(72 days)
Not Found
No
The device is a chromogenic agar medium for visual interpretation of bacterial growth and color. There is no mention of any computational analysis, image processing, or algorithms that would suggest the use of AI/ML.
No
Explanation: This device is for the detection and identification of carbapenemase-producing bacteria, which is a diagnostic purpose, not a therapeutic one. It aids in controlling colonization but does not treat the patient.
Yes
The device is a selective and differential chromogenic medium intended for the qualitative detection and presumptive identification of specific bacteria, aiding in the detection and identification of colonization, and control of these bacteria in a healthcare setting. This functionality directly aligns with the definition of a diagnostic device.
No
The device is a physical agar medium containing chemical components, not a software program.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "qualitative detection and presumptive identification of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in rectal swab specimens from patients at risk of colonization." This is a diagnostic purpose, aiming to identify the presence of specific bacteria in a clinical sample.
- Specimen Type: It uses "rectal swab specimens," which are human biological samples.
- Purpose: The device is intended as an "aid in the detection, identification of colonization and control of these bacteria in a healthcare setting." This directly aligns with the purpose of IVDs, which are used to diagnose, monitor, or screen for diseases or conditions.
- Device Description: The description details the components of the agar medium, which are used to facilitate the growth and differentiation of specific microorganisms from a clinical sample.
- Performance Studies: The document includes detailed descriptions of analytical and clinical studies conducted to evaluate the performance of the device in detecting the target organisms in clinical samples. This is a requirement for IVD devices to demonstrate their accuracy and reliability.
The information provided clearly indicates that this device is designed to be used in vitro (outside the body) to examine a human specimen for diagnostic purposes, which is the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
CHROMID® CARBA agar is a selective and differential chromogenic medium that is intended for the qualitative detection and presumptive identification of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in rectal swab specimens from patients at risk of colonization. CHROMID® CARBA agar is intended as an aid in the detection, identification of colonization and control of these bacteria in a healthcare setting.
Rectal swabs are inoculated directly onto CHROMID® CARBA agar without enrichment and results can be interpreted after incubation for 18-24 hours. Presumptive carbapenemase-producing colonies of E. coli appear pink to burgundy and those of K. pneumoniae appear blue-green or blue-grey.
Other organisms besides carbapenemase-producing E. coli and K. pneumoniae can also grow on CHROMID® CARBA agar with colonies that appear pink to burgundy or blue-green to blue-grey. Sub-culture to non-selective medium is required to confirm organism identity, for antimicrobial susceptibility testing, confirmation of carbapenemase production and epidemiological typing.
A lack of growth or the absence of pink to burgundy or blue-green to blue-grey colonies does not preclude the carriage of carbapenemase producing organisms.
Product codes
JSO
Device Description
CHROMID® CARBA agar consists of a nutritive base combining different peptones, 3 chromogenic substrates and antibiotics. These components enable the screening and presumptive identification of E. coli: spontaneous coloration (pink to burgundy) of strains producing ß-glucuronidase (ß-GUR) and/or ß-galactosidase (ß-GAL) and K. pneumoniae: spontaneous blue-green to bluish-grey coloration of strains producing ß-glucosidase (ß-GLU) from rectal swabs.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
rectal swab specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
healthcare setting
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
Analytical Studies:
- Interfering Substances: 21 interfering substances tested.
- Recovery Study (Limit of Detection (LOD)): Two well-characterized KPC strains K. pneumoniae ATCC® 1705™ and E. coli ATCC® 2340™ were tested.
- Cross Reactivity (Analytical Specificity): High concentrations (10^8 CFU/mL; 1000 times the LOD) of 59 target and non-target organisms were tested. Strains included bacterial and fungal species encountered in stools, CPE and E. coli and K. pneumoniae strains that produced other carbapenemases besides KPC type enzyme.
- Challenge Testing (Analytical Reactivity): Fifty-two well-characterized KPC-EK strains were tested using a calibrated inoculum at 4.5x10^9 CFU/mL (3 times the LOD).
- Mixed Infection: Four carbapenemase-producing strains (two E. coli and two K. pneumoniae, each harboring KPC carbapenemase) were tested at three times the LOD value in mixtures with other target and non-target organisms at 10^4 to 10^8 CFU/mL.
- Incubation: Ten well-characterized isolates representing KPC-EK strains were tested every two hours between 16 and 28 hours of incubation at +35°C ± 2°C.
Clinical Studies:
- Challenge Study: Fifty well characterized isolates were tested at one external site at two times the LOD in saline matrix. The strains tested were 11 KPC negative (6 K. pneumoniae and 5 E. coli) and 39 KPC positive (27 K. pneumoniae and 12 E. coli). KPC positive strains included KPC-2, KPC-3 and KPC-4 gene variants. Other resistance mechanisms tested among negative strains included ESBL, AmpC, and carbapenem non-susceptible carbapenemase-negative strains.
- Reproducibility and Quality Control: Ten well-characterized isolates of carbapenemase-producing E. coli (4) and K. pneumoniae (6) that harbored blakec were tested in a blinded fashion in triplicate each day for five days at three sites, and by two different operators at each site. Isolates were tested at approximately the LOD target level and plates were read at 24 hours.
- Prospective study on fresh clinical samples: Rectal swabs were collected from unique subjects. A total of 1099 swabs were initially enrolled, with 709 included in the analysis of performance. The characteristics of colonies on CHROMID® CARBA medium (pink-to-burgundy, blue-green to blue-grey, colorless, and other colors) at 18 to 24 hours were compared to the CDC enrichment culture method (selective Trypticase Soy broth, subculture to MacConkey agar, phenotypic and genetic characterization of isolated lactose fermenting colonies). Isolates from both methods were identified biochemically and carbapenemase status was determined by carbapenem susceptibility and CARBA NP testing, as well as PCR for carbapenemase resistance markers (blamp, blakpc, blandM, blaoxA-48 or blayM).
- Analysis of contrived samples: 210 contrived samples inoculated with one of the following concentrations of organisms: 1x LOD, 3x LOD, 10x LOD, were included in the study. The samples were blinded and tested at four different sites.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Studies
- Interfering Substances: No interference was observed with 21 interfering substances.
- Recovery Study (Limit of Detection (LOD)): The lowest dilution for the detection (Limit of Detection (LOD)) of both K. pneumoniae ATCC® 1705™ and E. coli ATCC® 2340™ was 1.5x10^3 CFU/mL after 18 to 24 hours of incubation.
- Cross Reactivity (Analytical Specificity):
- Sixteen CPE grew with pink to burgundy or blue-grey colonies, including KPC strains (C. freundii, P. rettgerii, E. cloacae, K. aerogenes), K. pneumoniae with VIM, IMP, OXA-48, NDM, E. coli with NDM, VIM, IMP, M. morganii with NDM, and S. marcescens with SME.
- Pseudomonas aeruginosa (VIM), Stenotrophomonas maltophilia (VIM), Pseudomonas putida and Acinetobacter baumanii (NDM) grew but without characteristic coloration.
- Challenge Testing (Analytical Reactivity): After 18 to 24 hours of incubation, all K. pneumoniae strains (52 tested) were recovered with characteristic blue-green color. Among 11 E. coli studied, 9 grew with characteristic burgundy color. Two E. coli failed to grow (one had an MIC in the susceptible range for ertapenem and was intermediate for imipenem and meropenem; the other was susceptible to all three carbapenems tested).
- Mixed Infection: When competitive species were present at
§ 866.1700 Culture medium for antimicrobial susceptibility tests.
(a)
Identification. A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
July 6, 2018
bioMérieux SA Asa Karlsson Sr. Regulatory Affairs Manager 376 Chemin de l'Orme Marcy l'Etoile, 69280 Fr
Re: K181092
Trade/Device Name: CHROMID CARBA agar (CARB) Regulation Number: 21 CFR 866.1700 Regulation Name: Culture medium for antimicrobial susceptibility tests Regulatory Class: Class II Product Code: JSO Dated: April 24, 2018 Received: April 25, 2018
Dear Asa Karlsson:
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.
1
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 comprehensive regulatory information about mediation-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
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) K181092
Device Name CHROMID® CARBA agar (CARB)
Indications for Use (Describe)
CHROMID® CARBA agar is a selective and differential chromogenic medium that is intended for the qualitative detection and presumptive identification of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in rectal swab specimens from patients at risk of colonization. CHROMID® CARBA agar is intended as an aid in the detection, identification of colonization and control of these bacteria in a healthcare setting.
Rectal swabs are inoculated directly onto CHROMID® CARBA agar without enrichment and results can be interpreted after incubation for 18-24 hours. Presumptive carbapenemase-producing colonies of E. coli appear pink to burgundy and those of K. pneumoniae appear blue-green or blue-grey.
Other organisms besides carbapenemase-producing E. coli and K. pneumoniae can also grow on CHROMID® CARBA agar with colonies that appear pink to burgundy or blue-grey. Sub-culture to non-selective medium is required to confirm organism identity, for antimicrobial susceptibility testing, confirmation of carbapenemase production and epidemiological typing.
A lack of growth or the absence of pink to burgundy or blue-grey colonies does not preclude the carriage of carbapenemase producing organisms.
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
SECTION 029. 510(k) SUMMARY
510(k) SUMMARY
CHROMID® CARBA agar
A. 510(k) Submission Information:
| 510(k) Submission: | K181092 |
|---|---|
| Submitter's Name: | bioMerieux SA |
| Address: | 376 Chemin de l'Orme |
| 69280 Marcy l'Etoile, FRANCE | |
| Contact Person: | Asa Karlsson |
| Sr. Regulatory Affairs Manager | |
| Phone Number: | +33 (0)6 48 61 68 49 |
| Email: | asa.karlsson@biomerieux.com |
| 510(k) Summary | |
| Date of Preparation: | June 28, 2018 |
| B. Device Name: | |
| Formal/Trade Name: | CHROMID® CARBA agar |
| Classification Name: | 21 CFR 866.1700 |
| Culture Medium for Antimicrobial Susceptibility Test | |
| Product Code | JSO |
| Culture Media, Antimicrobial Susceptibility Test, Excluding | |
| Mueller Hinton Agar | |
| Common Name: | CHROMID® CARBA agar (CARB) |
| C. Predicate Device: CHROMID® VRE agar (K091025) |
D. 510(k) Summary:
Intended Use:
CHROMID® CARBA agar is a selective and differential chromogenic medium that is intended for the qualitative detection and presumptive identification of carbapenemaseproducing Escherichia coli and Klebsiella pneumoniae in rectal swab specimens from
4
Traditional 510(k) Submission
patients at risk of colonization. CHROMID® CARBA agar is intended as an aid in the detection, identification of colonization and control of these bacteria in a healthcare setting.
Rectal swabs are inoculated directly onto CHROMID® CARBA agar without enrichment and results can be interpreted after incubation for 18-24 hours. Presumptive carbapenemase-producing colonies of E. coli appear pink to burgundy and those of K. pneumoniae appear blue-green or blue-grey.
Other organisms besides carbapenemase-producing E. coli and K. pneumoniae can also grow on CHROMID® CARBA agar with colonies that appear pink to burgundy or bluegreen to blue-grey. Sub-culture to non-selective medium is required to confirm organism identity, for antimicrobial susceptibility testing, confirmation of carbapenemase production and epidemiological typing.
A lack of growth or the absence of pink to burgundy or blue-green to blue-grey colonies does not preclude the carriage of carbapenemase producing organisms.
Indications for use:
See Intended Use
Device Description:
CHROMID® CARBA agar consists of a nutritive base combining different peptones, 3 chromogenic substrates and antibiotics. These components enable the screening and presumptive identification of E. coli: spontaneous coloration (pink to burgundy) of strains producing ß-glucuronidase (ß-GUR) and/or ß-galactosidase (ß-GAL) and K. pneumoniae: spontaneous blue-green to bluish-grey coloration of strains producing ß-glucosidase (ß-GLU) from rectal swabs.
Substantial Equivalence:
The similarities of CHROMID® CARBA agar when compared to the predicate device are described in the following table:
| Category | Predicate Device
bioMerieux SA
CHROMID® VRE agar
K091025 | Proposed Device
bioMerieux SA
CHROMID® CARBA agar
K181092 | Substantially equivalent |
|---------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | | |
| Classification, and
Product code | Class II, 21 CFR 866.1700
JSO | Class II, 21 CFR 866.1700
JSO | Equivalent |
| Intended Use | CHROMID® VRE agar is a
selective and differential
chromogenic medium containing
8 µg/mL vancomycin, for the
qualitative detection of
Enterococcus faecium and E.
faecalis showing acquired
vancomycin resistance (VRE) in
stool specimens. CHROMID®
VRE agar can be used as an aid
to identify, prevent and control | CHROMID® CARBA agar is a
selective and differential
chromogenic medium that is
intended for the qualitative
detection and presumptive
identification of carbapenemase-
producing Escherichia coli and
Klebsiella pneumoniae in rectal
swab specimens from patients at
risk of colonization.
CHROMID® CARBA agar is | Equivalent
Both agars are designed to
detect resistance
mechanisms but for
different antimicrobial
species. |
| | Predicate Device | Proposed Device | |
| Category | bioMerieux SA | bioMerieux SA | Substantially equivalent |
| | CHROMID® VRE agar | CHROMID® CARBA agar | |
| | K091025 | K181092 | |
| | VRE colonization in healthcare | intended as an aid in the | |
| | stings. | detection, identification of | |
| | | colonization and control of these | |
| | CHROMID® VRE agar is not | bacteria in a healthcare setting. | |
| | intended to diagnose VRE
infection nor to guide or monitor | Rectal swabs are inoculated | |
| | treatment for infections. | directly onto CHROMID® | |
| | Subculture to non-selective | CARBA agar without | |
| | media (e.g., trypticase soy agar | enrichment and results can be
interpreted after incubation for | |
| | with 5% sheep blood) is needed | 18-24 hours. Presumptive | |
| | for further identification, | carbapenemase-producing | |
| | susceptibility testing and
epidemiological typing. | colonies of E. coli appear pink to | |
| | | burgundy and those of K. | |
| | | pneumoniae appear blue-green
or blue-grey. | |
| | | | |
| | | Other organisms besides | |
| | | carbapenemase-producing E.
coli and K. pneumoniae can also | |
| | | grow on CHROMID® CARBA | |
| | | agar with colonies that appear | |
| | | pink to burgundy or blue-green | |
| | | to blue-grey. Sub-culture to non- | |
| | | selective medium is required to | |
| | | confirm organism identity, for
antimicrobial susceptibility | |
| | | testing, confirmation of | |
| | | carbapenemase production and | |
| | | epidemiological typing. | |
| | | A lack of growth or the absence | |
| | | of pink to burgundy or blue-
green to blue-grey colonies does | |
| | | not preclude the carriage of | |
| | | carbapenemase producing | |
| | | organisms. | |
| Test method | Manual, culture media | Manual, culture media | Identical |
| Method of | Direct inoculation of the sample | Direct inoculation of the sample | Identical |
| inoculation | type without enrichment. | type without enrichment. | |
| Storage of the | 2-8° C in their box until expiry | 2-8° C in their box until expiry | Identical |
| device | date. | date. | |
| | Outside the box, plates can be | Outside the box, plates can be | |
| | stored for 2 weeks in the dark in
the cellophane sachet at 2-8° C. | stored for 2 weeks in the dark in
the cellophane sachet at 2-8° C. | |
| | | | |
| Formula | Formula / Liter | Formula/ Liter | Equivalent |
| | Casein and meat peptone | Casein and meat peptone | |
| | (bovine or porcine) ........ 18g | (bovine or porcine) ........ 13g | The formulas contain |
| | Heart peptone ........ 3g | Soy peptone ........ 5g | similar ingredients and have |
| | Corn starch ........ 1g | Carbohydrates ........ 1g | |
| Category | Predicate Device
bioMerieux SA
CHROMID® VRE agar
K091025 | Proposed Device
bioMerieux SA
CHROMID® CARBA agar
K181092 | Substantially equivalent |
| | Sodium chloride...............6g
Agar........................15g
Selective mixture........28.8mg
Chromogenic mixture.....0.13g
Purified water................1L
Final pH: 7.2 | L-Tryptophan................0.9g
Phosphate buffer .............1g
Nutrient mixture...............2g
Agar........................18g
Selective mixture............1.35g
Chromogenic mixture......1.23g
Purified water................1L
Final pH: 7.4 | a similar final pH.
Both formulas can be adjusted and/or supplemented according to the performance criteria required. |
| Differences | | | |
| Analytes | Vancomycin resistant E. faecium
and E. faecalis . | Carbapenemase-producing E. coli
and K. pneumoniae . | Different target species and
antimicrobial resistance
phenotypes. |
| Specimen Types | Swabs
(stools) | Swabs
(rectal) | Different specimen types |
| Interpretation of
positive results | Observe bacterial growth and the
appearance of colonies.
Positive E. faecium : Violet
colonies.
Positive E. faecalis : Blue to
green colonies. | Observe bacterial growth and the
appearance of colonies.
Presumptive positive E. coli :
Pink to burgundy colonies.
Presumptive positive K.
pneumoniae : Blue-green to
bluish-grey colonies. | Equivalent
Different color changes
depending on bacterial
species provide a visual
interpretation of positive
results.
Positive results obtained on
CHROMID® CARBA agar
are presumptive. |
| Incubation time
and conditions | Incubate at 35-37°C in aerobic
conditions.
Examined for growth after 24 to
48 hours. | Incubate at 35-37°C in aerobic
conditions.
Examined for growth after 18 to
24 hours. | Identical.
Potential extended
incubation time for the
predicate. |
5
CHROMID® CARBA agar Traditional 510(k) Submission
6
CHROMID® CARBA agar Traditional 510(k) Submission
Both the devices use a selective mixture for the detection of resistance mechanisms and a chromogenic mixture for the presumptive identification of the bacterial species. Their formulas and method of inoculation on the agar are similar. The differences between the new device and the predicate device are related to the bacterial species and antimicrobial resistance mechanisms detected and the associated colony colors, the specimen type and incubation time. The performance data presented in this submission support a substantial equivalence
7
Performance Characteristics:
Analytical Studies
The following analytical studies were conducted to evaluate the performance of the CHROMID® CARBA agar: Interfering Substances, Recovery Study (Limit of Detection), Cross Reactivity (Analytical Specificity), Challenge Testing (Analytical Reactivity), Mixed Infection and Incubation Time. All analytical performance studies demonstrated acceptable results.
Interfering Substances: No interference was observed with 21 interfering substances including Zinc Oxide, Pramocaine hydrochloride, Miconazole nitrate, K-Y Jelly, Loperamide hydrochloride, Playtex Personal wipes, Witch Hazel, Diosmectite, Talc, K-Y Liquibeads vaginal moisturizer, Vaseline, Glycerol, Phenylephrine HCl, Trojan Enz condoms, Physiological saline, Bisacodyl, Ispaghula husk, Benzocaine + Resorcinol, Ruscoside + Lidocaine hydrochloride + Prednacinolone acetonide, Hydrocortisone and Human Blood.
Recovery Study (Limit of Detection (LOD)): Two well-characterized KPC strains K. pneumoniae ATCC® 1705™ and E. coli ATCC® 2340™ were tested to determine the lowest number of CFU/mL detected on CHROMID® CARBA agar. After 18 to 24 hours of incubation, the lowest dilution for the detection (Limit of Detection (LOD)) of both strains was 1.5x103 CFU/mL.
Cross Reactivity (Analytical Specificity): To evaluate the analytical specificity of CHROMID® CARBA agar, testing was performed with high concentrations (10° CFU/mL; 1000 times the LOD) of 59 target and non-target organisms. The strains tested included bacterial and fungal species encountered in stools, CPE and strains of E. coli and K. pneumoniae that produced other carbapenemases besides KPC type enzyme. After 18 to 24 hours of incubation, growth and colony coloration were analyzed.
- Sixteen CPE grew with pink to burgundy or blue-grey colonies:
Six KPC strains belonging to the following species: three C. freundii (blue-grey), one - P. rettgerii (blue-green), one E. cloacae (blue-green) and one K. aerogenes [E. aerogenes| (blue-green),
- . Four strains of K. pneumoniae with a resistant mechanism other than KPC: one VIM,
one IMP, one OXA-48, one NDM (all blue-green), - . Three strains of E. coli with a resistant mechanism other than KPC: one NDM, one VIM, one IMP (all pink-to burgundy)
- . Two strains of M. morganii with NDM (both blue-green),
- One strain of S. marcescens with SME (blue-green).
Pseudomonas aeruginosa (VIM), Stenotrophomonas maltophilia (VIM), Pseudomonas putida and Acinetobacter baumanii (NDM) grew on CHROMID® CARBA agar but without a characteristic coloration (colorless).
See Limitations section in the package insert.
Challenge Testing (Analytical Reactivity): Fifty-two well-characterized KPC-EK strains were tested on CHROMID® CARBA agar using a calibrated inoculum at 4.5x109 CFU/mL (3 times the LOD).
After 18 to 24 hours of incubation, all the K. pneumoniae strains were recovered with characteristic blue-green color. Among the 11 E. coli studied, 9 of them grew with a
8
Traditional 510(k) Submission
characteristic burgundy color. The two other E. coli failed to grow; of these, one had an MIC in the susceptible range for ertapenem and was intermediate for imipenem and meropenem and the other was susceptible to all three carbapenems tested.
Mixed Infection: Four carbapenemase-producing strains including two E. coli and two K. pneumoniae that each harbored KPC carbapenemase were tested at three times the LOD value in mixtures with other target and non-target organisms at 104 to 108 CFU/mL:
- one carbapenem non-susceptible carbapenemase-negative K. pneumoniae, .
- . one carbapenem non-susceptible Pseudomonas aeruginosa with VIM carbapenemase,
- . one carbapenem non-susceptible E. coli with NDM carbapenemase,
- one carbapenem susceptible K. pneumoniae.
- one carbapenem non-susceptible Enterobacter cloacae with KPC carbapenemase •
- one carbapenem non-susceptible Morganella morganii with NDM carbapenemase
- . one carbapenem non-susceptible Providencia rettgeri with KPC carbapenemase
After 18 to 24 hours of incubation, the results obtained showed that when the competitive species were present at K. pneumoniae | ATCC® BAA-1705TM | Blue-green/blue-grey colonies | 190/190
(100) |
| E. coli | ATCC® BAA-2340TM | Pink-burgundy colonies | 190/190
(100) |
| K. pneumoniae | ATCC® 700603TM | No growth | 189/190
(99.5) |
Overall, 569/570 (99.8%) of Quality Control test results for CHROMID® CARBA agar were as expected.
10
CLINICAL PERFORMANCE
Method Comparison
Prospective study on fresh clinical samples:
The performance of CHROMID® CARBA agar was evaluated at three external laboratories (2 in the US, 1 in Europe) using prospectively collected rectal swabs. A total of 1099 swabs from unique subjects were initially enrolled, of which 390 were excluded from the analysis of performance due to quality control failure (343), missing data (42) or questionable data reliability (5). Results from 709 swabs were therefore included in the analysis of performance. The characteristics of all colonies growing on CHROMID® CARBA medium (pink-to-burgundy, blue-green to blue-grey, colorless, and colors other than pink-to-burgundy or blue-green to blue-grey) at 18 to 24 hours were compared to the results obtained from the CDC enrichment culture method using selective Trypticase Soy broth, followed by subculture to MacConkey agar and phenotypic and genetic characterization of isolated lactose fermenting colonies.
Isolates from both the reference method and CHROMID® CARBA agar were identified biochemically and their carbapenemase status was determined by carbapenem susceptibility and CARBA NP testing, as well as PCR for carbapenemase resistance markers (Table 1).
| Carbapenem
MIC a | Carba NP Test | Carbapenemase
PCR b | Carbapenemase
Status |
|---------------------|---------------|------------------------|-------------------------|
| Non-susceptible | Positive | Positive | Positive |
| Non-susceptible | Positive | Negative | Negative |
| Non-susceptible | Negative | Positive | Positive |
| Non-susceptible | Negative | Negative | Negative |
| Susceptible | Positive | Positive | Positive |
| Susceptible | Positive | Negative | Negative |
| Susceptible | Negative | Positive | Negative c |
| Susceptible | Negative | Negative | Negative |
Table 1. Algorithm for determining carbapenemase status of isolates
a Non-susceptible: Intermediate or Resistant to one or more of the carbapenem antimicrobial agents tested (ertapenem, imipenem and meropenem)
b Multiplex PCR for blamp, blakpc, blandM, blaoxA-48 or blayM
C Phenotypic evidence of non-susceptibility to carbapenems in addition to a positive PCR result was required to establish the Carbapenemase Status as positive
The results of the study are presented in Tables 2 and 3 for carbapenemase-producing E. coli and K. pneumoniae, respectively.
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| CDC Reference Culture Method | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| CHROMID® | ||||
| CARBA agar | Positive a | 0 | 2 c | 2 |
| Negative b | 0 | 707 | 707 | |
| Total | 0 | 709 | 709 | |
| Positive Percent Agreement | Not applicable | |||
| Negative Percent Agreement | 99.7% (707/709); 95% CI 99.0-99.9% |
Table 2. Detection of carbapenemase-producing E. coli in the Prospective Clinical Study
95% CI: 95% score confidence interval
- a Pink-burgundy colonies
- b No growth or colonies not pink-burgundy
- C Colonies from 1/2 specimens confirmed as carbapenem non-susceptible, carbapenemase negative K. pneumoniae; colonies from 1/2 specimens identified as Enterococcus faecalis
| Table 3. Detection of carbapenemase-producing K. pneumoniae in the Prospective | |||||
|---|---|---|---|---|---|
| Clinical Study | |||||
| CDC Reference Culture Method | |||||
| Positive | Negative | Total | |||
| CHROMID® | Positive a | 43 | 15 e, f | 58 | |
| Negative b | 8 c, d | 643 | 651 | ||
| CARBA agar | Total | 51 | 658 | 709 | |
| Positive Percent Agreement | 84.3% (43/51); 95% CI 72.0-91.8% | ||||
| Negative Percent Agreement | 97.7% (643/658); 95% CI 96.3-98.6% |
95% CI: 95% score confidence interval
- a Blue-green/blue-grey colonies
- b No growth or colonies not blue-green/blue-grey
- C Includes 1 specimen from which carbapenemase-positive K. pneumoniae was recovered by the Reference Method but which yielded blue-green to blue-grey colonies on CHROMID® CARBA agar that were identified biochemically as P. aeruginosa
- d 8/8 isolates grew on CHROMID® CARBA agar when inoculated at approximately the LoD target level (103 CFU/mL in stool); all 8 carried blakec, were Carba NP Test positive and carbapenem non-susceptible (resistant to ertapenem, imipenem and meropenem)
- e 5/15 isolates on CHROMID® CARBA agar were confirmed as carbapenem nonsusceptible K. pneumoniae that carried: 4/5 isolates were Carbapenemase Statuspositive and carried blaker and 1/5 isolates was Carbapenemase Status-negative
- f 10/15 specimens produced blue-green/blue-grey colonies that were identified as Enterobacteriaceae other than K. pneumoniae (Serratia marcescens (6), Citrobacter freundii (2) and Enterobacter cloacae (2))
Analysis of contrived samples:
To supplement the prospective clinical study, testing was also performed using contrived specimens consisting of well-characterized isolates in simulated rectal swab matrix (stool diluted in saline).
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A total of 210 contrived samples inoculated with one of the following concentrations of organisms: 1x LOD, 3x LOD, 10x LOD, were included in the study. The samples were blinded and tested at four different sites.
The results of the study are summarized in Tables 4 and 5 for carbapenemase-producing E. coli and K. pneumoniae, respectively.
| Organism Identity & Carbapenemase Status | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| CHROMID | ||||
| CARBA agar | Positive a | 16 | 2 c | 18 |
| Negative b | 4 d | 188 | 192 | |
| Total | 20 | 190 | 210 | |
| Positive Percent Agreement | 80.0% (16/20); 58.4-91.9% | |||
| Negative Percent Agreement | 98.9% (188/190); 95% CI 96.2-99.7% |
Table 4. Detection of carbapenemase-producing E. coli in contrived specimens
95% CI: 95% score confidence interval
a Pink-burgundy colonies
- b No growth or colonies not pink-burgundy
- C 2/2 isolates were carbapenem non-susceptible E. coli (resistant to meropenem and ertapenem and an intermediate MIC for imipenem); both isolates were positive for Extended Spectrum ß-Lactamase (ESBL)
- d False negative results were obtained with 4 strains of carbapenem non-susceptible E. coli that harbored blaoxa8 (2), blaNDM (1) and blavM (1) and which were spiked at target levels ranging from 1X to 10X LoD; 2/4 strains had an intermediate MIC to at least one carbapenem including 1 strain that was also susceptible to ertapenem
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| Organism Identity & Carbapenemase Status | ||||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| CHROMID® | ||||
| CARBA agar | Positive a | 84 | 11 c, d | 95 |
| Negative b | 3 e | 112 f | 115 | |
| Total | 87 | 123 | 210 | |
| Positive Percent Agreement | 96.6% (84/87); 95% CI % 90.3-98.8% | |||
| Negative Percent Agreement | 91.1% (112/123); 95% CI 84.7-94.9% |
Table 5. Detection of carbapenemase-producing K. pneumoniae in contrived specimens
95% CI: 95% score confidence interval
- a Blue-green/blue-grey colonies
- b No growth or colonies not blue-green/blue-grey
- C 5/11 false positive results were obtained with carbapenem non-susceptible K. pneumoniae, all of which were positive for ESBL (3) or ESBL and AmpC (2)
- d 6/11 false positive results were due to Carbapenemase Status-positive species of Enterobacteriaceae other than K. pneumoniae that harbored blaxpc: E. cloacae (4), K. oxytoca (1) and K. ozaenae (1)
- e 3/3 false negative results were obtained with Carbapenemase Status positive isolates at the LoD target level; the strains carried carbapenemase resistance markers as follows: bland (1), blake (1) or blaoxA-48 (1); 2/3 strains had a susceptible or intermediate MIC to at least one of the three carbapenems tested (ertapenem, imipenem or meropenem)
- f 18/112 samples contained carbapenem non-susceptible strains of K. pneumoniae of which 17 were phenotypically carbapenemase negative; 11/18 were positive for ESBL and 6/18 were positive for AmpC
The clinical study which was performed under CLSI M100-S25, S26, S27 and S28, between April, 2016 through October, 2017 is also compliant to CLSI M100-S28. except the new requirement regarding the integrity check by a disk diffusion or MIC method for the QC strain ATCC® 700603™ which was not required by S26 and as such was not done. No impact on the performances is expected.