The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture. In addition, the ePlex BCID-GP Panel is capable of detecting a wide variety of gram-negative bacteria (Pan Gram-Negative assay) and several Candida species (Pan Candida assay). The ePlex BCID-GP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain gram-positive organism.

The following bacterial organisms and genes associated with antibiotic resistance are identified using the ePlex BCID-GP Panel: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (Propionibacterium acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB.

The ePlex BCID-GP Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA and mecC) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease.

The ePlex BCID-GP Panel also contains targets designed to detect a broad range of organisms with a potentially misleading Gram stain result or organisms that may be missed by Gram staining altogether, for example in the case of co-infections. These include a broad Pan Gram-Negative assay as well as a Pan Candida assay, which is designed to detect four of the most prevalent Candida species: Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis.

The detection and identification of specific bacterial and fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from the ePlex BCID-GP Panel are intended to be interpreted in conjunction with Gram stain results and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a suspected bloodstream infection may be due to infection with pathogens that are not detected by this test. Positive results do not rule out co-infection with other organisms; the organism(s) detected by the ePlex BCID-GP Panel may not be the definite cause of disease. Additional laboratory testing (e.g. sub-culturing of positive blood cultures for identification of organisms not detected by ePlex BCID-GP Panel and for susceptibility testing. differentiation of mixed growth and association of antimicrobial resistance marker genes to a specific organism) and clinical presentation must be taken into consideration in the final diagnosis of blood stream infection.

Device Description

The ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is based on the principles of competitive nucleic acid hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to a sequence-specific solution-phase signal probe and a solid-phase electrode-bound capture probe. The test employs nucleic acid extraction, target amplification via polymerase chain reaction (PCR) or reverse transcription PCR (RT-PCR) and hybridization of target DNA. In the process, the double-stranded PCR amplicons are digested with exonuclease to generate single-stranded DNA suitable for hybridization.

Nucleic acid extraction from biological samples occurs within the cartridge via cell lysis, nucleic acid capture onto magnetic beads, and release for amplification. The nucleic acid extraction is processed through microfluidic liquid handling. Once the nucleic acid targets are captured and inhibitors are washed away, the magnetic particles are delivered to the electrowetting environment on the printed circuit board (PCB) and the targets are eluted from the particles and amplified.

During hybridization, the single-stranded target DNA binds to a complementary, single-stranded capture probe immobilized on the working gold electrode surface. Single-stranded signal probes (labeled with electrochemically active ferrocenes) bind to specific target sequence / region adjacent to the capture probe. Simultaneous hybridization of target to signal probes and capture probe is detected by alternating current voltammetry (ACV). Each working electrode on the array contains specific capture probes, and sequential analysis of each electrode allows detection of multiple analyte targets.

AI/ML Overview

Here's an analysis of the provided text to extract information about the device's acceptance criteria and the study proving it meets them.

The document is a 510(k) Premarket Notification from the FDA regarding the GenMark ePlex Blood Culture Identification Panel - Gram Positive (BCID-GP) Panel (K181663). The core of the performance data revolves around clinical performance (sensitivity/PPA and specificity/NPA) against comparator methods, and analytical performance (Limit of Detection, Inclusivity, Exclusivity, Reproducibility, Interfering Substances, Competitive Inhibition).

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the clinical and analytical performance targets the device aimed to meet, typically demonstrating non-inferiority or substantial equivalence to a predicate device and adequate analytical performance. The tables provided (Table 6 through Table 30 for clinical performance, and Table 61 onwards for reproducibility) present the device's reported performance. A formal table of acceptance criteria with corresponding results isn't explicitly laid out with a "criteria" column alongside "performance" in the document, but we can infer the criteria from the achieved results and the FDA clearance itself, which implies acceptable performance.

For this device, the primary acceptance criteria would be high Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with established comparator methods for all targeted organisms and resistance genes, along with robust analytical performance.

Here's a summary of the reported performance, reflecting the device meeting implicit acceptance criteria for clinical accuracy:

Table 1: Derived Acceptance Criteria and Reported Device Performance (Selected Examples)

Target / Metric	Implied Acceptance Criteria (High Accuracy)	Reported Device Performance (Combined P/R samples)
Clinical Performance (PPA/Sensitivity)
Bacillus cereus group	High PPA (e.g., >90%)	91.7% (11/12)
Corynebacterium	High PPA (e.g., >80%)	78.4% (40/51) - Note: slightly below 80%
Enterococcus	High PPA (e.g., >95%)	96.2% (200/208)
Staphylococcus	High PPA (e.g., >95%)	97.7% (632/647)
Streptococcus	High PPA (e.g., >95%)	96.8% (274/283)
mecA (Staphylococcus)	High PPA (e.g., >95%)	97.1% (401/413)
vanA (Enterococcus)	High PPA (e.g., >90%)	93.8% (61/65)
Pan Gram-Negative	High PPA (e.g., >80%)	83.7% (36/43) (Retrospective)
Pan Candida	High PPA (e.g., >75%)	77.8% (7/9) (Retrospective)
Clinical Performance (NPA/Specificity)
All listed targets	High NPA (e.g., >98%)	Generally >99% for all targets
mecA (Staphylococcus)	High NPA (e.g., >90%)	95.3% (223/234)
vanA (Enterococcus)	High NPA (e.g., >95%)	98.6% (141/143)
Analytical Performance
Limit of Detection	Specific CFU/mL values	Ranges from 1x10^4 to 1x10^8 CFU/mL
Reproducibility	High Percent Agreement (e.g., >95%)	Generally >90% (e.g., Corynebacterium at 95.4%)

Detailed Information about the Study:

A table of acceptance criteria and the reported device performance
- See the table above for inferred criteria and reported performance based on clinical PPA/NPA. The acceptance criteria are not explicitly stated as quantitative thresholds in the provided text, but the successful clearance of the device implies that the observed performance was deemed acceptable by the FDA.
Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Test Set (Clinical Study):
  - Prospective Samples: Total 711 evaluable samples. Collected from 7 clinical sites. 312 were tested fresh (Jan-Feb 2018), and 399 were frozen (June 2014-July 2016).
  - Retrospective Samples: Total 586 evaluable samples. Collected to supplement low prevalence targets.
  - Combined Clinical Samples: 1297 (711 prospective + 586 retrospective).
  - Contrived Samples: 565 samples prepared by spiking isolates into blood culture bottles.
- Data Provenance: The document states "A prospective, multicenter clinical study was conducted at 7 clinical sites." While specific countries are not mentioned, FDA clearances typically involve studies predominantly conducted in the USA or with data acceptable to US regulatory standards. The terms "multicenter" and "clinical sites" imply different geographical locations although not explicitly named.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- The ground truth for the clinical test set was established using "Standard laboratory procedures" including traditional and automated culture, MALDI-TOF IVD, and microbiological and biochemical techniques for organism identification. Specific PCR assays followed by bi-directional sequencing (or 16S sequencing for Corynebacterium, Staphylococcus epidermidis, Candida parapsilosis) were used for confirmation where necessary. For antibiotic resistance genes (mecA, mecC, vanA, vanB), ground truth was established using analytically validated qPCR amplification assays followed by bi-directional sequencing.
- The document does not specify the number of experts or their qualifications (e.g., board-certified microbiologists, medical technologists with X years of experience) who performed these standard laboratory procedures or interpreted the sequencing results to establish ground truth.
Adjudication method (e.g. 2+1, 3+1, none) for the test set
- The document describes a comparison between the ePlex BCID-GP Panel results and "comparator method(s) results." For discrepant results (e.g., false positives, false negatives), additional analytically validated PCR assays and sequencing were used for confirmation (e.g., for Corynebacterium, S. epidermidis, Pan Candida, Staphylococcus for mecA, and Enterococcus for vanA/vanB).
- This is a form of adjudication, where discrepant results are further investigated. However, it's not a multi-reader adjudication method (like 2+1, 3+1) involving multiple human readers interpreting results, as this device performs automated detection. Instead, it's a discrepancy resolution method using a higher-level, analytically validated diagnostic test (PCR/sequencing) as the tie-breaker/confirmatory method.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic test for identifying microorganisms and resistance markers, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Its performance is evaluated against laboratory standard reference methods, not against human reader performance or improvement with AI assistance.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, the primary clinical and analytical performance studies are standalone (algorithm only) performance. The ePlex BCID-GP Panel is an automated test on the ePlex Instrument. Its results are generated by the device's assay and software, and then compared directly to the ground truth established by comparator laboratory methods. There is no explicit human-in-the-loop component described for its diagnostic performance evaluation, although clinical interpretation of the results by medical professionals is clearly indicated as necessary for patient management decisions (as stated in the Indications for Use).
The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- The ground truth for the clinical study was based on "Standard laboratory procedures" for organism identification (culture, MALDI-TOF IVD, microbiological/biochemical techniques) and analytically validated PCR assays with bi-directional sequencing for confirmation of specific organisms and all resistance genes. This would fall under laboratory reference standard/molecular confirmation. Clinical outcomes data was not primarily used for ground truth.
The sample size for the training set
- The document does not specify a separate "training set" size for the development of the ePlex BCID-GP Panel's algorithm. For in vitro diagnostic devices like this one, the development process might involve internal validation and optimization, but the regulatory submission focuses on the performance of the final, locked version of the device using a clinically representative "test set." The text primarily describes the clinical evaluation (prospective, retrospective, contrived samples) which serves as the independent test set for regulatory submission.
How the ground truth for the training set was established
- As a distinct "training set" is not explicitly mentioned as per typical machine learning contexts, the document doesn't detail how ground truth for such a set was established. It's plausible that internal development and optimization would have used similar laboratory reference methods as those used for the clinical validation.

Summary

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December 20, 2018

GenMark Diagnostics, Incorporated Alan Maderazo VP, Quality, Regulatory & Clinical Affairs 5964 La Place Court Carlsbad, California 92008

Re: K181663

Trade/Device Name: ePlex Blood Culture Identification Panel - Gram Positive (BCID-GP) Panel 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, PEN, PEO Dated: June 22, 2018 Received: June 25, 2018

Dear Alan Maderazo:

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

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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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Uwe Scherf -S

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181663

Device Name

ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel

Indications for Use (Describe)

The ePlex BCID-GP Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA and mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease.

The detection and identification of specific bacterial and fungal nucleic acids from individuals

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exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from the ePlex BCID-GP Panel are intended to be interpreted in conjunction with Gram stain results and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

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

Summary of Safety and Effectiveness

Submitter Information

GenMark Diagnostics, Incorporated Submitter: 5964 La Place Court Carlsbad, CA 92008

Manufacturer: GenMark Diagnostics, Incorporated 5964 La Place Court Carlsbad, CA 92008
Establishment Registration Number: 3008632402

Contact:	Alan Maderazo, Ph.D., RACVice President, Quality, Regulatory and Clinical Affairs
Phone:	760-448-4308
Fax:	760-683-6961
E-mail:	Al.Maderazo@genmarkdx.com
Alternate Contact:	Beth StofkaSr. Regulatory Affairs Specialist
Phone:	760-579-4778
Fax:	760-683-6961
E-mail:	Beth.Stofka@genmarkdx.com
Date Prepared:	June 22, 2018

Name of Device and Classification

Product Name:	ePlex® Blood Culture Identification Gram-Positive (BCID-GP) Panel
Device Classification:	866.3980, Multiplex nucleic acid assay for identification ofmicroorganisms and resistance markers from positive blood cultures,Class II
Product Code(s):	PAM, PEN, PEO

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Predicate Device

Predicate:

FilmArray Blood Culture Identification Panel; BioFire Diagnostics; K130914

Device Description

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Intended Use/Indications for Use

The GenMark ePlex® Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture. In addition, the ePlex BCID-GP Panel is capable of detecting a wide variety of gram-negative bacteria (Pan Gram-Negative assay) and several Candida species (Pan Candida assay). The ePlex BCID-GP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain gram-positive organism.

The following bacterial organisms and genes associated with antibiotic resistance are identified using the ePlex BCID-GP Panel: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (Propionibacterium acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB.

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Summary of Technological Characteristics of the Device Compared to the Predicate Device

The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel ("Subject Device") and the legally marketed device, FilmArray Blood Culture Identification Gram-Positive Panel, K130914, ("Predicate Device") are described below:

Characteristic	Subject Device	Predicate Device
Product Name	ePlex BCID-GP Panel	FilmArray BCID Panel
Manufacturer	GenMark Diagnostics, Inc.	BioFire Diagnostics, Inc.
OrganismsDetected	Bacillus cereus group Bacillus subtilis group Corynebacterium Cutibacterium acnes (P. acnes) Enterococcus Enterococcus facealis Enterococcus faecium Lactobacillus Listeria Listeria monocytogenes Micrococcus Staphylococcus Staphylococcus aureus Staphylococcus epidermidis	Enterococci, Listeria monocytogenes,commonly encountered Staphylococci(including specific differentiation ofStaphylococcus aureus), commonlyencountered Streptococci (withspecific differentiation ofStreptococcus agalactiae,Streptococcus pneumoniae, andStreptococcus pyogenes),Acinetobacter baumannii, commonlyencountered Enterobacteriaceae(including specific differentiation ofthe Enterobacter cloacae complex,Escherichia coli, Klebsiella oxytoca,
Characteristic	Subject Device	Predicate Device
	Staphylococcus lugdunensis Streptococcus Streptococcus agalactiae (GBS) Streptococcus anginosus group Streptococcus pneumonia Streptococcus pyogenes (GAS) Pan Gram-Negative Pan Candida	Klebsiella pneumoniae, Proteus, andSerratia marcescens), Haemophilusinfluenzae, Neisseria meningitidis(encapsulated), Pseudomonasaeruginosa, Candida albicans,Candida glabrata, Candida krusei,Candida parapsilosis, and Candidatropicalis.
Resistance GenesDetected	Genetic determinants of resistance tomethicillin ( mecA and mecC ) andvancomycin ( vanA and vanB )	Genetic determinants of resistance tomethicillin ( mecA ), vancomycin( vanA and vanB ), and carbapenems( bla KPC)
Indication forUse	The GenMark BCID-GP panel isindicated as an aid in the diagnosis ofspecific agents of bacteremia. The useof additional laboratory testing (e.g.sub-culturing of positive blood culturesfor identification of organisms notdetected by BCID-GP Panel and forsusceptibility testing, differentiation ofmixed growth, and association ofantimicrobial resistance marker genes toa specific organism) and clinicalpresentation must be taken intoconsideration in the final diagnosis ofblood stream infection.	FilmArray BCID is indicated as an aidin the diagnosis of specific agents ofbacteremia and fungemia and resultsshould be used in conjunction withother clinical and laboratory findings.
Specimen Type	Gram-Positive Blood Culture	Gram-Positive & Gram-NegativeBlood Culture
Chemistry	Reagents on cartridge include: samplelysis and nucleic acid extraction, PCRamplification and hybridization-basedelectrochemical detection reagents.	The FilmArray BCID pouch containsfreeze-dried reagents to performnucleic acid purification and nested,multiplex PCR with DNA meltanalysis.
Hardware	GenMark ePlex Instrument & SingleUse Cartridge	FilmArray Instrument and assay pouch
SoftwareInterfaceResult Reporting	GenMark ePlex System Software GenMark ePlex BCID-GP PanelSoftware	The FilmArray Software automaticallyinterprets the results of each DNAmelt curve analysis and combines thedata with the results of the internalpouch controls to provide a test resultfor each organism and antimicrobialresistance gene on the panel.

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Analysis of the similarities and differences indicate that the devices are substantially equivalent in their intended uses/indications for use, and are generally the same regarding user process, ease

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of use and general operator protocol. Comparison of technological similarities and differences between the proposed device and the predicate do not raise new or different questions of safety and effectiveness, and therefore render the proposed device as substantially equivalent to the predicate device.

Summary of Performance Data

EXPECTED VALUES

A prospective, multicenter clinical study was conducted to evaluate the clinical performance of the ePlex BCID-GP Panel in positive blood culture samples. A total of 711 samples were prospectively collected at 7 clinical sites in 2 phases from patients of all ages and genders. In the first phase from June 2014 through July 2016, 399 samples were prospectively collected and frozen; from January through February 2018, 312 samples were prospectively collected and tested fresh (never frozen). The expected values of individual analytes based on the ePlex BCID-GP Panel results in prospective samples are summarized by age group and by site in Table 1 and Table 2, respectively.

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Table 1: Expected Value by Age Group (Prospective Samples)

Target	All Ages(N=711)	Age <1(N=27)	Age 1-17(N=42)	Age 18-44(N=121)	Age 45-64(N=2500)	Age 65-84(N=217)	Age 85+(N=54)	Target	All Sites(N=711)	Site 1(N=161)	Site 2(N=58)	Site 3(N=164)	Site 4(N=145)	Site 5(N=77)	Site 6(N=33)	Site 7(N=73)
Bacillus cereus group	5 (0.7)	0 (0.0)	0 (0.0)	3 (2.5)	2 (0.8)	0 (0.0)	0 (0.0)	Bacillus cereus group	5 (0.7)	3 (1.9)	1 (1.7)	1 (0.6)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Bacillus subtilis group	2 (0.3)	0 (0.0)	0 (0.0)	1 (0.8)	0 (0.0)	0 (0.0)	1 (1.9)	Bacillus subtilis group	2 (0.3)	0 (0.0)	1 (1.7)	0 (0.0)	0 (0.0)	1 (1.3)	0 (0.0)	0 (0.0)
Corynebacterium	14 (2.0)	1 (3.7)	0 (0.0)	4 (3.3)	5 (2.0)	4 (1.8)	0 (0.0)	Corynebacterium	14 (2.0)	2 (1.2)	2 (3.4)	0 (0.0)	6 (4.1)	2 (2.6)	0 (0.0)	2 (2.7)
Cutibacterium acnes (P. acnes)	8 (1.1)	0 (0.0)	0 (0.0)	3 (2.5)	2 (0.8)	3 (1.4)	0 (0.0)	Cutibacterium acnes (P. acnes)	8 (1.1)	1 (0.6)	0 (0.0)	1 (0.6)	2 (1.4)	0 (0.0)	0 (0.0)	4 (5.5)
Enterococcus	62 (8.7)	0 (0.0)	6 (14.3)	8 (6.6)	20 (8.0)	24 (11.1)	4 (7.4)	Enterococcus	62 (8.7)	20 (12.4)	7 (12.1)	15 (9.1)	9 (6.2)	10 (13.0)	1 (3.0)	0 (0.0)
Enterococcus faecalis	50 (7.0)	0 (0.0)	6 (14.3)	6 (5.0)	15 (6.0)	20 (9.2)	3 (5.6)	Enterococcus faecalis	50 (7.0)	14 (8.7)	6 (10.3)	13 (7.9)	8 (5.5)	8 (10.4)	1 (3.0)	0 (0.0)
Enterococcus faecium	12 (1.7)	0 (0.0)	0 (0.0)	1 (0.8)	6 (2.4)	5 (2.3)	0 (0.0)	Enterococcus faecium	12 (1.7)	6 (3.7)	1 (1.7)	1 (0.6)	2 (1.4)	2 (2.6)	0 (0.0)	0 (0.0)
Lactobacillus	5 (0.7)	0 (0.0)	0 (0.0)	2 (1.7)	1 (0.4)	1 (0.5)	1 (1.9)	Lactobacillus	5 (0.7)	1 (0.6)	1 (1.7)	2 (1.2)	0 (0.0)	1 (1.3)	0 (0.0)	0 (0.0)
Listeria	1 (0.1)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.5)	0 (0.0)	Listeria	1 (0.1)	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.7)	0 (0.0)	0 (0.0)	0 (0.0)
Listeria monocytogenes	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	Listeria monocytogenes	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Micrococcus	19 (2.7)	0 (0.0)	3 (7.1)	2 (1.7)	8 (3.2)	5 (2.3)	1 (1.9)	Micrococcus	19 (2.7)	2 (1.2)	2 (3.4)	5 (3.0)	6 (4.1)	0 (0.0)	0 (0.0)	4 (5.5)
Staphylococcus	452 (63.6)	23 (85.2)	23 (54.8)	78 (64.5)	154 (61.6)	139 (64.1)	35 (64.8)	Staphylococcus	452 (63.6)	106 (65.8)	27 (46.6)	109 (66.5)	98 (67.6)	52 (67.5)	24 (72.7)	36 (49.3)
Staphylococcus aureus	162 (22.8)	8 (29.6)	4 (9.5)	37 (30.6)	69 (27.6)	38 (17.5)	6 (11.1)	Staphylococcus aureus	162 (22.8)	36 (22.4)	7 (12.1)	56 (34.1)	27 (18.6)	18 (23.4)	6 (18.2)	12 (16.4)
Staphylococcus epidermidis	182 (25.6)	10 (37.0)	11 (26.2)	26 (21.5)	54 (21.6)	62 (28.6)	19 (35.2)	Staphylococcus epidermidis	182 (25.6)	41 (25.5)	14 (24.1)	34 (20.7)	44 (30.3)	23 (29.9)	13 (39.4)	13 (17.8)
Staphylococcus lugdunensis	5 (0.7)	1 (3.7)	0 (0.0)	0 (0.0)	3 (1.2)	0 (0.0)	1 (1.9)	Staphylococcus lugdunensis	5 (0.7)	0 (0.0)	0 (0.0)	2 (1.2)	2 (1.4)	0 (0.0)	0 (0.0)	1 (1.4)
Streptococcus	110 (15.5)	5 (18.5)	9 (21.4)	16 (13.2)	40 (16.0)	31 (14.3)	9 (16.7)	Streptococcus	110 (15.5)	18 (11.2)	9 (15.5)	28 (17.1)	20 (13.8)	11 (14.3)	5 (15.2)	19 (26.0)
Streptococcus agalactiae	12 (1.7)	1 (3.7)	0 (0.0)	1 (0.8)	5 (2.0)	5 (2.3)	0 (0.0)	Streptococcus agalactiae	12 (1.7)	2 (1.2)	0 (0.0)	2 (1.2)	2 (1.4)	2 (2.6)	2 (6.1)	2 (2.7)
Streptococcus anginosus group	10 (1.4)	0 (0.0)	0 (0.0)	2 (1.7)	3 (1.2)	3 (1.4)	2 (3.7)	Streptococcus anginosus group	10 (1.4)	2 (1.2)	0 (0.0)	6 (3.7)	0 (0.0)	2 (2.6)	0 (0.0)	0 (0.0)
Streptococcus pneumoniae	28 (3.9)	2 (7.4)	2 (4.8)	3 (2.5)	12 (4.8)	8 (3.7)	1 (1.9)	Streptococcus pneumoniae	28 (3.9)	3 (1.9)	5 (8.6)	5 (3.0)	4 (2.8)	1 (1.3)	0 (0.0)	10 (13.7)
Streptococcus pyogenes	8 (1.1)	0 (0.0)	0 (0.0)	1 (0.8)	5 (2.0)	2 (0.9)	0 (0.0)	Streptococcus pyogenes	8 (1.1)	1 (0.6)	0 (0.0)	3 (1.8)	1 (0.7)	1 (1.3)	0 (0.0)	2 (2.7)
Pan Candida	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	Pan Candida	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Pan Gram-Negative	25 (3.5)	0 (0.0)	4 (9.5)	4 (3.3)	10 (4.0)	6 (2.8)	1 (1.9)	Pan Gram-Negative	25 (3.5)	9 (5.6)	4 (6.9)	3 (1.8)	2 (1.4)	5 (6.5)	1 (3.0)	1 (1.4)
mecA (Staphylococcus)	261 (36.7)	14 (51.9)	10 (23.8)	41 (33.9)	83 (33.2)	94 (43.3)	19 (35.2)	mecA (Staphylococcus)	261 (36.7)	69 (42.9)	17 (29.3)	68 (41.5)	55 (37.9)	25 (32.5)	13 (39.4)	14 (19.2)
mecA (S. aureus)	86 (12.1)	4 (14.8)	1 (2.4)	17 (14.0)	35 (14.0)	26 (12.0)	3 (5.6)	mecA (S. aureus)	86 (12.1)	19 (11.8)	5 (8.6)	28 (17.1)	19 (13.1)	7 (9.1)	3 (9.1)	5 (6.8)
mecA (S. epidermidis)	137 (19.3)	8 (29.6)	9 (21.4)	19 (15.7)	38 (15.2)	48 (22.1)	15 (27.8)	mecA (S. epidermidis)	137 (19.3)	36 (22.4)	10 (17.2)	31 (18.9)	29 (20.0)	17 (22.1)	8 (24.2)	6 (8.2)
mecA (S. lugdunensis)	1 (0.1)	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.4)	0 (0.0)	0 (0.0)	mecA (S. lugdunensis)	1 (0.1)	0 (0.0)	0 (0.0)	1 (0.6)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
mecA (CoNS excluding S.epidermidis / S. lugdunensis)	40 (5.6)	2 (7.4)	0 (0.0)	6 (5.0)	10 (4.0)	20 (9.2)	2 (3.7)	mecA (CoNS excluding S.epidermidis / S. lugdunensis)	40 (5.6)	15 (9.3)	2 (3.4)	9 (5.5)	7 (4.8)	2 (2.6)	2 (6.1)	3 (4.1)
mecC (Staphylococcus)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	mecC (Staphylococcus)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
vanA (Enterococcus)	9 (1.3)	0 (0.0)	0 (0.0)	0 (0.0)	6 (2.4)	3 (1.4)	0 (0.0)	vanA (Enterococcus)	9 (1.3)	6 (3.7)	0 (0.0)	1 (0.6)	1 (0.7)	1 (1.3)	0 (0.0)	0 (0.0)
vanA (E. faecalis)	1 (0.1)	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.4)	0 (0.0)	0 (0.0)	vanA (E. faecalis)	1 (0.1)	1 (0.6)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
vanA (E. faecium)	8 (1.1)	0 (0.0)	0 (0.0)	0 (0.0)	5 (2.0)	3 (1.4)	0 (0.0)	vanA (E. faecium)	8 (1.1)	5 (3.1)	0 (0.0)	1 (0.6)	1 (0.7)	1 (1.3)	0 (0.0)	0 (0.0)
vanB (Enterococcus)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	vanB (Enterococcus)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

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Table 2: Expected Value by Collection Site (Prospective Samples)

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PERFORMANCE CHARACTERISTICS

Clinical Performance

Samples with final, valid ePlex BCID-GP Panel test results and a valid comparator result were evaluable and included in summaries and analyses of demographics, expected values (positivity rate), and performance characteristics. Evaluable samples included 312 prospective fresh and 399 prospective frozen samples as well as 586 retrospective samples and 565 contrived samples.

Comparator Method

The performance of the ePlex BCID-GP Panel was compared to standard laboratory procedures, including traditional and automated culture, MALDI-TOF IVD, and microbiological and biochemical techniques for organism identification for samples with Corynebacterium, Staphylococcus epidermidis, Staphylococcus hominis, or Candida parapsilosis identified by standard laboratory procedures were confirmed using analytically validated PCR assays followed by bi-directional sequencing or 16S sequencing. For antibiotic resistance genes, the ePlex BCID-GP Panel was compared to analytically validated qPCR amplification assays followed by bi-directional sequencing in samples with an associated organism identified (i.e., Staphylococcus, Enterococcus).

The comparator method(s) results were used to determine the Detected / Not Detected status for each target organism on the ePlex BCID-GP Panel. The comparator methods for each target are summarized in Table 3.

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Table 3: Comparator Method(s) by ePlex BCID-GP Panel Target

Target	Comparator Method
Bacillus cereus group
Bacillus subtilis group
Cutibacterium acnes (Propionibacterium acnes)
Enterococcus
Enterococcus faecalis
Enterococcus faecium
Lactobacillus
Listeria
Listeria monocytogenes
Micrococcus	Standard laboratory procedures for organism identification.
Staphylococcus
Staphylococcus aureus
Staphylococcus lugdunensis
Streptococcus
Streptococcus agalactiae
Streptococcus anginosus group
Streptococcus pneumoniae
Streptococcus pyogenes
Pan Gram-Negative
Corynebacterium	Standard laboratory procedures for organism ID.PCR/sequencing and 16S sequencing to confirm (oridentify Coryneform) or exclude Corynebacterium speciesnot included in this panel target*
Staphylococcus epidermidis	Standard laboratory procedures for organism ID.PCR/sequencing to confirm S. epidermidis, S. hominis
Pan Candida	Standard laboratory procedures for organism ID.PCR/sequencing to confirm C. parapsilosis or identifyC. metapsilosis, C. orthopsilosis
mecA	qPCR/sequencing in samples with Staphylococcusidentified
mecC
vanA	qPCR/sequencing in samples with Enterococcus identified

The Corynebacterium assay is not designed to detect the following Corynebacterium species: C. amycolatum, C. argentoratense, C. bovis, C. durum, C. glucuronolyticum, C. macginleyi, C. propinquum, C. riegelii, and C. sundsvallense

Demographics of Clinical Samples

Clinical performance was evaluated in positive blood culture samples prospectively and retrospectively collected. Prospective samples were collected at 7 clinical sites in 2 phases. From June 2014 through July 2016, 400 samples were prospectively collected and frozen; from January through February 2018, 319 samples were prospectively collected and tested fresh (never frozen) for a total of 719 samples across the 2 phases. 8 of these samples were withdrawn;

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5 due to the sample coming from a patient already enrolled; 1 was collected outside of the required timeframe; 1 was not viable upon subculture and 1 was from an autopsy. Samples with final, valid ePlex BCID-GP Panel results and a valid comparator result were considered evaluable. Of the 711 prospectively-collected samples eligible for testing, all 711 were evaluable. Demographic information for prospectively-collected samples is described in Table 4. Subjects enrolled in this study were from a diverse demographic distribution and represent the intended patient population.

To supplement the number of positives for low prevalence targets in the prospective collection, 586 samples were collected retrospectively, and all 586 were evaluable. Demographic information for retrospectively-collected samples is described in Table 5.

	All SitesN = 711	Site 1N = 161	Site 2N = 58	Site 3N = 164	Site 4N = 145	Site 5N = 77	Site 6N = 33	Site 7N = 73
Sex
Male	377 (53.0)	93 (57.8)	28 (48.3)	91 (55.5)	66 (45.5)	42 (54.5)	17 (51.5)	40 (54.8)
Female	334 (47.0)	68 (42.2)	30 (51.7)	73 (44.5)	79 (54.5)	35 (45.5)	16 (48.5)	33 (45.2)
Age
<1 yr	27 (3.8)	3 (1.9)	0 (0.0)	8 (4.9)	10 (6.9)	4 (5.2)	2 (6.1)	0 (0.0)
1-17 yrs	42 (5.9)	8 (5.0)	2 (3.4)	11 (6.7)	10 (6.9)	7 (9.1)	2 (6.1)	2 (2.7)
18-44 yrs	121 (17)	32 (19.9)	9 (15.5)	24 (14.6)	24 (16.6)	13 (16.9)	4 (12.1)	15 (20.5)
45-64 yrs	250 (35.2)	66 (41.0)	18 (31.0)	67 (40.9)	36 (24.8)	25 (32.5)	11 (33.3)	27 (37.0)
65-84 yrs	217 (30.5)	44 (27.3)	20 (34.5)	41 (25.0)	51 (35.2)	23 (29.9)	13 (39.4)	25 (34.2)
85+ yrs	54 (7.6)	8 (5.0)	9 (15.5)	13 (7.9)	14 (9.7)	5 (6.5)	1 (3.0)	4 (5.5)

Table 4: Demographic Data for Clinical Samples by Collection Site (Prospective Collection)

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	All SitesN = 586	Site 1N = 80	Site 2N = 98	Site 3N = 51	Site 4N = 43	Site 5N = 3	Site 6N = 61	Site 7N = 85	Site 8N = 25	Site 9N = 46	Site 10N = 94
Sex
Male	317 (54.1)	39 (48.8)	59 (60.2)	24 (47.1)	20 (46.5)	1 (33.3)	36 (59.0)	45 (52.9)	17 (68.0)	28 (60.9)	48 (51.1)
Female	269 (45.9)	41 (51.3)	39 (39.8)	27 (52.9)	23 (53.5)	2 (66.7)	25 (41.0)	40 (47.1)	8 (32.0)	18 (39.1)	46 (48.9)
Age
<1 yr	11 (1.9)	1 (1.3)	2 (2)	0 (0)	3 (7)	0 (0)	1 (1.6)	0 (0)	0 (0)	1 (2.2)	3 (3.2)
1-17 yrs	17 (2.9)	6 (7.5)	1 (1)	0 (0)	4 (9.3)	0 (0)	0 (0)	0 (0)	1 (4)	1 (2.2)	4 (4.3)
18-44 yrs	104 (17.7)	14 (17.5)	13 (13.3)	5 (9.8)	9 (20.9)	0 (0)	15 (24.6)	11 (12.9)	7 (28)	5 (10.9)	25 (26.6)
45-64 yrs	193 (32.9)	25 (31.3)	33 (33.7)	17 (33.3)	15 (34.9)	1 (33.3)	21 (34.4)	30 (35.3)	10 (40)	12 (26.1)	29 (30.9)
65-84 yrs	209 (35.7)	26 (32.5)	42 (42.9)	22 (43.1)	9 (20.9)	0 (0)	20 (32.8)	35 (41.2)	7 (28)	18 (39.1)	30 (31.9)
85+ yrs	50 (8.5)	8 (10)	7 (7.1)	7 (13.7)	3 (7)	2 (66.7)	4 (6.6)	7 (8.2)	0 (0)	9 (19.6)	3 (3.2)
Unknown	2 (0.3)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	2 (2.4)	0 (0)	0 (0)	0 (0)

Table 5: Demographic Data for Clinical Samples by Collection Site (Retrospective Collection)

Clinical Performance

Sensitivity or positive percent agreement (PPA) was calculated by dividing the number of true positive (TP) results by the sum of TP and false negative (FN) results, while specificity or negative percent agreement (NPA) was calculated by dividing the number of true negative (TN) results by the sum of TN and false positive (FP) result being defined as a sample where the detected ePlex BCID-GP Panel result matched the detected comparator method result, while a TN result was one where a negative ePlex BCID-GP Panel result matched a negative comparator method result. The two-sided 95% confidence interval was also calculated.

A total of 711 prospectively-collected samples (312 tested fresh and 399 tested after previously frozen) and 586 retrospectively collected samples as well as 565 contrived samples were evaluated for the ePlex BCID-GP Panel targets. Contrived samples were prepared by spiking an isolate into a blood culture bottle and growing until flagged positive by a continuously monitoring blood culture system. Samples were removed from the system within 8 hours of positivity and stored frozen until the time of testing. PPA and NPA results are summarized by target in Tables 6-30 and the strains used to contrive samples are summarized in Table 31.

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		Sensitivity/PPA		Specificity/NPA
Target	Sample Type	TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Bacillus cereus group	Prospective (Fresh)	2/2	100 (34.2-100)	310/310	100 (98.8-100)
	Prospective (Frozen)	3/3	100 (43.9-100)	396/396	100 (99.0-100)
	Prospective (All)	5/5	100 (56.6-100)	706/706	100 (99.5-100)
	Retrospective	6/7	85.7 (48.7-97.4)	579/579	100 (99.3-100)
	Prospective/Retrospective	11/12	91.7 (64.6-98.5)	1765/1765	100 (99.8-100)
	Contrived	46/46	100 (92.3-100)	519/519	100 (99.3-100)
	Overall	57/58	98.3 (90.9-99.7)	2284/2284	100 (99.8-100)

Table 6: Clinical Performance for Bacillus cereus group

CI= Confidence Interval

Table 7: Clinical Performance for Bacillus subtilis group

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Bacillus subtilis group	Prospective (Fresh)	2/2	100 (34.2-100)	309/309	100 (98.8-100)
	Prospective (Frozen)	0/0	---	399/399	100 (99.0-100)
	Prospective (All)	2/2	100 (34.2-100)	708/708	100 (99.5-100)
	Retrospective	0/0	---	586/586	100 (99.3-100)
	Prospective/Retrospective	2/2	100 (34.2-100)	1294/1294	100 (99.7-100)
	Contrived	50/50	100 (92.9-100)	515/515	100 (99.3-100)
	Overall	52/52	100 (93.1-100)	1809/1809	100 (99.8-100)

Table 8: Clinical Performance for Corynebacterium

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Corynebacterium	Prospective (Fresh)	5/7	71.4 (35.9-91.8)	304/305	99.7 (98.2-99.9)
	Prospective (Frozen)	8/12	66.7 (39.1-86.2)	387/387	100 (99.0-100)
	Prospective (All)	13/19	68.4 (46.0-84.6)	691/692	99.9 (99.2-100)
	Retrospective	27/32	84.4 (68.2-93.1)	553/554	99.8 (99.0-100)
	Prospective/Retrospective	40/51A	78.4 (65.4-87.5)	1244/1246B	99.8 (99.4-100)
	Contrived	20/20	100 (83.9-100)	545/545	100 (99.3-100)
	Overall	60/71	84.5 (74.3-91.1)	1789/1791	99.9 (99.6-100)

A. Corynebacterium was not detected in 4 of the false negative samples using but 16S sequencing instead detected Staphylococus pettenkoferi, Macrococcus caseolyticus, Lactobacterium and Cutibacterium acnes, which were not dentified by standard laboratory procedures.

B. Corynebacterium was detected in 2/2 false positive samples using PCR/sequencing.

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Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Cutibacterium acnes	Prospective (Fresh)	4/5	80.0 (37.6-96.4)	306/307	99.7 (98.2-99.9)
	Prospective (Frozen)	2/2	100 (34.2-100)	396/397	99.7 (98.6-100)
	Prospective (All)	6/7	85.7 (48.7-97.4)	702/704	99.7 (99.0-99.9)
	Retrospective	12/13	92.3 (66.7-98.6)	573/573	100 (99.3-100)
	Prospective/Retrospective	18/20	90.0 (69.9-97.2)	1275/1277A	99.8 (99.4-100)
	Contrived	25/26	96.2 (81.1-99.3)	539/539	100 (99.3-100)
	Overall	43/46	93.5 (82.5-97.8)	1814/1816	99.9 (99.6-100)

Table 9: Clinical Performance for Cutibacterium acnes

A. Cutibacterium acnes was detected in 1/2 false positive samples using PCR/sequencing.

Table 10: Clinical Performance for Enterococcus

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Enterococcus	Prospective (Fresh)	25/25	100 (86.7-100)	287/287	100 (98.7-100)
	Prospective (Frozen)	36/36	100 (90.4-100)	362/363	99.7 (98.5-100)
	Prospective (All)	61/61	100 (94.1-100)	649/650	99.8 (99.1-100)
	Retrospective	139/147	94.6 (89.6-97.2)	439/439	100 (99.1-100)
	Prospective/Retrospective	200/208A	96.2 (92.6-98.0)	1088/1089B	99.9 (99.5-100)
	Contrived	126/126	100 (97.0-100)	439/439	100 (99.1-100)
	Overall	326/334	97.6 (95.3-98.8)	1527/1528	99.9 (99.6-100)

A. Enterococcus was not detected in 1 false negative sample, but PCR/sequencing instead detected Lactis, which was not identified by standard laboratory procedures.

B. Enterococcus was detected in 1/1 false positive samples using PCR/sequencing.

Table 11: Clinical Performance for Enterococcus faecalis

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Enterococcus faecalis	Prospective (Fresh)	21/21	100 (84.5-100)	291/291	100 (98.7-100)
	Prospective (Frozen)	28/28	100 (87.9-100)	370/370	100 (99.0-100)
	Prospective (All)	49/49	100 (92.7-100)	661/661	100 (99.4-100)
	Retrospective	82/90	91.1 (83.4-95.4)	496/496	100 (99.2-100)
	Prospective/Retrospective	131/139^	94.2 (89.1-97.1)	1157/1157	100 (99.7-100)
	Contrived	52/52	100 (93.1-100)	513/513	100 (99.3-100)
	Overall	183/191	95.8 (92.0-97.9)	1670/1670	100 (99.8-100)

A. Enterococcus faecalis was not detected in 4 false negative samples, but PCR/sequencing instead detected Enterococcus faccium (3) and Lactococcus lactis (1), which were not identified by standard laboratory procedures.

Confidential

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Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Enterococcus faecium	Prospective (Fresh)	3/3	100 (43.9-100)	309/309	100 (98.8-100)
	Prospective (Frozen)	8/9	88.9 (56.5-98.0)	388/389	99.7 (98.6-100)
	Prospective (All)	11/12	91.7 (64.6-98.5)	697/698	99.9 (99.2-100)
	Retrospective	52/53	98.1 (90.1-99.7)	526/533	98.7 (97.3-99.4)
	Prospective/Retrospective	63/65	96.9 (89.5-99.2)	1223/1231A	99.4 (98.7-99.7)
	Contrived	60/60	100 (94.0-100)	505/505	100 (99.2-100)
	Overall	123/125	98.4 (94.4-99.6)	1728/1736	99.5 (99.1-99.8)

Table 12: Clinical Performance for Enterococcus faecium

A. Enterococcus faecium was detected in 5/8 false positive samples using PCR/sequencing.

Table 13: Clinical Performance for Lactobacillus

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Lactobacillus	Prospective (Fresh)	2/2	100 (34.2-100)	309/310	99.7 (98.2-99.9)
	Prospective (Frozen)	2/2	100 (34.2-100)	397/397	100 (99.0-100)
	Prospective (All)	4/4	100 (51.0-100)	706/707	99.9 (99.2-100)
	Retrospective	9/9	100 (70.1-100)	576/577	99.8 (99.0-100)
	Prospective/Retrospective	13/13	100 (77.2-100)	1282/1284A	99.8 (99.4-100)
	Contrived	32/33	97.0 (84.7-99.5)	532/532	100 (99.3-100)
	Overall	45/46	97.8 (88.7-99.6)	1814/1816	99.9 (99.6-100)

A. Lactobacillus casei was detected in 1/2 false positive samples using PCR/sequencing.

Table 14: Clinical Performance for Listeria

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Listeria	Prospective (Fresh)	0/0	---	312/312	100 (98.8-100)
	Prospective (Frozen)	0/0	---	398/399	99.7 (98.6-100)
	Prospective (All)	0/0	---	710/711	99.9 (99.2-100)
	Retrospective	2/2	100 (34.2-100)	584/584	100 (99.3-100)
	Prospective/Retrospective	2/2	100 (34.2-100)	1294/1295	99.9 (99.6-100)
	Contrived	74/75	98.7 (92.8-99.8)	490/490	100 (99.2-100)
	Overall	76/77	98.7 (93.0-99.8)	1784/1785	99.9 (99.7-100)

{19}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Listeriamonocytogenes	Prospective (Fresh)	0/0	--	312/312	100 (98.8-100)
	Prospective (Frozen)	0/0	--	399/399	100 (99.0-100)
	Prospective (All)	0/0	--	711/711	100 (99.5-100)
	Retrospective	2/2	100 (34.2-100)	584/584	100 (99.3-100)
	Prospective/Retrospective	2/2	100 (34.2-100)	1295/1295	100 (99.7-100)
	Contrived	46/46	100 (92.3-100)	519/519	100 (99.3-100)
	Overall	48/48	100 (92.6-100)	1814/1814	100 (99.8-100)

Table 15: Clinical Performance for Listeria monocytogenes

Table 16: Clinical Performance for Micrococcus

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Micrococcus	Prospective (Fresh)	9/10	90.0 (59.6-98.2)	302/302	100 (98.7-100)
	Prospective (Frozen)	10/11	90.9 (62.3-98.4)	388/388	100 (99.0-100)
	Prospective (All)	19/21	90.5 (71.1-97.3)	690/690	100 (99.4-100)
	Retrospective	20/23	87.0 (67.9-95.5)	562/563	99.8 (99.0-100)
	Prospective/Retrospective	39/44^	88.6 (76.0-95.0)	1252/1253	99.9 (99.5-100)
	Contrived	27/27	100 (87.5-100)	538/538	100 (99.3-100)
	Overall	66/71	93.0 (84.6-97.0)	1790/1791	99.9 (99.7-100)

A. Micrococcus was not detected in 3 false negative samples, but PCR/sequencing instead detected Brevibacterium ravense, Nesterenkonia halotolerans, and Staphylococcus pettenkoferi, which were not identified by standard laboratory procedures.

Table 17: Clinical Performance for Staphylococcus

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Staphylococcus	Prospective (Fresh)	178/182	97.8 (94.5-99.1)	127/130	97.7 (93.4-99.2)
	Prospective (Frozen)	269/274	98.2 (95.8-99.2)	123/125	98.4 (94.4-99.6)
	Prospective (All)	447/456	98.0 (96.3-99.0)	250/255	98.0 (95.5-99.2)
	Retrospective	185/191	96.9 (93.3-98.6)	390/395	98.7 (97.1-99.5)
	Prospective/Retrospective	632/647A	97.7 (96.2-98.6)	640/650B	98.5 (97.2-99.2)
	Contrived	105/105	100 (96.5-100)	460/460	100 (99.2-100)
	Overall	737/752	98.0 (96.7-98.8)	1100/1110	99.1 (98.3-99.5)

A. Staphylococcus not detected in 3 false negative samples, but PCR/sequencing instead detected Escherichia coli, Klebsiella pneumoniae,

and Streptococcus salivarius, which were not identified by standard laboratory procedures.

B. Staphylococcus was detected in 9/10 false positive samples using PCR/sequencing.

{20}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Staphylococcusaureus	Prospective (Fresh)	62/65	95.4 (87.3-98.4)	244/245	99.6 (97.7-99.9)
	Prospective (Frozen)	98/101	97.0 (91.6-99.0)	222/223	99.6 (97.5-99.9)
	Prospective (All)	160/166	96.4 (92.3-98.3)	466/468	99.6 (98.5-99.9)
	Retrospective	122/125	97.6 (93.2-99.2)	454/458	99.1 (97.8-99.7)
	Prospective/Retrospective	282/291A	96.9 (94.2-98.4)	920/926B	99.4 (98.6-99.7)
	Contrived	59/59	100 (93.9-100)	506/506	100 (99.2-100)
	Overall	341/350	97.4 (95.2-98.6)	1426/1432	99.6 (99.1-99.8)

Table 18: Clinical Performance for Staphylococcus aureus

A. Staphylococus aureus was not detected in 3 false negative samples, but PCR/sequencing instead detected Klebsiella pneumoniae,

Staphylococcus simulans, and Streptococcus agalactiae, which were not identified by standard laboratory procedures.

B. Staphylococcus aureus was detected in 5/6 false positive samples using PCR/sequencing.

Table 19: Clinical Performance for Staphylococcus epidermidis

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Staphylococcusepidermidis	Prospective (Fresh)	59/63	93.7 (84.8-97.5)	223/229	97.4 (94.4-98.8)
	Prospective (Frozen)	56/58	96.6 (88.3-99.0)	258/265	97.4 (94.6-98.7)
	Prospective (All)	115/121	95.0 (89.6-97.7)	481/494	97.4 (95.6-98.5)
	Retrospective	33/38	86.8 (72.7-94.2)	539/545	98.9 (97.6-99.5)
	Prospective/Retrospective	148/159A	93.1 (88.0-96.1)	1020/1039B	98.2 (97.2-98.8)
	Contrived	1/1	100 (20.7-100)	564/564	100 (99.3-100)
	Overall	149/160	93.1 (88.1-96.1)	1584/1603	98.8 (98.2-99.2)

A. Staphylococcus epidermidis was not detected in 7 false negative samples, but PCR/sequencing instead detected Staphylococcus aureus (4). Staphylococus capitis (1), Staphylococcus pettenkoferi (1), and Escherichia coli (1), which were not identified by standard laboratory procedures.

B. Staphylococcus epidermidis was detected in 3/19 false positive samples using PCR/sequencing.

Table 20: Clinical Performance for Staphylococcus lugdunensis

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Staphylococcuslugdunensis	Prospective (Fresh)	1/1	100 (20.7-100)	290/291	99.7 (98.1-99.9)
	Prospective (Frozen)	1/1	100 (20.7-100)	321/322	99.7 (98.3-99.9)
	Prospective (All)	2/2	100 (34.2-100)	611/613	99.7 (98.8-99.9)
	Retrospective	4/4	100 (51.0-100)	579/579	100 (99.3-100)
	Prospective/Retrospective	6/6	100 (61.0-100)	1190/1192A	99.8 (99.4-100)
	Contrived	45/45	100 (92.1-100)	519/520	99.8 (98.9-100)
	Overall	51/51	100 (93.0-100)	1709/1712	99.8 (99.5-99.9)

A. Staphylococcus lugdunensis was detected in 2/2 false positive samples using PCR/sequencing.

{21}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Streptococcus	Prospective (Fresh)	54/55	98.2 (90.4-99.7)	253/257	98.4 (96.1-99.4)
	Prospective (Frozen)	49/55	89.1 (78.2-94.9)	341/344	99.1 (97.5-99.7)
	Prospective (All)	103/110	93.6 (87.4-96.9)	594/601	98.8 (97.6-99.4)
	Retrospective	171/173	98.8 (95.9-99.7)	411/413	99.5 (98.3-99.9)
	Prospective/Retrospective	274/283	96.8 (94.1-98.3)	1005/1014A	99.1 (98.3-99.5)
	Contrived	57/57	100 (93.7-100)	508/508	100 (99.2-100)
	Overall	331/340	97.4 (95.0-98.6)	1513/1522	99.4 (98.9-99.7)

Table 21: Clinical Performance for Streptococcus

A. Streptococcus was detected in 8/9 false positive samples using PCR/sequencing.

Table 22: Clinical Performance for Streptococcus agalactiae

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Streptococcusagalactiae	Prospective (Fresh)	5/6	83.3 (43.6-97.0)	298/300	99.3 (97.6-99.8)
	Prospective (Frozen)	5/5	100 (56.6-100)	374/374	100 (99.0-100)
	Prospective (All)	10/11	90.9 (62.3-98.4)	672/674	99.7 (98.9-99.9)
	Retrospective	36/37	97.3 (86.2-99.5)	548/548	100 (99.3-100)
	Prospective/Retrospective	46/48 A	95.8 (86.0-98.8)	1220/1222B	99.8 (99.4-100)
	Contrived	8/8	100 (67.6-100)	557/557	100 (99.3-100)
	Overall	54/56	96.4 (87.9-99.0)	1777/1779	99.9 (99.6-100)

A. Streptococcus agalactive was not detected in 1 false negative sample, but PCR/sequencing instead detected Streptococcus mitis, which was not identified by standard laboratory procedures.

B. Streptococcus agalactiae was detected in 1/2 false positive samples using PCR/sequencing.

Table 23: Clinical Performance for Streptococcus anginosus group

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Streptococcusanginosus group	Prospective (Fresh)	3/3	100 (43.9-100)	303/303	100 (98.7-100)
	Prospective (Frozen)	1/2	50.0 (9.5-90.5)	375/377	99.5 (98.1-99.9)
	Prospective (All)	4/5	80.0 (37.6-96.4)	678/680	99.7 (98.9-99.9)
	Retrospective	38/40	95.0 (83.5-98.6)	544/545	99.8 (99.0-100)
	Prospective/Retrospective	42/45A	93.3 (82.1-97.7)	1222/1225B	99.8 (99.3-99.9)
	Contrived	23/23	100 (85.7-100)	542/542	100 (99.3-100)
	Overall	65/68	95.6 (87.8-98.5)	1764/1767	99.8 (99.5-99.9)

A. Sireptococcus anginosus group was not detected in 3 false negative samples, instead detected Gramlicatella adiacens,

Streptococcus dysgalactiae, and Streptococcus lutetiess, which were not identified by standard laboratory procedures.

B. Streptococcus intermedius was detected in 1/3 false positive samples using PCR/sequencing.

{22}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Streptococcuspneumoniae	Prospective (Fresh)	19/19	100 (83.2-100)	286/287	99.7 (98.1-99.9)
	Prospective (Frozen)	8/9	88.9 (56.5-98.0)	370/370	100 (99.0-100)
	Prospective (All)	27/28	96.4 (82.3-99.4)	656/657	99.8 (99.1-100)
	Retrospective	39/41	95.1 (83.9-98.7)	542/543	99.8 (99.0-100)
	Prospective/Retrospective	66/69A	95.7 (88.0-98.5)	1198/1200B	99.8 (99.4-100)
	Contrived	0/0	---	565/565	100 (99.3-100)
	Overall	66/69	95.7 (88.0-98.5)	1763/1765	99.9 (99.6-100)

Table 24: Clinical Performance for Streptococcus pneumoniae

A. Streptococcus pneumoniae was not detected in 3 false negative samples, but PCR/sequencing instead detected Streptococcus milis (2) and

Streptococcus anginosus (1), which were not detected by standard laboratory procedures.

B. Streptococcus pneumoniae was detected in 1/2 false positive samples using PCR/sequencing.

Table 25: Clinical Performance for Streptococcus pyogenes

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Streptococcuspyogenes	Prospective (Fresh)	4/4	100 (51.0-100)	302/302	100 (98.7-100)
	Prospective (Frozen)	4/4	100 (51.0-100)	375/375	100 (99.0-100)
	Prospective (All)	8/8	100 (67.6-100)	677/677	100 (99.4-100)
	Retrospective	19/20	95.0 (76.4-99.1)	564/564	100 (99.3-100)
	Prospective/Retrospective	27/28	96.4 (82.3-99.4)	1241/1241	100 (99.7-100)
	Contrived	26/26	100 (87.1-100)	539/539	100 (99.3-100)
	Overall	53/54	98.1 (90.2-99.7)	1780/1780	100 (99.8-100)

{23}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
mecAStaphylococcus	Prospective (Fresh)	86/89	96.6 (90.6-98.8)	85/93	91.4 (83.9-95.6)
	Prospective (Frozen)	164/171	95.9 (91.8-98.0)	101/103	98.1 (93.2-99.5)
	Prospective (All)	250/260	96.2 (93.1-97.9)	186/196	94.9 (90.9-97.2)
	Retrospective	151/153	98.7 (95.4-99.6)	37/38	97.4 (86.5-99.5)
	Prospective/Retrospective	401/413	97.1 (95.0-98.3)	223/234^	95.3 (91.8-97.4)
	Contrived	11/11	100 (74.1-100)	94/94	100 (96.1-100)
	Overall	412/424	97.2 (95.1-98.4)	317/328	96.6 (94.1-98.1)
	Prospective (Fresh)	27/28	96.4 (82.3-99.4)	34/37	91.9 (78.7-97.2)
	Prospective (Frozen)	56/58	96.6 (88.3-99.0)	43/43	100 (91.8-100)
mecAStaphylococcusaureus	Prospective (All)	83/86	96.5 (90.2-98.8)	77/80	96.3 (89.5-98.7)
	Retrospective	107/108	99.1 (94.9-99.8)	16/17	94.1 (73.0-99.0)
	Prospective/Retrospective	190/194	97.9 (94.8-99.2)	93/97	95.9 (89.9-98.4)
	Contrived	10/10	100 (72.2-100)	49/49	100 (92.7-100)
	Overall	200/204	98.0 (95.1-99.2)	142/146	97.3 (93.2-98.9)
	Prospective (Fresh)	36/36	100 (90.4-100)	24/27	88.9 (71.9-96.1)
	Prospective (Frozen)	41/43	95.3 (84.5-98.7)	15/15	100 (79.6-100)
mecAStaphylococcusepidermidis	Prospective (All)	77/79	97.5 (91.2-99.3)	39/42	92.9 (81.0-97.5)
	Retrospective	30/30	100 (88.6-100)	43/49	87.5 (52.9-97.8)
	Prospective/Retrospective	107/109	98.2 (93.6-99.5)	46/50	92.0 (81.2-96.8)
	Contrived	1/1	100 (20.7-100)	0/0	---
	Overall	108/110	98.2 (93.6-99.5)	46/50	92.0 (81.2-96.8)
mecAStaphylococcuslugdunensis	Prospective (Fresh)	0/0	---	1/1	100 (20.7-100)
	Prospective (Frozen)	0/0	---	1/1	100 (20.7-100)
	Prospective (All)	0/0	---	2/2	100 (34.2-100)
	Retrospective	1/1	100 (20.7-100)	3/3	100 (43.9-100)
	Prospective/Retrospective	1/1	100 (20.7-100)	5/5	100 (56.6-100)
	Contrived	0/0	---	45/45	100 (92.1-100)
	Overall	1/1	100 (20.7-100)	50/50	100 (92.9-100)
Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
mecCStaphylococcus	Prospective (Fresh)	0/0	---	182/182	100 (97.9-100)
	Prospective (Frozen)	0/0	---	274/274	100 (98.6-100)
	Prospective (All)	0/0	---	456/456	100 (99.2-100)
	Retrospective	0/0	---	191/191	100 (98.0-100)
	Prospective/Retrospective	0/0	---	647/647	100 (99.4-100)
	Contrived	49/49	100 (92.7-100)	56/56	100 (93.6-100)
	Overall	49/49	100 (92.7-100)	703/703	100 (99.5-100)
mecCStaphylococcusaureus	Prospective (Fresh)	0/0	---	65/65	100 (94.4-100)
	Prospective (Frozen)	0/0	---	101/101	100 (96.3-100)
	Prospective (All)	0/0	---	166/166	100 (97.7-100)
	Retrospective	0/0	---	125/125	100 (97.0-100)
	Prospective/Retrospective	0/0	---	291/291	100 (98.7-100)
	Contrived	49/49	100 (92.7-100)	10/10	100 (72.2-100)
	Overall	49/49	100 (92.7-100)	301/301	100 (98.7-100)
mecCStaphylococcusepidermidis	Prospective (Fresh)	0/0	---	63/63	100 (94.3-100)
	Prospective (Frozen)	0/0	---	58/58	100 (93.8-100)
	Prospective (All)	0/0	---	121/121	100 (96.9-100)
	Retrospective	0/0	---	38/38	100 (90.8-100)
	Prospective/Retrospective	0/0	---	159/159	100 (97.6-100)
	Contrived	0/0	---	1/1	100 (20.7-100)
	Overall	0/0	---	160/160	100 (97.7-100)
mecCStaphylococcuslugdunensis	Prospective (Fresh)	0/0	---	1/1	100 (20.7-100)
	Prospective (Frozen)	0/0	---	1/1	100 (20.7-100)
	Prospective (All)	0/0	---	2/2	100 (34.2-100)
	Retrospective	0/0	---	4/4	100 (51.0-100)
	Prospective/Retrospective	0/0	---	6/6	100 (61.0-100)
	Contrived	0/0	---	45/45	100 (92.1-100)
	Overall	0/0	---	51/51	100 (93.0-100)

mecA was detected in 4 of the 7 false positive samples that were tested with an FDA-cleared multiplex assay. A.

{24}------------------------------------------------

Table 27: Clinical Performance for mecC

{25}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
vanAEnterococcus	Prospective (Fresh)	0/0	---	24/25	96.0 (80.5-99.3)
	Prospective (Frozen)	8/8	100 (67.6-100)	28/28	100 (87.9-100)
	Prospective (All)	8/8	100 (67.6-100)	52/53	98.1 (90.1-99.7)
	Retrospective	53/57	93.0 (83.3-97.2)	89/90	98.9 (94.0-99.8)
	Prospective/Retrospective	61/65A	93.8 (85.2-97.6)	141/143B	98.6 (95.0-99.6)
	Contrived	60/60	100 (94.0-100)	66/66	100 (94.5-100)
	Overall	121/125	96.8 (92.1-98.7)	207/209	99.0 (96.6-99.7)
	Prospective (Fresh)	0/0	---	21/21	100 (84.5-100)	Prospective (Frozen)	1/1	100 (20.7-100)	27/27	100 (87.5-100)	Prospective (All)	1/1	100 (20.7-100)	48/48	100 (92.6-100)	vanAEnterococcus faecalis	Retrospective	11/14	78.6 (52.4-92.4)	76/76	100 (95.2-100)	Prospective/Retrospective	12/15	80.0 (54.8-93.0)	124/124	100 (97.0-100)	Contrived	10/10	100 (72.2-100)	42/42	100 (91.6-100)	Overall	22/25	88.0 (70.0-95.8)	166/166	100 (97.7-100)	Prospective (Fresh)	0/0	---	2/3	66.7 (20.8-93.9)	Prospective (Frozen)	7/7	100 (64.6-100)	2/2	100 (34.2-100)	Prospective (All)	7/7	100 (64.6-100)	4/5	80.0 (37.6-96.4)	vanAEnterococcus faecium	Retrospective	44/44	100 (92.0-100)	8/9	88.9 (56.5-98.0)	Prospective/Retrospective	51/51	100 (93.0-100)	12/14	85.7 (60.1-96.0)	Contrived	50/50	100 (92.9-100)	10/10	100 (72.2-100)	Overall	101/101	100 (96.3-100)	22/24	91.7 (74.2-97.7)
	Prospective (Fresh)	0/0	---	21/21	100 (84.5-100)
	Prospective (Frozen)	1/1	100 (20.7-100)	27/27	100 (87.5-100)
	Prospective (All)	1/1	100 (20.7-100)	48/48	100 (92.6-100)
vanAEnterococcus faecalis	Retrospective	11/14	78.6 (52.4-92.4)	76/76	100 (95.2-100)
	Prospective/Retrospective	12/15	80.0 (54.8-93.0)	124/124	100 (97.0-100)
	Contrived	10/10	100 (72.2-100)	42/42	100 (91.6-100)
	Overall	22/25	88.0 (70.0-95.8)	166/166	100 (97.7-100)
	Prospective (Fresh)	0/0	---	2/3	66.7 (20.8-93.9)
	Prospective (Frozen)	7/7	100 (64.6-100)	2/2	100 (34.2-100)
	Prospective (All)	7/7	100 (64.6-100)	4/5	80.0 (37.6-96.4)
vanAEnterococcus faecium	Retrospective	44/44	100 (92.0-100)	8/9	88.9 (56.5-98.0)
	Prospective/Retrospective	51/51	100 (93.0-100)	12/14	85.7 (60.1-96.0)
	Contrived	50/50	100 (92.9-100)	10/10	100 (72.2-100)
	Overall	101/101	100 (96.3-100)	22/24	91.7 (74.2-97.7)

Table 28: Clinical Performance for vanA

A. vanA was not detected in 1 false negative sample using an FDA-cleared multiplex assay.

B. vanA was detected in the 1 false positive sample that was tested using an FDA-cleared multiplex assay.

{26}------------------------------------------------

Target	Sample Type	Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
vanBEnterococcus	Prospective (Fresh)	0/0	---	25/25	100 (86.7-100)
	Prospective (Frozen)	0/0	---	36/36	100 (90.4-100)
	Prospective (All)	0/0	---	61/61	100 (94.1-100)
	Retrospective	1/1	100 (20.7-100)	146/146	100 (97.4-100)
	Prospective/Retrospective	1/1	100 (20.7-100)	207/207	100 (98.2-100)
	Contrived	52/52	100 (93.1-100)	74/74	100 (95.1-100)
	Overall	53/53	100 (93.2-100)	281/281	100 (98.7-100)
vanBEnterococcus faecalis	Prospective (Fresh)	0/0	---	21/21	100 (84.5-100)
	Prospective (Frozen)	0/0	---	28/28	100 (87.9-100)
	Prospective (All)	0/0	---	49/49	100 (92.7-100)
	Retrospective	1/1	100 (20.7-100)	89/89	100 (95.9-100)
	Prospective/Retrospective	1/1	100 (20.7-100)	138/138	100 (97.3-100)
	Contrived	42/42	100 (91.6-100)	10/10	100 (72.2-100)
	Overall	43/43	100 (91.8-100)	148/148	100 (97.5-100)
vanBEnterococcus faecium	Prospective (Fresh)	0/0	---	3/3	100 (43.9-100)
	Prospective (Frozen)	0/0	---	9/9	100 (70.1-100)
	Prospective (All)	0/0	---	12/12	100 (75.8-100)
	Retrospective	0/0	---	53/53	100 (93.2-100)
	Prospective/Retrospective	0/0	---	65/65	100 (94.4-100)
	Contrived	10/10	100 (72.2-100)	50/50	100 (92.9-100)
	Overall	10/10	100 (72.2-100)	115/115	100 (96.8-100)

Table 29: Clinical Performance for vanB

Pan Targets

In addition to the evaluable prospective and retrospective samples that contain gram-positive organisms, the clinical performance of the Pan Candida and Pan Gram-Negative targets was evaluated by testing an additional 480 non-intended use retrospective samples with gramnegative or fungal organisms; these are denoted as Retrospective (Non-Intended Use) samples. Results from those samples are summarized in Table 30.

{27}------------------------------------------------

Target	Sample Type	TP/TP+FN	Sensitivity/PPA% (95% CI)	TN/TN+FP	Specificity/NPA% (95% CI)
Pan Candida	Prospective (Fresh)	0/0	---	312/312	100 (98.8-100)
	Prospective (Frozen)	0/0	---	399/399	100 (99.0-100)
	Prospective (All)	0/0	---	711/711	100 (99.5-100)
	Retrospective	7/9	77.8 (45.3-93.7)	576/577	99.8 (99.0-100)
	Retrospective (Non-Intended Use)	90/96	93.8 (87.0-97.1)	383/384A	99.7 (98.5-100)
	Contrived	0/0	---	565/565	100 (99.3-100)
Pan Gram-Negative	Prospective (Fresh)	10/11	90.9 (62.3-98.4)	299/301	99.3 (97.6-99.8)
	Prospective (Frozen)	12/12	100 (75.8-100)	386/387	99.7 (98.6-100)
	Prospective (All)	22/23	95.7 (79.0-99.2)	685/688B	99.6 (98.7-99.9)
	Retrospective	36/43	83.7 (70.0-91.9)	540/543C	99.4 (98.4-99.8)
	Retrospective (Non-Intended Use)	364/375	97.1 (94.8-98.4)	104/105	99.0 (94.8-99.8)
	Contrived	0/0	---	565/565	100 (99.3-100)

Table 30: Clinical Performance for Pan Targets

A. Candida glabrata was detected in 1/1 false positive samples using PCR/sequencing.

A gram-negative organism, Klebsiella pneumoniae, was detected in 1/3 false positive samples using PCR sequencing. B.

C. A gram-negative organism, Escherichia coli, was detected in 1/3 false positive samples using PCR/sequencing.

Table 31: Contrived Sample Summary

Target	Organism	Strain	Independent ContrivedSamples Tested
Bacillus cereusgroup	Bacillus cereus	ATCC 10876	11
		ATCC 21769	10
		ATCC 31430	9
		ATCC 53522	10
	Bacillus thuringiensis	ATCC 33679	1
		ATCC 10792	2
		ATCC 55173	3
	Bacillus cereus group total		46
Bacillus subtilisgroup	Bacillus amyloliquefaciens	ATCC 23350	3
		ATCC 23845	4
		ATCC 53495	3
	Bacillus atrophaeus	ATCC 51189	4
		ATCC 6455	3
		ATCC 6537	4
	Bacillus licheniformis	ATCC 21039	3
		ATCC 21667	3
		ATCC 53926	4
	Bacillus subtilis	ATCC 15040	5
		ATCC 15561	8
		ATCC 55614	6
	Bacillus subtilis group total		50
Corynebacterium	Corynebacterium coyleae	ATCC 700219	7
	Corynebacterium falsenii	ATCC BAA-596	9
	Corynebacterium striatum	ATCC BAA-1293	4
	Corynebacterium total		20
Target	Organism	Strain	Independent ContrivedSamples Tested
Enterococcus	Enterococcus faecalis, vanA	JMI 876745	10
		ATCC 51299	11
		ATCC 51575	11
	Enterococcus faecalis, vanB	ATCC 700802	10
		ATCC BAA-2365	10
		ATCC 51559	4
	Enterococcus faecium, vanA	ATCC 700221	3
		ATCC BAA-2316	5
		ATCC BAA-2317	3
		ATCC BAA-2318	5
		ATCC BAA-2319	5
		ATCC BAA-2320	3
		LMC 002867	3
		LMC 003921	4
		LMC 032261	4
		LMC 055971	3
		LMC 103676	5
		LMC 104266	3
	Enterococcus faecium, vanB	ATCC 51858	10
	Enterococcus flavescens	ATCC 49996	3
	Enterococcus gallinarum	ATCC 49610ATCC 700425	13
	Enterococcus hirae	ATCC 10541	1
	Enterococcus malodoratus	ATCC 43197	3
	Enterococcus raffinosus	ATCC 49464	2
	Enterococcus saccharolyticus	ATCC 43076	1
	Enterococcus total		126
Lactobacillus	Lactobacillus casei	ATCC 25598	2
		ATCC 334	6
		ATCC 39392	4
		148-260 *	3
	Lactobacillus paracasei	ATCC 27092	2
		ATCC BAA-52	6
		ATCC 39595	3
		ATCC 53103	5
	Lactobacillus rhamnosus	ATCC 55915	2
	Lactobacillus total		33
Listeria	Listeria innocua	ATCC 33090NCTC 11288	45
	Listeria ivanovii	ATCC 19119ATCC 700402ATCC BAA-139	244
	Listeria monocytogenes	ATCC 13932	5
		ATCC 19111	3
		ATCC 19112	4
		ATCC 19114	5
		ATCC 19116	5
		ATCC 19117	5
		ATCC 19118	5
		ATCC 7644	5
		ATCC BAA-751	5
		NCTC 10890	4
Target	Organism	Strain	Independent ContrivedSamples Tested
	Listeria seeligeri	ATCC 35967	5
	Listeria welshimeri	ATCC 35897	5
	Listeria total		75
Micrococcus	Micrococcus luteus	ATCC 10240	3
		ATCC 19212	3
		ATCC 400	3
		ATCC 4698	3
		ATCC 49732	3
		ATCC 53598	4
	Micrococcus lylae	ATCC 27566	4
	Micrococcus yunnanensis	ATCC 7468	4
	Micrococcus total		27
Cutibacteriumacnes	Cutibacterium acnes	ATCC 11827	8
		ATCC 11828	6
		ATCC 33179	4
		ATCC 6919	8
	Cutibacterium acnes total		26
Staphylococcus	Staphylococcus aureus, mecA	ATCC 33591	3
		ATCC BAA-44	5
		NCTC 12493	2
	Staphylococcus aureus, mecC	ATCC BAA-2312	23
		ATCC BAA-2313	26
	Staphylococcus epidermidis, mecA	ATCC 35984	1
		ATCC 49576	9
	Staphylococcus lugdunensis	NRS 878	9
		NRS 879	9
		NRS 880	9
		NRS 881	9
	Staphylococcus total		105
Streptococcus	Streptococcus agalactiae	ATCC 12403	2
		ATCC 12973	2
		ATCC 13813	2
		ATCC 27956	2
	Streptococcus anginosus	ATCC 700231	5
		ATCC 9895	3
		NCTC 10713	5
	Streptococcus constellatus	ATCC 27513	4
		ATCC 27823	2
	Streptococcus intermedius	ATCC 27335	4
	Streptococcus pyogenes	ATCC 12344	5
		ATCC 12384	4
		ATCC 14289	4
		ATCC 19615	4
		ATCC 49399	5
		NCIMB 13285	4

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*Derived from clinical specimen

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Genus and Group Assay Species Stratification

The ePlex BCID-GP Panel reports genus or group level results for Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Enterococcus, Lactobacillus, Listeria, Micrococcus, Staphylococcus, Streptococcus, Streptococcus anginosus group, Pan Gram-Negative and Pan Candida targets. Sensitivity/PPA of these genus and group level targets for species as determined by comparator methods for all evaluable samples tested are summarized in Table 32.

Target	Sensitivity/PPA(Prospective)		Sensitivity/PPA(Retrospective)		Sensitivity/PPA(Contrived)		Sensitivity/PPA(Combined)
Species detected byComparator Method	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)
Bacillus cereus group	5/5	100 (56.6-100)	6/7	85.7 (48.7-97.4)	46/46	100 (92.3-100)	57/58	98.3 (90.9-99.7)
Bacillus cereus	3/3	100 (43.9-100)	6/7	85.7 (48.7-97.4)	40/40	100 (91.2-100)	49/50	98.0 (89.5-99.6)
Bacillus thuringiensis	2/2	100 (34.2-100)	-	-	6/6	100 (61.0-100)	8/8	100 (67.6-100)
Bacillus subtilis group	2/2	100 (34.2-100)	-	-	50/50	100 (92.9-100)	52/52	100 (93.1-100)
Bacillus amyloliquefaciens	1/1	100 (20.7-100)	-	-	10/10	100 (72.2-100)	11/11	100 (74.1-100)
Bacillus atrophaeus	-	-	-	-	11/11	100 (74.1-100)	11/11	100 (74.1-100)
Bacillus licheniformis	-	-	-	-	10/10	100 (72.2-100)	10/10	100 (72.2-100)
Bacillus subtilis	1/1	100 (20.7-100)	-	-	19/19	100 (83.2-100)	20/20	100 (83.9-100)
Corynebacterium	13/19	68.4 (46.0-84.6)	27/32	84.4 (68.2-93.1)	20/20	100 (83.9-100)	60/71	84.5 (74.3-91.1)
Corynebacterium	4/9	44.4 (18.9-73.3)	5/7	71.4 (35.9-91.8)	-	-	9/16	56.3 (33.2-76.9)
Corynebacterium afermentans	0/1	0.0 (0.0-79.3)	3/3	100 (43.9-100)	-	-	3/4	75.0 (30.1-95.4)
Corynebacterium amycolatum	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Corynebacteriumaurimucosum	1/1	100 (20.7-100)	1/1	100 (20.7-100)	-	-	2/2	100 (34.2-100)
Corynebacterium casei	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Corynebacterium coyleae	1/1	100 (20.7-100)	2/2	100 (34.2-100)	7/7	100 (64.6-100)	10/10	100 (72.2-100)
Corynebacterium falsenii	-	-	-	-	9/9	100 (70.1-100)	9/9	100 (70.1-100)
Corynebacterium imitans	2/2	100 (34.2-100)	2/2	100 (34.2-100)	-	-	4/4	100 (51.0-100)
Corynebacterium jeikeium	-	-	4/5	80.0 (37.6-96.4)	-	-	4/5	80.0 (37.6-96.4)
Corynebacteriumkroppenstedtii	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Corynebacterium matruchotii	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Corynebacterium mucifaciens	1/1	100 (20.7-100)	2/2	100 (34.2-100)	-	-	3/3	100 (43.9-100)
Corynebacteriumpseudotuberculosis	-	-	0/1	0.0 (0.0-79.3)	-	-	0/1	0.0 (0.0-79.3)
Corynebacterium striatum	1/1	100 (20.7-100)	6/6	100 (61.0-100)	4/4	100 (51.0-100)	11/11	100 (74.1-100)
Corynebacteriumtuberculostearicum	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Corynebacterium urealyticum	-	-	0/1	0.0 (0.0-79.3)	-	-	0/1	0.0 (0.0-79.3)
TargetSpecies detected byComparator Method	Sensitivity/PPA(Prospective)		Sensitivity/PPA(Retrospective)		Sensitivity/PPA(Contrived)		Sensitivity/PPA(Combined)
	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)
Enterococcus	61/61	100 (94.1-100)	139/147	94.6 (89.6-97.2)	126/126	100 (97.0-100)	326/334	97.6 (95.3-98.8)
Enterococcus avium	1/1	100 (20.7-100)	2/3	66.7 (20.8-93.9)	-	-	3/4	75.0 (30.1-95.4)
Enterococcus casseliflavus	-	-	0/1	0.0 (0.0-79.3)	-	-	0/1	0.0 (0.0-79.3)
Enterococcus casseliflavus /gallinarum	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Enterococcus faecalis	49/49	100 (92.7-100)	85/90	94.4 (87.6-97.6)	52/52	100 (93.1-100)	186/191	97.4 (94.0-98.9)
Enterococcus faecium	12/12	100 (75.8-100)	52/53	98.1 (90.1-99.7)	60/60	100 (94.0-100)	124/125	99.2 (95.6-99.9)
Enterococcus flavescens	-	-	-	-	3/3	100 (43.9-100)	3/3	100 (43.9-100)
Enterococcus gallinarum	-	-	2/2	100 (34.2-100)	4/4	100 (51.0-100)	6/6	100 (61.0-100)
Enterococcus hirae	-	-	-	-	1/1	100 (20.7-100)	1/1	100 (20.7-100)
Enterococcus malodoratus	-	-	-	-	3/3	100 (43.9-100)	3/3	100 (43.9-100)
Enterococcus raffinosus	-	-	-	-	2/2	100 (34.2-100)	2/2	100 (34.2-100)
Enterococcus saccharolyticus	-	-	-	-	1/1	100 (20.7-100)	1/1	100 (20.7-100)
Lactobacillus	4/4	100 (51.0-100)	9/9	100 (70.1-100)	32/33	97.0 (84.7-99.5)	45/46	97.8 (88.7-99.6)
Lactobacillus casei	-	-	1/1	100 (20.7-100)	12/12	100 (75.8-100)	13/13	100 (77.2-100)
Lactobacillus paracasei	1/1	100 (20.7-100)	-	-	11/11	100 (74.1-100)	12/12	100 (75.8-100)
Lactobacillus rhamnosus	2/2	100 (34.2-100)	8/8	100 (67.6-100)	9/10	90.0 (59.6-98.2)	19/20	95.0 (76.4-99.1)
Lactobacillus zeae	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Listeria	-	-	2/2	100 (34.2-100)	74/75	98.7 (92.8-99.8)	76/77	98.7 (93.0-99.8)
Listeria innocua	-	-	-	-	9/9	100 (70.1-100)	9/9	100 (70.1-100)
Listeria ivanovii	-	-	-	-	9/10	90.0 (59.6-98.2)	9/10	90.0 (59.6-98.2)
Listeria monocytogenes	-	-	2/2	100 (34.2-100)	46/46	100 (92.3-100)	48/48	100 (92.6-100)
Listeria seeligeri	-	-	-	-	5/5	100 (56.6-100)	5/5	100 (56.6-100)
Listeria welshimeri	-	-	-	-	5/5	100 (56.6-100)	5/5	100 (56.6-100)
Micrococcus	19/21	90.5 (71.1-97.3)	20/23	87.0 (67.9-95.5)	27/27	100 (87.5-100)	66/71	93.0 (84.6-97.0)
Micrococcus	8/9	88.9 (56.5-98.0)	10/13	76.9 (49.7-91.8)	-	-	18/22	81.8 (61.5-92.7)
Micrococcus luteus	9/9	100 (70.1-100)	8/8	100 (67.6-100)	19/19	100 (83.2-100)	36/36	100 (90.4-100)
Micrococcus luteus/lylae	2/3	66.7 (20.8-93.9)	2/2	100 (34.2-100)	-	-	4/5	80.0 (37.6-96.4)
Micrococcus lylae	-	-	-	-	4/4	100 (51.0-100)	4/4	100 (51.0-100)
Micrococcus yunnanensis	-	-	-	-	4/4	100 (51.0-100)	4/4	100 (51.0-100)
Target	Sensitivity/PPA(Prospective)		Sensitivity/PPA(Retrospective)		Sensitivity/PPA(Contrived)		Sensitivity/PPA(Combined)
Species detected byComparator Method	TP/TP+FN	% (95% CI)	ТР/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	ТР/TP+FN	% (95% CI)
Staphylococcus	447/456	98.0 (96.3-99.0)	185/191	96.9 (93.3-98.6)	105/105	100 (96.5-100)	7371752	98.0 (96.7-98.8)
Coagulase-negativestaphylococci (CoNS)	18/18	100 (82.4-100)					18/18	100 (82.4-100)
CoNS (Not S. epidermidis, S.lugdunensis)	2/2	100 (34.2-100)	-		-		2/2	100 (34.2-100)
Staphylococcus	74/78	94.9 (87.5-98.0)	1/3	33.3 (6.1-79.2)	-		75/81	92.6 (84.8-96.6)
Staphylococcus aureus	158/160	98.8 (95.6-99.7)	121/123	98.4 (94.3-99.6)	રતેન્દિતે	100 (93.9-100)	338/342	98.8 (97.0-99.5)
Staphylococcus aureus subsp.aureus	6/6	100 (61.0-100)	2/2	100 (34.2-100)	-		8/8	100 (67.6-100)
Staphylococcus auricularis	2/2	100 (34.2-100)	2/2	100 (34.2-100)	-		4/4	100 (51.0-100)
Staphylococcus capitis	14/14	100 (78.5-100)	7/7	100 (64.6-100)	-		21/21	100 (84.5-100)
Staphylococcus carnosussubsp. carnosus			0/1	0.0 (0.0-79.3)	-		0/1	0.0 (0.0-79.3)
Staphylococcus cohnii	1/2	50.0 (9.5-90.5)			-		1/2	50.0 (9.5-90.5)
Staphylococcus epidermidis	117/121	96.7 (91.8-98.7)	37/38	97.4 (86.5-99.5)	1/1	100 (20.7-100)	155/160	96.9 (92.9-98.7)
Staphylococcus haemolyticus	6/6	100 (61.0-100)	2/2	100 (34.2-100)	-		8/8	100 (67.6-100)
Staphylococcus hominis	24/24	100 (86.2-100)	13/13	100 (77.2-100)	-		37/37	100 (90.6-100)
Staphylococcus hominis subsp.hominis	22/22	100 (85.1-100)	ર્ટાર	100 (56.6-100)	-		27/27	100 (87.5-100)
Staphylococcus hominis subsp.novobiosepticus	1/1	100 (20.7-100)			-		1/1	100 (20.7-100)
Staphylococcus lugdunensis	2/2	100 (34.2-100)	4/4	100 (51.0-100)	45/45	100 (92.1-100)	રી/રી	100 (93.0-100)
Staphylococcus pettenkoferi	2/2	100 (34.2-100)	-		-		2/2	100 (34.2-100)
Staphylococcussaccharolyticus	1/1	100 (20.7-100)	-		-		1/1	100 (20.7-100)
Staphylococcus saprophyticus	1/1	100 (20.7-100)	1/1	100 (20.7-100)	-		2/2	100 (34.2-100)
Staphylococcus schleiferi	-		1/1	100 (20.7-100)	-		1/1	100 (20.7-100)
Staphylococcus simulans	3/3	100 (43.9-100)	-				3/3	100 (43.9-100)
Staphylococcus warneri	4/4	100 (51.0-100)					4/4	100 (51.0-100)
Target	Sensitivity/PPA(Prospective)		Sensitivity/PPA(Retrospective)		Sensitivity/PPA(Contrived)		Sensitivity/PPA(Combined)
Species detected byComparator Method	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)
Streptococcus	103/110	93.6 (87.4-96.9)	171/173	98.8 (95.9-99.7)	57/57	100 (93.7-100)	331/340	97.4 (95.0-98.6)
Alpha HemolyticStreptococcus	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Gamma HemolyticStreptococcus	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Streptococcus	5/7	71.4 (35.9-91.8)	-	-	-	-	5/7	71.4 (35.9-91.8)
Streptococcus (Group G)	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Streptococcus agalactiae	10/11	90.9 (62.3-98.4)	37/37	100 (90.6-100)	8/8	100 (67.6-100)	55/56	98.2 (90.6-99.7)
Streptococcus anginosus	1/1	100 (20.7-100)	13/13	100 (77.2-100)	13/13	100 (77.2-100)	27/27	100 (87.5-100)
Streptococcus anginosusgroup	4/4	100 (51.0-100)	22/22	100 (85.1-100)	-	-	26/26	100 (87.1-100)
Streptococcus bovis	-	-	2/2	100 (34.2-100)	-	-	2/2	100 (34.2-100)
Streptococcus bovis group	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Streptococcus constellatus	-	-	-	-	6/6	100 (61.0-100)	6/6	100 (61.0-100)
Streptococcus constellatussubsp. constellatus	-	-	2/2	100 (34.2-100)	-	-	2/2	100 (34.2-100)
Streptococcus constellatussubsp. pharyngis	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Streptococcus dysgalactiae	-	-	2/2	100 (34.2-100)	-	-	2/2	100 (34.2-100)
Streptococcus dysgalactiae(Group G)	4/4	100 (51.0-100)	1/1	100 (20.7-100)	-	-	5/5	100 (56.6-100)
Streptococcus gallolyticus	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Streptococcus gordonii	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Streptococcus infantarius	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Streptococcus intermedius	-	-	2/2	100 (34.2-100)	4/4	100 (51.0-100)	6/6	100 (61.0-100)
Streptococcus mitis	9/10	90.0 (59.6-98.2)	14/15	93.3 (70.2-98.8)	-	-	23/25	92.0 (75.0-97.8)
Streptococcus mitis group	10/10	100 (72.2-100)	-	-	-	-	10/10	100 (72.2-100)
Streptococcus mutans	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Streptococcus oralis	-	-	3/3	100 (43.9-100)	-	-	3/3	100 (43.9-100)
Streptococcus parasanguinis	2/2	100 (34.2-100)	4/4	100 (51.0-100)	-	-	6/6	100 (61.0-100)
Streptococcus pneumoniae	28/28	100 (87.9-100)	41/41	100 (91.4-100)	-	-	69/69	100 (94.7-100)
Streptococcus pyogenes	8/8	100 (67.6-100)	19/20	95.0 (76.4-99.1)	26/26	100 (87.1-100)	53/54	98.1 (90.2-99.7)
Streptococcus salivarius	4/4	100 (51.0-100)	5/5	100 (56.6-100)	-	-	9/9	100 (70.1-100)
Streptococcus vestibularis	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Streptococcus viridans group	14/17	82.4 (59.0-93.8)	2/2	100 (34.2-100)	-	-	16/19	84.2 (62.4-94.5)
Streptococcus anginosus group	4/5	80.0 (37.6-96.4)	38/40	95.0 (83.5-98.6)	23/23	100 (85.7-100)	65/68	95.6 (87.8-98.5)
Streptococcus anginosus	0/1	0.0 (0.0-79.3)	12/13	92.3 (66.7-98.6)	13/13	100 (77.2-100)	25/27	92.6 (76.6-97.9)
Streptococcus anginosus group	4/4	100 (51.0-100)	21/22	95.5 (78.2-99.2)	-	-	25/26	96.2 (81.1-99.3)
Streptococcus constellatus	-	-	-	-	6/6	100 (61.0-100)	6/6	100 (61.0-100)
Streptococcus constellatus sppconstellatus	-	-	2/2	100 (34.2-100)	-	-	2/2	100 (34.2-100)
Streptococcus constellatus spppharynges	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Streptococcus intermedius	-	-	2/2	100 (34.2-100)	4/4	100 (51.0-100)	6/6	100 (61.0-100)
TargetSpecies detected byComparator Method	Sensitivity/PPA(Prospective)		Sensitivity/PPA(Retrospective)		Sensitivity/PPA(Contrived)		Sensitivity/PPA(Combined)
	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)	TP/TP+FN	% (95% CI)
Pan Candida	-	-	7/9	77.8 (45.3-93.7)	-	-	7/9	77.8 (45.3-93.7)
Candida albicans	-	-	4/4	100 (51.0-100)	-	-	4/4	100 (51.0-100)
Candida glabrata	-	-	1/2	50 (9.5-90.5)	-	-	1/2	50 (9.5-90.5)
Candida krusei	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Candida parapsilosis	-	-	1/2	50 (9.5-90.5)	-	-	1/2	50 (9.5-90.5)
Pan Gram-Negative	22/23	95.7 (79.0-99.2)	36/43	83.7 (70.0-91.9)	-	-	58/66	87.9 (77.9-93.7)
Acinetobacter baumannii	3/3	100 (43.9-100)	2/4	50.0 (15.0-85.0)	-	-	5/7	71.4 (35.9-91.8)
Acinetobacter lwoffii	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Aeromonas caviae	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Bacteroides fragilis	2/2	100 (34.2-100)	-	-	-	-	2/2	100 (34.2-100)
Campylobacter gracilis	0/1	0.0 (0.0-79.3)	-	-	-	-	0/1	0.0 (0.0-79.3)
Citrobacter braakii	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Citrobacter freundii	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Citrobacter koseri	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)
Enterobacter aerogenes	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Enterobacter cloacae	-	-	4/4	100 (51.0-100)	-	-	4/4	100 (51.0-100)
Escherichia coli	4/4	100 (51.0-100)	14/14	100 (78.5-100)	-	-	18/18	100 (82.4-100)
Klebsiella oxytoca	1/1	100 (20.7-100)	3/3	100 (43.9-100)	-	-	4/4	100 (51.0-100)
Klebsiella pneumoniae	4/4	100 (51.0-100)	4/5	80.0 (37.6-96.4)	-	-	8/9	88.9 (56.5-98.0)
Moraxella (Branhamella)catarrhalis	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Moraxella catarrhalis	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Morganella morganii	-	-	2/2	100 (34.2-100)	-	-	2/2	100 (34.2-100)
Pediococcus pentosaceus	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Proteus mirabilis	5/5	100 (56.6-100)	4/5	80.0 (37.6-96.4)	-	-	9/10	90.0 (59.6-98.2)
Proteus vulgaris	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Providencia stuartii	1/1	100 (20.7-100)	0/1	0.0 (0.0-79.3)	-	-	1/2	50.0 (9.5-90.5)
Pseudomonas	-	-	1/1	100 (20.7-100)	-	-	1/1	100 (20.7-100)
Pseudomonas aeruginosa	1/1	100 (20.7-100)	1/2	50.0 (9.5-90.5)	-	-	2/3	66.7 (20.8-93.9)
Serratia marcescens	2/2	100 (34.2-100)	-	-	-	-	2/2	100 (34.2-100)
Stenotrophomonas maltophilia	1/1	100 (20.7-100)	1/1	100 (20.7-100)	-	-	2/2	100 (34.2-100)
Veillonella species	-	-	0/1	0.0 (0.0-79.3)	-	-	0/1	0.0 (0.0-79.3)
Non-fermenting gram-negative bacilli	1/1	100 (20.7-100)	-	-	-	-	1/1	100 (20.7-100)

Table 32: Species Detected in Genus and Group Assays by Comparator Methods

{31}------------------------------------------------

{32}------------------------------------------------

{33}------------------------------------------------

{34}------------------------------------------------

{35}------------------------------------------------

Resistance Gene Assay Species Stratification

Test results for resistance genes are only reported when an associated organism assay is positive in the same sample. See Table 33 for organisms specifically associated with the four resistance markers on the ePlex BCID-GP Panel.

Table 33: Resistance Marker Organism Associations

Resistance GeneResult	Associated Targets
mecA and/or mecC	Any Staphylococcus assay ( Staphylococcus , S. aureus , S. epidermidis , S. lugdunensis )
vanA and/or vanB	Any Enterococcus assay ( Enterococcus , E. faecalis , E. faecium )

mecA/mecC

The PPA and NPA of the BCID-GP Panel mecA target stratified by the Staphylococcus species identified by comparator methods for prospective, retrospective and contrived samples are shown in Table 34.

Table 34: Clinical Performance of mecA Target by Staphylococcus Species Detected by

Comparator Methods

Species detected by Comparator Method		Sensitivity/PPA		Specificity/NPA
Coagulase-negativeStaphylococci (CoNS)	Prospective	12/12	100 (75.8-100)	6/6	100 (61.0-100)
	Retrospective	-	-	-	-
	Contrived	-	-	-	-
	Combined	12/12	100 (75.8-100)	6/6	100 (61.0-100)
CoNS (not S. epidermidis /S. lugdunensis)	Prospective	1/1	100 (20.7-100)	0/1	0.0 (0.0-79.3)
	Retrospective	-	-	-	-
	Contrived	-	-	-	-
	Combined	1/1	100 (20.7-100)	0/1	0.0 (0.0-79.3)
Staphylococcus	Prospective	49/52	94.2 (84.4-98.0)	24/26	92.3 (75.9-97.9)
	Retrospective	1/2	50.0 (9.5-90.5)	1/1	100 (20.7-100)
	Contrived	-	-	-	-
	Combined	50/54	92.6 (82.4-97.1)	25/27	92.6 (76.6-97.9)
Staphylococcus aureus	Prospective	80/83	96.4 (89.9-98.8)	74/77	96.1 (89.2-98.7)
	Retrospective	105/106	99.1 (94.8-99.8)	16/17	94.1 (73.0-99.0)
	Contrived	10/10	100 (72.2-100)	49/49	100 (92.7-100)
	Combined	195/199	98.0 (94.9-99.2)	139/143	97.2 (93.0-98.9)
			Sensitivity/PPA			Specificity/NPA
Species detected by Comparator Method		TP/TP+FN	% (95% CI)		TN/TN+FP	% (95% CI)
Staphylococcus aureus subsp. aureus	Prospective	3/3	100 (43.9-100)		3/3	100 (43.9-100)
	Retrospective	2/2	100 (34.2-100)		0/0	-
	Contrived	-	-		-	-
	Combined	5/5	100 (56.6-100)		3/3	100 (43.9-100)
Staphylococcus auricularis	Prospective	1/1	100 (20.7-100)		1/1	100 (20.7-100)
	Retrospective	0/0	-		2/2	100 (34.2-100)
	Contrived	-	-		-	-
	Combined	1/1	100 (20.7-100)		3/3	100 (43.9-100)
Staphylococcus capitis	Prospective	4/5	80.0 (37.6-96.4)		5/5	100 (56.6-100)
	Retrospective	4/4	100 (51.0-100)		7/7	100 (64.6-100)
	Contrived	-	-		-	-
	Combined	8/9	88.9 (56.5-98.0)		12/12	100 (75.8-100)
Staphylococcus carnosus subsp. carnosus	Prospective	-	-		-	-
	Retrospective	0/0	-		1/1	100 (20.7-100)
	Contrived	-	-		-	-
	Combined	0/0	-		1/1	100 (20.7-100)
Staphylococcus cohnii	Prospective	0/1	0.0 (0.0-79.3)		1/1	100 (20.7-100)
	Retrospective	-	-		-	-
	Contrived	-	-		-	-
	Combined	0/1	0.0 (0.0-79.3)		1/1	100 (20.7-100)
Staphylococcus epidermidis	Prospective	77/79	97.5 (91.2-99.3)		39/42	92.9 (81.0-97.5)
	Retrospective	30/30	100 (88.6-100)		7/8	87.5 (52.9-97.8)
	Contrived	1/1	100 (20.7-100)		0/0	-
	Combined	108/110	98.2 (93.6-99.5)		46/50	92.0 (81.2-96.8)
Staphylococcus haemolyticus	Prospective	4/4	100 (51.0-100)		2/2	100 (34.2-100)
	Retrospective	2/2	100 (34.2-100)		0/0	-
	Contrived	-	-		-	-
	Combined	6/6	100 (61.0-100)		2/2	100 (34.2-100)
Staphylococcus hominis	Prospective	12/13	92.3 (66.7-98.6)		10/11	90.9 (62.3-98.4)
	Retrospective	12/12	100 (75.8-100)		1/1	100 (20.7-100)
	Contrived	-	-		-	-
	Combined	24/25	96.0 (80.5-99.3)		11/12	91.7 (64.6-98.5)
Staphylococcus hominis subsp. hominis	Prospective	10/11	90.9 (62.3-98.4)		11/11	100 (74.1-100)
	Retrospective	2/2	100 (34.2-100)		3/3	100 (43.9-100)
	Contrived	-	-		-	-
	Combined	12/13	92.3 (66.7-98.6)		14/14	100 (78.5-100)
Staphylococcus hominis subsp. novobiosepticus	Prospective	1/1	100 (20.7-100)		0/0	-
	Retrospective	-	-		-	-
	Contrived	-	-		-	-
	Combined	1/1	100 (20.7-100)		0/0	-
Species detected by Comparator Method		Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Staphylococcus lugdunensis	Prospective	0/0	---	2/2	100 (34.2-100)
	Retrospective	1/1	100 (20.7-100)	3/3	100 (43.9-100)
	Contrived	0/0	---	45/45	100 (92.1-100)
	Combined	1/1	100 (20.7-100)	50/50	100 (92.9-100)
Staphylococcus pettenkoferi	Prospective	0/0	---	1/2	50.0 (9.5-90.5)
	Retrospective	-	-	-	-
	Contrived	-	-	-	-
	Combined	0/0	---	1/2	50.0 (9.5-90.5)
Staphylococcus saccharolyticus	Prospective	0/0	---	1/1	100 (20.7-100)
	Retrospective	-	-	-	-
	Contrived	-	-	-	-
	Combined	0/0	---	1/1	100 (20.7-100)
Staphylococcus saprophyticus	Prospective	1/1	100 (20.7-100)	0/0	---
	Retrospective	0/0	---	1/1	100 (20.7-100)
	Contrived	-	-	-	-
	Combined	1/1	100 (20.7-100)	1/1	100 (20.7-100)
Staphylococcus schleiferi	Prospective	-	-	-	-
	Retrospective	0/0	---	1/1	100 (20.7-100)
	Contrived	-	-	-	-
	Combined	0/0	---	1/1	100 (20.7-100)
Staphylococcus simulans	Prospective	1/1	100 (20.7-100)	2/2	100 (34.2-100)
	Retrospective	-	-	-	-
	Contrived	-	-	-	-
	Combined	1/1	100 (20.7-100)	2/2	100 (34.2-100)
Staphylococcus warneri	Prospective	0/0	---	4/4	100 (51.0-100)
	Retrospective	-	-	-	-
	Contrived	-	-	-	-
	Combined	0/0	---	4/4	100 (51.0-100)

{36}------------------------------------------------

{37}------------------------------------------------

{38}------------------------------------------------

A comparison of specific Staphylococcus species and mecA identified by comparator methods versus the ePlex BCID-GP Panel results are shown in Table 36 for prospective and retrospective samples.

Table 35: Distribution of mecA Results in Staphylococcus aureus Prospective/Retrospective Samples

	Comparator Method
BCID-GP	Org+/ARG+	Org+/ARG-	Org-	Total
Org+/ARG+	190	2	2	194
Org+/ARG-	വ	88	ব	94
Org-	2	7	1000	1009
Total	1006129719497
% Agreement (95% CI) for Org+/ARG+: 190/194=97.9 (94.8-99.2)
% Agreement (95% CI) for Org+/ARG-: 88/97=90.7 (83.3-95.0)

| % Agreement (95% CI) for Org-: 1000/1006=99.4 (98.7-99.7)

Table 36: Distribution of mecA Results in Staphylococcus Species (Excluding Known S. aureus, S. epidermidis, S. lugdunensis) Prospective/Retrospective Samples

	Comparator Method
BCID-GP	Org+/ARG+	Org+/ARG-	Org-	Total
Org+/ARG+	33	1	4	38
Org+/ARG-	3	45	8	56
Org-	10*	4	1091	1105
Total	46	50	1103	1199
% Agreement (95% CI) for Org+/ARG+: 33/46=71.7 (57.5-82.7)% Agreement (95% CI) for Org+/ARG-: 45/50=90.0 (78.6-95.7)% Agreement (95% CI) for Org-: 1091/1103=98.9 (98.1-99.4)

10 samples had a Staphylococcus species (not S. epidermidis, or S. lugdunensis) with mecA identified by comparator methods, whereas ePlex BCID-GP Panel detected S. epidermidis with mecA.

A table for mecC is not provided because mecC was only detected in a single species,

Staphylococcus aureus. In the 49 contrived samples with Staphylococcus aureus containing

mecC, the resulting PPA and NPA were both 100%.

{39}------------------------------------------------

vanA/vanB

The PPA and NPA of the BCID-GP Panel vanA target stratified by the Enterococcus species identified by comparator methods for 208 clinical prospective samples and 126 contrived samples are shown in Table 37.

A table for vanB is not provided because vanB was only detected in 53 samples comprised of two species, E. faecalis (n=43) and E. faecium (n=10), resulting in PPA and NPA of 100%.

Species detected by Comparator Method		Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Enterococcus	Prospective	0/0	---	1/1	100 (20.7-100)
	Retrospective	---	---	---	---
	Contrived	---	---	---	---
	Combined	0/0	---	1/1	100 (20.7-100)
Enterococcus avium	Prospective	0/0	---	1/1	100 (20.7-100)
	Retrospective	0/1	0.0 (0.0-79.3)	2/2	100 (34.2-100)
	Contrived	---	---	---	---
	Combined	0/1	0.0 (0.0-79.3)	3/3	100 (43.9-100)
Enterococcus casseliflavus	Prospective	---	---	---	---
	Retrospective	0/0	---	1/1	100 (20.7-100)
	Contrived	---	---	---	---
	Combined	0/0	---	1/1	100 (20.7-100)
Enterococcus casseliflavus /E. gallinarum	Prospective	---	---	---	---
	Retrospective	0/0	---	1/1	100 (20.7-100)
	Contrived	---	---	---	---
	Combined	0/0	---	1/1	100 (20.7-100)
Enterococcus faecalis	Prospective	1/1	100 (20.7-100)	48/48	100 (92.6-100)
	Retrospective	11/14	78.6 (52.4-92.4)	76/76	100 (95.2-100)
	Contrived	10/10	100 (72.2-100)	42/42	100 (91.6-100)
	Combined	22/25	88.0 (70.0-95.8)	166/166	100 (97.7-100)
Enterococcus faecium	Prospective	7/7	100 (64.6-100)	4/5	80.0 (37.6-96.4)
	Retrospective	44/44	100 (92.0-100)	8/9	88.9 (56.5-98.0)
	Contrived	50/50	100 (92.9-100)	10/10	100 (72.2-100)
	Combined	101/101	100 (96.3-100)	22/24	91.7 (74.2-97.7)
Enterococcus flavescens	Prospective	---	---	---	---
	Retrospective	---	---	---	---
	Contrived	0/0	---	3/3	100 (43.9-100)
	Combined	0/0	---	3/3	100 (43.9-100)

Table 37: Clinical Performance of vanA Target by Enterococcus Species Detected by Comparator Methods

{40}------------------------------------------------

Species detected by Comparator Method		Sensitivity/PPA		Specificity/NPA
		TP/TP+FN	% (95% CI)	TN/TN+FP	% (95% CI)
Enterococcus gallinarum	Prospective	-	-	-	-
	Retrospective	0/0	-	2/2	100 (34.2-100)
	Contrived	0/0	---	4/4	100 (51.0-100)
	Combined	0/0	-	6/6	100 (61.0-100)
Enterococcus hirae	Prospective	-	-	-	-
	Retrospective	-	-	-	-
	Contrived	0/0	---	1/1	100 (20.7-100)
	Combined	0/0	-	1/1	100 (20.7-100)
Enterococcus malodoratus	Prospective	-	-	-	-
	Retrospective	-	-	-	-
	Contrived	0/0	---	3/3	100 (43.9-100)
	Combined	0/0	-	3/3	100 (43.9-100)
Enterococcus raffinosus	Prospective	-	-	-	-
	Retrospective	-	-	-	-
	Contrived	0/0	---	2/2	100 (34.2-100)
	Combined	0/0	-	2/2	100 (34.2-100)
Enterococcus saccharolyticus	Prospective	-	-	-	-
	Retrospective	-	-	-	-
	Contrived	0/0	---	1/1	100 (20.7-100)
	Combined	0/0	-	1/1	100 (20.7-100)

{41}------------------------------------------------

A comparison of Enterococcus faecalis/Enterococcus faecium and vanA identified by comparator methods versus the ePlex BCID-GP Panel results is shown in Table 38 and Table 39 for prospective and retrospective samples.

Table 38: Distribution of vanA Results in Enterococcus faecalis Prospective/Retrospective Samples

	Comparator Method
BCID-GP	Org+/ARG+	Org+/ARG-	Org-	Total
Org+/ARG+	10	0	0	10
Org+/ARG-		120	1	122
Org-	4*	4	1157	1165
Total	15	124	1158	1297
0/ 1 - 1 - 1 - 1 / 0 - 1 / 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 -

% Agreement (95% CI) for Org+/ARG+: 10/15=66.7 (41.7-84.8)

% Agreement (95% CI) for Org+/ARG-: 120/124=96.8 (92.0-98.7)

% Agreement (95% CI) for Org-: 1157/1158=99.9 (99.5-100)

*2 of the 4 samples had E. faecium with vanA detected by the ePlex BCID-GP Panel.

Table 39: Distribution of vanA Results in Enterococcus faecium Prospective/Retrospective Samples

	Comparator Method
BCID-GP	Org+/ARG+	Org+/ARG-	Org-	Total
Org+/ARG+	51	2	3	56
Org+/ARG-	0	10	5	15
Org-	0	2	1224	1226
Total	51	14	1232	1297
% Agreement (95% CI) for Org+/ARG+: 51/51=100.0 (93.0-100)
% Agreement (95% CI) for Org+/ARG-: 10/14=71.4 (45.4-88.3)
% Agreement (95% CI) for Org-: 1224/1232=99.4 (98.7-99.7)

{42}------------------------------------------------

Co-detections in Clinical Samples

The ePlex BCID-GP Panel identified a total of 103 bacterial co-detections in 1297 clinical samples (prospective/retrospective). In the 711 prospective samples of the clinical study, 38/711 (5.3%) had double detections and 1/711 (0.1%) had a triple detection. In the 586 retrospective samples, 56/586 (9.6%) had co-detections and 8/586 (1.4%) had triple detections. Neither the prospective nor the retrospective arms of the clinical studies contained a sample with more than 3 organisms detected.

In prospective samples, the most common co-detection combination identified by the ePlex BCID-GP Panel was Enterococcus faecalis with Pan Gram-Negative which was detected in 6 samples. Pan Gram-Negative was identified in 17 co-detections, Staphylococcus was identified in 26 co-detections, Enterococcus was identified in 13 co-detections, and Streptococcus was identified in 12 co-detections.

In retrospective samples, the most common co-detection combination identified by the ePlex BCID-GP Panel was Enterococcus faecalis with Pan Gram-Negative which was detected in 9 samples, 2 of which also had vanA detected. Pan Gram-Negative was identified in 33 codetections, Staphylococcus was identified in 22 co-detections, Enterococcus was identified in 34 co-detections, and Streptococcus was identified in 24 co-detections. See Tables 40-41 below for summaries of co-detections in prospective and retrospective samples in targets as determined by the ePlex BCID-GP Panel.

Table 40: Co-Detections Identified by the ePlex BCID-GP Panel in Prospective Clinical
Samples by Target

Distinct Co-Detection Combinations Detected by the ePlex BCID-GPPanel in Prospective Clinical Samples				Number Samples(NumberDiscrepant)	DiscrepantOrganism(s) /ResistanceMarker(s)*
Target 1	Target 2	Target 3	ResistanceMarker
C. acnes	Staphylococcus			1 (1)	C. acnes (1)
Corynebacterium	S. epidermidis		mecA	2 (0)
E. faecalis	E. faecium			2 (1)	E. faecium (1)
E. faecalis	Pan GN			6 (0)
E. faecalis	S. epidermidis		mecA	1 (0)
E. faecalis	Staphylococcus			1 (0)
E. faecalis	Staphylococcus		mecA	1 (0)

{43}------------------------------------------------

Distinct Co-Detection Combinations Detected by the ePlex BCID-GPPanel in Prospective Clinical Samples				Number Samples(Number Discrepant)	DiscrepantOrganism(s) /ResistanceMarker(s)*
Target 1	Target 2	Target 3	ResistanceMarker
E. faecium	Pan GN	Staphylococcus	mecA, vanA	1 (0)
E. faecium	S. epidermidis		mecA, vanA	1 (0)
Lactobacillus	Streptococcus			1 (1)	Lactobacillus (1)
Listeria	Staphylococcus			1 (1)	Listeria (1)
Pan GN	S. anginosus group			2 (0)
Pan GN	S. aureus			1 (0)
Pan GN	S. epidermidis		mecA	2 (2)	Pan GN (1),S. epidermidis (1)
Pan GN	S. pneumoniae			1 (1)	S. pneumoniae (1)
Pan GN	Staphylococcus			2 (0)
Pan GN	Staphylococcus		mecA	1 (0)
Pan GN	Streptococcus			1 (0)
S. agalactiae	S. aureus			1 (0)
S. anginosus group	Staphylococcus			2 (2)	S. anginosus gp (1),Staphylococcus (1)
S. aureus	S. epidermidis		mecA	2 (2)	S. epidermidis (2)
S. epidermidis	S. lugdunensis			1 (1)	S. epidermidis (1),S. lugdunensis (1)
S. epidermidis	S. lugdunensis		mecA	1 (1)	S. lugdunensis (1)
S. epidermidis	Streptococcus			2 (1)	S. epidermidis (1)
Staphylococcus	Streptococcus			1 (0)
Staphylococcus	Streptococcus		mecA	1 (1)	Streptococcus (1)

A discrepant result is one that was detected by the ePlex BCID-GP Panel but not by the comparator method(s). 7/16 discrepant organisms were detected using PCR/sequencing as shown below:

-In 1/1 false positive E. faecium samples, E. faecium was detected.

-In 1/1 false positive Lactobacillus samples, Lactobacillus was detected.

-In 2/5 false positive S. epidermidis samples, S. epidermidis was detected.

-In 2/2 false positive S. lugdunensis samples, S. lugdunensis was detected.

-In 1/1 false positive Streptococcus samples, Streptococcus was detected.

Table 41: Co-Detections Identified by the ePlex BCID-GP Panel in Retrospective Clinical

Samples by Target

Distinct Co-Detection Combinations Detected by the ePlex BCID-GPPanel in Retrospective Clinical Samples				Number Samples(NumberDiscrepant)	DiscrepantOrganism(s) /Resistance Marker(s)*
Target 1	Target 2	Target 3	ResistanceMarker
Corynebacterium	S. epidermidis	S. lugdunensis	mecA	1 (1)	Corynebacterium (1)
Corynebacterium	Staphylococcus			1 (0)
Corynebacterium	Staphylococcus		mecA	1 (0)
E. faecalis	E. faecium			4 (3)	E. faecium (3)
E. faecalis	E. faecium		vanA	3 (1)	E. faecium (1)
Distinct Co-Detection Combinations Detected by the ePlex BCID-GPPanel in Retrospective Clinical Samples				Number Samples(NumberDiscrepant)	DiscrepantOrganism(s) /Resistance Marker(s)*
Target 1	Target 2	Target 3	ResistanceMarker
E. faecalis	Pan Candida			1 (0)
E. faecalis	Pan GN			6 (0)
E. faecalis	Pan GN		vanA	2 (0)
E. faecalis	Pan GN	S. aureus		1 (0)
E. faecalis	S. aureus		mecA	1 (0)
E. faecalis	Staphylococcus		vanA	1 (1)	Staphylococcus (1)
E. faecium	Lactobacillus	Pan GN	vanA	1 (1)	Lactobacillus (1)
E. faecium	Pan Candida		vanA	1 (1)	E. faecium (1)
E. faecium	Pan Candida	S. epidermidis	mecA, vanA	1 (1)	S. epidermidis (1)
E. faecium	Pan GN			3 (0)
E. faecium	Pan GN		vanA	5 (0)
E. faecium	Pan GN	Staphylococcus	mecA, vanA	1 (0)
E. faecium	S. aureus		mecA, vanA	1 (0)
E. faecium	Streptococcus		vanA	1 (1)	Streptococcus (1)
Enterococcus	S. anginosus group			1 (0)
Lactobacillus	S. anginosus group			1 (0)
Micrococcus	S. pyogenes			1 (1)	Micrococcus (1)
Pan Candida	S. epidermidis		mecA	2 (0)
Pan Candida	S. pneumoniae			1 (0)
Pan GN	S. agalactiae			2 (1)	Pan GN (1)
Pan GN	S. anginosus group			4 (0)
Pan GN	S. anginosus group	S. aureus		1 (1)	Pan GN (1)
Pan GN	S. aureus			1 (0)
Pan GN	S. aureus	S. epidermidis	mecA	1 (1)	S. epidermidis (1)
Pan GN	S. pneumoniae			2 (0)
Pan GN	Streptococcus			3 (0)
S. agalactiae	S. aureus			2 (0)
S. agalactiae	S. aureus		mecA	1 (0)
S. agalactiae	S. aureus	S. epidermidis	mecA	1 (1)	S. epidermidis (1)
S. aureus	S. epidermidis		mecA	1 (0)
S. aureus	Streptococcus		mecA	2 (1)	Streptococcus (1)
S. epidermidis	Streptococcus		mecA	1 (0)

{44}------------------------------------------------

A discrepant result is one that was detected by the ePlex BCID-GP Panel but not by the comparator method(s). 6/16 discrepant organisms were detected using PCR/sequencing as shown below:

-In 1/1 false positive Corynebacterium samples, Corynebacterium was detected.

-In 2/5 false positive E. faecium samples, E. faecium was detected.

-In 1/1 false positive Staphylococcus samples, Staphylococcus was detected.

-In 2/2 false positive Streptococcus samples, Streptococcus was detected.

{45}------------------------------------------------

Additional co-detection combinations identified by comparator method(s) are summarized in

Table 42 and Table 43 for prospective and retrospective samples, respectively.

Table 42: Additional Co-Detections Identified by Comparator Method(s) in Prospective
Clinical Samples by Organism

Distinct Co-Detection Combinations Detected by theComparator Methods in Prospective Clinical Samples					NumberSamples(NumberDiscrepant)	DiscrepantOrganism(s)/ResistanceMarkers(s)*
Organism 1	Organism 2	Organism 3	Organism 4	ResistanceMarker
A. baumannii	E. faecium	Staphylococcus		mecA, vanA	1 (0)
A. baumannii	S. aureus				1 (0)
A. baumannii	Staphylococcus			mecA	1 (0)
Acinetobacter lwoffii	Staphylococcushominis			mecA	1 (0)
Aerococcus viridansA	K. oxytoca	S. epidermidis	Staphylococcuscohnii	mecA	1 (1)	S. cohnii (1),S. epidermidis (1),mecA (1)
Aerococcus viridansA	Staphylococcushominis				1 (0)
B. fragilis	ClostridiumspeciesA				1 (0)
B. fragilis	S. anginosus gp				1 (0)
C. acnes	S. epidermidis				1 (1)	S. epidermidis (1)
C. acnes	S. lugdunensis				1 (1)	C. acnes (1)
Citrobacter freundii	K. pneumoniae	Staphylococcushominis		mecA	1 (1)	mecA (1)
Citrobacter koseri	E. faecalis				1 (0)
Corynebacterium	S. epidermidis	Streptococcus		mecA	1 (1)	Streptococcus (1)
Corynebacterium	Streptococcus				1 (1)	Corynebacterium (1)
E. coli	E. faecalis	P. mirabilis			1 (0)
E. coli	LactococcuslactisA				1 (0)
E. coli	P. mirabilis	Providenciastuartii	S. anginosus gp		1 (0)
E. faecalis	E. faecium				1 (1)	E. faecium (1)
E. faecalis	K. pneumoniae				2 (0)
E. faecalis	P. mirabilis				1 (0)
E. faecalis	S. aureus			mecA	1 (1)	S. aureus (1),mecA (1)
E. faecalis	S. marcescens				1 (0)
E. faecalis	Staphylococcus(CoNS)			mecA	1 (0)
E. faecium	S. epidermidis	Staphylococcushaemolyticus		mecA, vanA	1 (0)
K. pneumoniae	Staphylococcushaemolyticus	non-fermentingGN bacilli			1 (0)
P. aeruginosa	P. mirabilis	Streptococcus -viridans group			1 (0)
P. mirabilis	Staphylococcus			mecA	1 (1)	Staphylococcus (1),mecA (1)
PeptostreptococcusspeciesA	Staphylococcus				1 (0)

{46}------------------------------------------------

Distinct Co-Detection Combinations Detected by theComparator Methods in Prospective Clinical Samples					NumberSamples(NumberDiscrepant)	DiscrepantOrganism(s)/ResistanceMarkers(s)*
Organism 1	Organism 2	Organism 3	Organism 4	ResistanceMarker
Rothia(stomatococcus)mucilaginosusA	S. epidermidis				1 (0)
Rothia mucilaginosaA	Streptococcus -viridans group				1 (0)
S. agalactiae	S. aureus	Staphylococcus		mecA	1 (1)	S. aureus (1),Staphylococcus (1),mecA (1)
S. anginosus	Streptococcusmitis				1 (1)	S. anginosus (1)
S. epidermidis	Staphylococcuscapitis			mecA	1 (0)
S. epidermidis	Staphylococcushominis				2 (0)
S. epidermidis	Staphylococcushominis			mecA	4 (1)	S. epidermidis (1)
S. epidermidis	Staphylococcushominis	Staphylococcuswarneri			1 (0)
S. epidermidis	Streptococcus -viridans group				1 (1)	S. epidermidis (1)
S. epidermidis	Streptococcusparasanguinis				1 (0)
S. maltophilia	Streptococcus				1 (1)	Streptococcus (1)
S. marcescens	Streptococcusmitis group	Streptococcussalivarius			1 (0)
Staphylococcus cohnii	Streptococcus -viridans group				1 (1)	S. viridans group (1)
Staphylococcushominis	Staphylococcuspettenkoferi				1 (0)
Staphylococcushominis	Streptococcusmitis			mecA	1 (1)	mecA (1)

A discrepant result is one that was detected by the comparator method(s) but not by the ePlex BCID-GP Panel (excludes organisms not targeted by the ePlex BCID-GP Panel). 16 discrepant organisms were investigated using PCR/sequencing; 1 discrepant organism was not detected:

-In 1/1 false negative S. anginosus group sample, PCR/Sequencing instead detected Streptococcus dysgalactiae.

A. Off-panel organisms not targeted by the ePlex BCID-GP Panel.

Table 43: Additional Co-Detections Identified by Comparator Method(s) in Retrospective

Clinical Samples by Organism

Distinct Co-Detection Combinations Detected by theComparator Methods in Retrospective Clinical Samples					NumberSamples(NumberDiscrepant)	DiscrepantOrganism(s)/ResistanceMarkers(s)*
Organism 1	Organism 2	Organism 3	Organism 4	ResistanceMarker
A. baumannii	E. faecalis			vanA	2 (2)	A. baumannii (2)
A. baumannii	E. faecalis	S. aureus		mecA	1 (1)	mecA (1)
A. baumannii	E. faecium			vanA	1 (0)
AerococcussanguinicolaA	Corynebacterium	Staphylococcussaprophyticus			1 (0)
Distinct Co-Detection Combinations Detected by theComparator Methods in Retrospective Clinical Samples					NumberSamples(NumberDiscrepant)	DiscrepantOrganism(s)/ResistanceMarkers(s)*
Organism 1	Organism 2	Organism 3	Organism 4	ResistanceMarker	(NumberDiscrepant)	ResistanceMarkers(s)*
Aeromonas caviae	E. coli	Enterococcuscasseliflavus	K. oxytoca		1 (1)	E. casseliflavus(1)
C. acnes	Enterococcusavium			vanA	1 (1)	E. avium (1),vanA (1)
C. albicans	E. faecalis			vanA	1 (1)	E. faecalis (1)
C. albicans	E. faecium	Staphylococcushominis		mecA, vanA	1 (0)
C. albicans	S. epidermidis			mecA	1 (0)
C. glabrata	Lactobacillusrhamnosus				1 (1)	C. glabrata (1)
C. glabrata	S. pneumoniae				1 (0)
C. krusei	S. epidermidis			mecA	1 (0)
C. parapsilosis	E. faecalis				1 (0)
C. parapsilosis	E. faecalis			vanA	1 (1)	C. parapsilosis(1)
Citrobacter braakii	Streptococcusoralis				1 (0)
E. cloacae	E. faecalis				1 (0)
E. cloacae	E. faecium			vanA	1 (0)
E. cloacae	E. faecium	Staphylococcushominis		mecA, vanA	1 (0)
E. cloacae	S. anginosus gp				1 (0)
E. coli	E. faecalis				3 (0)
E. coli	E. faecalis	K. pneumoniae			1 (0)
E. coli	E. faecalis	P. mirabilis			1 (0)
E. coli	E. faecium				2 (0)
E. coli	K. oxytoca	Streptococcusinfantarius			1 (0)
E. coli	S. agalactiae				1 (0)
E. coli	S. anginosus gp				1 (0)
E. coli	S. aureus			mecA	1 (0)
E. coli	S. pneumoniae				1 (0)
E. coli	Streptococcusbovis				1 (0)
E. faecalis	K. pneumoniae			vanA	1 (1)	E. faecalis (1),K. pneumoniae(1)
E. faecalis	M. morganii			vanA	1 (0)
E. faecalis	M. morganii	Proteus vulgaris		vanA	1 (1)	E. faecalis (1),vanA (1)
E. faecalis	P. aeruginosa	S. aureus		mecA	1 (1)	E. faecalis (1),P. aeruginosa (1)
E. faecalis	P. mirabilis				2 (2)	E. faecalis (1),P. mirabilis (1)
E. faecalis	P. mirabilis			vanA	1 (1)	E. faecalis (1),vanA (1)
E. faecalis	Providenciastuartii				1 (1)	P. stuartii (1)
E. faecalis	S. maltophilia			vanA	1 (0)
Distinct Co-Detection Combinations Detected by theComparator Methods in Retrospective Clinical Samples	NumberSamples(NumberDiscrepant)	DiscrepantOrganism(s)/ResistanceMarkers(s)*
Organism 1	Organism 2	Organism 3	Organism 4	ResistanceMarker
E. faecium	Moraxella(Branhamella)catarrhalis	Pediococcuspentosaceus		vanA	1 (0)
E. faecium	P. aeruginosa			vanA	1 (0)
E. faecium	P. mirabilis			vanA	1 (0)
E. faecium	Pseudomonas			vanA	1 (0)
E. faecium	S. epidermidis	Staphylococcushominis		mecA	1 (1)	E. faecium (1)
Enterobacteraerogenes	S. anginosus gp				1 (0)
Enterococcus avium	S. anginosus gp				1 (0)
K. oxytoca	S. anginosus gp				1 (0)
K. pneumoniae	S. aureus				2 (1)	S. aureus (1)
L. monocytogenes	Staphylococcus			mecA	1 (1)	Staphylococcus(1), mecA (1)
Lactobacillus casei	Veillonellaspecies				1 (1)	Veillonellaspecies (1)
Lactobacillusrhamnosus	PediococcusacidilacticiA				1 (0)
Lactobacillusrhamnosus	S. anginosus gp	Staphylococcus	Streptococcus -viridans group		1 (1)	Staphylococcus(1)
Micrococcus	PseudoclavibacterA				1 (0)
Moraxella catarrhalis	S. pneumoniae				1 (0)
S. agalactiae	S. aureus				1 (1)	S. aureus (1)
S. agalactiae	S. aureus	Streptococcus -viridans group			1 (0)
S. aureus	S. epidermidis				1 (1)	S. aureus (1)
S. aureus	S. pyogenes			mecA	1 (1)	S. pyogenes (1)
S. aureus	Staphylococcuscapitis				1 (0)
S. aureus	Streptococcusmitis			mecA	1 (0)
S. epidermidis	Staphylococcushominis				1 (0)
S. epidermidis	Staphylococcushominis			mecA	3 (0)
S. epidermidis	Staphylococcushominis	Streptococcusparasanguinis		mecA	1 (0)
Staphylococcus capitis	Staphylococcushominis			mecA	1 (0)

{47}------------------------------------------------

{48}------------------------------------------------

A discrepant result is one that was detected by the comparator method(s) but not by the ePlex BCID-GP Panel (excludes organisms not targeted by the ePlex BCID-GP Panel). 24 discrepant organisms were investigated using PCR/sequencing; 2 discrepant organisms were not detected:

-In 2/6 false negative E. faecalis samples, PCR/Sequencing instead detected Enterococcus faecium.

A. Off-panel organisms not targeted by the ePlex BCID-GP Panel.

{49}------------------------------------------------

Clinical Study ePlex Instrument Performance

A total of 2354 samples (including prospective, retrospective, and contrived samples) were initially tested in the clinical evaluations. Of these, 24/2354 (1.0%) did not complete the run and the sample was retested. After repeat testing, all 2354 samples completed testing and 2246/2354 (95.4%, 95% CI: 94.5%-96.2%) generated valid results and 108/2354 (4.6%, 95% CI: 3.8%-5.5%) generated invalid results on the first completed attempt.

Upon repeat testing of the 108 samples with initially invalid results, 3/108 (2.8%) did not complete the run and the sample was retested. After repeat testing, all 108 samples completed testing and 106/108 (98.1%) generated valid results. Overall, after final testing, 2/2354 (0.1%, 95% CI: 0.0%-0.3%) had final, invalid results, resulting in a final validity rate of 2352/2354 (99.9%, 95% CI: 99.7%-100%).

ANALYTICAL PERFORMANCE CHARACTERISTICS

Limit of Detection (Analytical Sensitivity)

The limit of detection (LoD), or analytical sensitivity, was identified and verified for each assay on the BCID-GP Panel using at least two quantified reference strains in simulated blood culture sample matrix, which is defined as a whole blood with EDTA added to a blood culture bottle in the same ratio as the manufacturer recommends and incubated for 8 hours. At least 20 replicates per target were tested for each condition. The limit of detection was defined as the lowest concentration of each target that is detected in ≥95% of tested replicates. The confirmed LoD for each ePlex BCID-GP Panel organism is shown in Table 44.

{50}------------------------------------------------

Table 44: LoD Results Summary

Target	Organism	Strain	LoD Concentration(CFU/mL)
B. cereus group	Bacillus cereus	ATCC 21769	1 x 105
B. cereus group	Bacillus thuringiensis	ATCC 35646	1 x 105
B. subtilis group	Bacillus subtilis	ATCC 55614	1 x 106
B. subtilis group	Bacillus atrophaeus	ATCC 51189	1 x 106
Corynebacterium	Corynebacterium striatum	ATCC 43735	1 x 106
Corynebacterium	Corynebacterium jeikeium	ATCC 43217	1 x 107
Cutibacterium acnes (P. acnes)	Cutibacterium acnes (P. acnes)	ATCC 33179	1 x 107
Cutibacterium acnes (P. acnes)	Cutibacterium acnes (P. acnes)	ATCC 6919	1 x 108
Enterococcus	Enterococcus faecium	ATCC BAA-2316	1 x 105
Enterococcus	Enterococcus faecium	ATCC BAA-2317	1 x 106
Enterococcus	Enterococcus raffinosus	ATCC 49464	1 x 106
Enterococcus faecium	Enterococcus faecium	ATCC BAA-2316	1 x 105
Enterococcus faecium	Enterococcus faecium	ATCC BAA-2317	1 x 106
Enterococcus faecalis	Enterococcus faecalis	ATCC 51575	1 x 106
Enterococcus faecalis	Enterococcus faecalis	ATCC 700802	1 x 106
Lactobacillus	Lactobacillus paracasei	ATCC 25598	1 x 105
Lactobacillus	Lactobacillus casei	ATCC 334	1 x 105
Listeria	Listeria seeligeri	ATCC 35967	1 x 105
Listeria	Listeria monocytogenes	ATCC 10890	1 x 105
Listeria monocytogenes	Listeria monocytogenes	ATCC 19111	1 x 106
Listeria monocytogenes	Listeria monocytogenes	ATCC 10890	1 x 105
Listeria monocytogenes	Listeria monocytogenes	ATCC 19111	1 x 105
Micrococcus	Micrococcus luteus	ATCC 19212	1 x 106
Micrococcus	Micrococcus luteus	ATCC 10240	1 x 107
Staphylococcus	Staphylococcus aureus	ATCC BAA-2313	1 x 104
Staphylococcus	Staphylococcus aureus	ATCC BAA-2312	1 x 105
Staphylococcus	Staphylococcus epidermidis	ATCC 35983	1 x 105
Staphylococcus	Staphylococcus epidermidis	ATCC 35984	1 x 105
Staphylococcus	Staphylococcus lugdunensis	NRS 879	1 x 105
Staphylococcus	Staphylococcus lugdunensis	ATCC 49576	1 x 106
Staphylococcus	Staphylococcus haemolyticus	NRS 62	1 x 107
Staphylococcus aureus	Staphylococcus aureus	ATCC BAA-2313	1 x 105
Staphylococcus aureus	Staphylococcus aureus	ATCC BAA-2312	1 x 105
Staphylococcus epidermidis	Staphylococcus epidermidis	ATCC 35983	1 x 105
Staphylococcus epidermidis	Staphylococcus epidermidis	ATCC 35984	1 x 105
Staphylococcus lugdunensis	Staphylococcus lugdunensis	NRS 879	1 x 105
	Staphylococcus lugdunensis	ATCC 49576	1 x 105
Streptococcus	Streptococcus pneumoniae	ATCC BAA-475	1 x 105
Streptococcus	Streptococcus pneumoniae	ATCC 10357	1 x 105
Streptococcus	Streptococcus gordonii	ATCC 10558	1 x 106
Streptococcus	Streptococcus agalactiae	ATCC 12401	1 x 106
Streptococcus	Streptococcus agalactiae	ATCC 13813	1 x 107
Target	Organism	Strain	LoD Concentration(CFU/mL)
Streptococus agalactiae	Streptococus agalactiae	ATCC 12401	1 x 105
Streptococus agalactiae	Streptococus agalactiae	ATCC 13813	1 x 106
Streptococcus anginosus group	Streptococus intermedius	ATCC 27335	1 x 104
Streptococcus anginosus group	Streptococus anginosus	ATCC 9895	1 x 106
Streptococus pneumoniae	Streptococus pneumoniae	ATCC BAA-475	1 x 105
Streptococus pneumoniae	Streptococus pneumoniae	ATCC 10357	1 x 105
Streptococus pyogenes	Streptococus pyogenes	ATCC 12384	1 x 105
Streptococus pyogenes	Streptococus pyogenes	ATCC 49399	1 x 105
Pan Gram-Negative	Stenotrophomonas maltophilia	ATCC 13636	1 x 106
Pan Gram-Negative	Enterobacter cloacae	ATCC 13047	1 x 106
Pan Gram-Negative	Escherichia coli	ATCC 4157	1 x 106
Pan Gram-Negative	Klebsiella pneumoniae	ATCC BAA-1706	1 x 106
Pan Gram-Negative	Serratia marcescens	ATCC 8100	1 x 106
Pan Gram-Negative	Proteus mirabilis	ATCC 43071	1 x 106
Pan Gram-Negative	Acinetobacter baumannii	NCTC13302	1 x 107
Pan Gram-Negative	Neisseria meningitidis	ATCC 13113	1 x 107
Pan Gram-Negative	Pseudomonas aeruginosa	ATCC 15442	1 x 107
Pan Candida	Candida albicans	ATCC 24433	1 x 106
Pan Candida	Candida glabrata	ATCC 66032	1 x 106
mecA	Staphylococcus epidermidis	ATCC 35983	1 x 105
mecA	Staphylococcus epidermidis	ATCC 35984	1 x 105
mecC	Staphylococcus aureus	ATCC BAA-2313	1 x 104
mecC	Staphylococcus aureus	ATCC BAA-2312	1 x 104
vanA	Enterococcus faecium	ATCC BAA-2316	1 x 104
vanA	Enterococcus faecium	ATCC BAA-2317	1 x 105
vanB	Enterococcus faecalis	ATCC 51575	1 x 105
vanB	Enterococcus faecalis	ATCC 700802	1 x 105

{51}------------------------------------------------

Analytical Reactivity (Inclusivity)

A panel of 459 strains/isolates representing the genetic, temporal and geographic diversity of each target on the ePlex BCID-GP Panel was evaluated to demonstrate analytical reactivity. Each bacterial strain was tested in triplicate at 1 x 10° CFU/mL or less and each fungal strain was tested at 1 x 106 CFU/mL. In the cases where the initial testing concentration did not result in a "Detected" result, the concentration was increased to the point where detection was observed (see footnotes for concentrations of these strains). Organisms detected are shown in Table 45. Additional strains were detected as a part of the Limit of Detection (Analytical Sensitivity) study and can be found in Table 44.

{52}------------------------------------------------

	Table 45: Analytical Reactivity (Inclusivity) Results

Organism	Strain
Bacillus cereus	ATCC 21769
Bacillus cereus	ATCC 10876
Bacillus cereus	ATCC 31430
Bacillus cereus	ATCC 53522
Bacillus cereus	ATCC 35646
Bacillus cereus	ATCC 33679
Bacillus thuringiensis	ATCC 55173
Bacillus thuringiensis	ATCC 10792
Bacillus subtilis
Bacillus amyloliquefaciens	ATCC 23845
Bacillus amyloliquefaciens	ATCC 23842
Bacillus amyloliquefaciens	ATCC 23350
Bacillus amyloliquefaciens	ATCC 53495
Bacillus amyloliquefaciens	ATCC 51189
Bacillus atrophaeus	ATCC 6455
Bacillus atrophaeus	ATCC 49337
Bacillus atrophaeus	ATCC 7972
Bacillus atrophaeus	ATCC 6537
Bacillus licheniformis	ATCC 53926
Bacillus licheniformis	ATCC 55768
Bacillus licheniformis	ATCC 21039
Bacillus licheniformis	ATCC 21667
Bacillus licheniformis	ATCC 55614
Bacillus licheniformis	ATCC 15561
Bacillus subtilis	ATCC 21008
Bacillus subtilis	ATCC 15040
Corynebacterium
Corynebacterium afermentans subsp. afermentans	ATCC 51403A
Corynebacterium afermentans subsp. lipophilum	ATCC 51404
Corynebacterium confusum	ATCC 38268A
Corynebacterium coyleae	ATCC 700219
Corynebacterium diphtheriae	ATCC 13812
Corynebacterium falsenii	ATCC BAA-596A
Corynebacterium freneyi	ATCC 64424B
Corynebacterium imitans	ATCC 700354B
Corynebacterium jeikeium	ATCC 43217
Corynebacterium jeikeium	ATCC 43216
Corynebacterium jeikeium	ATCC 43734
Corynebacterium jeikeium	ATCC BAA-949
Corynebacterium minutissimum	ATCC 23348
Corynebacterium resistens	CCUG 50093T
Corynebacterium simulans	ATCC BAA-15
Corynebacterium simulans	ATCC BAA-1293
Corynebacterium striatum	ATCC 43735
Organism	Strain
Staphylococcus lentus	ATCC 700403
Staphylococcus lugdunensis	NRS-879
Staphylococcus lugdunensis	ATCC 49576
Staphylococcus lugdunensis	NRS-878
Staphylococcus lugdunensis	NRS-880
Staphylococcus muscae	ATCC 49910
Staphylococcus pasteuri	ATCC 51129
Staphylococcus pasteuri (mecC+)	ATCC 51128
Staphylococcus pettenkoferi	DSM-19554
Staphylococcus pseudintermedius	ATCC 49444
Staphylococcus saccharolyticus	ATCC 14953
Staphylococcus saprophyticus	ATCC 15305
Staphylococcus saprophyticus	ATCC 35552
Staphylococcus schleiferi	ATCC 49545
Staphylococcus schleiferi	ATCC 43808
Staphylococcus sciuri	ATCC 29060
Staphylococcus sciuri	ATCC 29061
Staphylococcus sciuri	ATCC 29059
Staphylococcus sciuri	ATCC 49575
Staphylococcus sciuri	ATCC 29062
Staphylococcus simulans	ATCC 27848
Staphylococcus simulans	ATCC 27850
Staphylococcus simulans	ATCC 31432
Staphylococcus simulans	ATCC 27851
Staphylococcus species	ATCC 155
Staphylococcus species (mecA+)	ATCC 27626
Staphylococcus vitulinus	ATCC 51699
Staphylococcus vitulinus	ATCC 51161
Staphylococcus warneri	ATCC 27836
Staphylococcus xylosus	ATCC 49148
Staphylococcus xylosus	ATCC 29971
Staphylococcus aureus	ATCC 25923
Staphylococcus aureus	ATCC 29247
Staphylococcus aureus	ATCC 6538P
Staphylococcus aureus	ATCC 29213
Staphylococcus aureus	NR-45889
Staphylococcus aureus	NR-45890
Staphylococcus aureus	NR-46074
Staphylococcus aureus	NR-45881
Staphylococcus aureus	NR-46411
Staphylococcus aureus	NR-46414
Staphylococcus aureus	NR-46418
Staphylococcus aureus	NR-46417
Staphylococcus aureus	NR-13524

{53}------------------------------------------------

Organism	Strain
Corynebacterium timonense	CCUG 64728A
Corynebacterium ulcerans	ATCC 51799
Corynebacterium urealyticum	ATCC 43044
Corynebacterium urealyticum	ATCC 43042
Corynebacterium urealyticum	ATCC 43043
Corynebacteriumureicelerivorans	CCUG 59144
Cutibacterium acnes	ATCC 11827
Cutibacterium acnes	ATCC 11828
Cutibacterium acnes	ATCC 33179
Cutibacterium acnes	ATCC 6919
Enterococcus
Enterococcus avium	ATCC 14025
Enterococcus casseliflavus	ATCC 700668
Enterococcus casseliflavus	ATCC 25788
Enterococcus casseliflavus	ATCC 700327
Enterococcus cecorum	ATCC 43198
Enterococcus dispar	ATCC 51266
Enterococcus durans	ATCC 11576
Enterococcus durans	ATCC 51575
Enterococcus durans	ATCC 700802
Enterococcus durans	ATCC 10100
Enterococcus durans	ATCC 12399
Enterococcus faecalis	ATCC 14506
Enterococcus faecalis	ATCC 33186
Enterococcus faecalis	ATCC 49532
Enterococcus faecalis	ATCC 49533
Enterococcus faecalis	ATCC 7080
Enterococcus faecalis	ATCC 49474
Enterococcus faecalis	ATCC 49332
Enterococcus faecalis	ATCC 29200
Enterococcus faecalis	ATCC BAA-2128
Enterococcus faecalis	ATCC 51188
Enterococcus faecalis	ATCC 49149
Enterococcus faecalis	NCTC-775
Enterococcus faecalis	ATCC 19433
Enterococcus faecalis	ATCC 49452
Enterococcus faecalis (vanA+)	JMI 876745
Enterococcus faecalis (vanB+)	ATCC BAA-2365
Enterococcus faecalis (vanB+)	ATCC 51299
Enterococcus faecium	ATCC 19434
Enterococcus faecium	ATCC 23828
Enterococcus faecium	ATCC 27273
Enterococcus faecium	ATCC BAA-2127
Enterococcus faecium	ATCC 6057
Enterococcus faecium	ATCC 49624
Enterococcus faecium	ATCC 6569
Enterococcus faecium	ATCC BAA-472
Organism	Strain
	NR-13525
	NR-13526
	NRS-123
	NR-46805
	NRS-662
	ATCC BAA-1707
	ATCC 43300
	NRS-383
	NCTC-12493
	NRS-676
	NRS-678
	NRS-648
	NRS-651
	NRS-643
	NRS-484
	NRS-385
	NRS-384
	ATCC BAA-40
	ATCC 700698
	NRS-382
	NRS-659
	NRS-657
	NRS-655
	NRS-654
	NRS-647
	ATCC BAA-42
	ATCC BAA-41
	NRS-483
	NRS-675
	NRS-645
	NRS-687
	NRS-667
	NRS-677
	NRS-683
	NRS-688
	NRS-22
	NRS-387
	NRS-70
Staphylococcus aureus(mecA+)	ATCC 33591
Staphylococcus aureus(mecC+)	ATCC BAA-2312
	ATCC BAA-2313
Staphylococcus epidermidis	ATCC 12228
	ATCC 49134
Staphylococcus epidermidis	NCIMB-8853
	ATCC 700583
	ATCC 14990
Staphylococcus epidermidis(mecA+)	ATCC 35983
	ATCC 35984

{54}------------------------------------------------

Organism	Strain
Enterococcus faecium (vanA+)	ATCC 49224
	ATCC BAA-2846
	ATCC 19953
	ATCC 27270
	ATCC 35667
	ATCC BAA-2316
	ATCC BAA-2317
	ATCC 700221
	ATCC BAA-2319
	ATCC BAA-2320
	LMC 003921
	LMC 103676
Enterococcus faecium (vanA+)	LMC 089524
	LMC 104266
	LMC 032261
	LMC 110371
	LMC 002867
	LMC 055971
	ATCC 51559
	ATCC BAA-2318
Enterococcus faecium (vanB+)	ATCC 51858
	ATCC 49573
	ATCC 49609
Enterococcus gallinarum	ATCC 49610
	ATCC 700425
	ATCC 49608
Enterococcus hirae	ATCC 49479
	ATCC 10541
Enterococcus italicus	CCUG 47860
Enterococcus malodoratus	ATCC 43197
Enterococcus pseudoavium	CCUG 33310T
Enterococcus raffinosus	ATCC 49464
Enterococcus saccharolyticus	ATCC 43076
Enterococcus sanguinicola	DSM-21767
Enterococcus faecalis
	ATCC 51575
	ATCC 700802
Enterococcus faecalis	ATCC 10100
	ATCC 12399
	ATCC 14506
	ATCC 33186
	ATCC 49532
Enterococcus faecalis	ATCC 49533
	ATCC 7080
	ATCC 49474
	ATCC 49332
Enterococcus faecalis	ATCC 29200
	ATCC BAA-2128
	ATCC 51188
Organism	Strain
	ATCC 29887
	ATCC 49461
	ATCC 700565
	ATCC 51625
Staphylococcus lugdunensis
	NRS-879
Staphylococcus lugdunensis	ATCC 49576
	NRS-878
	NRS-880
Streptococcus	ATCC 12401
	ATCC 13813
	ATCC 12386
Streptococcus agalactiae	ATCC 12973
	ATCC 27956
	NCTC-8017
	ATCC 12403
	ATCC 9895
Streptococcus anginosus	ATCC 33397
	NCTC-10713
Streptococcus bovis	ATCC 33317
	ATCC 35034
Streptococcus constellatus	ATCC 27513
Streptococcus criceti	ATCC 19642c
	ATCC 35666
Streptococcus dysgalactiae	ATCC 43078
	ATCC 12394
Streptococcus equi	ATCC 43079
	ATCC 9528
	ATCC 15351
Streptococcus equinus	ATCC 9812
	ATCC 49475
Streptococcus gallolyticus	ATCC 9809
	ATCC 43144
Streptococcus gordonii	ATCC 10558
	ATCC 35557
	ATCC BAA-102
Streptococcus infantarius	ATCC BAA-103
	ATCC BAA-2089
Streptococcus infantis	ATCC 700779
Streptococcus intermedius	ATCC 27335
Streptococcus mitis	ATCC 15914
	ATCC 6249
	ATCC 49456
Streptococcus mitis	NCIMB-13770
Streptococcus oralis	ATCC 35037
Streptococcus oralis	ATCC 55229
Streptococcus parasanguinis	ATCC 15909
Streptococcus peroris	ATCC 700780

Confidential

Page 51

{55}------------------------------------------------

Organism	Strain
Enterococcus faecalis	ATCC 49149
	NCTC-775
	ATCC 19433
	ATCC 49452
Enterococcus faecalis (vanA+)	JMI 876745
Enterococcus faecalis (vanB+)	ATCC BAA-2365
Enterococcus faecium	ATCC 51299
Enterococcus faecium	ATCC 19434
	ATCC 23828
	ATCC 27273
	ATCC BAA-2127
	ATCC 6057
	ATCC 49624
	ATCC 6569
	ATCC BAA-472
	ATCC 9756
	ATCC 49224
Enterococcus faecium	ATCC BAA-2846
	ATCC 19953
	ATCC 27270
	ATCC 35667
Enterococcus faecium (vanA+)	ATCC BAA-2316
Enterococcus faecium (vanA+)	ATCC BAA-2317
Enterococcus faecium (vanA+)	ATCC 700221
	ATCC BAA-2319
	ATCC BAA-2320
	LMC 003921
	LMC 103676
	LMC 089524
	LMC 104266
	LMC 032261
Enterococcus faecium (vanA+)	LMC 110371
	LMC 002867
	LMC 055971
	ATCC 51559
Enterococcus faecium (vanA+)	ATCC BAA-2318
Enterococcus faecium (vanB+)	ATCC 51858
Lactobacillus casei	ATCC 334
Organism	Strain
Streptococcus pneumoniae	ATCC BAA-475
	ATCC 10357
	ATCC 49619
	ATCC 49136
	ATCC BAA-659
	ATCC 6315
	ATCC BAA-1667
	ATCC 700674
	ATCC 6321
	ATCC 700673
	ATCC 51916
	ATCC 8338
	ATCC 6301
	ATCC 8335
	NCIMB-13286
Streptococcus pyogenes	ATCC BAA-1656
	ATCC 12384
	ATCC 49399
	ATCC 12344
	ATCC 19615
	NCIMB-13285
	ATCC 14289

Streptococcus salivarius	ATCC 13419c
	ATCC 7073
Streptococcus salivarius	ATCC 25975
	ATCC 31067c
Streptococcus sanguinis	ATCC 10556
Streptococcus thoraltensis	ATCC 700865
Streptococcus agalactiae	ATCC 12401
	ATCC 13813
	ATCC 12386
	ATCC 12973
	ATCC 27956
	NCTC-8017
	ATCC 12403
Streptococcus anginosus group
Streptococcus anginosus	ATCC 9895
	ATCC 33397NCTC-10713
Streptococcus constellatus	ATCC 27513

{56}------------------------------------------------

Organism	Strain
Lactobacillus paracasei	ATCC 39392
	ATCC 25598
	ATCC BAA-52
	ATCC 27092
Lactobacillus rhamnosus	ATCC 39595
	ATCC 53103
	ATCC 55915
Lactobacillus zeae	ATCC 15820
Listeria
Listeria innocua	NCTC-11288
	ATCC 33090
Listeria ivanovii	ATCC 19119
	ATCC BAA-139
	ATCC 700402
Listeria monocytogenes	ATCC 10890
	ATCC 19111
	ATCC 13932
	ATCC 19114
	ATCC 7644
	ATCC 19112
	ATCC BAA-751
	ATCC 19118
Listeria seeligeri	ATCC 19115
Listeria welshimeri	ATCC 35967
Listeria monocytogenes	ATCC 35897
Listeria monocytogenes	ATCC 10890
Listeria monocytogenes	ATCC 19111
Listeria monocytogenes	ATCC 13932
Listeria monocytogenes	ATCC 19114
Listeria monocytogenes	ATCC 7644
Listeria monocytogenes	ATCC 19112
Listeria monocytogenes	ATCC BAA-751
Listeria monocytogenes	ATCC 19118
Listeria monocytogenes	ATCC 19115
Micrococcus
	ATCC 19212
	ATCC 10240
Micrococcus luteus	ATCC 400
	ATCC 53598
	ATCC 49732
	ATCC 4698
Micrococcus lylae	ATCC 27566
Micrococcus yunnanensis	ATCC 7468
Staphylococcus

Staphylococcus arlettae	ATCC 43957
Staphylococcus aureus	ATCC 25923
	ATCC 29247
Organism	Strain
Streptococcus intermedius	ATCC 27335
Streptococcus pneumoniae	ATCC BAA-475
Streptococcus pneumoniae	ATCC 10357
	ATCC 49619
	ATCC 49136
	ATCC BAA-659
	ATCC 6315
	ATCC BAA-1667
	ATCC 700674
	ATCC 6321
	ATCC 700673
	ATCC 51916
	ATCC 8338
	ATCC 6301
	ATCC 8335
	NCIMB-13286
Streptococcus pyogenes	ATCC BAA-1656
	ATCC 12384
	ATCC 49399
	ATCC 12344
Streptococcus pyogenes	ATCC 19615
	NCIMB-13285
	ATCC 14289
Pan Candida	ATCC 24433
	ATCC MYA-4441
Candida albicans	ATCC 14053
Candida albicans	ATCC 90028
	ATCC 66032
	ATCC 15126
Candida glabrata	ATCC MYA-2950
	ATCC 2001
Candida krusei	ATCC 34135
	ATCC 32196
	ATCC 14243
	ATCC 90018D
Candida parapsilosis	ATCC 58895
	ATCC 22019
Pan Gram-Negative
Acinetobacter baumannii	NCTC-13302
	NCTC-13422
Acinetobacter haemolyticus	ATCC 19002
Acinetobacter junii	ATCC 17908
Acinetobacter lwoffii	ATCC 15309
Acinetobacter ursingii	ATCC BAA-617
Bacteroides fragilis	NCTC-9343

{57}------------------------------------------------

Organism	Strain	Organism	Strain
	ATCC 6538P	Burkholderia cepacia	ATCC 25416
	ATCC 29213	Cedecea davisiae	ATCC 43025
	NR-45889	Citrobacter freundii	NCTC-9750
	NR-45890	Citrobacter koseri	ATCC 27156
	NR-46074	Cronobacter muytjensii	ATCC 51329
	NR-45881	Cronobacter sakazakii	ATCC 12868
	NR-46411	Edwardsiella tarda	ATCC 15947
	NR-46414	Enterobacter aerogenes	ATCC 13048
	NR-46418	Enterobacter amnigenus	ATCC 51816
	NR-46417	Enterobacter asburiae	ATCC 35953
	NR-13524		ATCC 13047
	NR-13527		ATCC 23373
	NR-13525	Enterobacter cloacae	ATCC 23355
	NR-13526		ATCC 35030
	NRS-123	Enterobacter hormaechei	ATCC 700322
	NR-46805	Erwinia aphidicola	ATCC 27991
Staphylococcus aureus (mecA+)	NRS-662		ATCC 4157
	ATCC BAA-1707		ATCC 14948
	ATCC 43300	Escherichia coli	ATCC 25922
	NRS-383		ATCC BAA-
	NCTC-12493	Escherichia fergusonii	ATCC 35469
	NRS-676	Escherichia hermannii	ATCC 700368
	NRS-678	Escherichia vulneris	ATCC 33821
	NRS-648	Fusobacterium necrophorum	ATCC 25286
	NRS-651	Fusobacterium nucleatum	ATCC 25586
	NRS-643	Haemophilus influenzae	ATCC 10211
	NRS-484		ATCC 49144
	NRS-385		ATCC 43065
Staphylococcus aureus (mecA+)	NRS-384	Haemophilus influenzae	NCTC-8468
	ATCC BAA-40	Haemophilus parainfluenzae	ATCC 9796
	ATCC 700698	Hafnia alvei	ATCC 51815
	NRS-382		ATCC 700324
	NRS-659	Klebsiella oxytoca	ATCC 43165
	NRS-657		ATCC 43863
	NRS-655	Klebsiella ozaenae	ATCC 11296
	NRS-654		ATCC BAA-
	NRS-647		NCTC-9633
Staphylococcus aureus (mecA+)	ATCC BAA-42	Klebsiella pneumoniae	NCTC-13440
	ATCC BAA-41		ATCC 51503
	NRS-483	Kluyvera ascorbata	ATCC 14236
	NRS-675	Kluyvera cryocrescens	ATCC 14240

{58}------------------------------------------------

Organism	Strain
	NRS-645
	NRS-687
	NRS-667
	NRS-677
	NRS-683
	NRS-688
	NRS-22
	NRS-387
	NRS-70
	ATCC 33591
Staphylococcus aureus (mecC+)	ATCC BAA-2312
	ATCC BAA-2313
Staphylococcus auricularis	ATCC 33750
	ATCC 33753
Staphylococcus capitis	ATCC 27840
	NRS-866
	ATCC 35661
Staphylococcus caprae	ATCC 51548
Staphylococcus carnosus	ATCC 51365
Staphylococcus chromogenes	ATCC 43764
Staphylococcus cohnii	ATCC 29974
	ATCC 12228
	ATCC 49134
Staphylococcus epidermidis	NCIMB-8853
	ATCC 700583
	ATCC 14990
	ATCC 35983
	ATCC 35984
	ATCC 29887
Staphylococcus epidermidis(mecA+)	ATCC 49461
	ATCC 700565
	ATCC 51625
Staphylococcus gallinarum	ATCC 700401
	ATCC 35539
Staphylococcus haemolyticus	ATCC 29970
	ATCC 31874
Staphylococcus haemolyticus(mecA+)	NRS-62
	ATCC BAA-1693
	NRS-69
Organism	Strain
Legionella pneumophila	ATCC 33823
Moraxella catarrhalis	ATCC 23246
Moraxella nonliquefaciens	ATCC 17953
Moraxella osloensis	ATCC 10973
Morganella morganii	ATCC 25829
Neisseria lactamica	ATCC 23970
Neisseria meningitidis	ATCC 13090
	ATCC 13113
	ATCC 13077
	ATCC 13102
Neisseria mucosa	ATCC 19695
Neisseria sicca	ATCC 29193
Pantoea agglomerans	ATCC 14537
Pasteurella aerogenes	ATCC 27883
Proteus mirabilis	ATCC 43071
	CDC#0155
	CDC#0159
Proteus penneri	ATCC 35197
Proteus vulgaris	ATCC 6380
Providencia alcalifaciens	ATCC 9886
Providencia rettgeri	ATCC 9919
Providencia stuartii	ATCC 33672
Pseudomonas aeruginosa	ATCC 15442
	NCIMB-12469
	ATCC 10145
Pseudomonas fluorescens	ATCC 13525
Pseudomonas luteola	ATCC 35970
Pseudomonas putida	ATCC 31483
Raoultella terrigena	ATCC 55553
Salmonella bongori	ATCC 43975
Salmonella enterica subsp. enterica	ATCC 51957
Salmonella enterica Choleraesuis	ATCC 12011
Salmonella enterica Paratyphi	FSL S5-0447
Salmonella typhi	ATCC 19430
Serratia fonticola	ATCC 29844
Serratia liquefaciens	ATCC 27592
Serratia marcescens	ATCC 8100
	ATCC 14756
	ATCC 13880
Serratia odorifera	ATCC 33077

Page 55

{59}------------------------------------------------

Organism	Strain
	NRS-870
	ATCC 27844
Staphylococcus hominis(mecA+)	ATCC 700237
	ATCC 700236
Staphylococcus hyicus	ATCC 11249
Staphylococcus intermedius	ATCC 29663
	ATCC 49052

Organism	Strain
Serratia rubidaea	ATCC 27593
Shigella boydii	ATCC 9207
Shigella dysenteriae	ATCC 13313
Shigella sonnei	ATCC 29930
Stenotrophomonas maltophilia	ATCC 13636
Tatumella ptyseos	ATCC 33302
Yersinia enterocolitica subsp.Enterocolitica	ATCC 9610

^A Detected at 2 x 10^6 CFU/mL

^ Detected at 2 x 10°CFU/mL
B Detected at 2 x 10°CFU/mL
C Detected at 2 x 10°CFU/mL
C Detected at 2 x 10°CFU/mL

Detected at 4 x 10⁶ CFU/mL
Detected at 1 x 10⁷ CFU/L

C Detected at 4 x 108 CFU/mL

り Detected at 1 x 107 CFU/mL

{60}------------------------------------------------

Predicted (in silico) Reactivity for Genus and Group Assays

Note: the performance of the ePlex BCID-GP Panel has not been established for all of the organisms listed in the tables below. See the Analytical Reactivity (Inclusivity) and Limit of Detection (Analytical Sensitivity) sections for data on organisms for which performance characteristics have been established (indicated with an asterisk in Tables 46-57). Some species were not assessed in silico due to lack of sequence data, though they may appear in the analytical sensitivity or specificity studies.

In addition to species-specific assays, the ePlex BCID-GP Panel contains a number of broader genus or group-level assays; including Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Enterococcus, Lactobacillus, Listeria, Micrococcus, Staphylococcus, Streptococcus, Streptococcus anginosus group, Pan Candida and Pan Gram-Negative assays. Tables 46-57 summarize the predicted (in silico) reactivity (inclusivity) for these assay targets.

Detection Predicted for ≥95% of target sequences
Bacillus thuringiensis*	Bacillus toyonensis	Bacillus weihenstephanensis
Detection Predicted for 85%-94% of target sequences
Bacillus cereus*
Detection Predicted for <85% of target sequences
None Identified
Detection Not Predicted
Bacillus mycoides*	Bacillus pseudomycoides

Table 46: Predicted (in silico) Reactivity (Inclusivity) Results for Bacillus cereus group

			Table 47 Predicted (in silico) Reactivity (Inclusivity) Results for Bacillus subtilis group

Detection Predicted for ≥95% of target sequences
Bacillus subtilis*	Bacillus licheniformis*	Bacillus siamensis
Bacillus amyloliquefaciens*	Bacillus methylotrophicus /Bacillus velezensis	Bacillus tequilensis
Bacillus atrophaeus*	Bacillus paralicheniformis	Bacillus vallismortis
Detection Predicted for 85%-94% of target sequences
None Identified
Detection Predicted for <85% of target sequences
Bacillus mojavensis (77.8%)	Bacillus sonorensis (83.3%)
Detection Not Predicted
None Identified

Confidential

{61}------------------------------------------------

Table 48: Predicted (in silico) Reactivity (Inclusivity) Results for Corynebacterium

Detection Predicted for ≥95% of target sequences
Corynebacterium afermentans	Corynebacterium glaucum	Corynebacterium renale
Corynebacterium afermentanssubsp. afermentans*	Corynebacterium halotolerans	Corynebacterium simulans*
Corynebacterium afermentanssubsp. lipophilium*	Corynebacterium hansenii	Corynebacterium singulare
Corynebacterium appendicis	Corynebacterium humireducens	Corynebacterium sputi
Corynebacterium auris	Corynebacterium imitans*	Corynebacterium striatum*
Corynebacterium auriscanis	Corynebacterium lipophiloflavum	Corynebacterium suicordis
Corynebacterium camporealensis	Corynebacterium lowii	Corynebacterium terpenotabidum
Corynebacterium casei	Corynebacterium marinum	Corynebacterium testudinoris
Corynebacterium ciconiae	Corynebacterium massiliense	Corynebacterium timonense*
Corynebacterium coyleae*	Corynebacterium minutissimum*	Corynebacterium tuscaniense
Corynebacterium doosanense	Corynebacterium mucifaciens	Corynebacterium ulceribovis
Corynebacterium falsenii*	Corynebacterium mycetoides	Corynebacterium urealyticum*
Corynebacterium felinum	Corynebacterium nuruki	Corynebacterium ureicelerivorans*
Corynebacterium freneyi*	Corynebacterium oculi	Corynebacterium xerosis
Corynebacterium genitalium	Corynebacterium pilosum
Detection Predicted for 85%-94% of target sequences
None Identified
Detection Predicted for <85% of target sequences
Corynebacterium aurimucosum(50.0%)	Corynebacterium jeikeium(38.7%)*A	Corynebacterium variabile(75.0%)
Corynebacterium diphtheriae(76.4%)*	Corynebacterium ulcerans(47.4%)*A	Corynebacterium vitaeruminis(75.0%)
Detection Not Predicted
Corynebacterium accolens	Corynebacterium epidermidicanis	Corynebacterium propinquum
Corynebacterium ammoniagenes	Corynebacterium flavescens	Corynebacterium pseudodiphtheriticum
Corynebacterium amycolatum	Corynebacterium frankenforstense	Corynebacterium pseudogenitalium
Corynebacterium aquilae	Corynebacterium freiburgense	Corynebacterium pseudotuberculosis
Corynebacterium argentoratense	Corynebacterium glucuronolyticum	Corynebacterium pyruviciproducens
Corynebacterium atypicum	Corynebacterium glutamicum	Corynebacterium resistens
Corynebacterium bovis	Corynebacterium glyciniphilum	Corynebacterium riegelii
Corynebacterium callunae	Corynebacterium kroppenstedtii	Corynebacterium sphenisci
Corynebacterium capitovis	Corynebacterium kutscheri	Corynebacterium spheniscorum
Corynebacterium caspium	Corynebacterium lactis	Corynebacterium stationis
Corynebacterium confusum	Corynebacterium lubricantis	Corynebacterium sundsvallense
Corynebacterium crenatum	Corynebacterium maris	Corynebacterium thomssenii
Corynebacterium cystitidis	Corynebacterium mastitidis	Corynebacterium tuberculostearicum
Corynebacterium deserti	Corynebacterium matruchotii	Corynebacterium uropygiale
Corynebacterium durum	Corynebacterium mustelae	Corynebacterium uterequi
Corynebacterium efficiens	Corynebacterium phocae

{62}------------------------------------------------

A. 38.7% of sequences in NCBI for C. jeikeium were predicted to be detected bioinformatically; 47.4% of sequences in NCBI for C. ulcerans were predicted to be detected bioinformatically. All strains tested for these species were detected as a part of the Analytical Reactivity (Inclusivity) or Limit of Detection (Analytical Sensitivity) studies.

Table 49: Predicted (in silico) Reactivity (Inclusivity) Results for Enterococcus

Detection Predicted for ≥95% of target sequences
Enterococcus avium*	Enterococcus flavescens	Enterococcus raffinosus
Enterococcus dispar*	Enterococcus italicus*	Enterococcus saccharolyticus*
Enterococcus durans	Enterococcus lactis	Enterococcus thailandicus
Enterococcus faecalis*	Enterococcus malodoratus
Enterococcus faecium*	Enterococcus pseudoavium
Detection Predicted for 85%-94% of target sequences
Enterococcus casseliflavus	Enterococcus gallinarum
Enterococcus cecorum	Enterococcus hirae*
Detection Predicted for <85% of target sequences
Enterococcus mundtii (9.1%)
Detection Not Predicted
Enterococcus aquimarinus	Enterococcus hawaiiensis	Enterococcus rotai
Enterococcus asini	Enterococcus hermanniensis	Enterococcus silesiacus
Enterococcus caccae	Enterococcus pallens	Enterococcus sulfureus
Enterococcus camelliae	Enterococcus pernyi	Enterococcus termitis
Enterococcus canintestini	Enterococcus phoeniculicola	Enterococcus ureasiticus
Enterococcus canis	Enterococcus plantarum	Enterococcus ureilyticus
Enterococcus columbae	Enterococcus quebecensis	Enterococcus villorum
Enterococcus devriesei	Enterococcus ratti
Enterococcus haemoperoxidus	Enterococcus rivorum

{63}------------------------------------------------

Detection Predicted for ≥95% of target sequences
Lactobacillus casei*	Lactobacillus rhamnosus*
Lactobacillus paracasei*	Lactobacillus zeae*
Detection Predicted for 85%-94% of target sequences
	None Identified
	Detection Predicted for <85% of target sequences
	None Identified
	Detection Not Predicted
Lactobacillus acetotolerans	Lactobacillus ghanensis	Lactobacillus panis
Lactobacillus acidifarinae	Lactobacillus gigeriorum	Lactobacillus pantheris
Lactobacillus acidipiscis	Lactobacillusginsenosidimutans	Lactobacillus parabrevis
Lactobacillus acidophilus	Lactobacillus gorillae	Lactobacillus parabuchneri
Lactobacillus agilis	Lactobacillus graminis	Lactobacillus paracollinoides
Lactobacillus algidus	Lactobacillus hammesii	Lactobacillus parafarraginis
Lactobacillus alimentarius	Lactobacillus hamsteri	Lactobacillus parakefiri
Lactobacillus amylolyticus	Lactobacillus harbinensis	Lactobacillus paralimentarius
Lactobacillus amylophilus	Lactobacillus hayakitensis	Lactobacillus paraplantarum
Lactobacillus amylotrophicus	Lactobacillus heilongjiangensis	Lactobacillus pasteurii
Lactobacillus amylovorus	Lactobacillus helsingborgensis	Lactobacillus paucivorans
Lactobacillus animalis	Lactobacillus helveticus	Lactobacillus pentosus
Lactobacillus antri	Lactobacillus herbarum	Lactobacillus perolens
Lactobacillus apinorum	Lactobacillus hilgardii	Lactobacillus plantarum
Lactobacillus apis	Lactobacillus hokkaidonensis	Lactobacillus pobuzihii
Lactobacillus apodemi	Lactobacillus hominis	Lactobacillus pontis
Lactobacillus aquaticus	Lactobacillus homohiochii	Lactobacillus psittaci
Lactobacillus aviarius	Lactobacillus hordei	Lactobacillus rapi
Lactobacillus backii	Lactobacillus iners	Lactobacillus rennini
Lactobacillus bifermentans	Lactobacillus ingluviei	Lactobacillus reuteri
Lactobacillus bombi	Lactobacillus intestinalis	Lactobacillus rodentium
Lactobacillus bombicola	Lactobacillus jensenii	Lactobacillus rossiae
Lactobacillus brantae	Lactobacillus johnsonii	Lactobacillus ruminis
Lactobacillus brevis	Lactobacillus kalixensis	Lactobacillus saerimneri
Lactobacillus buchneri	Lactobacillus kefiranofaciens	Lactobacillus sakei
Lactobacillus cacaonum	Lactobacillus kefiri	Lactobacillus salivarius
Lactobacillus camelliae	Lactobacillus kimbladii	Lactobacillus sanfranciscensis
Lactobacillus capillatus	Lactobacillus kimchicus	Lactobacillus saniviri
Lactobacillus ceti	Lactobacillus kimchiensis	Lactobacillus satsumensis

Lactobacillus coleohominis	Lactobacillus kisonensis	Lactobacillus secaliphilus
Lactobacillus collinoides	Lactobacillus kitasatonis	Lactobacillus selangorensis
Lactobacillus composti	Lactobacillus koreensis	Lactobacillus senioris
Lactobacillus concavus	Lactobacillus kullabergensis	Lactobacillus senmaizukei
Lactobacillus coryniformis	Lactobacillus kunkeei	Lactobacillus sharpeae
Lactobacillus crispatus	Lactobacillus letivazi	Lactobacillus shenzhenensis
Lactobacillus crustorum	Lactobacillus lindneri	Lactobacillus silagei
Lactobacillus curieae	Lactobacillus malefermentans	Lactobacillus siliginis
Lactobacillus curvatus	Lactobacillus mali	Lactobacillus similis
Lactobacillus delbrueckii	Lactobacillus manihotivorans	Lactobacillus spicheri
Lactobacillus dextrinicus	Lactobacillus mellifer	Lactobacillus sucicola
Lactobacillus diolivorans	Lactobacillus mellis	Lactobacillus suebicus
Lactobacillus equi	Lactobacillus melliventris	Lactobacillus sunkii
Lactobacillus equicursoris	Lactobacillus mindensis	Lactobacillus suntoryeus
Lactobacillus equigenerosi	Lactobacillus mucosae	Lactobacillus taiwanensis
Lactobacillus fabifermentans	Lactobacillus murinus	Lactobacillus thailandensis
Lactobacillus farciminis	Lactobacillus nagelii	Lactobacillus tucceti
Lactobacillus farraginis	Lactobacillus namurensis	Lactobacillus ultunensis
Lactobacillus fermentum	Lactobacillus nantensis	Lactobacillus uvarum
Lactobacillus floricola	Lactobacillus nasuensis	Lactobacillus vaccinostercus
Lactobacillus florum	Lactobacillus nodensis	Lactobacillus vaginalis
Lactobacillus fructivorans	Lactobacillus odoratitofui	Lactobacillus versmoldensis
Lactobacillus frumenti	Lactobacillus oeni	Lactobacillus vini
Lactobacillus fuchuensis	Lactobacillus oligofermentans	Lactobacillus wasatchensis
Lactobacillus futsaii	Lactobacillus oris	Lactobacillus xiangfangensis
Lactobacillus gallinarum	Lactobacillus oryzae	Lactobacillus zymae
Lactobacillus gasseri	Lactobacillus otakiensis
Lactobacillus gastricus	Lactobacillus ozensis

Table 50 Predicted (in silico) Reactivity (Inclusivity) Results for Lactobacillus

{64}------------------------------------------------

{65}------------------------------------------------

Detection Predicted for ≥95% of target sequences
Listeria monocytogenes*	Listeria marthii	Listeria welshimeri*
Listeria ivanovii*	Listeria seeligeri*
Detection Predicted for 85%-94% of target sequences
Listeria innocua*
Detection Predicted for <85% of target sequences
None Identified
Detection Not Predicted
Listeria grayi

Table 51: Predicted (in silico) Reactivity (Inclusivity) Results for Listeria

Table 52: Predicted (in silico) Reactivity (Inclusivity) Results for Micrococcus

Detection Predicted for ≥95% of target sequences
Micrococcus luteus*	Micrococcus aquilus	Micrococcus yunnanensis*
Micrococcus alkanovora	Micrococcus flavus
Micrococcus aloeverae	Micrococcus thailandicus
Detection Predicted for 85%-94% of target sequences
Micrococcus endophyticus	Micrococcus indicus
Detection Predicted for <85% of target sequences
Micrococcus lylae (50.0%)*
Detection Not Predicted
Micrococcus antarcticus	Micrococcus lactis
Micrococcus chenggongense	Micrococcus terreus

{66}------------------------------------------------

Detection Predicted for ≥95% of target sequences
Staphylococcus aureus*	Staphylococcus haemolyticus*	Staphylococcus pseudintermedius*
Staphylococcus agnetis	Staphylococcus hominis*	Staphylococcus pseudolugdunensis
Staphylococcus argensis	Staphylococcus hominis subsp.novobiosepticus	Staphylococcus pulvereri
Staphylococcus argenteus	Staphylococcus hyicus*	Staphylococcus rostri
Staphylococcus auricularis*	Staphylococcus jettensis	Staphylococcus saprophyticus*
Staphylococcus capitis*	Staphylococcus kloosii	Staphylococcus schleiferi*
Staphylococcus caprae*	Staphylococcus lentus*	Staphylococcus schweitzeri
Staphylococcus carnosus*	Staphylococcus lugdunensis*	Staphylococcus sciuri*
Staphylococcus chromogenes*	Staphylococcus lutrae	Staphylococcus simiae
Staphylococcus cohnii*	Staphylococcus massiliensis	Staphylococcus simulans*
Staphylococcus delphini	Staphylococcus microti	Staphylococcus stepanovicii
Staphylococcus devriesei	Staphylococcus muscae*	Staphylococcus succinus
Staphylococcus epidermidis*	Staphylococcus nepalensis	Staphylococcus vitulinus *
Staphylococcus equorum	Staphylococcus pasteuri*	Staphylococcus warneri *
Staphylococcus felis	Staphylococcus petrasii	Staphylococcus xylosus*
Staphylococcus fleurettii	Staphylococcus pettenkoferi*
Staphylococcus gallinarum*	Staphylococcus piscifermentans
Detection Predicted for 85%-94% of target sequences
Staphylococcus arlettae	Staphylococcus intermedius*
Staphylococcus condimenti	Staphylococcus saccharolyticus*
Detection Predicted for <85% of target sequences
None Identified
Detection Not Predicted
Staphylococcus caseolyticus^

Table 53: Predicted (in silico) Reactivity (Inclusivity) Results for Staphylococcus

A Data for only one strain available in NCBI.

Table 54: Predicted (in silico) Reactivity (Inclusivity) Results for Streptococcus

Detection Predicted for ≥95% of target sequences
Streptococcus agalactiae*	Streptococcus infantarius*	Streptococcus phocae
Streptococcus alactolyticus	Streptococcus infantis*	Streptococcus pneumoniae*
Streptococcus anginosus*	Streptococcus intermedius*	Streptococcus porcinus
Streptococcus australis	Streptococcus intestinalis	Streptococcus porcorum
Streptococcus caballi	Streptococcus lactarius	Streptococcus pseudopneumoniae
Streptococcus constellatus*	Streptococcus loxodontasalivarius	Streptococcus pseudoporcinus
Streptococcus criceti*	Streptococcus luteciae	Streptococcus pyogenes*

{67}------------------------------------------------

Streptococcus cristatus	Streptococcus lutetiensis	Streptococcus rifensis
Streptococcus danieliae	Streptococcus macedonicus	Streptococcus rubneri
Streptococcus dentasini	Streptococcus marimammalium	Streptococcus salivarius*
Streptococcus dentisani	Streptococcus massiliensis	Streptococcus saliviloxodontae
Streptococcus didelphis	Streptococcus mitis*	Streptococcus sanguinis*
Streptococcus difficilis	Streptococcus moroccensis	Streptococcus seminale
Streptococcus dysgalactiaesubsp. dysgalactiae	Streptococcus oligofermentans	Streptococcus sinensis
Streptococcus dysgalactiaesubsp. equisimilis	Streptococcus oralis*	Streptococcus suis
Streptococcus dysgalactiae*	Streptococcus oricebi	Streptococcus thermophilus
Streptococcus equi*	Streptococcus orisratti	Streptococcus thoraltensis*
Streptococcus equinus*	Streptococcus panodentis	Streptococcus tigurinus
Streptococcus fryi	Streptococcus parasanguinis*	Streptococcus troglodytae
Streptococcus gallolyticus*	Streptococcus parasuis	Streptococcus troglodytidis
Streptococcus gordonii*	Streptococcus parauberis	Streptococcus urinalis
Streptococcus himalayensis	Streptococcus pasteuri	Streptococcus ursoris
Streptococcus hongkongensis	Streptococcus pasteurianus	Streptococcus vestibularis
Streptococcus hyointestinalis	Streptococcus peroris*	Streptococcus waiu
Detection Predicted for 85%-94% of target sequences
Streptococcus bovis*	Streptococcus uberis
Detection Predicted for <85% of target sequences
Streptococcus canis (15.8%)	Streptococcus henryi (10.0%)	Streptococcus ratti (75.0%)
Streptococcus halichoeri(66.7%)	Streptococcus iniae (6.9%)
Detection Not Predicted
Streptococcus acidominimus	Streptococcus entericus	Streptococcus orisasini
Streptococcus azizii	Streptococcus ferus	Streptococcus orisuis
Streptococcus cameli	Streptococcus gallinaceus	Streptococcus ovis
Streptococcus castoreus	Streptococcus hyovaginalis	Streptococcus pharyngis
Streptococcus cremoris	Streptococcus ictaluri	Streptococcus pluranimalium
Streptococcus criae	Streptococcus lactis	Streptococcus plurextorum
Streptococcus cuniculi	Streptococcus macacae	Streptococcus plutanimalium
Streptococcus dentapri	Streptococcus marmotae	Streptococcus porci
Streptococcus dentiloxodontae	Streptococcus merionis	Streptococcus rupicaprae
Streptococcus dentirousetti	Streptococcus milleri	Streptococcus sobrinus
Streptococcus devriesei	Streptococcus minor	Streptococcus tangierensis

{68}------------------------------------------------

Table 55: Predicted (in silico) Reactivity (Inclusivity) Results for Streptococcus anginosus group

Detection Predicted for ≥95% of target sequences
Streptococcus anginosus*	Streptococcus constellatus*	Streptococcus intermedius*
Detection Predicted for 85%-94% of target sequences
None Identified
Detection Predicted for <85% of target sequences
None Identified
Detection Not Predicted
None Identified

Table 56: Predicted (in silico) Reactivity (Inclusivity) Results for Pan Candida

Detection Predicted for ≥95% of target sequences
Candida albicans*	Candida glabrata*	Candida krusei*
Candida parapsilosis*
Detection Predicted for 85%-94% of target sequences
None Identified
Detection Predicted for <85% of target sequences
None Identified
Detection Not Predicted
Candida lusitaniae*	Candida orthopsilosis*
Candida metapsilosis*	Candida tropicalis*

Table 57: Predicted (in silico) Reactivity (Inclusivity) Results for Pan Gram-Negative

The Pan Gram-Negative assay was designed to be broadly inclusive of the majority of gram-negative organisms.

{69}------------------------------------------------

Analytical Specificity (Cross-Reactivity and Exclusivity)

Cross-reactivity of on-panel and off-panel analytes was evaluated with the BCID-GP Panel. Bacterial targets were tested in triplicate at a concentration of ≥1x10° CFU/mL while fungi were tested in triplicate at a concentration of ≥1x10? CFU/mL. If the target concentration could not be reached, the organism was diluted 2-fold from stock for use.

No cross reactivity was observed for any of the on-panel gram-positive organisms. Three organisms showed cross-reactivity, Burkholderia cepacia cross reacts with the Corynebacterium assay at levels ≥1x107 CFU/mL, an unspeciated Rhodococcus strain (ATCC 49988) cross reacts with the Micrococcus assay at levels ≥1x107 CFU/mL and Bacillus badius cross reacts with the Bacillus subtilis group assay at 7 x 107 CFU/mL. See Table 45 for summaries of the on-panel strains tested as a part of the Limit of Detection (Analytical Sensitivity) and Analytical Reactivity (Inclusivity) studies and Table 58 for a summary of off-panel strains tested.

Off Panel Exclusivity

Table 58: Targets Assessed for Cross-Reactivity with the ePlex BCID-GP Panel
(Exclusivity)

Organism	Strain ID	Organism	Strain ID
Abiotrophia defectiva	ATCC 49176	Granulicatella elegans	ATCC 700633C
Actinomyces odontolyticus	ATCC 17929	Kocuria kristinae	ATCC BAA-752
Aerococcus sanguinicola	ATCC BAA-465	Kocuria rhizophila	ATCC 9341
Aerococcus urinae	ATCC 700306	Kytococcus sedentarius	ATCC 27575
Aerococcus viridans	ATCC 10400	Lactococcus garvieae	ATCC 43921D
Anaerococcus prevotii	ATCC 9321	Lactococcus lactis	ATCC 49032
Arcanobacterium bernardiae	ATCC 51728	Leuconostoc carnosum	ATCC 49367
Arcanobacterium haemolyticum	ATCC BAA-1784A	Leuconostoc citreum	ATCC 13146
Arthrobacter psychrolactophilus	ATCC 700733	Leuconostoc mesenteroides	ATCC 8293
Aspergillus fumigatus	ATCC 204305B	Macrococcus caseolyticus	ATCC 29750
Bacillus badius	ATCC 14574	Macrococcus caseolyticus	ATCC 51834
Bacillus pumilus	ATCC 14884	Mycobacterium avium complex	ATCC 15769
Brochothrix thermosphacta	ATCC 11509	Mycobacterium fortuitum	ATCC 6841
Candida lusitaniae	ATCC 34449	Mycobacterium mucogenicum	ATCC 49650
Candida metapsilosis	ATCC 96144	Mycobacterium tuberculosis	ATCC 25177
Candida orthopsilosis	ATCC 96139	Mycoplasma pneumoniae	ATCC 39505
Candida tropicalis	ATCC 1369	Pediococcus acidilactici	ATCC 8042
Carnobacterium divergens	ATCC 35677	Pediococcus pentosaceus	ATCC 33316
Carnobacterium maltaromaticum	ATCC 27865C	Penicillium marneffei	ATCC 200050

{70}------------------------------------------------

Organism	Strain ID
Cellulomonas turbata	ATCC 25835
Cellulosimicrobium cellulans	ATCC 27402
Clostridium clostridioforme	ATCC 25537
Clostridium perfringens	ATCC 13124
Clostridium ramosum	ATCC 25582
Cryptococcus gattii	ATCC 76108
Cryptococcus grubii	ATCC 208821
Cryptococcus neoformans	ATCC 14116
Cutibacterium granulosum	ATCC 11829
Erysipelothrix rhusiopathiae	ATCC 35457
Gemella haemolysans	ATCC 10379
Gemella morbillorum	ATCC 27824
Geotrichum capitatum	ATCC 10663
Granulicatella adiacens	ATCC 43205
Organism	Strain ID
Peptostreptococcus anaerobius	ATCC 27337
Planococcus species	ATCC 35671
Propionibacterium propionicum	ATCC 14157
Rhodococcus equi	ATCC 6939
Rhodococcus species	ATCC 49988
Rhodotorula glutinis	ATCC 32766
Rhodotorula minuta	ATCC 36236
Rhodotorula mucilaginosa	ATCC 9449
Rothia dentocariosa	ATCC 31918
Rothia mucilaginosa	ATCC 25296
Saccharomyces cerevisiae	ATCC 18824
Trichosporon asahii	ATCC 201110
Vagococcus fluvialis	ATCC 49515
Weissella paramesenteroides	ATCC 33313

A Final testing concentration of 4.05x108 CFU/mL

B Final testing concentration of 2.5x106 CFU/mL

C Final testing concentration of 3.63x108 CFU/mL

D Final testing concentration of 2.78x108 CFU/mL

Bottle Positivity

Several representative bacterial and fungal organisms were spiked into blood culture bottles along with the manufacturer's recommended volume of human whole blood and grown to positivity in a commercially-available continuously monitoring blood culture system. Bottles were removed from the incubator within two hours of being identified as positive as well as eight hours after bottle positivity. At least two independent positive blood culture replicates were quantified for each organism on culture plates. Organisms tested and approximate bottle positivity concentrations are summarized in Table 59. Concentrations shown below represent approximate levels that may be observed in a clinical setting. All estimated bottle positivity concentrations are equivalent or greater than the established Limit of Detection (LOD) for each of the assays of the ePlex BCID-GP Panel.

{71}------------------------------------------------

Organism	Strain ID	Mean Bottle PositivityConcentration	Mean Bottle Positivity+8 hours Concentration
Gram-positive Organisms
Corynebacterium striatum	ATCC BAA-1293	4.5 x 106 CFU/mL	2.7 x 109 CFU/mL
Cutibacterium acnes (P. acnes)	ATCC 6919	3.0 x 108 CFU/mL	3.5 x 108 CFU/mL
Enterococcus faecium	ATCC BAA-2317	4.9 x 107 CFU/mL	3.6 x 107 CFU/mL
Lactobacillus casei	ATCC 39392	4.8 x 107 CFU/mL	3.1 x 1011 CFU/mL
Staphylococcus aureus	NRS 483	2.8 x 107 CFU/mL	2.1 x 107 CFU/mL
Streptococcus anginosus	ATCC 33397	4.1 x 107 CFU/mL	4.0 x 108 CFU/mL
Gram-negative Organisms
Acinetobacter baumannii	NCTC 13301	4.4 x 108 CFU/mL	3.8 x 108 CFU/mL
Bacteroides fragilis	ATCC 700786	4.7 x 108 CFU/mL	6.7 x 109 CFU/mL
Enterobacter cloacae	NCTC 13464	2.8 x 108 CFU/mL	7.7 x 108 CFU/mL
Escherichia coli	NCTC 13476	2.3 x 108 CFU/mL	1.5 x 109 CFU/mL
Fusobacterium nucleatum	ATCC 31647	6.5 x 107 CFU/mL	4.9 x 108 CFU/mL
Haemophilus influenzae	ATCC 19418	6.9 x 108 CFU/mL	1.2 x 109 CFU/mL
Klebsiella oxytoca	CDC #0147	9.3 x 108 CFU/mL	1.5 x 109 CFU/mL
Neisseria meningitidis	ATCC 13102	3.1 x 107 CFU/mL	2.1 x 108 CFU/mL
Pseudomonas aeruginosa	NCTC 13476	1.6 x 108 CFU/mL	8.4 x 108 CFU/mL
Serratia marcescens	ATCC 14041	1.2 x 109 CFU/mL	2.2 x 109 CFU/mL
Fungal Organism
Candida albicans	ATCC 90082	1.6 x 106 CFU/mL	1.4 x 106 CFU/mL

Table 59: Bottle Positivity Concentrations

Reproducibility

Four positive mixes including 9 on-panel organisms and 3 antibiotic resistance genes representing 15 targets at two concentrations and one negative mix including an off-panel organism were tested. Concentrations in the positive mixes reflected those observed at time of bottle positivity plus 8 hours (BP+8) and time of bottle positivity (BP) and one mix containing an off-panel organism grown to bottle positivity, which is expected to yield a negative result. Bottle concentrations used in this study are summarized in Table 60. Testing occurred at three sites with two operators testing the mixes over six days using three cartridge lots.

The percent agreement of each target with the expected result is summarized in Tables 61-75. The ePlex BCID-GP Panel demonstrates a high level of agreement with the expected results.

{72}------------------------------------------------

Table 60: Bottle Positivity Concentrations

Organism	Bottle PositivityConcentration	Bottle Positivity +8 HoursConcentration
Corynebacterium striatum	4 x 106 CFU/mL	1 x 108 CFU/mL
Cutibacterium acnes (P. acnes)	1 x 108 CFU/mL	4.4 x 107 CFU/mL
Enterococcus faecium (vanA+)	1 x 107 CFU/mL	1 x 108 CFU/mL
Enterococcus faecalis (vanB+)	1 x 107 CFU/mL	1 x 108 CFU/mL
Lactobacillus casei	1 x 107 CFU/mL	1 x 108 CFU/mL
Staphylococcus aureus (mecA+)	1 x 107 CFU/mL	1 x 108 CFU/mL
Streptococcus anginosus	1 x 107 CFU/mL	1 x 108 CFU/mL
Candida albicans (Pan Candida target)	1 x 106 CFU/mL	1 x 107 CFU/mL
Klebsiella pneumoniae (Pan Gram-Negative target)	1 x 108 CFU/mL	1 x 109 CFU/mL

Table 61: Percent Agreement for Corynebacterium

Concentration ofCorynebacterium striatum	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(4x106 CFU/mL)	1	35/36	97.2	(85.8-99.5)
	2	35/36	97.2	(85.8-99.5)
	3	33/36	91.7	(78.2-97.1)
	All	103/108	95.4	(89.6-98.0)
Negative	1	108/108	100	(96.6-100)
	2	107/108	99.1	(94.9-99.8)
	3	107/107	100	(96.5-100)
	All	322/323	99.7	(98.3-99.9)

CI=Confidence Interval

{73}------------------------------------------------

Concentration ofCutibacterium acnes	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(4.4x107 CFU/mL)	1	32/36	88.9	(74.7-95.6)
	2	33/36	91.7	(78.2-97.1)
	3	36/36	100	(90.4-100)
	All	101/108	93.5A	(87.2-96.8)
Bottle Positive(1.1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	33/36	91.7	(78.2-97.1)
	3	35/36	97.2	(85.8-99.5)
	All	104/108	96.3B	(90.9-98.6)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

Table 62: Percent Agreement for Cutibacterium acnes (Propionibacterium acnes)

A. <95% agreement is expected because the C. acnes organism concentration is more than 0.5 log below the limit of detection of this assay (1.0 x 108 CFU/mL).

B. 95% agreement is expected because the C. acnes organism concentration is approximately equal to the limit of detection of this assay (1.0 x 108 CFU/mL).

Table 63: Percent Agreement for Enterococcus

Concentration of Enterococcus	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	72/72	100	(94.9-100)
	2	72/72	100	(94.9-100)
	3	72/72	100	(94.9-100)
	All	216/216	100	(98.3-100)
Bottle Positive(1x107 CFU/mL)	1	72/72	100	(94.9-100)
	2	72/72	100	(94.9-100)
	3	72/72	100	(94.9-100)
	All	216/216	100	(98.3-100)
Negative	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	35/35	100	(90.1-100)
	All	107/107	100	(96.5-100)

{74}------------------------------------------------

Concentration ofEnterococcus faecalis	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

Table 64: Percent Agreement for Enterococcus faecalis

Table 65: Percent Agreement for Enterococcus faecium

Concentration ofEnterococcus faecium	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

{75}------------------------------------------------

Concentration ofLactobacillus casei	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.1-100)
	2	36/36	100	(89.8-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.5-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(89.8-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.1-100)
	All	108/108	100	(96.5-100)
Negative	1	108/108	100	(90.4-100)
	2	108/108	100	(89.8-100)
	3	107/107	100	(90.1-100)
	All	323/323	100	(96.5-100)

Table 66: Percent Agreement for Lactobacillus

Table 67: Percent Agreement for Staphylococcus

Concentration ofStaphylococcus	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.48-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	106/108	98.1	(93.5-99.5)
	3	107/107	100	(96.5-100)
	All	321/323	99.4	(97.8-99.8)

{76}------------------------------------------------

Concentration ofStaphylococcus aureus	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

Table 68: Percent Agreement for Staphylococcus aureus

Table 69: Percent Agreement for Streptococcus

Concentration of Streptococcus	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	35/36	97.2	(85.8-99.5)
	3	36/36	100	(90.4-100)
	All	107/108	99.1	(94.9-99.8)
Negative	1	108/108	100	(96.6-100)
	2	107/108	99.1	(94.9-99.8)
	3	107/107	100	(96.5-100)
	All	322/323	99.7	(98.3-99.9)

{77}------------------------------------------------

Concentration ofStreptococcus anginosus	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	35/36	97.2	(85.8-99.5)
	3	36/36	100	(90.4-100)
	All	107/108	99.1	(94.9-99.8)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

Table 70: Percent Agreement for Streptococcus anginosus group

Table 71: Percent Agreement for Pan Candida

Concentration ofCandida albicans	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x106 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

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Concentration ofKlebsiella pneumoniae	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x109 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	107/108	99.1	(94.9-99.8)
	3	107/107	100	(96.5-100)
	All	322/323	99.7	(98.3-99.9)

Table 72: Percent Agreement for Pan Gram-Negative

Table 73: Percent Agreement for mecA

Concentration ofStaphylococcus aureus	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

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Concentration of	Site	Agreement with Expected Results
Enterococcus faecium		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

Table 75: Percent Agreement for vanB

Concentration ofEnterococcus faecalis	Site	Agreement with Expected Results
		Agreed / N	%	95% CI
Bottle Positive+ 8 Hours(1x108 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Bottle Positive(1x107 CFU/mL)	1	36/36	100	(90.4-100)
	2	36/36	100	(90.4-100)
	3	36/36	100	(90.4-100)
	All	108/108	100	(96.6-100)
Negative	1	108/108	100	(96.6-100)
	2	108/108	100	(96.6-100)
	3	107/107	100	(96.5-100)
	All	323/323	100	(98.8-100)

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Interfering Substances and Sample Matrix Equivalency (Bottle Evaluation)

Two organism mixes consisting of 9 on-panel organisms representing 14 targets and negative blood matrix were used to assess potentially interfering substances and bottle types for interference. The concentration of each organism tested is summarized in Table 76.

Organism	Concentration
Cutibacterium acnes	3 x 108 CFU/mL
Enterococcus faecalis (vanB+)	4 x 107 CFU/mL
Enterococcus faecium (vanA+)	4 x 107 CFU/mL
Lactobacillus casei	4 x 107 CFU/mL
Staphylococcus aureus	2 x 107 CFU/mL
Staphylococcus epidermidis	2 x 107 CFU/mL
Streptococcus pneumoniae	4 x 107 CFU/mL
Klebsiella pneumoniae (Pan Gram-Negative target)	5 x 108 CFU/mL
Candida albicans (Pan Candida target)	1 x 106 CFU/mL

Table 76: Interfering Substance and Bottle Equivalency Concentrations

Interfering Substances

Eighteen substances were used to assess the ePlex BCID-GP Panel for potential interference. The organisms in Table 76 were spiked into negative blood matrix and tested in triplicate with and without each potentially interfering substance. Negative blood matrix was tested to control for potential positive interference. Potentially interfering substances are summarized in Table 77. None of the eighteen substances commonly found in blood culture specimens or as medications commonly used to treat skin or bloodstream infections were found to inhibit the ePlex BCID-GP Panel at clinically relevant concentrations. The effect of interfering substances has only been evaluated for the organisms listed in Table 76. Interference due to substances other than those described in this section can lead to erroneous results.

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Endogenous Substances	Testing Concentration
Bilirubin	60 μg/mL
Hemoglobin	0.6 g/L
Human Genomic DNA	6 x 105 copies/mL
Triglycerides	1000 mg/dL
γ-globulin	0.425 g/dL
Exogenous Substances	Testing Concentration
Amoxicillin/Clavulanate	3.5 μg/mL
Amphotericin B	2 μg/mL
Caspofungin	5 μg/mL
Ceftriaxone	0.23 mg/mL
Ciprofloxacin	3 mg/L
Fluconazole	25 mg/L
Flucytosine	90 μg/mL
Gentamicin sulfate	3 μg/mL
Heparin	0.9 U/mL
Imipenem	83 μg/mL
Sodium Polyanethol Sulfonate	0.25% w/v
Tetracycline	5 mg/L
Vancomycin	30 mg/L

	Table 77: Potentially Interfering Substances: Substance List

Sample Matrix Equivalency (Bottle Evaluation)

Thirteen bottle types were tested for interference with each of the organisms listed in Table 76. Five replicates of each organism were tested in each of two bottle lots. Negative blood matrix was run as a negative control. Eleven of the bottle types tested showed no interference for any of the targets tested. One lot of the BACTEC™ Plus Anaerobic bottles showed false positive results for Pan Gram-Negative. The BacT/ALERT® FN Plus bottle type showed lower sensitivity for some targets (Pan Gram-Negative and E. faecium with vanA). A summary of the bottle types assessed and the study outcomes is found in Table 78.

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Manufacturer	Bottle Brand	Bottle Type	Study Outcome
BD	BACTEC™	Plus Aerobic	No interference observed
BD	BACTEC™	Plus Anaerobic	False positive results for PanGram-Negative target wereobserved in one lot.
BD	BACTEC™	Standard Aerobic	No interference observed
BD	BACTEC™	Standard Anaerobic	No interference observed
BD	BACTEC™	Peds Plus™	No interference observed
BD	BACTEC™	Lytic Anaerobic	No interference observed
bioMérieux	BACT/ALERT®	SA Standard Aerobic	No interference observed
bioMérieux	BACT/ALERT®	SN Standard Anaerobic	No interference observed
bioMérieux	BACT/ALERT®	FA Plus	No interference observed
bioMérieux	BACT/ALERT®	FN Plus	False negative results wereobserved for Pan Gram-Negativeand E.faecium/vanA targets
bioMérieux	BACT/ALERT®	PF Plus	No interference observed
Thermo Scientific™	VersaTREK™	REDOX™ 1 EZ Draw Aerobic	No interference observed
Thermo Scientific™	VersaTREK™	REDOX™ 2 EZ Draw Anaerobic	No interference observed

Carryover and Cross-Contamination

Carryover and cross-contamination were evaluated for the ePlex BCID-GP Panel within and between runs by alternating high positive and negative samples across multiple runs over 5 rounds of testing. A high-titer mix of mecA positive Staphylococcus aureus, vanA positive Enterococcus faecium and Klebsiella pneumoniae (a Pan Gram-Negative target organism) was prepared at 1 x 10° CFU/mL each as well as Candida albicans (a Pan Candida target organism) at 1x107 CFU/mL to simulate clinically relevant high positive samples for positive testing. Negative blood culture matrix was used to represent negative samples. Over 120 runs, all valid positive runs resulted in detection of Staphylococcus aureus, mecA, Enterococcus faecium, vanA, Pan Gram-Negative and Pan Candida and no false positives were detected in the negative runs.

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Competitive Inhibition Study

Competitive inhibition was evaluated for the ePlex BCID-GP Panel by pairing eight clinically relevant organisms (including a Pan Gram-Negative assay target, a Pan Candida assay target, and an off-panel gram-positive organism) in four simulated dual infection sample mixes. Each dual infection mix was tested in combination with each of the three other mixes, such that all organisms were tested at low titer (concentrations expected at bottle positivity) while in the presence of other organisms at higher titer (concentrations expected at 8 hours beyond bottle positivity, or one log higher than that expected at bottle positivity). No competitive inhibition was observed in any replicates of the twelve testing conditions. A summary of the organisms assessed and testing concentrations is found in Table 79.

Organism	HighConcentration	LowConcentration
Enterococcus faecium	1 x 108 CFU/mL	4 x 107 CFU/mL
Staphylococcus aureus	1 x 108 CFU/mL	2 x 107 CFU/mL
Staphylococcus epidermidis	1 x 108 CFU/mL	2 x 107 CFU/mL
Streptococcus agalactiae	4 x 108 CFU/mL	4 x 107 CFU/mL
Streptococcus pneumoniae	4 x 108 CFU/mL	4 x 107 CFU/mL
Candida albicans	1 x 107 CFU/mL	1 x 106 CFU/mL
Escherichia coli	1 x 109 CFU/mL	2 x 108 CFU/mL
Cutibacterium granulosumA	1 x 109 CFU/mL	3 x 108 CFU/mL

Table 79: Competitive Inhibition Organisms and Concentrations Tested

A Off-panel organism

Regulation Number and Section

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

(a)
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.(b)
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).