Who is the manufacturer of iC-GN iC-Cassette for use on the iC-System?

Icubate, Inc. submitted the Traditional clearance for iC-GN iC-Cassette for use on the iC-System (K190341).

What is the FDA product code for iC-GN iC-Cassette for use on the iC-System?

PEN. It is classified under 21 CFR 866.3365 as a Class 2 device in the Microbiology panel.

What is the regulatory pathway for iC-GN iC-Cassette for use on the iC-System?

510(k) clearance (submission type: Traditional).

What are the predicate devices for iC-GN iC-Cassette for use on the iC-System?

Verigene® Gram Negative Blood Culture Nucleic Acid Test (GC-GN) (K132843).

iC-GN iC-Cassette for use on the iC-System

K190341 · Icubate, Inc. · PEN · Jun 28, 2019 · Microbiology

Device Facts

Record ID	K190341
Device Name	iC-GN iC-Cassette for use on the iC-System
Applicant	Icubate, Inc.
Product Code	PEN · Microbiology
Decision Date	Jun 28, 2019
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.3365
Device Class	Class 2

Intended Use

The iCubate, Inc. iC-GN Assay™ for use on the iC-System™ is a qualitative, multiplexed, in vitro diagnostic test for the detection and identification of potentially pathogenic gram negative bacteria, which may cause bloodstream infection (BSI). The iC-GN Assay™ is performed directly on positive blood cultures, confirmed by Gram stain gram negative bacilli. Cultures demonstrating mixed Gram stain results should not be tested on the assay. The iC-GN Assay™ is validated for use with select BACTEC™, BacT/ALERT® and VersaTREK® blood culture bottles. The iC-GN Assay™ is indicated for use in conjunction with other clinical and laboratory findings, such as culture, to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor bloodstream infections.

Device Story

The iC-GN Assay is a qualitative, multiplexed, in vitro diagnostic test for the detection of gram-negative bacteria and resistance markers directly from positive blood cultures. The device uses ARM-PCR (Amplicon Rescued Multiplex PCR) technology for amplification and microarray hybridization for detection. The process is performed in a self-contained, disposable iC-Cassette on the iC-Processor, which automates extraction, amplification, and detection. The iC-Reader then reads the microarray, and iC-Report software interprets the results for display on an iMac. The device is used in clinical laboratories by trained personnel. It aids in the diagnosis of bloodstream infections by identifying specific pathogens and resistance markers (KPC, NDM, CTX-M group 1), allowing for faster clinical decision-making and targeted therapy compared to traditional culture methods. Sub-culturing remains necessary for susceptibility testing and differentiation of mixed growth.

Clinical Evidence

Clinical performance was evaluated at five sites using 1,002 prospective clinical specimens (fresh and frozen) and 170 contrived samples. Comparator methods were culture/MALDI for organism identification and PCR/bidirectional sequencing for resistance markers. Prospective fresh specimen sensitivity ranged from 94.5% to 100% and specificity from 99.3% to 100% across targets. Reproducibility was 99.3%. The study confirmed performance across different blood culture systems (VersaTREK, BACTEC, BacT/ALERT).

Technological Characteristics

The device utilizes ARM-PCR (Amplicon Rescued Multiplex PCR) and microarray hybridization. It is a closed, automated system using a disposable iC-Cassette. The system includes the iC-Processor for extraction/amplification and the iC-Reader for detection. Connectivity is via the iC-Report software on an iMac. The device is validated for use with BACTEC, BacT/ALERT, and VersaTREK blood culture bottles.

Indications for Use

Indicated for patients with suspected bacterial bloodstream infections. Performed on positive blood cultures confirmed by Gram stain to contain gram-negative bacilli. Not for use in monitoring infections. Prescription use only.

Regulatory Classification

Identification

A multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures is a qualitative in vitro device intended to simultaneously detect and identify microorganism nucleic acids from blood cultures that test positive by Gram stain or other microbiological stains. The device detects specific nucleic acid sequences for microorganism identification as well as for antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device does not replace traditional methods for culture and susceptibility testing.

Special Controls

In combination with the general controls of the FD&C Act, the Verigene® Gram Positive Blood Culture Nucleic Acid Test is subject to the following special controls: The special controls for the BC-GP Assay are contained in the guideline document entitled "Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures."

*Classification.* Class II (special controls). The special control for this device is FDA's guideline document entitled “Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures.” For availability of the guideline document, see § 866.1(e).

Predicate Devices

Verigene® Gram Negative Blood Culture Nucleic Acid Test (GC-GN) (K132843)

Related Devices

K163390 — iC-GPC Assay TM for use on the iC-SystemTM · Icubate, Inc. · Aug 8, 2017
K243013 — LIAISON PLEX Gram-Negative Blood Culture Assay · Luminex Corporation · Apr 18, 2025
K213236 — ePlex Blood Culture Identification Gram Negative (BCID-GN) Panel · Genmark Diagnostics, Incorporated · Apr 27, 2022
K182619 — ePlex Blood Culture Identification Gram Negative (BCID-GN) Panel · Genmark Diagnostics, Incorporated · Apr 12, 2019

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains two logos. On the left is the Department of Health & Human Services logo. On the right is the FDA logo, which includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text. June 28, 2019 iCubate, Inc. % Fran White President MDC Associates, LLC 180 Cabot Street Beverly, Massachusetts 01915 Re: K190341 Trade/Device Name: iC-GN iC-Cassette for use on the iC-System Regulation Number: 21 CFR 866.3365 Regulation Name: Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures Regulatory Class: Class II Product Code: PEN Dated: February 11, 2019 Received: February 14, 2019 Dear Fran White: 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. 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 {1}------------------------------------------------ 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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems. For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, for Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ # 510(k) SUMMARY #### Date of Summary: June 22, 2019 ### Product Name: iC-GN Assay™ for use on the iC-System™ ### Sponsor: iCubate, Inc. 601 Genome Way Huntsville, AL 35806 ### Correspondent: MDC Associates, Inc. Fran White, President 180 Cabot Street Beverly, MA 01915 Phone: (978) 705 5011 Fax: (866) 540 3448 Email: regulatory@mdcassoc.com #### Common Name: Gram-Negative Bacteria and Associated Resistance Markers #### Regulation Number: 866.3365 ## Classification: PEN, Class II {3}------------------------------------------------ # Substantial Equivalency | Characteristic | iCubate, Inc. iC-GN Assay™ for use on the iC-System™ (New Device) | Nanosphere, Inc. Verigene® Gram Negative Blood Culture Nucleic Acid Test (GC-GN) K132843 (Predicate Device) | | | | | |----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Similarities | | | | | | | | Intended Use | The iCubate, Inc. iC-GN Assay™ for use on the iC-System™ is a qualitative, multiplexed, in vitro diagnostic test for the detection and identification of potentially pathogenic gram negative bacteria, which may cause bloodstream infection (BSI). The iC-GN Assay™ is performed directly on positive blood cultures, confirmed by Gram stain to contain gram negative bacilli. Cultures demonstrating mixed Gram stain results should not be tested on the assay. The iC-GN Assay™ is validated for use with select BACTEC™ , BacT/ALERT® and VersaTREK® blood culture bottles. The iC- GN Assay™ is indicated for use in conjunction with other clinical and laboratory findings, such as culture, to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor bloodstream infections. The iC-GN Assay™ detects target DNA and identifies the following: | The Verigene® Gram Negative Blood Culture Nucleic Acid Test (BC- GN), performed using the sample- to-results Verigene System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative bacteria and resistance markers. BC-GN is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitor blood culture system and which contain gram- negative bacteria as determined by Gram stain. BC-GN detects and identifies the following: Acinetobacter spp. Citrobacter spp. Enterobacter spp. Proteus spp. Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Pseudomonas aeruginosa | | | | | | | Bacterial Genera and Species Resistance Markers Acinetobacter baumannii complex Enterobacter cloacae complex Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Pseudomonas aeruginosa Proteus species Serratia marcescens KPC (blaKPC)- associated with resistance to carbapenems NDM (blaNDM)- associated with resistance to carbapenems CTX-M group 1(blaCTX-M group 1)- associated with resistance to extended spectrum beta-lactams | | | | | Pseudomonas aeruginosa BC-GN is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however, is not to be used to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for susceptibility testing, identification of organisms not detected by BC-GN, differentiation of mixed growth, association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing. | | | In mixed growth, the iC-GN Assay™ does not specifically attribute detection of KPC, NDM, or CTX-M group 1 to a specific genera or species. Sub-culturing of positive blood cultures is necessary to recover organisms for | | | | | | {4}------------------------------------------------ | Characteristic | iCubate, Inc. iC-GN Assay™ for use on the iC-System™ (New Device) | Nanosphere, Inc. Verigene® Gram Negative Blood Culture Nucleic Acid Test (GC-GN) K132843 (Predicate Device) | |-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------| | | susceptibility testing, identification of organisms not detected by the iC-GN Assay™, differentiation of mixed growth, association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing. | | | Sample Type | Positive Blood Culture | Positive Blood Culture | | Differences | | | | INSTRUMENT REQUIREMENTS | iC-System™ | Verigene System | | TEST PRINCIPLE | ARM-PCR | Gold nanoparticle probe-based PCR | | COMPATIBLE BLOOD CULTURE BOTTLES | BD BACTEC Standard/10 Aerobic/F BD BACTEC Standard/10 Anaerobic/F BD BACTEC Plus Aerobic/F BD BACTEC Plus Anaerobic/F BD BACTEC Lytic/10 Anaerobic/F BacT/Alert SA Standard Aerobic BacT/Alert SN Standard Anaerobic BacT/Alert FA Aerobic FAN BacT/Alert FN Anaerobic FAN BacT/Alert FA Plus Aerobic BacT/Alert FN Plus Anaerobic VersaTREK REDOX 1 VersaTREK REDOX 2 | BACTEC™ Plus Aerobic/F BacT/ALERT FA FAN | | THROUGHPUT | Four (4) samples/iC-Processor™ | One (1) Sample/Processor | {5}------------------------------------------------ ### Intended Use The iCubate, Inc. iC-GN Assay™ for use on the iC-System™ is a qualitative, multiplexed, in vitro diagnostic test for the detection and identification of potentially pathogenic gram negative bacteria, which may cause bloodstream infection (BSI). The iC-GN Assay™ is performed directly on positive blood cultures, confirmed by Gram stain gram negative bacilli. Cultures demonstrating mixed Gram stain results should not be tested on the assay. The iC-GN Assay™ is validated for use with select BACTEC™, BacT/ALERT® and VersaTREK® blood culture bottles. The iC-GN Assay™ is indicated for use in conjunction with other clinical and laboratory findings, such as culture, to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor bloodstream infections. The iC-GN Assay™ detects target DNA and identifies the following: | Bacterial Genera and Species | Resistance Markers | |---------------------------------|-----------------------------------------------------------------------------------------------| | Acinetobacter baumannii complex | KPC (blaKPC)- associated with resistance to carbapenems | | Enterobacter cloacae complex | NDM (blaNDM)- associated with resistance to carbapenems | | Escherichia coli | CTX-M group 1(blaCTX-M group 1)- associated with resistance to extended spectrum beta-lactams | | Klebsiella oxytoca | | | Klebsiella pneumoniae | | | Pseudomonas aeruginosa | | | Proteus species | | | Serratia marcescens | | In mixed growth, the iC-GN Assay™ does not specifically attribute detection of KPC, NDM, or CTX-M group 1 to a specific genera or species. Sub-culturing of positive blood cultures is necessary to recover organisms for susceptibility testing, identification of organisms not detected by the iC-GN Assay™, differentiation of mixed growth, association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing. ### Limitations For prescription use only. Please refer to the iC-GN Assay™ labeling for a more complete list of warnings, precautions and contraindications. ### Methodology The iC-GN Assay™ utilizes polymerase chain reaction (PCR) for the multiplex amplification of specific targets and detects the amplified targets with microarray hybridization. Targets are detected directly from patient positive blood cultures confirmed by Gram stain to contain gram negative bacilli. The iC-GN Assay utilizes proprietary ARM-PCR (Amplicon Rescued Multiplex PCR) technology allowing for multiple targets to be amplified in one reaction. Testing is done in a self-contained, automated, disposable cassette using the iCubate™ processor (iC-Processor™). After the reaction is complete, the cassette is read on the {6}------------------------------------------------ iCubate® reader (iC-Reader™). Results from the iC-Reader™ are interpreted by iC-Report™ software and a final report is displayed on the iMac® computer. To operate, the user opens the iC-Cassette™ cap and pipettes an aliquot of the diluted positive blood culture sample into the sample/PCR well in the bottom well plate of the cassette. Once inoculated, the cassette cap is closed, and all extraction, amplification and detection processes are completed in the cassette, a closed system. Extraction, amplification and detection sequences are defined by an assay script controlled by the iC-Processor™. The processing script is defined within a barcode label positioned on the top of each iC-Cassette™ which communicates with the iC-Processor™. To access and pierce the foilsealed reagent wells located in the bottom well plate of the cassette, the processor manipulates the cassette to move the cassette pipette horizontally and vertically. The script directs the transfer of reagents between the wells in the bottom well plate and finally to the array within the cassette. The iC-Processor™ is capable of processing four (4) iC-Cassettes™ with random access. Once processing is complete, the cassette is manually transferred from the iC-Processor™ to the iC-Reader™ where the microarray within the cassette is read. The iC-Reader™ is capable of reading up to four (4) iC-Cassettes™ at one time. The results are interpreted via the iC-Report™ software and displayed for the user on the iMac®. Raw data and result interpretations are stored within the iMac®; raw data is accessible to iCubate® service personnel only and not to the end user. When finished with a loaded iC-GN Cassette™, it should be disposed as biohazardous waste. ### Performance Data For ease of reference, the following table defines iC-GN target organisms and common acronyms used in the study descriptions. | TABLE 1: iC-GN Assay Targets | | |---------------------------------------------------------------|---------| | Target | Acronym | | Acinetobacter baumannii complex | ABX | | Enterobacter cloacae complex | ECX | | Escherichia coli | EC | | Klebsiella oxytoca | KO | | Klebsiella pneumoniae | KPN | | Proteus mirabilis | PM | | Pseudomonas aeruginosa | PA | | Serratia marcescens | SM | | KPC carbapenemase resistance marker | KPC | | NDM carbapenemase resistance marker | NDM | | CTX-M group 1 extended spectrum β-lactamase resistance marker | CTXM | {7}------------------------------------------------ #### Reproducibility To confirm the site-to-site, operator-to-operator, system-to-system, and lot-to-lot reproducibility of the iC-GN Assay, a representative panel of target organisms and one nontarget organism were evaluated at two clinically relevant concentrations: initial bottle positivity and eight hours beyond initial bottle positivity. Organisms were grown to the appropriate concentrations in BD BACTEC Plus Aerobic blood culture bottles with human blood added on the BD BACTEC System. Testing was performed by two independent operators at each of three sites, two external and one internal. Each operator tested the eighteen-organism panel in triplicate across five, non-consecutive days. Testing was performed on six iC-GN Cassette lots and multiple iC-Systems. Performance is based on all expected targets detected and no false positive targets detected. Table 2 below summarizes Reproducibility results stratified by iC-GN target and concentration. Overall Reproducibility performance was 99.3%, confirming that iC-GN Assay performance is reproducible across sites, operators, systems and lots. | TABLE 2: iC-GN Assay Reproducibility Performance by Target | | | | | | | |------------------------------------------------------------|------------------------|--------------------------------------|--------------------|--------------------|----------------------|--------------------| | Target/Concentration | Overall Performance | Overall Performance % [95% CI] | False Negatives | False Positives | PC Check Failures | System Failures | | A. baumannii complex Bottle Ring | 90/90 | 100.0 [95.91-100.0] | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | | A. baumannii complex Bottle Ring + 8 hours | 87/90 | 96.7 [90.65-98.86] | 0/90 (0.00%) | 3/90 (3.33%) | 0/90 (0.00%) | 0/90 (0.00%) | | E. cloacae complex Bottle Ring | 86/88 | 97.7 [92.09-99.37] | 1/88 (1.14%) | 1/88 (1.14%) | 2/90 (2.22%) | 0/90 (0.00%) | | E. cloacae complex Bottle Ring + 8 hours | 90/90 | 100.0 [95.91-100.0] | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | | E. coli Bottle Ring | 90/90 | 100.0 [95.91-100.0] | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | | E. coli Bottle Ring + 8 hours | 89/89 | 100.0 [95.86-100.0] | 0/89 (0.00%) | 0/89 (0.00%) | 0/90 (0.00%) | 1/90 (1.11%) | | K. oxytoca Bottle Ring | 89/90 | 98.9 [93.97-99.80] | 0/90 (0.00%) | 1/90 (1.11%) | 0/90 (0.00%) | 0/90 (0.00%) | | K. oxytoca Bottle Ring + 8 hours | 89/89 | 100.0 [95.86-100.0] | 0/89 (0.00%) | 0/89 (0.00%) | 1/90 (1.11%) | 0/90 (0.00%) | | K. pneumoniae Bottle Ring | 90/90 | 100.0 [95.91-100.0] | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | 0/90 (0.00%) | | K. pneumoniae Bottle Ring + 8 hours | 89/89 | 100.0 [95.86-100.0] | 0/89 (0.00%) | 0/89 (0.00%) | 1/90 (1.11%) | 0/90 (0.00%) | | Proteus species Bottle Ring | 89/89 | 100.0 [95.86-100.0] | 0/89 (0.00%) | 0/89 (0.00%) | 1/90 (1.11%) | 0/90 (0.00%) | | Proteus species Bottle Ring + 8 hours | 88/88 | 100.0 [95.92-100.0] | 0/88 (0.00%) | 0/88 (0.00%) | 0/90 (0.00%) | 2/90 (2.22%) | {8}------------------------------------------------ | TABLE 2: iC-GN Assay Reproducibility Performance by Target | | | | | | | |-------------------------------------------------------------|------------------------|--------------------------------------|--------------------|--------------------|----------------------|--------------------| | Target/Concentration | Overall Performance | Overall Performance % [95% CI] | False Negatives | False Positives | PC Check Failures | System Failures | | P. aeruginosa | 88/89 | 98.9 | 1/89 | 0/89 | 1/90 | 0/90 | | Bottle Ring | | [93.91-99.80] | (1.12%) | (0.00%) | (1.11%) | (0.00%) | | P. aeruginosa | 89/90 | 98.9 | 1/90 | 0/90 | 0/90 | 0/90 | | Bottle Ring + 8 hours | | [93.97-99.80] | (1.11%) | (0.00%) | (0.00%) | (0.00%) | | S. marcescens | 87/89 | 97.8 | 0/89 | 2/89 | 1/90 | 0/90 | | Bottle Ring | | [92.17-99.38] | (0.00%) | (2.25%) | (1.11%) | (0.00%) | | S. marcescens | 87/89 | 97.8 | 0/89 | 2/89 | 1/90 | 0/90 | | Bottle Ring + 8 hours | | [92.17-99.38] | (0.00%) | (2.25%) | (1.11%) | (0.00%) | | CTX-M group 1 | 90/90 | 100.0 | 0/90 | 0/90 | 0/90 | 0/90 | | Bottle Ring | | [95.91-100.0] | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | CTX-M group 1 | 89/89 | 100.0 | 0/89 | 0/89 | 0/90 | 1/90 | | Bottle Ring + 8 hours | | [95.86-100.0] | (0.00%) | (0.00%) | (0.00%) | (1.11%) | | KPC | 90/90 | 100.0 | 0/90 | 0/90 | 0/90 | 0/90 | | Bottle Ring | | [95.91-100.0] | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | KPC | 89/89 | 100.0 | 0/89 | 0/89 | 1/90 | 0/90 | | Bottle Ring + 8 hours | | [95.86-100.0] | (0.00%) | (0.00%) | (1.11%) | (0.00%) | | NDM | 89/89 | 100.0 | 0/89 | 0/89 | 1/90 | 0/90 | | Bottle Ring | | [95.86-100.0] | (0.00%) | (0.00%) | (1.11%) | (0.00%) | | NDM | 89/90 | 98.9 | 1/90 | 0/90 | 0/90 | 0/90 | | Bottle Ring + 8 hours | | [93.97-99.80] | (1.11%) | (0.00%) | (0.00%) | (0.00%) | ## Limit of Detection (LoD) A study was performed to determine the limit of detection for each iC-GN Assay target, defined as the lowest concentration (CFU/mL) of analyte that can be detected approximately 95% of the time. For the eleven targets detected by the iC-GN Assay, a panel of twenty-seven representative strains were evaluated, a minimum of three per target. For complex and genus level targets, at least two representative species were evaluated. LoD testing was conducted in two phases, the first to narrow the range for LoD analysis. In phase II, the approximated 95% performance point determined in phase I was confirmed by testing a minimum of twenty replicates on each of three unique cassette lots. Plating and subsequent colony counts were used to determine organism concentrations. The final limit of detection for each target, provided in Table 3 below, was defined as the concentration that produced a positive result ≥ 95% but < 100% of the time. | TABLE 3: iC-GN Assay LoD Results | | | | |----------------------------------|--------------------------|---------------------------|-------------------------------------| | Target | Strain | Concentration (CFU/mL) | Defined Target LoD (CFU/mL) | | A. baumannii complex | 307-0294 | $5.3 \times 10^5$ | | | A. baumannii complex | CDC-83 | $5.2 \times 10^6$ | $5.3 \times 10^5 - 5.2 \times 10^6$ | | A. baumannii complex | ATCC 23055 | $9.0 \times 10^5$ | | | TABLE 3: iC-GN Assay LoD Results | | | | | Target | Strain | Concentration (CFU/mL) | Defined Target LoD (CFU/mL) | | E. cloacae complex | Z101 | $5.0 × 10^6$ | $4.9 × 10^5-5.5 × 10^6$ | | | CDC-164 | $5.5 × 10^6$ | | | | ATCC 700323 | $4.9 × 10^5$ | | | E. coli | ATCC 43895 | $7.7 × 10^5$ | | | | ATCC BAA-2326 | $7.9 × 10^5$ | $7.7 × 10^5-8.4 × 10^5$ | | | CDC-55 | $8.4 × 10^5$ | | | K. oxytoca | Z115 | $6.2 × 10^5$ | | | | ATCC 13182 | $5.4 × 10^5$ | $5.4 × 10^5-1.1 × 10^6$ | | | CDC-147 | $1.1 × 10^6$ | | | K. pneumoniae | ATCC 35657 | $1.9 × 10^6$ | | | | CDC-40 | $3.6 × 10^6$ | | | | CDC-42 | $1.9 × 10^6$ | $6.0 × 10^5-4.2 × 10^6$ | | | KPC-2 | $4.2 × 10^6$ | | | Proteus species | LACNY 11 | $6.0 × 10^5$ | | | | Z050 | $1.1 × 10^6$ | | | | CDC-59 | $9.9 × 10^5$ | $6.9 × 10^5-1.1 × 10^6$ | | | Z028 | $7.6 × 10^5$ | | | P. aeruginosa | Z129 | $6.9 × 10^5$ | | | | Z139 | $1.2 × 10^6$ | $5.0 × 10^5-1.2 × 10^6$ | | | CDC-231 | $5.0 × 10^5$ | | | | CDC-250 | $6.9 × 10^5$ | | | S. marcescens | ATCC 43297 | $7.2 × 10^5$ | | | | ATCC 21212 | $8.1 × 10^5$ | $6.4 × 10^5-8.1 × 10^5$ | | | CDC-91 | $6.4 × 10^5$ | | | CTX-M group 1 | ATCC BAA-2326 (CTX-M-15) | $7.9 × 10^5$ | | | | CDC-40 (CTX-M-15) | $2.3 × 10^6$ | $7.9 × 10^5-2.3 × 10^6$ | | | CDC-42 (CTX-M-15) | $1.9 × 10^6$ | | | KPC | CDC-147 (KPC-3) | $2.3 × 10^6$ | | | | KPC-2 | $4.2 × 10^6$ | $1.5 × 10^5-4.2 × 10^6$ | | | CDC-231 (KPC-5) | $1.5 × 10^5$ | | | NDM | CDC-83 (NDM-1) | $5.2 × 10^6$ | | | | CDC-55 (NDM-1) | $4.0 × 10^6$ | $3.3 × 10^5-5.2 × 10^6$ | | | CDC-250 (NDM-1) | $3.3 × 10^5$ | | {9}------------------------------------------------ ### Bottle Ring A study was performed to establish the levels of each iC-GN target organism at two clinically relevant concentrations: initial bottle positivity (bottle "ring") and eight hours beyond initial positivity. Twenty-seven representative organisms were evaluated, a minimum of three per iC-GN target. Organisms were grown in BD BACTEC Plus Aerobic blood culture bottles with human blood added on the BD BACTEC System. Within two hours of initial bottle positivity, the bottles were removed for plating and subsequent colony counts to determine organism concentrations. The bottles were then returned to the incubator and approximately eight hours after initial bottle positivity, the bottles were again removed for plating and subsequent colony counts to determine organism concentrations. Three bottles were grown for each {10}------------------------------------------------ strain, and the average concentrations at initial bottle positivity and eight hours beyond initial bottle positivity are provided in Table 4 below. The concentrations at initial bottle positivity, representative of the lowest levels that may be observed in a clinical setting, are above the limits of detection determined for each strain. | TABLE 4: iC-GN Target Organism Concentrations at Bottle “Ring” | | | | |----------------------------------------------------------------|---------------|----------------------------------------------------------------|------------------------------------------------------------| | Organism | Strain ID | Initial Bottle Positivity Average Concentration (CFU/mL) | Bottle Positivity + 8 Average Concentration (CFU/mL) | | Acinetobacter baumannii | 307-0294 | 4.24 × 108 | 8.27 × 108 | | Acinetobacter baumannii | CDC-83 | 3.39 × 108 | 7.23 × 108 | | Acinetobacter calcoaceticus | ATCC 23055 | 6.78 × 107 | 2.93 × 108 | | Enterobacter cloacae | Z101 | 2.17 × 108 | 1.97 × 109 | | Enterobacter cloacae | CDC-164 | 5.62 × 108 | 2.31 × 109 | | Enterobacter hormaechei | ATCC 700323 | 4.36 × 108 | 2.75 × 109 | | Escherichia coli | ATCC 43895 | 1.50 × 108 | 9.48 × 108 | | Escherichia coli | ATCC BAA-2326 | 6.23 × 108 | 1.52 × 109 | | Escherichia coli | CDC-55 | 4.93 × 108 | 1.51 × 109 | | Klebsiella oxytoca | Z115 | 5.32 × 108 | 2.07 × 109 | | Klebsiella oxytoca | ATCC 13182 | 4.16 × 108 | 4.52 × 109 | | Klebsiella oxytoca | CDC-147 | 9.67 × 108 | 1.31 × 109 | | Klebsiella pneumoniae | ATCC 35657 | 9.78 × 108 | 1.08 × 109 | | Klebsiella pneumoniae | CDC-40 | 2.16 × 108 | 1.36 × 109 | | Klebsiella pneumoniae | CDC-42 | 2.55 × 108 | 1.10 × 109 | | Klebsiella pneumoniae | KPC-2 | 7.70 × 108 | 1.66 × 109 | | Klebsiella pneumoniae | LACNY 11 | 5.43 × 107 | 1.67 × 109 | | Proteus mirabilis | Z050 | 1.71 × 108 | 7.40 × 108 | | Proteus mirabilis | CDC-59 | 7.37 × 107 | 8.10 × 108 | | Proteus penneri | Z028 | 8.88 × 107 | 4.33 × 108 | | Proteus vulgaris | Z129 | 4.37 × 107 | 5.00 × 108 | | Pseudomonas aeruginosa | Z139 | 9.18 × 107 | 1.37 × 1010 | | Pseudomonas aeruginosa | CDC-231 | 3.26 × 108 | 7.98 × 108 | | Pseudomonas aeruginosa | CDC-250 | 1.64 × 108 | 8.97 × 108 | | Serratia marcescens | ATCC 43297 | 8.55 × 108 | 2.03 × 109 | | Serratia marcescens | ATCC 21212 | 1.07 × 108 | 8.83 × 108 | | Serratia marcescens | CDC-91 | 7.28 × 108 | 1.67 × 109 | ## Blood Culture Bottle Equivalency Commonly used blood culture bottle (BCB) media types were evaluated to demonstrate that variability in BCB media composition does not interfere with iC-GN Assay performance. Twenty-seven (27) representative iC-GN target organisms plus one non-target organism were tested in thirteen (13) BCB media types. Target organisms were tested near LoD {11}------------------------------------------------ concentrations (2-3×LoD). Each strain was tested in triplicate in each BCB media type. Target performance is based on all expected targets detected and no false positive targets detected. Non-target performance is based on all expected negative results. In the event of a false negative result, the strain was retested in replicates of ten. In the event of a false positive result or other failure, the strain was retested in triplicate. The results of iC-GN BCB equivalency testing are summarized in Table 5 below. Performance in all bottle types met the acceptance criteria of ≥ 95% performance; all bottle types are validated for use with the iC-GN Assay. | TABLE 5: iC-GN Assay BCB Equivalency Results | | | | | | |----------------------------------------------|-------------------------------|---------------------------|---------------------------|--------------------------------|---------------------------| | BCB Media Type | Overall Performance (%) | False Negatives (%) | False Positives (%) | PC Check Failures (%) | System Failures (%) | | BACTEC Standard Aerobic | 93/94 (98.9%) | 1/94 (1.1%) | 0/94 (0.0%) | 3/97 (3.1%) | 0/97 (0.0%) | | BACTEC Standard Anaerobic | 85/86 (98.8%) | 0/86 (0.0%) | 1/86 (1.2%) | 0/87 (0.0%) | 1/87 (1.1%) | | BACTEC Plus Aerobic | 93/94 (98.9%) | 1/94 (1.1%) | 0/94 (0.0%) | 2/97 (2.1%) | 1/97 (1.1%) | | BACTEC Plus Anaerobic | 95/96 (98.6%) | 1/96 (1.0%) | 0/96 (0.0%) | 2/100 (2.0%) | 2/100 (2.0%) | | BACTEC Lytic/10 Anaerobic | 81/81 (100.0%) | 0/81 (0.0%) | 0/81 (0.0%) | 0/81 (0.0%) | 0/81 (0.0%) | | BACT/ALERT SA Standard Aerobic | 97/99 (98.0%) | 1/99 (1.0%) | 1/99 (1.0%) | 4/103 (3.9%) | 0/103 (0.0%) | | BACT/ALERT SN Standard Anaerobic | 87/88 (98.9%) | 0/88 (0.0%) | 1/88 (1.1%) | 2/90 (2.2%) | 0/90 (0.0%) | | BACT/ALERT FA Aerobic FAN | 94/96 (97.9%) | 0/96 (0.0%) | 2/96 (2.1%) | 1/97 (1.0%) | 0/97 (0.0%) | | BACT/ALERT FN Anaerobic FAN | 92/94 (97.9%) | 0/94 (0.0%) | 2/94 (2.1%) | 2/97 (2.1%) | 1/97 (1.0%) | | BACT/ALERT FA Plus Aerobic | 94/95 (98.9%) | 1/95 (1.1%) | 0/95 (0.0%) | 1/97 (1.1%) | 1/97 (1.1%) | | BACT/ALERT FN Plus Anaerobic | 87/87 (100.0%) | 0/87 (0.0%) | 0/87 (0.0%) | 2/90 (2.2%) | 1/90 (1.1%) | | VersaTREK REDOX 1 | 81/81 (100.0%) | 0/81 (0.0%) | 0/81 (0.0%) | 0/81 (0.0%) | 0/81 (0.0%) | | VersaTREK REDOX 1 | 92/93 (98.9%) | 1/93 (1.1%) | 0/93 (0.0%) | 1/94 (1.1%) | 0/94 (0.0%) | An increased rate of false positive Proteus results was observed in some lots of BD BACTEC blood culture bottles. The high rate of false positive results observed prompted an {12}------------------------------------------------ investigation by the manufacturer, BD Life Sciences. The false positives are due to the presence of nucleic acids or non-viable organisms present in the culture media at concentrations near or above the target's limit of detection. While the observed contamination was resolved at the time of publication, positive Proteus results observed in BD BACTEC media types should be confirmed using alternative methods. #### Inclusivity To demonstrate the inclusivity of the iC-GN Assay, eighty-two (82) representative strains were evaluated, a minimum of ten strains for each target analyte. Strains were tested at the lowest level of bottle positivity, considered within two hours of bottle "ring." Organisms were grown in BD BACTEC Plus Aerobic blood culture bottles with human blood added on the BD BACTEC System. Each strain was tested in triplicate. Performance is based on all expected targets detected and no false positive targets detected. In the event of a false negative result, the strain was retested in replicates of ten. In the event of a false positive result or other failure, the strain was retested in triplicate. The results of iC-GN Inclusivity testing are summarized in Table 6 below. Two strains were not detected by the iC-GN Assay: Acinetobacter calcoaceticus ATCC 31926 was not detected as A. baumannii complex and Enterobacter kobei ATCC BAA-260 was not detected as E. cloacae complex. An in silico analysis was also performed, and the predicted reactivity of each resistance marker detected by the iC-GN Assay is summarized in Tables 7-9 below. | TABLE 6: iC-GN Assay Inclusivity Results | | | | |------------------------------------------|---------------|----------------------|-------------| | Organism | Strain | Targets | Performance | | Acinetobacter baumannii | ATCC 19606 | ABX | 5/5 | | Acinetobacter baumannii | NCIMB 12457 | ABX | 3/3 | | Acinetobacter baumannii | CDC-36 | ABX | 3/3 | | Acinetobacter baumannii | CDC-37 | ABX, NDM-1 | 3/3 | | Acinetobacter baumannii | CDC-45 | ABX | 3/3 | | Acinetobacter baumannii | CDC-52 | ABX | 3/3 | | Acinetobacter baumannii | CDC-56 | ABX | 3/3 | | Acinetobacter baumannii | CDC-88 | ABX, NDM-1 | 3/3 | | Acinetobacter baumannii | CDC-101 | ABX | 3/3 | | Acinetobacter calcoaceticus | ATCC 14987 | ABX | 3/3 | | Acinetobacter calcoaceticus | ATCC 31926 | ABX | 2/111 | | Enterobacter cloacae | ATCC BAA-1143 | ECX | 3/3 | | Enterobacter cloacae | ATCC BAA-2341 | ECX, KPC | 3/3 | | Enterobacter cloacae | NCTC 10005 | ECX | 14/162 | | Enterobacter cloacae | NCTC 13464 | ECX | 3/3 | | Enterobacter cloacae | CDC-32 | ECX, KPC-3 | 3/3 | | Enterobacter cloacae | CDC-38 | ECX, CTX-M-15, NDM-1 | 3/3 | | Enterobacter cloacae | CDC-65 | ECX | 3/3 | | Enterobacter cloacae | CDC-163 | ECX, CTX-M-15, KPC-2 | 3/3 | | Enterobacter asburiae | ATCC 35923 | ECX | 3/3 | | Enterobacter hormaechei | ATCC 49162 | ECX | 3/3 | | TABLE 6: iC-GN Assay Inclusivity Results | | | | | Organism | Strain | Targets | Performance | | Enterobacter kobei | ATCC BAA-260 | ECX | 0/133 | | Escherichia coli | ATCC 10536 | EC | 3/3 | | Escherichia coli | ATCC BAA-2469 | EC, NDM-1 | 3/3 | | Escherichia coli | NCTC 9001 | EC | 3/3 | | Escherichia coli | NCTC 10538 | EC | 5/5 | | Escherichia coli | NCTC 13476 | EC | 3/3 | | Escherichia coli | CDC-48 | EC, CTX-M-15, NDM-1 | 3/3 | | Escherichia coli | CDC-61 | EC, KPC-3 | 3/3 | | Escherichia coli | CDC-104 | EC, KPC-4 | 7/84 | | Escherichia coli | CDC-119 | EC, CTX-M-15, NDM-1 | 3/3 | | Escherichia coli | CDC-162 | EC, CTX-M-15, NDM-7 | 3/3 | | Klebsiella oxytoca | ATCC 8724 | KO | 3/3 | | Klebsiella oxytoca | ATCC 43086 | KO | 3/3 | | Klebsiella oxytoca | ATCC 43165 | KO | 3/3 | | Klebsiella oxytoca | ATCC 43863 | KO | 3/3 | | Klebsiella oxytoca | ATCC 49134 | KO | 3/3 | | Klebsiella oxytoca | ATCC 49334 | KO | 3/3 | | Klebsiella oxytoca | ATCC 51817 | KO | 3/3 | | Klebsiella oxytoca | ATCC 700324 | KO | 3/3 | | Klebsiella oxytoca | NCTC 11686 | KO | 3/3 | | Klebsiella oxytoca | CDC-71 | KO | 3/3 | | Klebsiella pneumoniae | ATCC-13882 | KPN | 3/3 | | Klebsiella pneumoniae | ATCC BAA-1705 | KPN, KPC-2 | 3/3 | | Klebsiella pneumoniae | NCTC 9633 | KPN | 3/3 | | Klebsiella pneumoniae | NCTC 13438 | KPN, KPC-3 | 3/3 | | Klebsiella pneumoniae | NCTC 13443 | KPN, CTX-M-15, NDM-1 | 3/3 | | Klebsiella pneumoniae | CDC-44 | KPN, CTX-M-15 | 3/3 | | Klebsiella pneumoniae | CDC-46 | KPN, CTX-M-15 | 5/5 | | Klebsiella pneumoniae | CDC-49 | KPN, CTX-M-15, NDM-1 | 3/3 | | Klebsiella pneumoniae | CDC-66 | KPN, CTX-M-15 | 3/3 | | Klebsiella pneumoniae subsp. ozaenae | ATCC 11296 | KPN | 3/3 | | Proteus mirabilis | ATCC 7002 | Proteus | 3/3 | | Proteus mirabilis | ATCC 21100 | Proteus | 3/3 | | Proteus mirabilis | ATCC 43071 | Proteus | 3/3 | | Proteus mirabilis | NCIMB 13283 | Proteus | 3/3 | | Proteus mirabilis | CDC-155 | Proteus, KPC-6 | 3/3 | | Proteus mirabilis | CDC-156 | Proteus, KPC-2 | 3/3 | | Proteus mirabilis | CDC-159 | Proteus, NDM-1 | 3/3 | | Proteus penneri | ATCC 33519 | Proteus | 3/3 | | Proteus vulgaris | ATCC 9484 | Proteus | 3/3 | | Proteus vulgaris | ATCC 29905 | Proteus | 3/3 | | Pseudomonas aeruginosa | ATCC 10145 | PA | 3/3 | | Pseudomonas aeruginosa | ATCC 19429 | PA | 3/3 | | TABLE 6: iC-GN Assay Inclusivity Results | | | | | Organism | Strain | Targets | Performance | | Pseudomonas aeruginosa | ATCC BAA-1744 | PA | 3/3 | | Pseudomonas aeruginosa | CDC-54 | PA | 3/3 | | Pseudomonas aeruginosa | CDC-64 | PA | 3/3 | | Pseudomonas aeruginosa | CDC-90 | PA, KPC-5 | 3/3 | | Pseudomonas aeruginosa | CDC-94 | PA | 3/3 | | Pseudomonas aeruginosa | CDC-105 | PA | 3/3 | | Pseudomonas aeruginosa | CDC-108 | PA | 3/3 | | Pseudomonas aeruginosa | CDC-246 | PA, NDM-1 | 5/5 | | Serratia marcescens | ATCC 8100 | SM | 3/3 | | Serratia marcescens | ATCC 13880 | SM | 3/3 | | Serratia marcescens | ATCC 14041 | SM | 3/3 | | Serratia marcescens | ATCC 14756 | SM | 3/3 | | Serratia marcescens | ATCC 29634 | SM | 3/3 | | Serratia marcescens | ATCC 29635 | SM | 3/3 | | Serratia marcescens | ATCC 43861 | SM | 3/3 | | Serratia marcescens | ATCC 43862 | SM | 3/3 | | Serratia marcescens | NCTC 9743 | SM | 3/3 | | Serratia marcescens | CDC-99 | SM | 3/3 | {13}------------------------------------------------ {14}------------------------------------------------ - 1) 2/2 false negative ABX in initial testing. 7/9 false negative ABX in repeat testing. See limitation. - 2) 1/3 false positive ABX in initial testing. 1/3 false positive ABX in repeated in replicates of 10, 10/10 repeats passed. - 3) 3/3 false negative ECX in initial testing. 10/10 false negative ECX in repeat testing. See limitation. - 1/3 processor error in initial testing. 1/3 false positive KPN in repeat testing. Strain repeated in 4) triplicate, 3/3 repeats passed. | TABLE 7: Predicted (in silico) Reactivity for CTX-M group 1 | | | | |-------------------------------------------------------------|------------------|----------------------------|------------------| | Associated Target Organism | Variant Detected | Associated Target Organism | Variant Detected | | Acinetobacter baumannii complex | CTX-M-3 | Klebsiella oxytoca | CTX-M-3 | | | CTX-M-15 | | CTX-M-15 | | | CTX-M-1 | | CTX-M-35 | | | CTX-M-3 | | CTX-M-36 | | | CTX-M-15 | | CTX-M-162 | | Enterobacter cloacae complex | CTX-M-22 | Klebsiella pneumoniae | CTX-M-1 | | | CTX-M-37 | | CTX-M-3 | | | CTX-M-55 | | CTX-M-15 | | | CTX-M-167 | | CTX-M-22 | | | CTX-M-177 | | CTX-M-28 | | | CTX-M-187 | | CTX-M-32 | | | CTX-M-224 | | CTX-M-54 | | | Escherichia coli | | CTX-M-1 | | | | CTX-M-2 | | | | | CTX-M-3 | | | | | CTX-M-4 | | | | | CTX-M-5 | | | | | CTX-M-6 | | | | | CTX-M-7 | | | TABLE 7: Predicted (in silico) Reactivity for CTX-M group 1 | | | | | Associated Target Organism | Variant Detected | Associated Target Organism | Variant Detected | | | CTX-M-8 | | CTX-M-133 | | | CTX-M-9 | | CTX-M-135 | | | CTX-M-10 | | CTX-M-138 | | | CTX-M-11 | | CTX-M-139 | | | CTX-M-12 | | CTX-M-173 | | | CTX-M-15 | | CTX-M-176 | | | CTX-M-28 | | CTX-M-183 | | | CTX-M-29 | | CTX-M-188 | | | CTX-M-32 | | CTX-M-197 | | | CTX-M-33 | | CTX-M-204 | | | CTX-M-36 | | CTX-M-208 | | | CTX-M-42 | | CTX-M-210 | | | CTX-M-55 | | CTX-M-220 | | | CTX-M-58 | | CTX-M-15 | | | CTX-M-69 | | CTX-M-66 | | | CTX-M-71 | | CTX-M-116 | | | CTX-M-79 | Proteus species | CTX-M-136 | | | CTX-M-82 | | CTX-M-164 | | | CTX-M-90 | | CTX-M-167 | | | CTX-M-101 | | CTX-M-212 | | | CTX-M-102 | | CTX-M-1 | | | CTX-M-103 | Pseudomonas aeruginosa | CTX-M-15 | | | CTX-M-109 | | CTX-M-32 | | | CTX-M-117 | | CTX-M-3 | | | CTX-M-120 | | CTX-M-15 | | | CTX-M-125 | Serratia marcescens | CTX-M-22 | | | CTX-M-127 | | CTX-M-55 | | | CTX-M-128 | | CTX-M-221 | | | CTX-M-131 | | | | | CTX-M-132 | | | | | CTX-M-134 | | | | | CTX-M-137 | | | | | CTX-M-138 | | | | | CTX-M-139 | | | | | CTX-M-140 | | | | | CTX-M-141 | | | | | CTX-M-142 | | | | | CTX-M-143 | | | | | CTX-M-146 | | | | | CTX-M-158 | | | | | CTX-M-163 | | | | | CTX-M-166 | | | | | CTX-M-167 | | | | | CTX-M-170 | | | | | CTX-M-172 | | | | | CTX-M-175 | | | | | CTX-M-178 | | | | | CTX-M-179 | | | | | CTX-M-180 | | | | | CTX-M-181 | | | | | CTX-M-182 | |…