iC-GPC Assay TM for use on the iC-SystemTM

K163390 · Icubate, Inc. · PAM · Aug 8, 2017 · Microbiology

Device Facts

• Record ID: K163390
• Device Name: iC-GPC Assay TM for use on the iC-SystemTM
• Applicant: Icubate, Inc.
• Product Code: PAM · Microbiology
• Decision Date: Aug 8, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3365
• Device Class: Class 2

Intended Use

The iCubate iC-GPC Assay™ for use on the iC-System™ is a qualitative, multiplexed, in vitro diagnostic test for the detection and identification of potentially pathogenic gram positive bacteria, which may cause bloodstream infection (BSI). The iC-GPC Assay™ is performed directly on positive blood cultures, confirmed by Gram stain to contain gram positive cocci. Cultures demonstrating mixed Gram stain results should not be tested on the assay. The iC-GPC Assay™ is validated for use with select BACTEC™, BacT/ALERT® and VersaTREK® blood culture bottles. The iC-GPC Assay™ is indicated for use in conjunction with other clinical and laboratory findings, such as blood culture isolate identification and antimicrobial susceptibility testing, to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor bloodstream infections. The iC-GPC Assay™ detects organism DNA and identifies the following bacterial species and resistance markers: Bacterial Species: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium. Resistance Markers: mecA- associated with methicillin resistance, vanA- associated with vancomycin resistance, vanB- associated with vancomycin resistance. The iC-GPC Assay™ detects the mecA resistance marker, inferring mecA-mediated methicillin resistance, and the vanA and vanB resistance markers, inferring vanA/vanB-mediated vancomycin resistance. In mixed growth, the iC-GPC Assay™ does not specifically attribute van-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA-mediated methicillin resistance to either S. aureus or S. epidermidis. Sub-culturing of positive blood cultures is necessary to recover organisms for susceptibility testing, identification of organisms not detected by the iC-GPC Assay™, differentiation of mixed growth, association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

Device Story

Device performs qualitative, multiplexed detection of gram-positive bacterial DNA and resistance markers directly from positive blood culture samples. Input: positive blood culture aliquot. Process: DNA extraction, multiplex amplification (ARM-PCR), and fluorescence-based microarray hybridization within a closed, disposable cassette. Output: identification of specific bacterial species and resistance genes. Used in clinical laboratories; operated by trained personnel. Processor handles 4 cassettes; reader performs detection. Results interpreted by iC-Report software on iMac. Benefits: rapid identification of BSI pathogens and resistance markers, aiding clinical decision-making regarding antimicrobial therapy.

Clinical Evidence

Clinical method comparison study evaluated 966 positive blood culture specimens across four sites. Performance compared to FDA-cleared multiplex assay and traditional culture/AST. Results showed high agreement: S. aureus (97.0% positive, 99.7% negative), S. epidermidis (98.3% positive, 97.9% negative), S. pneumoniae (85.2% positive, 99.9% negative), E. faecalis (96.7% positive, 99.9% negative), E. faecium (96.6% positive, 99.8% negative), mecA (96.1% positive, 98.2% negative), vanA (95.0% positive, 99.4% negative), and vanB (100% positive, 99.9% negative).

Technological Characteristics

Multiplex nucleic acid assay using ARM-PCR (Amplicon Rescued Multiplex PCR) and fluorescence-based microarray hybridization. Closed, disposable cassette system. Instrument: iC-Processor (extraction/amplification) and iC-Reader (detection). Connectivity: iMac workstation. Software: iC-Report for data acquisition/analysis. Validated for BACTEC, BacT/ALERT, and VersaTREK blood culture bottles.

Indications for Use

Indicated for qualitative detection/identification of pathogenic gram-positive bacteria (S. aureus, S. epidermidis, S. pneumoniae, E. faecalis, E. faecium) and resistance markers (mecA, vanA, vanB) in positive blood cultures confirmed to contain gram-positive cocci. For prescription use in conjunction with clinical/lab findings to aid diagnosis of bloodstream infections. Not for monitoring infections. Contraindicated for cultures with mixed Gram stain results.

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 Positive Blood Culture Nucleic Acid Test (BC-GP) (K122514)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 8, 2017

ICUBATE, INC. C/O FRAN WHITE MDC ASSOCIATES, LLC 180 CABOT STREET BEVERLY, MA 01915

Re: K163390

Trade/Device Name: iC-GPC Assay, 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: PAM, NSU Dated: July 14, 2017 Received: July 17, 2017

Dear Ms. 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. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of

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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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Steven R. Gitterman -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

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# Indications for Use

510(k) Number (if known) K163390

Device Name iC-GPC Assay for use on the iC-System

#### Indications for Use (Describe)

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

The iC-GPC Assay detects organism DNA and identifies the following bacterial species and resistance markers:

Bacterial Species Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Enterococcus faecalis Enterococcus faecium

### Resistance Markers

mecA- associated with methicillin resistance vanA- associated with vancomycin resistance vanB- associated with vancomycin resistance

The iC-GPC Assay detects the mecA resistance marker, inferring mecA-mediated methicillin resistance, and the vanA and vanB resistance markers, inferring vanAlvanB-mediated vancomycin resistance. In mixed growth, the iC-GPC Assay does not specifically attribute van-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA-mediated methicillin resistance to either S. aureus or S. epidermidis.

Sub-culturing of positive blood cultures is necessary to recover organisms for susceptibility testing. identification of organisms not detected by the iC-GPC Assay, differentiation of mixed growth, association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

| 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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# 510(k) SUMMARY

| Date of Summary: | August 2, 2017 |
|------------------|----------------------------------------------------|
| Product Name | iC-GPC Assay™ for use on the iC-System™ |
| Sponsor | iCubate®<br>601 Genome Way<br>Huntsville, AL 35806 |

Correspondent MDC Associates, LLC Fran White, President 180 Cabot Street Beverly, MA 01915 Phone: [phone]

### Device Trade or Proprietary Name

iC-GPC Assay™ for use on the iC-System™

# Common Name

Gram positive bacteria and their resistance markers

### Regulation

21 CFR 866.3365, Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures.

Fax: [phone]

# Product Codes

PAM, NSU

#### Classification

Class II

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# Substantial Equivalency

| Characteristic | iC-GPC Assay™ for use on the iC-System™<br>(New Device) | VERIGENE® Gram Positive Blood Culture Nucleic<br>Acid Test (BC-GP) (K122514)<br>(Primary Predicate Device) | | | | |
|----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|
| Similarities | | | | | | |
| Intended Use | The iCubate iC-GPC Assay™ for use on the iC-<br>System™ is a qualitative, multiplexed, <i>in vitro</i><br>diagnostic test for the detection and<br>identification of potentially pathogenic gram<br>positive bacteria, which may cause bloodstream<br>infection (BSI). The iC-GPC Assay™ is performed<br>directly on positive blood cultures, confirmed by<br>Gram Stain to contain gram positive cocci.<br>Cultures demonstrating mixed Gram stain results<br>should not be tested on the assay. The iC-GPC<br>Assay™ is validated for use with select BACTEC™,<br>BacT/ALERT® and VersaTREK® blood culture<br>bottles. The iC-GPC Assay™ is indicated for use in<br>conjunction with other clinical and laboratory<br>findings, such as blood culture isolate<br>identification and antimicrobial susceptibility<br>testing, to aid in the diagnosis of bacterial<br>bloodstream infections; however, it is not used to<br>monitor bloodstream infections.<br><br>The iC-GPC Assay™ detects organism DNA and<br>identifies the following bacterial species and<br>resistance markers: | The Verigene® Gram Positive Blood Culture Nucleic<br>Acid Test (BC-GP) performed using the sample-to-<br>result Verigene System is a qualitative, multiplexed <i>in vitro</i> diagnostic test for the simultaneous detection<br>and identification of potentially pathogenic gram-<br>positive bacteria which may cause bloodstream<br>infection (BSI). BC-GP is performed directly on<br>positive blood culture using BACTEC™ Plus Aerobic/F<br>and BacT/ALERT FA FAN® Aerobic blood culture<br>bottles, which contain gram positive bacteria. BC-GP<br>is indicated for use in conjunction with other clinical<br>and laboratory findings, such as culture, to aid in the<br>diagnosis of bacterial bloodstream infections;<br>however, it is not used to monitor bloodstream<br>infections.<br><br>BC-GP detects and identifies the following bacterial<br>genera and species:<br><i>Staphylococcus spp.</i><br><i>Staphylococcus aureus</i><br><i>Staphylococcus epidermidis</i><br><i>Staphylococcus lugdunensis</i><br><i>Streptococcus spp.</i><br><i>Streptococcus pneumoniae</i><br><i>Streptococcus pyogenes</i><br><i>Streptococcus agalactiae</i><br><i>Streptococcus anginosus group</i><br><i>Enterococcus faecalis</i><br><i>Enterococcus faecium</i><br><i>Listeria spp.</i><br><br>In addition, BC-GP detects the <i>mecA</i><br>resistance marker, inferring <i>mecA</i> -mediated<br>methicillin resistance, and<br>the <i>vanA</i> and <i>vanB</i> resistance markers, inferring<br><i>vanA/vanB</i> -mediated vancomycin resistance. In<br>mixed growth, BC-GP does not specifically attribute<br><i>van</i> -mediated vancomycin resistance to either <i>E.</i><br><i>faecalis</i> or <i>E. faecium</i> , or <i>mecA</i> -mediated methicillin<br>resistance to either <i>S. aureus</i> or <i>S. epidermidis</i> . | | | | |
| | Bacterial Species Resistance<br>Markers <i>Staphylococcus aureus</i><br><i>Staphylococcus epidermidis</i><br><i>Streptococcus pneumoniae</i><br><i>Enterococcus faecalis</i><br><i>Enterococcus faecium mecA</i> - associated<br>with methicillin<br>resistance<br><i>vanA</i> - associated<br>with vancomycin<br>resistance<br><i>vanB</i> - associated<br>with vancomycin<br>resistance The iC-GPC Assay™ detects the <i>mecA</i> resistance<br>marker, inferring <i>mecA</i> -mediated methicillin<br>resistance, and the <i>vanA</i> and <i>vanB</i> resistance<br>markers, inferring <i>vanA/vanB</i> -mediated<br>vancomycin resistance. In mixed growth, the iC-<br>GPC Assay™ does not specifically attribute <i>van</i> -<br>mediated vancomycin resistance to either <i>E</i> . | | | | | |

#### Comparison of New Device with Predicate Device TABLE 1.

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| Characteristic | iC-GPC Assay™ for use on the iC-System™<br>(New Device) | VERIGENE® Gram Positive Blood Culture Nucleic<br>Acid Test (BC-GP) (K122514)<br>(Primary Predicate Device) |
|----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | <i>faecalis</i> or <i>E. faecium</i> , or mecA-mediated<br>methicillin resistance to either <i>S. aureus</i> or <i>S.</i><br><i>epidermidis</i> . | |
| | Sub-culturing of positive blood cultures is<br>necessary to recover organisms for susceptibility<br>testing, identification of organisms not detected<br>by the iC-GPC Assay™, differentiation of mixed<br>growth, association of antimicrobial resistance<br>marker genes to a specific organism, or for<br>epidemiological typing. | |
| Indication for<br>Use | The iC-GPC Assay™ is indicated for use in<br>conjunction with other clinical and laboratory<br>findings to aid in the diagnosis of bacterial<br>bloodstream infections; however, is not to be<br>used to monitor these infections. Sub-culturing of<br>positive blood cultures is necessary to recover<br>organisms for susceptibility testing, identification<br>of organisms not detected by the iC-GPC Assay™,<br>differentiation of mixed growth, association of<br>antimicrobial resistance marker genes to a<br>specific organism, or for epidemiological typing. | BC-GP is indicated for use in conjunction with other<br>clinical and laboratory findings to aid in the diagnosis<br>of bacterial bloodstream infections; however, is not<br>to be used to monitor these infections. Sub-culturing<br>of positive blood cultures is necessary to recover<br>organisms for susceptibility testing, identification of<br>organisms not detected by BC-GP, differentiation of<br>mixed growth, association of antimicrobial resistance<br>marker genes to a specific organism, or for<br>epidemiological typing. |
| Sample Type | Positive Blood Culture | Positive Blood Culture |
| | <i>Differences</i> | |
| Instrument<br>Requirements | iC-System™ | VERIGENE® System |
| Test Principal | Arm-PCR | Gold nanoparticle probe-based PCR |
| Compatible<br>Blood Culture<br>Bottles | BACTEC™ Standard Aerobic/Anaerobic, BACTEC™<br>Plus Aerobic/Anaerobic, BACTEC™ Lytic/10<br>Anaerobic, BacT/ALERT Standard Aerobic,<br>BacT/ALERT FA Aerobic FAN®, BacT/ALERT FA<br>Plus Aerobic, VersaTREK® REDOX 1/2 | BACTEC™ Standard Aerobic/Anaerobic, BACTEC™<br>Plus Aerobic/Anaerobic, BACTEC™ Lytic/10<br>Anaerobic, BACTEC™ Peds Plus, BacT/ALERT<br>Standard Aerobic/Anaerobic, BacT/ALERT FA Aerobic<br>FAN®, BacT/ALERT FN Anaerobic FAN®, BacT/ALERT<br>PF Pediatric FAN, VersaTREK® REDOX 1/2 |
| Throughput | Four (4) samples/iC-Processor™ | One (1) sample/processor |

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# Intended Use

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

The iC-GPC Assay™ detects organism DNA and identifies the following bacterial species and resistance markers:

| Bacterial Species | Resistance Markers |
|----------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------|
| Staphylococcus aureus<br>Staphylococcus epidermidis<br>Streptococcus pneumoniae<br>Enterococcus faecalis<br>Enterococcus faecium | mecA- associated with methicillin resistance<br>vanA- associated with vancomycin resistance<br>vanB- associated with vancomycin resistance |

The iC-GPC Assay™ detects the mecA resistance marker, inferring mecA-mediated methicillin resistance, and the vanA and vanB resistance markers, inferring vanA/vanB-mediated vancomycin resistance. In mixed growth, the iC-GPC Assay™ does not specifically attribute van-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA-mediated methicillin resistance to either S. aureus or S. epidermidis.

Sub-culturing of positive blood cultures is necessary to recover organisms for susceptibility testing, identification of organisms not detected by the iC-GPC 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-GPC Assay™ labeling for a more complete list of warnings, precautions and contraindications.

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# Methodology

The iC-GPC Assay™ utilizes polymerase chain reaction (PCR) for the amplification of specific targets and detects the amplified target DNA with fluorescence-based microarray hybridization. The iC-GPC Assay™ uses proprietary ARM-PCR (Amplicon Rescued Multiplex PCR) technology allowing for multiple targets to be amplified in one reaction. Targets are detected directly from patient positive blood cultures, confirmed by Gram stain to contain gram positive cocci. Testing is performed within a closed, disposable cassette that contains all the reagents required to complete the iC-GPC Assay™, including a universal microarray.

To operate, the user opens the iC-GPC Cassette™ cap and pipettes an aliquot of the positive blood culture sample into the sample well of the cassette is then inserted into the iC-Processor™, which performs the processes of DNA extraction, multiplex amplification, and microarray After processing is complete, the cassette is inserted into the iC-Reader™ for hybridization. fluorescence-based detection and data analysis. Final results are generated by iC-Report, computer software for data acquisition, analysis, and display.

Extraction, amplification, and hybridization 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-GPC Cassette™ which communicates with the iC-Processor™. To access and pierce the foil-sealed reagent wells located in the bottom well plate of the cassette, the processor manipulates the cassette to move the internal 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 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 4 iC-Cassettes™ at one time. The results are interpreted via the iC-Report™ software and displayed for the user on an iMac® computer. Raw data and result interpretations are stored within the iMac®; raw data is accessible to authorized personnel only and is not available to the end user.

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## Performance Data

For ease of reference, the following table defines iC-GPC target organisms, corresponding gene targets, and common acronyms used in the following study descriptions.

| TABLE 1: iC-GPC Assay Targets | | |
|-------------------------------|---------------|---------|
| Organism | Target Gene | Acronym |
| Staphylococcus epidermidis | gseA | SE |
| Staphylococcus aureus | nuc | SA |
| Streptococcus pneumoniae | lytA | SPN |
| Enterococcus faecalis | ddl | EFLS |
| Enterococcus faecium | fcm (ddlEFCM) | EFCM |

# Bottle Ring

A study was performed to establish the lowest level of each iC-GPC Assay target organism at initial bottle positivity (bottle "ring"). The nineteen organisms used to define target limits of detection were evaluated. Organisms were inoculated into BD BACTEC Plus Aerobic blood culture bottles with human Bottles were allowed to incubate on the blood culture system until initial bottle blood added. positivity. Bottles were removed from the incubator within two hours of bottle ring, and plating and subsequent colony counts were performed to confirm organism concentrations. A minimum of five bottles were evaluated for each strain. The average concentrations at bottle ring are presented in Table 2 below. These concentrations, representative of the lowest levels that may be observed in a clinical setting, are equivalent to or greater than the respective target limits of detection (see below).

| TABLE 2: Target Organism Concentrations at Bottle "Ring" | |
|----------------------------------------------------------|--------------------------------|
| Organism | Average Concentration (CFU/mL) |
| SE 700566 | $2.68 \times 10^7$ |
| SE 35984 | $2.04 \times 10^7$ |
| SE 12228 | $2.59 \times 10^7$ |
| SE 49134 | $1.01 \times 10^7$ |
| SA 700699 | $5.00 \times 10^8$ |
| SA BAA 1768 | $5.24 \times 10^7$ |
| SA BAA 977 | $1.14 \times 10^8$ |
| SA 25923 | $6.06 \times 10^8$ |
| SPN 6301 | $5.40 \times 10^6$ |
| SPN 700673 | $5.95 \times 10^6$ |
| EFLS 51299 | $4.72 \times 10^{10}$ |
| EFLS 700802 | $2.22 \times 10^8$ |
| EFLS JMI 12536 | $2.27 \times 10^8$ |
| EFLS 29212 | $5.53 \times 10^{10}$ |
| EFLS BAA 2128 | $5.77 \times 10^7$ |
| EFCM 700221 | $1.16 \times 10^9$ |
| EFCM 51559 | $5.87 \times 10^8$ |
| EFCM 35667 | $2.86 \times 10^7$ |
| EFCM BAA 2127 | $2.70 \times 10^8$ |

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#### Reproducibility

To confirm site-to-site, operator, system-to-system, and lot-to-lot reproducibility of the iC-GPC Assay, a representative panel of target organisms and one non-target organism were tested at two concentrations: initial bottle positivity and eight hours beyond initial bottle positivity. Organisms were grown to the appropriate concentration in BD BACTEC Plus Aerobic/F 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 in-house. The six organism panel was tested in replicates of three across five, non-consecutive days. Testing was evaluated across three cassette lots and four iC-Systems. Table 3 below summarizes results by iC-GPC Assay target and concentration. Testing confirmed that performance of the iC-GPC Assay for use on the iC-System is reproducible across sites, operators, systems, and lots.

| TABLE 3: iC-GPC Reproducibility Performance by Target & Concentration | | | | | | |
|-----------------------------------------------------------------------|------------------------|--------------------------------------|--------------------|--------------------|-------------------------------------|--------------------|
| Organism/Gene Target/<br>Concentration | Overall<br>Performance | Overall<br>Performance %<br>[95% CI] | False<br>Negatives | False<br>Positives | Positive Controls<br>Check Failures | System<br>Failures |
| S. epidermidis (gseA)<br>Bottle Ring | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 1/976<br>(0.10%) | 0/90<br>(0.00%) | 1/90<br>(1.11%) |
| S. epidermidis (gseA)<br>Bottle Ring + 8 hours | 90/90 | 100.0<br>[95.91-100.0] | 0/90<br>(0.00%) | 0/975<br>(0.00%) | 0/90<br>(0.00%) | 0/90<br>(0.00%) |
| S. aureus (nuc)<br>Bottle Ring | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 0/976<br>(0.00%) | 1/90<br>(1.11%) | 0/90<br>(0.00%) |
| S. aureus (nuc)<br>Bottle Ring + 8 hours | 89/90 | 98.9<br>[93.97-99.80] | 1/90<br>(1.12%) | 0/975<br>(0.00%) | 0/90<br>(0.00%) | 0/90<br>(0.00%) |
| S. pneumoniae (lytA)<br>Bottle Ring | 88/88 | 100.0<br>[95.82-100.0] | 0/88<br>(0.00%) | 0/977<br>(0.00%) | 1/90<br>(1.11%) | 1/90<br>(1.11%) |
| S. pneumoniae (lytA)<br>Bottle Ring + 8 hours | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 0/976<br>(0.00%) | 0/90<br>(0.00%) | 1/90<br>(1.11%) |
| E. faecalis (ddl)<br>Bottle Ring | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 2/976<br>(0.20%) | 0/90<br>(0.00%) | 1/90<br>(1.11%) |
| E. faecalis (ddl)<br>Bottle Ring + 8 hours | 89/89 | 100.0<br>[95.86, 100.0] | 0/89<br>(0.00%) | 3/976<br>(0.31%) | 1/90<br>(1.11%) | 0/90<br>(0.00%) |
| E. faecium (fcm)<br>Bottle Ring | 90/90 | 100.0<br>[95.91-100.0] | 0/90<br>(0.00%) | 0/975<br>(0.00%) | 0/90<br>(0.00%) | 0/90<br>(0.00%) |
| E. faecium (fcm)<br>Bottle Ring + 8 hours | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 0/976<br>(0.00%) | 1/90<br>(1.11%) | 0/90<br>(0.00%) |
| mecA<br>Bottle Ring | 177/178 | 99.4<br>[96.89-99.90] | 1/178<br>(0.56%) | 1/887<br>(0.11%) | 1/180<br>(0.56%) | 1/180<br>(0.56%) |
| mecA<br>Bottle Ring + 8 hours | 180/180 | 100.0<br>[97.91-100.0] | 0/180<br>(0.00%) | 0/885<br>(0.00%) | 0/180<br>(0.00%) | 0/180<br>(0.00%) |
| vanA<br>Bottle Ring | 90/90 | 100.0<br>[95.91-100.0] | 0/90<br>(0.00%) | 0/975<br>(0.00%) | 0/90<br>(0.00%) | 0/90<br>(0.00%) |
| vanA<br>Bottle Ring + 8 hours | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 0/976<br>(0.00%) | 1/90<br>(1.11%) | 0/90<br>(0.00%) |
| vanB<br>Bottle Ring | 89/89 | 100.0<br>[95.86-100.0] | 0/89<br>(0.00%) | 0/976<br>(0.00%) | 0/90<br>(0.00%) | 1/90<br>(1.11%) |
| vanB<br>Bottle Ring + 8 hours | 89/89 | 100.0<br>[95.86, 100.0] | 0/89<br>(0.00%) | 0/976<br>(0.00%) | 1/90<br>(1.11%) | 0/90<br>(0.00%) |

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## Limit of Detection (LoD)

A study was conducted to determine the limit of detection, defined as the lowest concentration (CFU/mL) of analyte that can be detected approximately 95% of the time, for the eight targets detected by the iC-GPC Assay. A panel of nineteen organisms was evaluated, including a minimum of two bacterial strains per target analyte. Three concentrations were tested for each LoD panel member in replicates of twenty on three unique cassette lots. The LoD of each target is considered the lowest concentration with an approximately 95% detection rate, presented in Table 4 below.

| TABLE 4: iC-GPC Assay Target LoD | | |
|----------------------------------|----------------------------------------|-------------------------------------|
| iC-GPC Assay Target | Phenotype Identification | Defined LoD (CFU/mL) |
| gseA | Staphylococcus epidermidis | $1.6 \times 10^6 - 1.7 \times 10^7$ |
| nuc | Staphylococcus aureus | $1.7 \times 10^6 - 4.4 \times 10^6$ |
| mecA | Associated with methicillin resistance | $7.4 \times 10^5 - 9.5 \times 10^6$ |
| lytA | Streptococcus pneumoniae | $1.3 \times 10^6 - 6.0 \times 10^6$ |
| ddl | Enterococcus faecalis | $3.0 \times 10^5 - 5.8 \times 10^6$ |
| fcm | Enterococcus faecium | $4.9 \times 10^6 - 7.9 \times 10^6$ |
| vanA | Associated with vancomycin resistance | $7.2 \times 10^5 - 1.1 \times 10^7$ |
| vanB | Associated with vancomycin resistance | $3.9 \times 10^6 - 5.8 \times 10^6$ |

# Analytical Reactivity (Inclusivity)

The analytical reactivity (inclusivity) for each iC-GPC Assay target was evaluated using multiple wellcharacterized and clinically relevant strains chosen to represent temporal, geographic, and genetic diversity. Inclusivity panel organisms included the following:

- 5 Staphylococcus epidermidis, mecA negative strains O
- 6 Staphylococcus epidermidis, mecA positive strains O
- O 5 Staphylococcus aureus, mecA negative strains
- 58 Staphylococcus aureus, mecA positive strains, representing various pulse-O
- field gel electrophoresis types and including the following:
- . Vancomycin-intermediate SA (VISA)
- . Panton-Valentine Leukocidin (PVL)-producing SA
- . ATCC 43300 (hetero-resistant, mecA positive)
- 2 borderline oxacillin-resistant Staphylococcus aureus strains (BORSA) O
- O 10 Streptococcus pneumoniae strains
- 5 Enterococcus faecalis, vanA/vanB negative strains O
- 5 Enterococcus faecalis, vanA or vanB positive strains O
- 5 Enterococcus faecium, vanA/vanB negative strains O
- 5 Enterococcus faecium, vanA or vanB positive strains O

A total of 106 organisms were evaluated for iC-GPC Assay Inclusivity testing. Strains were tested near the target LoD (2-3x LoD) or at the lowest level of bottle positivity. Testing was performed in the event of a false negative result, the stain was retested near the target LoD in replicates of ten. All expected targets were detected by the iC-GPC Assay. Results of inclusivity testing are summarized in Table 5 below.

{12}------------------------------------------------

| TABLE 5: iC-GPC Inclusivity Results | | | | |
|-------------------------------------|-------------|-----------------------------------|---------------------------------------|--|
| Species | Strain ID | Other IDs/Notes | Targets Detected/<br>Total Replicates | |
| S. epidermidis | Z318 | N/A | 3/3 | |
| S. epidermidis | Z0801689 | HER 1292 | 3/3 | |
| S. epidermidis | ATCC 700583 | N/A | 3/3 | |
| S. epidermidis | Z291 | ATCC 14990 | 3/3 | |
| S. epidermidis | Z049 | N/A | 3/3 | |
| S. epidermidis, mecA (+) | Z0801651 | RP62A | 3/3 | |
| S. epidermidis, mecA (+) | Z256 | N/A | 3/3 | |
| S. epidermidis, mecA (+) | Z257 | N/A | 3/3 | |
| S. epidermidis, mecA (+) | Z258 | N/A | 12/13 | |
| S. epidermidis, mecA (+) | Z259 | N/A | 3/3 | |
| S. epidermidis, mecA (+) | ATCC 29887 | N/A | 3/3 | |
| S. aureus | Z021 | ATCC 6538P | 3/3 | |
| S. aureus | ATCC 12600 | N/A | 3/3 | |
| S. aureus | Z0801675 | N/A | 3/3 | |
| S. aureus | Z057 | N/A | 3/3 | |
| S. aureus | Z153 | N/A | 3/3 | |
| S. aureus, mecA (+) | HM-466 | 131 | 3/3 | |
| S. aureus, mecA (+) | HM-467 | 177 | 3/3 | |
| S. aureus, mecA (+) | NR-10129 | TCH60 | 3/3 | |
| S. aureus, mecA (+) | NR-10189 | HFH-30364, USA400, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-10192 | HFH-30106, non USA100-1100 | 3/3 | |
| S. aureus, mecA (+) | NR-13524 | H342087 | 3/3 | |
| S. aureus, mecA (+) | NR-28983 | S0385 | 3/3 | |
| S. aureus, mecA (+) | NR-45872 | HIP07930, USA600 | 3/3 | |
| S. aureus, mecA (+) | NR-45880 | LIM1 | 3/3 | |
| S. aureus, mecA (+) | NR-45890 | BR 5, VISA | 3/3 | |
| S. aureus, mecA (+) | NR-46062 | H2138 (isolate 10) | 3/3 | |
| S. aureus, mecA (+) | NR-46063 | P1V44, VISA | 3/3 | |
| S. aureus, mecA (+) | NR-46072 | 1078, USA700 | 3/3 | |
| S. aureus, mecA (+) | NR-46080 | AIS 2006061, USA1000, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-46081 | HIP12899, USA1100, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-46218 | GA-442, USA700 | 3/3 | |
| S. aureus, mecA (+) | NR-46070 | USA300-0114 | 3/3 | |
| S. aureus, mecA (+) | NR-46171 | CA-126, USA100 | 3/3 | |
| S. aureus, mecA (+) | NR-46172 | CA-127, USA300, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-46177 | CA-347, USA600 | 3/3 | |
| S. aureus, mecA (+) | NR-46180 | CA-409, USA200 | 3/3 | |
| S. aureus, mecA (+) | NR-46182 | CA-513, USA800 | 3/3 | |
| S. aureus, mecA (+) | NR-46191 | CO-34, USA300, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-46197 | CO-72, USA800 | 3/3 | |
| TABLE 5: iC-GPC Inclusivity Results | | | | |
| Species | Strain ID | Other IDs/Notes | Targets Detected/<br>Total Replicates | |
| S. aureus, mecA (+) | NR-46199 | CT-110, USA100 | 3/3 | |
| S. aureus, mecA (+) | NR-46207 | CT-58, USA500 | 3/3 | |
| S. aureus, mecA (+) | NR-46215 | GA-356 | 3/3 | |
| S. aureus, mecA (+) | NR-46221 | GA-656, USA800 | 3/3 | |
| S. aureus, mecA (+) | NR-46223 | GA-92, USA300, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-46224 | NY-315, USA600 | 3/3 | |
| S. aureus, mecA (+) | NR-46250 | OR-130, USA100 | 3/3 | |
| S. aureus, mecA (+) | NR-46251 | OR-131, USA200 | 3/3 | |
| S. aureus, mecA (+) | NR-46261 | TN-112, USA300 | 3/3 | |
| S. aureus, mecA (+) | NR-46269 | TN-82, USA200 | 3/3 | |
| S. aureus, mecA (+) | NR-41875 | M0001 | 3/3 | |
| S. aureus, mecA (+) | NR-41876 | M0006 | 3/3 | |
| S. aureus, mecA (+) | NR-41877 | M0055 | 3/3 | |
| S. aureus, mecA (+) | NR-41878 | M0102 | 3/3 | |
| S. aureus, mecA (+) | NR-41879 | M0108 | 3/3 | |
| S. aureus, mecA (+) | NR-41880 | M0197 | 3/3 | |
| S. aureus, mecA (+) | NR-41881 | M0200 | 3/3 | |
| S. aureus, mecA (+) | NR-41882 | M0288 | 3/3 | |
| S. aureus, mecA (+) | NR-41883 | M0334 | 3/3 | |
| S. aureus, mecA (+) | NR-41887 | M0663 | 3/3 | |
| S. aureus, mecA (+) | NR-41889 | M0934 | 3/3 | |
| S. aureus, mecA (+) | NR-41890 | M0943 | 3/3 | |
| S. aureus, mecA (+) | NR-41895 | M1510 | 12/13 | |
| S. aureus, mecA (+) | NR-41896 | M1565 | 3/3 | |
| S. aureus, mecA (+) | NR-10187 | HFH-29994, USA100 | 3/3 | |
| S. aureus, mecA (+) | NR-13525 | F338081 | 3/3 | |
| S. aureus, mecA (+) | NR-13526 | W342179 | 3/3 | |
| S. aureus, mecA (+) | NR-13533 | S247312 | 3/3 | |
| S. aureus, mecA (+) | NR-13546 | SU-1 | 3/3 | |
| S. aureus, mecA (+) | NR-30544 | HI049, USA300, PVL+ | 3/3 | |
| S. aureus, mecA (+) | NR-45924 | LinR #12 | 3/3 | |
| S. aureus, mecA (+) | ATCC 700698 | N/A | 3/3 | |
| S. aureus, mecA (+) | ATCC BAA44 | N/A | 3/3 | |
| S. aureus, mecA (+) | ATCC 43300 | Hetero-resistant | 3/3 | |
| BORSA | MCW 109 | N/A | 3/3 | |
| BORSA | MCW 141 | N/A | 3/3 | |
| S. pneumoniae | Z022 | Clinical isolate, serotype 19F | 3/3 | |
| S. pneumoniae | Z073 | Clinical isolate, serotype 19F | 3/3 | |
| S. pneumoniae | Z319 | Clinical isolate, serotype 12F | 3/3 | |
| S. pneumoniae | Z278 | ATCC BAA-255, R6 (non-virulent) | 3/3 | |
| TABLE 5: iC-GPC Inclusivity Results | | | | |
| Species | Strain ID | Other IDs/Notes | Targets Detected/<br>Total Replicates | |
| S. pneumoniae | Z279 | PHE NCTC 11910, serotype 23F | 3/3 | |
| S. pneumoniae | Z280 | PHE NCTC 11897, serotype 9V | 3/3 | |
| S. pneumoniae | Z282 | ATCC 33400, NCTC 7465, serotype 1 | 3/3 | |
| S. pneumoniae | Z295 | ATCC 49619, serotype 19F | 3/3 | |
| S. pneumoniae | Z261 | Clinical isolate | 3/3 | |
| S. pneumoniae | Z262 | Clinical isolate | 3/3 | |
| E. faecalis | Z0801637 | N/A | 3/3 | |
| E. faecalis | ATCC 33186 | N/A | 3/3 | |
| E. faecalis | ATCC 49532 | N/A | 3/3 | |
| E. faecalis | Z289 | ATCC 19433 | 3/3 | |
| E. faecalis | Z266 | ATCC 6055 | 3/3 | |
| E. faecalis, vanB (+) | Z0801693 | vanB | 3/3 | |
| E. faecalis, vanA (+) | Z324 | vanA | 3/3 | |
| E. faecalis, vanA (+) | Z267 | PHE NCTC 12201- vanA | 3/3 | |
| E. faecalis, vanA (+) | Z269 | PHE NCTC 12203- vanA | 3/3 | |
| E. faecalis, vanB (+) | ATCC 51575 | vanB | 3/3 | |
| E. faecium | Z322 | N/A | 3/3 | |
| E. faecium | ATCC 8459 | N/A | 3/3 | |
| E. faecium | Z265 | ATCC 9756 | 3/3 | |
| E. faecium | Z290 | ATCC 19434 | 3/3 | |
| E. faecium | Z320 | ATCC 19634 | 3/3 | |
| E. faecium, vanA (+) | Z0801892 | vanA | 3/3 | |
| E. faecium, vanB (+) | Z323 | vanB | 3/3 | |
| E. faecium, vanA (+) | Z270 | PHE NCTC 12202- vanA | 3/3 | |
| E. faecium, vanA (+) | Z271 | PHE NCTC 12204- vanA | 3/3 | |
| E. faecium, vanA (+) | Z260 | vanA | 3/3 | |

{13}------------------------------------------------

{14}------------------------------------------------

### Analytical Exclusivity

Analytical specificity of the iC-GPC Assay was evaluated by testing a comprehensive panel of non-target microorganisms that may be encountered in positive blood cultures. Exclusivity panel members included organisms phylogenetically related to iC-GPC target organisms as well as common blood culture contaminants. A total of ninety-four (94) exclusivity organisms were tested. Potential cross-reactivity was evaluated by testing the exclusivity panel organisms at high concentrations in blood culture bottle/blood media. Exclusivity results are presented in Table 6 below; performance is based on the observation of all expected negative results. In the event of a false positive result, the organism was retested in replicates of three (3) or ten (10). One organism, Streptococcus bovis, demonstrated reproducible cross-reactivity with the iC-GPC target Enterococcus faecalis.

{15}------------------------------------------------

| TABLE 6: iC-GPC Exclusivity Results | Test Concentration (CFU/mL, or<br>as designated, bottle ring or<br>TCID50/mL) | Exclusivity |
|--------------------------------------------|-------------------------------------------------------------------------------|-------------|
| Abiotrophia defectiva | 3.09 × 108 | 3/3 |
| Acinetobacter baumannii | 6.55 × 108 | 3/3 |
| Acinetobacter lwoffi | 5.70 × 108 | 3/3 |
| Aerococcus viridans | 5.05 × 107 | 3/3 |
| Aeromonas hydrophila | 3.50 × 108 | 3/3 |
| Alcaligenes faecalis | 1.01 × 1010 | 3/3 |
| Anaerococcus tetradius | 3.55 × 108 | 3/3 |
| Aspergillus niger | 8.10 × 107 | 3/3 |
| Bacillus cereus | 7.30 × 106 | 3/3 |
| Bacteroides fragilis | 4.20 × 109 | 3/3 |
| Campylobacter coli | 2.55 × 108 | 3/3 |
| Campylobacter jejuni | 2.24 × 108 | 3/3 |
| Candida albicans | 8.00 × 107 | 3/3 |
| Candida catenulata | 1.14 × 109 | 3/3 |
| Candida dubliniensis | 7.05 × 106 | 3/3 |
| Candida glabrata | 1.15 × 108 | 3/3 |
| Candida guilliermondii | 1.03 × 107 | 3/3 |
| Candida krusei | 2.82 × 107 | 5/61 |
| Candida parapsilosis | 3.15 × 107 | 3/3 |
| Candida tropicalis | 7.65 × 107 | 2/2 |
| Citrobacter amalonaticus | 2.35 × 109 | 3/3 |
| Citrobacter freundii | 6.40 × 108 | 3/3 |
| Citrobacter koseri | 3.29 × 109 | 3/3 |
| Citrobacter sedlakii | 1.70 × 109 | 3/3 |
| Clostridium difficile (NAP-1 toxigenic) | 2.44 × 107 | 3/3 |
| Clostridium difficile (non-toxigenic) | 2.97 × 107 | 3/3 |
| Clostridium oedematiens (novyi) | 5.70 × 106 | 3/3 |
| Collinsella aerofaciens | 5.95 × 107 | 3/3 |
| Corynebacterium amycolatum | 3.79 × 108 | 5/62 |
| Corynebacterium genitalium | 2.50 × 108 | 3/3 |
| Corynebacterium jeikeium | 4.19 × 108 | 3/3 |
| Coxsackie virus | 1 × 106.34 (TCID50) | 3/3 |
| Cryptococcus neoformans | 1.08 × 108 | 3/3 |
| Cytomegalovirus | 1 × 105.07 (TCID50) | 3/3 |
| Echovirus | 1 × 107.77 (TCID50) | 3/3 |
| Edwardsiella tarda | 5.05 × 109 | 3/3 |
| Eggerthella lenta | 1.42 × 108 | 3/3 |
| Enterobacter aerogenes | 6.50 × 109 | 3/3 |
| TABLE 6: iC-GPC Exclusivity Results | | |
| Exclusivity Organism | Test Concentration (CFU/mL, or<br>as designated, bottle ring or<br>TCID50/mL) | Exclusivity |
| Enterococcus avium | $5.85 \times 10^7$ | 3/3 |
| Enterococcus casseliflavus | $9.60 \times 10^6$ | 3/3 |
| Enterococcus cecorum | $3.80 \times 10^8$ | 3/3 |
| Enterococcus dispar | $6.10 \times 10^8$ | 3/3 |
| Enterococcus gallinarum | $3.20 \times 10^8$ | 3/3 |
| Enterococcus hirae | $1.04 \times 10^9$ | 3/3 |
| Enterococcus raffinosus | $4.67 \times 10^8$ | 3/3 |
| Enterovirus Type 71 | $1 \times 10^{6.10}$ (TCID50) | 3/3 |
| Escherichia coli | $1.27 \times 10^9$ | 3/3 |
| Escherichia hermannii | $3.09 \times 10^9$ | 3/3 |
| Fusobacterium varium | $1.25 \times 10^9$ | 3/3 |
| Klebsiella oxytoca | $7.25 \times 10^9$ | 3/3 |
| Klebsiella pneumoniae | $2.27 \times 10^9$ | 3/3 |
| Kocuria kristinae | $3.45 \times 10^8$ | 3/3 |
| Kytococcus schroeteri | $1.85 \times 10^8$ | 3/3 |
| Lactobacillus acidophilus | $5.30 \times 10^7$ | 3/3 |
| Lactobacillus plantarum subsp.plantarum | $1.53 \times 10^9$ | 3/3 |
| Lactobacillus reuteri | $1.24 \times 10^8$ | 5/63 |
| Lactococcus lactis | $2.57 \times 10^9$ | 3/3 |
| Leminorella grimontii | $1.22 \times 10^9$ | 3/3 |
| Leuconostoc mesenteroides | $3.17 \times 10^7$ | 3/3 |
| Micrococcus luteus | $1.13 \times 10^7$ | 3/3 |
| Oerskovia enterophila | $1.33 \times 10^{10}$ | 3/3 |
| Pediococcus pentosaceus | $2.82 \times 10^9$ | 3/3 |
| Planococcus citreus | $1.14 \times 10^9$ | 3/3 |
| Propionibacterium acnes | $9.75 \times 10^7$ | 3/3 |
| Proteus mirabilis | $9.25 \times 10^8$ | 3/3 |
| Proteus penneri | $1.11 \times 10^9$ | 3/3 |
| Proteus vulgaris | $1.13 \times 10^9$ | 3/3 |
| Providencia alcalifaciens | $1.62 \times 10^9$ | 10/114 |
| Providencia rettgeri | $1.05 \times 10^9$ | 3/3 |
| Providencia stuartii | $1.48 \times 10^9$ | 3/3 |
| Ps…