem-non-susceptible bacteria.
Device Story
Automated in vitro diagnostic test using real-time PCR to detect carbapenemase resistance genes (blaKPC, blaNDM, blaVIM, blaOXA-48, blaIMP). Input: pure bacterial colonies or rectal/perirectal swab specimens. Process: sample preparation, DNA extraction, amplification, and detection within a single-use, multi-chambered disposable cartridge. Operation: performed on Cepheid GeneXpert Instrument Systems (Dx, Infinity-48, Infinity-48s, Infinity-80) by laboratory personnel. Output: qualitative results (DETECTED/NOT DETECTED) displayed via system software. Clinical utility: aids infection control by identifying colonized patients; assists clinicians in therapeutic strategy selection for confirmed infections when used with pure colonies. Benefits: rapid (approx. 50 min) detection of resistance markers to support hospital infection control and antibiotic stewardship.
Clinical Evidence
Multi-site clinical study evaluated 924 prospective perirectal swabs vs. reference culture/sequencing. PPA for targets was 100%; NPA ranged 99.6-100%. Contrived specimen study (n=432) showed 100% PPA/NPA. Equivalence study (n=201) compared rectal vs. perirectal swabs, showing 94.7% PPA and 97.8% NPA. Reproducibility study across 3 sites/lots/operators confirmed consistent performance.
Technological Characteristics
Real-time PCR assay using TaqMan probes. Single-use, multi-chambered fluidic cartridges. Platform: GeneXpert Instrument Systems (Dx, Infinity-48, Infinity-48s, Infinity-80). Features: internal Sample Processing Control (SPC) and Probe Check Control (PCC). Automated sample prep, lysis (ultrasonic), and thermocycling (I-CORE).
Indications for Use
Indicated for qualitative detection of blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP gene sequences in pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa, and in rectal/perirectal swab specimens from patients at risk for intestinal colonization with carbapenem-non-susceptible bacteria. Not for bacterial identification, susceptibility reporting, or treatment monitoring.
Regulatory Classification
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.
Predicate Devices
- Xpert Carba-R Assay (K160901)
Related Devices
Submission Summary (Full Text)
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January 9, 2018
Cepheid Jim Kelly Executive Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089
Re: K173263
Trade/Device Name: Xpert Carba-R Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: POC, PMY, OOI Dated: October 10, 2017 Received: October 12, 2017
Dear Jim 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 Part 801 and Part 809); medical device 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.
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K173263
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.
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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
# Ribhi Shawar -S
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
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### Indications for Use
510(k) Number (if known) K173263
Device Name
Xpert Carba-R Assay
#### Indications for Use (Describe)
The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test designed for the detection and differentiation of the blakes, blaypy, blaxx -8, and blang gene sequences associated with carbapenem-non-susceptibility. The test utilizes automated real-time polymerase chain reaction (PCR).
The Xpert Carba-R Assay is intended as an aid to infection of carbapenem-non-susceptible bacteria that colonize patients in healthcare settings. A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms.
The Xpert Carba R-Assay is for use with the following sample types:
### Pure Colonies
The assay is performed on carbapentible pure colonies of Enterobacteriaceae. Acinetobacter baumannii. or Pseudomonas aeruginosa, when grown on blood agar or MacConkey agar. For testing pure colonies, the Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing.
The identification of a blawy, blayin metallo-beta-lactamase gene (i.e., the genes that encode the INP, NDM, and VIM metallo-beta-lactamases, respectively) may be used as an aid to clinicians in determining appropriate therapeutic strategies for patients with known or suspected carbapenem-non- susceptible bacterial infections.
### Rectal and Perirectal Swab Specimens
The assay is performed on rectal swab specimens from patients at risk for intestinal colonization with carbapenem-non-susceptible bacteria. Concomitant cultures are necessary to recover organisms for epidemiological typing, antimicrobial susceptibility testing, and for further confirmatory bacterial identification.
The Xpert Carba-R Assay, when performed on rectal and perirectal swab specimens, is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections or to determine infection from carbapenem-nonsusceptible bacteria.
| 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) |
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#### 8.0 510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid<br>904 Caribbean Drive<br>Sunnyvale, CA 90489<br>Phone number: (408) 745-4183<br>Fax number: (408) 744-1479 |
|--------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Jim Kelly, Ph.D. |
| Date of Preparation: | January 04, 2018 |
| Device: | |
| Trade name: | Xpert® Carba-R |
| Common name: | Xpert Carba-R Assay |
| Type of Test: | Qualitative nucleic acid amplification test of the blaKPC<br>blaNDM, blaVIM, blaOXA-48, and blaIMP gene sequences<br>associated with carbapenem-non-susceptibility in gram-<br>negative bacteria obtained from rectal swab specimens,<br>perirectal swab specimens, and bacterial isolates |
| Classification:<br>Regulation number:<br>Classification name:<br>Product code: | II<br>866.1640<br>Antimicrobial susceptibility test powder<br>POC, OOI |
| Classification<br>Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device<br>Assay: | Cepheid Xpert® Carba-R<br>[510(k) #K160901] |
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### 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 blakpo, blaymy, blavny, blaoxa-as, and blamp gene sequences from rectal or perirectal swab specimens or 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 blaxpy blayDM blaym, blacks, and blandp 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, blagxA-48 and blamp gene sequences from rectal or perirectal swab specimens or isolates of pure cultures of carbapenem-non- susceptibility 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.
Rectal or perirectal swab specimens or 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 blakers, blayDM blaym, blacks, and blamp gene sequences. The results are automatically generated at the end of the process in a report that can be viewed and printed.
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### Device Intended Use:
The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test designed for the detection and differentiation of the blaker, blaNDM, blaoxs-48, and blaMp gene sequences associated with carbapenemnon-susceptibility. The test utilizes automated real-time polymerase chain reaction (PCR).
The Xpert Carba-R Assay is intended as an aid to infection control in the detection of carbapenem-non-susceptible bacteria that colonize patients in healthcare settings. A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms.
The Xpert Carba R-Assay is for use with the following sample types:
### Pure Colonies
The assay is performed on carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa, when grown on blood agar or MacConkey agar. For testing pure colonies, the Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing.
The identification of a blanp, blaNDM, or blaviM metallo-beta-lactamase gene (i.e., the genes that encode the IMP, NDM, and VIM metallo-beta-lactamases, respectively) may be used as an aid to clinicians in determining appropriate therapeutic strategies for patients with known or suspected carbapenem-non- susceptible bacterial infections.
### Rectal and Perirectal Swab Specimens
The assay is performed on rectal and perirectal swab specimens from patients at risk for intestinal colonization with carbapenem-non-susceptible bacteria. Concomitant cultures are necessary to recover organisms for epidemiological typing, antimicrobial susceptibility testing, and for further confirmatory bacterial identification.
The Xpert Carba-R Assay, when performed on rectal and perirectal swab specimens, is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections or to determine infection from carbapenem-non-susceptible bacteria.
### Substantial Equivalence:
The Cepheid Xpert Carba-R Assay is substantially equivalent to the Xpert® Carba-R Assay, 510(k) #K160901. Both assays utilize the same GeneXpert cartridge and detect target gene sequences using real-time PCR amplification and fluorogenic target-specific hybridization detection. The performance of the Xpert Carba-R Assay for an expanded indication was determined in a multi-site clinical study in which the performance of the Xpert Carba-R Assay was evaluated relative to culture and reference DNA sequence analysis and in a second separate clinical study using rectal and perirectal swab specimens to demonstrate the equivalency of both sample types. The results of the study demonstrated that the performance of the Xpert Carba-R Assay is substantially equivalent to the predicate device. Please refer to K160901 for information on the
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performance of the Xpert Carba-R Assay with rectal swab specimens.
Table 8-1 shows the similarities and differences between the Xpert Carba-R Assay and the predicate device.
| Similarities | | |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert Carba-R Assay<br>K160901 |
| General Intended Use | The Xpert® Carba-R Assay, performed<br>on the GeneXpert® Instrument Systems,<br>is a qualitative <i>in vitro</i> diagnostic test<br>designed for the detection and<br>differentiation of the blaKPC, blaNDM,<br>blaVIM, blaOXA-48, and blaIMP gene<br>sequences associated with carbapenem-<br>non-susceptibility. The test utilizes<br>automated real-time polymerase chain<br>reaction (PCR).<br>The Xpert Carba-R Assay is intended as<br>an aid to infection control in the<br>detection of carbapenem-non-<br>susceptible bacteria that colonize<br>patients in healthcare settings. A<br>negative Xpert Carba-R Assay result<br>does not preclude the presence of other<br>resistance mechanisms. | The Xpert® Carba-R Assay, performed<br>on the GeneXpert® Instrument Systems,<br>is a qualitative <i>in vitro</i> diagnostic test<br>designed for the detection and<br>differentiation of the blaKPC, blaNDM,<br>blaVIM, blaOXA-48, and blaIMP gene<br>sequences associated with carbapenem-<br>non-susceptibility. The test utilizes<br>automated real-time polymerase chain<br>reaction (PCR).<br>The Xpert Carba-R Assay is intended as<br>an aid to infection control in the<br>detection of carbapenem-non-<br>susceptible bacteria that colonize<br>patients in healthcare settings. The Xpert<br>Carba-R Assay is not intended to guide<br>or monitor treatment for carbapenem-<br>non-susceptible bacterial infections. A<br>negative Xpert Carba-R Assay result<br>does not preclude the presence of other<br>resistance mechanisms. |
| | The Xpert Carba R-Assay is for use with<br>the following sample types:<br><br>Pure Colonies<br>The assay is performed on carbapenem-<br>non-susceptible pure colonies of<br><i>Enterobacteriaceae, Acinetobacter<br/>baumannii,</i> or <i>Pseudomonas<br/>aeruginosa</i> , when grown on blood agar<br>or MacConkey agar. For testing pure<br>colonies, the Xpert Carba-R Assay<br>should be used in conjunction with other<br>laboratory tests including phenotypic<br>antimicrobial susceptibility testing.<br><br>The identification of a blaIMP blaNDM<br>or blaVIM metallo-beta-lactamase gene<br>(i.e., the genes that encode the IMP,<br>NDM, and VIM metallo-beta- | The Xpert Carba R-Assay is for use with<br>the following sample types:<br><br>Pure Colonies<br>The assay is performed on carbapenem-<br>non-susceptible pure colonies of<br><i>Enterobacteriaceae, Acinetobacter<br/>baumannii,</i> or <i>Pseudomonas<br/>aeruginosa</i> , when grown on blood agar<br>or MacConkey agar. For testing pure<br>colonies, the Xpert Carba-R Assay<br>should be used in conjunction with other<br>laboratory tests including phenotypic<br>antimicrobial susceptibility testing. |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert Carba-R Assay<br>K160901 |
| | as an aid to clinicians in determining<br>appropriate therapeutic strategies for<br>patients with known or suspected<br>carbapenem-non- susceptible bacterial<br>infections. | |
| | Rectal and Perirectal Swab Specimens<br>The assay is performed on rectal and<br>perirectal swab specimens from patients<br>at risk for intestinal colonization with<br>carbapenem-non-susceptible bacteria.<br>Concomitant cultures are necessary to<br>recover organisms for epidemiological<br>typing, antimicrobial susceptibility<br>testing, and for further confirmatory<br>bacterial identification.<br>The Xpert Carba-R Assay, when<br>performed on rectal and perirectal swab<br>specimens, is not intended to guide or<br>monitor treatment for carbapenem-non-<br>susceptible bacterial infections or to<br>determine infection from carbapenem-<br>non-susceptible bacteria. | Rectal Swab Specimens<br>The assay is performed on rectal swab<br>specimens from patients at risk for<br>intestinal colonization with carbapenem-<br>non-susceptible bacteria.<br>Concomitant cultures are necessary to<br>recover organisms for epidemiological<br>typing, antimicrobial susceptibility<br>testing, and for further confirmatory<br>bacterial identification. |
| Type of test | Same | Qualitative |
| Technological<br>Principles | Same | Fully-automated nucleic acid<br>amplification (DNA); real-time<br>PCR |
| Test Cartridge | Same | Disposable single-use, multi-chambered<br>fluidic cartridge |
| Probes | Same | TaqMan® Probes |
| Controls | Same | Internal sample processing<br>control (SPC) and probe<br>check control (PCC)<br>External controls available |
| Instrument System | Same | GeneXpert Instrument System<br>(includes GeneXpert Dx, Infinity-48,<br>Infinity-48s, and Infinity-80) |
| Time to obtain test<br>results | Same | Approximately 50 minutes to results |
| Interpretation of test<br>results | Same | Diagnostic software of the GeneXpert<br>Instrument System |
| Similarities | | |
| Item | Device | Predicate Device |
| Laboratory Users | Same | Operators in CLIA Moderate or High<br>Complexity labs |
| Differences | | |
| Item | New Device | Predicate Device |
| Sample Types | Bacterial isolates from culture, rectal<br>swab and perirectal swab specimens | Bacterial isolates from culture and<br>rectal swab specimens |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert Carba-R Assay<br>K160901 |
#### Table 8-1: Comparison of Similarities and Differences of the Xpert Carba-R Assay with the Predicate Device
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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 Sensitivity (Limit of Detection) -Perirectal Swabs
The analytical sensitivity or Limit of Detection (LoD) of the Xpert Carba-R Assay was assessed using carbapenemase-producing organisms seeded into pooled negative human perirectal swab matrix. The LoD was determined for two carbapenemase-producing bacteria for each gene analyte, i.e., the genes encoding KPC, NDM, VIM, OXA-48, and IMP. Bacteria were titered by plate counts and spiked onto clean swabs. Swabs were placed into pooled negative perirectal swab matrix and replicates of 20 were evaluated at a minimum of five different concentrations over four days. The LoD for each of the ten carbapenemase-producing organisms was estimated by probit analysis. The LoD is defined as the lowest concentration of target cells (CFU/swab) that can be reproducibly distinguished from negative samples with 95% confidence. The study was performed with two different lots of Xpert Carba-R reagents and the claimed LoD is the higher of the two determinations. The estimated LoDs were verified by preparing and testing 10 replicates from two independent dilutions of each bacterium at each estimated LoD.
The claimed LoD for each pair of carbapenemase-producing organism in perirectal swab matrix are shown in Table 8-2.
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| Target Gene and Organism | LoD Estimates (Probit) CFU/swab | | LOD Claim CFU/swab | Estimated LoD In Sample Reagent CFU/mL | Verification (Positives/20) |
|-------------------------------------------|---------------------------------|-------|--------------------|----------------------------------------|-----------------------------|
| | Lot 1 | Lot 2 | | | |
| IMP-1 Acinetobacter baumannii | 90 | 118 | 118 | 24 | 19/20 |
| IMP-1 Klebsiella pneumoniae | 269 | 635 | 635 | 127 | 20/20 |
| VIM-1 Klebsiella pneumoniae | 901 | 514 | 901 | 180 | 20/20 |
| VIM-4 Escherichia coli | 446 | 403 | 446 | 89 | 20/20 |
| NDM-1 Klebsiella pneumoniae ATCC BAA-2146 | 133 | 113 | 133 | 27 | 20/20 |
| NDM Klebsiella pneumoniae | 56 | 54 | 56 | 11 | 20/20 |
| KPC-3 Klebsiella pneumoniae NCTC 13438 | 358 | 292 | 358 | 72 | 20/20 |
| KPC Enterobacter cloacae | 1259 | 1303 | 1303 | 261 | 20/20 |
| OXA-48 Enterobacter cloacae | 223 | 166 | 223 | 45 | 20/20 |
| OXA-48 Escherichia coli | 126 | 137 | 137 | 27 | 20/20 |
Table 8-2: LoD Estimates and Verification for Organisms Harboring anenemase Genes using the Xpert Carba-R Assay in Perirectal Swah Matriy
### Analytical Reactivity (Inclusivity)
The analytical reactivity of the Xpert Carba-R Assay with perirectal swab matrices was evaluated by testing a panel of 72 samples. This panel consisted of 11 blakec (KPC), 11 blavm (VIM), 8 blaoxa-48 (OXA-48), 5 blayDM/blaoxA-181 (NDM/OXA-181), 6 blaoxA-181(OXA-181), 17 blamp (IMP), and one blaxpc/blavIM (KPC/VIM) well-characterized bacterial strains. The strains tested in perirectal swab matrix and their test concentrations are presented in Table 8-3.
For testing in perirectal swab matrix, organisms were seeded into pooled negative perirectal swab matrix. All bacterial strains were tested in triplicate at approximately 3X LoD. Xpert Carba-R Assay target genes were detected in 69 of 72 carbapenemaseproducing bacterial strains although IMP-4 was detected only using a higher concentration (Table 8-3). Xpert Carba-R Assay target DNA sequences were not detected in three bacterial strains as shown in Table 8-3. 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 other three bacterial strains, the IMP-7 and IMP-14 genes were not predicted to be detected by in silico analysis and were not detected by the assay. See Limitations 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 8-4.
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| Strain ID | Organism | Resistance Marker with Variant Information | Concentration Tested in Perirectal Swab Matrix (CFU/mL) |
|---------------|---------------------------------|-----------------------------------------------------|---------------------------------------------------------------------|
| NCTC 13438 | Klebsiella pneumoniae | KPC-3 | 153 |
| 31551 | Klebsiella pneumoniae | KPC-4 | 50 |
| ATCC BAA-1705 | Klebsiella pneumoniae | KPC-2 | 130 |
| PA-Col | Pseudomonas aeruginosa | KPC-2 | 250 |
| KBM18 | Enterobacter aerogenes | KPC-2 | 250 |
| BM9 | Klebsiella pneumoniae | KPC-3 | 330 |
| PA3 | Klebsiella pneumoniae | KPC-2 | 100 |
| CGNC | Serratia marcescens | KPC-2 | 300 |
| CFVL | Enterobacter cloacae | KPC-2 | 160 |
| COL | Escherichia coli | KPC-2 | 147 |
| GR-04/KP-69 | Klebsiella pneumoniae | KPC-2, VIM | 80 |
| 164-3 | Klebsiella oxytoca | KPC | 70 |
| NCTC 13437 | Pseudomonas aeruginosa | VIM-10 | 500 |
| NCTC 13439 | Klebsiella pneumoniae | VIM-1 | 130 |
| NCTC 13440 | Klebsiella pneumoniae | VIM-1 | 70 |
| 758 | Pseudomonas aeruginosa | VIM | 250 |
| PA-87 | Klebsiella pneumoniae | VIM | 200 |
| B92A | Pseudomonas aeruginosa | VIM | 2000 |
| Coll | Pseudomonas aeruginosa | VIM-2 | 500 |
| BM19 | Serratia marcescens | VIM-2 | 250 |
| KOW7 | Escherichia coli | VIM-4 | 250 |
| DIH | Klebsiella pneumoniae | VIM-19 | 250 |
| MSH2014-3 | Enterobacter cloacae | VIM | 500 |
| NCTC 13443 | Klebsiella pneumoniae | NDM-1 | 80 |
| ATCC BAA-2146 | Klebsiella pneumoniae | NDM-1 | 80 |
| 34262 | Klebsiella pneumoniae | NDM | 80 |
| GEN | Acinetobacter baumannii | NDM-1 | 130 |
| 3047 | Enterobacter cloacae | NDM-1 | 70 |
| 7892 | Proteus mirabilis | NDM-1 | 30 |
| CAN | Salmonella spp. | NDM-1 | 70 |
| EGY | Acinetobacter baumannii | NDM-2 | 40 |
| 15 | Escherichia coli | NDM-4 | 30 |
| 405 | Escherichia coli | NDM-5 | 30 |
| CF-ABE | Citrobacter freundii | NDM | 30 |
| 73999 | Pseudomonas aeruginosa | NDM | 50 |
| 39365 | Providencia rettgeri | NDM-1 | 70 |
| NCTC 13442 | Klebsiella pneumoniae | OXA-48 | 40 |
| OM11 | Klebsiella pneumoniae | OXA-48 | 60 |
| 501 | Enterobacter cloacae | OXA-48 | 80 |
| Strain ID | Organism | Resistance<br>Marker with<br>Variant<br>Information | Concentration<br>Tested in<br>Perirectal Swab<br>Matrix<br>(CFU/mL) |
| DUW | <i>Klebsiella pneumoniae</i> | OXA-48 | 120 |
| OM22 | <i>Escherichia coli</i> | OXA-48 | 80 |
| BOU | <i>Enterobacter cloacae</i> | OXA-48 | 80 |
| TUR | <i>Enterobacter cloacae</i> | OXA-48 | 120 |
| 11670 | <i>Escherichia coli</i> | OXA-48 | 100 |
| 166643 | <i>Klebsiella pneumoniae</i> | OXA-181 | 20 |
| 42194 | <i>Klebsiella pneumoniae</i> | OXA-181 | 20 |
| MSH2014-64 | <i>Klebsiella pneumoniae</i> | OXA-181 | 280 |
| MSH2014-72 | <i>Escherichia coli</i> | OXA-181 | 100 |
| 74 | <i>Escherichia coli</i> | OXA-181 | 100 |
| CDC0051 | <i>Klebsiella ozaenae</i> a | OXA-181 | 250 |
| B108A | <i>Klebsiella pneumoniae</i> | NDM, OXA-181 | 10 |
| C10192-DISCS | <i>Enterobacter aerogenes</i> | NDM, OXA-181 | 10 |
| KP-OMA3 | <i>Klebsiella pneumoniae</i> | NDM, OXA-181 | 60 |
| 1300920 | <i>Klebsiella pneumoniae</i> | NDM, OXA-181 | 15 |
| MSH2014-69 | <i>Klebsiella pneumoniae</i> | NDM, OXA-181 | 20 |
| NCTC 13476 | <i>Escherichia coli</i> | IMP-1 | 250 |
| 695 | <i>Acinetobacter baumannii</i> | IMP-1 | 1720 |
| 2340 | <i>Enterobacter cloacae</i> | IMP-1 | 250 |
| IMPBMI | <i>Klebsiella pneumoniae</i> | IMP-1 | 100 |
| Yonsei_1 | <i>Acinetobacter baumannii</i> | IMP-1 | 1000 |
| Yonsei_2 | <i>Acinetobacter baumannii</i> | IMP-1 | 500 |
| 6852 | <i>Klebsiella pneumoniae</i> | IMP-1 | 100 |
| MKAM | <i>Pseudomonas aeruginosa</i> | IMP-1 | 500 |
| 70450-1 | <i>Pseudomonas aeruginosa</i> | IMP-1 | 250 |
| 3994 | <i>Pseudomonas</i> spp. | IMP-10 | 250 |
| CDC0161 | <i>Enterobacter aerogenes</i> a | IMP-4 | 5.00E+04 |
| 5344 | <i>Pseudomonas aeruginosa</i> | IMP-2 | 60 |
| 3985 | <i>Pseudomonas aeruginosa</i> | IMP-11 | 2000 |
| 4032 | <i>Pseudomonas aeruginosa</i> | IMP-6 | 80 |
| 3424 | <i>Pseudomonas aeruginosa</i> | IMP-7b, c | 1.00E+06 |
| 32443 | <i>Klebsiella pneumoniae</i> | IMP-13c | 1.00E+06 |
| 92 | <i>Pseudomonas aeruginosa</i> | IMP-14b, c | 1.00E+06 |
### Table 8-3: Analytical Reactivity of the Xpert Carba-R Assay in Perirectal Swab Matrix
{11}------------------------------------------------
a. These organisms were not tested as bacterial isolates.
b. 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).
{12}------------------------------------------------
- c. 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).
| Marker<br>(or Traditional Subgroup) | No. of Samples | Wet testing | | Not tested but predicted to be detected Based on <i>In Silico</i> Analysis |
|-------------------------------------|----------------|----------------------------------------|----------------------|-----------------------------------------------------------------------------------------------------------------------|
| | | Type(s) Detected | Type(s) not Detected | |
| 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 | 19 | OXA-48, 181(OXA-48 variant) | -- | OXA-162, 163, 204, 2…
