ePlex Blood Culture Identification Panel Fungal Pathogen (BCID-FP) Panel
Device Facts
| Record ID | K182690 |
|---|---|
| Device Name | ePlex Blood Culture Identification Panel Fungal Pathogen (BCID-FP) Panel |
| Applicant | Genmark Diagnostics, Incorporated |
| Product Code | PEO · Microbiology |
| Decision Date | Dec 21, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3365 |
| Device Class | Class 2 |
Intended Use
The GenMark ePlex® Blood Culture Identification Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The ePlex BCID-FP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organism. The following fungal organisms are identified using the ePlex BCID-FP Panel: Candida albicans, Candida auris, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus gattii, Cryptococcus neoformans, Fusarium and Rhodotorula. The detection and identification of specific 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-FP 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-FP 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-FP Panel, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.
Device Story
The ePlex BCID-FP Panel is a qualitative multiplex nucleic acid test for identifying fungal pathogens in positive blood cultures. It uses a single-use cartridge on the ePlex Instrument. The process involves automated cell lysis, nucleic acid extraction via magnetic beads, and PCR/RT-PCR amplification. The device uses competitive nucleic acid hybridization: target DNA binds to a capture probe on a gold electrode and a ferrocene-labeled signal probe. Detection is performed via alternating current voltammetry (ACV). The system identifies 15 fungal targets (Candida spp., Cryptococcus spp., Fusarium, Rhodotorula). It is used in clinical laboratories by trained personnel. Results are provided to healthcare providers to aid in the diagnosis of bloodstream infections, alongside Gram stain and other clinical data. It helps clinicians initiate appropriate antifungal therapy faster than traditional culture methods.
Clinical Evidence
Clinical performance was evaluated using 866 positive blood culture samples (11 fresh prospective, 10 frozen prospective, 120 retrospective, 725 contrived). Comparator methods included standard culture, MALDI-TOF, and PCR/sequencing. Sensitivity (PPA) and specificity (NPA) were calculated for each target. Overall sensitivity ranged from 92.9% to 100% for most targets, with specificity generally >99%. No clinical data for Candida auris, Fusarium, or Rhodotorula in prospective samples; these were validated via contrived samples.
Technological Characteristics
The device uses competitive nucleic acid hybridization on a printed circuit board (PCB) with gold electrodes. It employs PCR/RT-PCR for amplification and exonuclease digestion to generate single-stranded DNA. Detection is via alternating current voltammetry (ACV) using ferrocene-labeled signal probes. The system is a standalone instrument using single-use cartridges. It is a qualitative multiplex nucleic acid assay.
Indications for Use
Indicated for individuals exhibiting signs/symptoms of bloodstream infection to aid in diagnosis of fungemia. Performed on positive blood culture samples containing fungal organisms.
Regulatory Classification
Identification
A multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures is a qualitative in vitro device intended to simultaneously detect and identify microorganism nucleic acids from blood cultures that test positive by Gram stain or other microbiological stains. The device detects specific nucleic acid sequences for microorganism identification as well as for antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device does not replace traditional methods for culture and susceptibility testing.
Special Controls
In combination with the general controls of the FD&C Act, the Verigene® Gram Positive Blood Culture Nucleic Acid Test is subject to the following special controls: The special controls for the BC-GP Assay are contained in the guideline document entitled "Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures."
*Classification.* Class II (special controls). The special control for this device is FDA's guideline document entitled “Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures.” For availability of the guideline document, see § 866.1(e).
Predicate Devices
- FilmArray Blood Culture Identification Panel (K130914)
Related Devices
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- K182619 — ePlex Blood Culture Identification Gram Negative (BCID-GN) Panel · Genmark Diagnostics, Incorporated · Apr 12, 2019
- K213236 — ePlex Blood Culture Identification Gram Negative (BCID-GN) Panel · Genmark Diagnostics, Incorporated · Apr 27, 2022
- K181663 — ePlex Blood Culture Identification Panel - Gram Positive (BCID-GP) Panel · Genmark Diagnostics, Incorporated · Dec 20, 2018
Submission Summary (Full Text)
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December 21, 2018
GenMark Diagnostics, Incorporated Beth Stofka Sr. Regulatory Affairs Specialist 5964 La Place Court Carlsbad, California 92008
Re: K182690
Trade/Device Name: ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) 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: PEO Dated: September 26, 2018 Received: September 27, 2018
Dear Beth Stofka:
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 mav, 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 avare 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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (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 (OS) 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) K182690
#### Device Name
ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel
Indications for Use (Describe)
The GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The ePlex BCID-FP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organism.
The following fungal organisms are identified using the ePlex BCID-FP Panel: Candida albicans, Candida auris, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus gattii, Cryptococcus neoformans, Fusarium and Rhodotorula.
The detection and identification of specific 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-FP 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-FP 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-FP Panel, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.
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#### 510(k) Summary
Summary of Safety and Effectiveness
#### Submitter Information
| Submitter: | GenMark Diagnostics, Incorporated<br>5964 La Place Court<br>Carlsbad, CA 92008 |
|------------------------------------|---------------------------------------------------------------------------------------|
| Manufacturer: | GenMark Diagnostics, Incorporated<br>5964 La Place Court<br>Carlsbad, CA 92008 |
| Establishment Registration Number: | 3008632402 |
| Contact: | Beth Stofka<br>Sr. Regulatory Affairs Specialist |
| Phone: | 760-579-4778 |
| Fax: | 760-683-6961 |
| E-mail: | Beth.Stofka@genmarkdx.com |
| Alternate Contact: | Alan Maderazo, Ph.D., RAC<br>Vice President, Quality, Regulatory and Clinical Affairs |
| Phone: | 760-448-4308 |
| Fax: | 760-683-6961 |
| E-mail: | Al.Maderazo@genmarkdx.com |
| Date Prepared: | September 27, 2018 |
#### Name of Device and Classification
ePlex® Blood Culture Identification Fungal Pathogen (BCID-FP) Panel Product Name: Device Classification: 866.3980, Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures, Class II Product Code(s): PEO
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#### Predicate Device
Predicate:
FilmArray Blood Culture Identification Panel; BioFire Diagnostics; K130914
# Device Description
The ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) 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.
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#### Intended Use/Indications for Use
The GenMark ePlex® Blood Culture Identification Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The ePlex BCID-FP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organism.
The following fungal organisms are identified using the ePlex BCID-FP Panel: Candida albicans, Candida auris, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus gattii, Cryptococcus neoformans, Fusarium and Rhodotorula.
The detection and identification of specific 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-FP 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-FP 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-FP Panel, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.
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# Summary of Technological Characteristics of the Device Compared to the Predicate Device
The GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel ("Subject Device") and the legally marketed device, FilmArray Blood Culture Identification Panel, K130914, ("Predicate Device") are described below:
| Characteristic | Subject Device | Predicate Device |
|-------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Product Name | ePlex BCID-FP Panel | FilmArray BCID Panel |
| Manufacturer | GenMark Diagnostics, Inc. | BioFire Diagnostics, Inc. |
| Organisms<br>Detected | • Candida albicans<br>• Candida auris<br>• Candida dubliniensis,<br>• Candida famata<br>• Candida glabrata<br>• Candida guilliermondii<br>• Candida kefyr<br>• Candida krusei<br>• Candida lusitaniae<br>• Candida parapsilosis<br>• Candida tropicalis<br>• Cryptococcus gattii<br>• Cryptococcus neoformans<br>• Fusarium<br>• Rhodotorula | Enterococci, Listeria monocytogenes,<br>commonly encountered Staphylococci<br>(including specific differentiation of<br>Staphylococcus aureus), commonly<br>encountered Streptococci (with<br>specific differentiation of<br>Streptococcus agalactiae,<br>Streptococcus pneumoniae, and<br>Streptococcus pyogenes),<br>Acinetobacter baumannii, commonly<br>encountered Enterobacteriaceae<br>(including specific differentiation of<br>the Enterobacter cloacae complex,<br>Escherichia coli, Klebsiella oxytoca,<br>Klebsiella pneumoniae, Proteus, and<br>Serratia marcescens), Haemophilus<br>influenzae, Neisseria meningitidis<br>(encapsulated), Pseudomonas<br>aeruginosa, Candida albicans,<br>Candida glabrata, Candida krusei,<br>Candida parapsilosis, and Candida<br>tropicalis. |
| Indication for<br>Use | The ePlex BCID-FP Panel is indicated<br>as an aid in the diagnosis of<br>bloodstream infections. The use of<br>additional laboratory testing (e.g. sub-<br>culturing of positive blood cultures for<br>identification of organisms not detected<br>by the ePlex BCID-FP Panel and for<br>susceptibility testing, differentiation of<br>mixed growth) and clinical presentation<br>must be taken into consideration in the<br>final diagnosis of blood stream<br>infection. | FilmArray BCID is indicated as an aid<br>in the diagnosis of specific agents of<br>bacteremia and fungemia and results<br>should be used in conjunction with<br>other clinical and laboratory findings. |
| Characteristic | Subject Device | Predicate Device |
| Specimen Type | Blood culture samples identified as<br>positive by a continuous monitoring<br>blood culture system and which<br>contain fungal organism. | Blood culture samples identified as<br>positive by a continuous monitoring<br>blood culture system that demonstrates<br>the presence of organisms as<br>confirmed by Gram stain. |
| Chemistry | Reagents on cartridge include: sample<br>lysis and nucleic acid extraction, PCR<br>amplification and hybridization-based<br>electrochemical detection reagents. | The FilmArray BCID pouch contains<br>freeze-dried reagents to perform<br>nucleic acid purification and nested,<br>multiplex PCR with DNA melt<br>analysis. |
| Hardware | GenMark ePlex Instrument & Single<br>Use Cartridge | FilmArray Instrument and assay pouch |
| Software<br>Interface<br>Result Reporting | GenMark ePlex System Software GenMark ePlex BCID-FP Panel<br>Software | The FilmArray Software automatically<br>interprets the results of each DNA<br>melt curve analysis and combines the<br>data with the results of the internal<br>pouch controls to provide a test result<br>for each organism and antimicrobial<br>resistance gene on the panel. |
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#### Summary of Performance Data
# EXPECTED VALUES
A prospective, multicenter clinical study was conducted to evaluate the clinical performance of the ePlex BCID-FP Panel in positive blood culture samples. A total of 447 positive blood culture samples were collected at 6 clinical sites in 2 phases from patients of all ages and genders. Samples were collected and frozen for future testing from May 2015 through July 2016. Samples were collected from July through August 2018 and tested fresh (never frozen). Of these 447 samples, 21 had a Gram stain result indicating fungal organism. The expected values of individual analytes based on the ePlex BCID-FP Panel results in the 21 prospective samples are summarized by age group and by site in Tables 1 and 2 below.
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| Target | All Ages<br>(N=21)<br>n (%) | Age <1<br>(N=1)<br>n (%) | Age 1-17<br>(N=2)<br>n (%) | Age 18-44<br>(N=4)<br>n (%) | Age 45-64<br>(N=11)<br>n (%) | Age 65-84<br>(N=2)<br>n (%) | Age 85+<br>(N=1)<br>n (%) |
|-------------------------|-----------------------------|--------------------------|----------------------------|-----------------------------|------------------------------|-----------------------------|---------------------------|
| Candida albicans | 4 (19.0) | 1 (100) | 0 (0.0) | 0 (0.0) | 2 (18.2) | 1 (50.0) | 0 (0.0) |
| Candida auris | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida dubliniensis | 1 (4.8) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) |
| Candida famata | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida glabrata | 6 (28.6) | 0 (0.0) | 1 (50.0) | 1 (25.0) | 3 (27.3) | 1 (50.0) | 0 (0.0) |
| Candida guilliermondii | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida kefyr | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida krusei | 2 (9.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (18.2) | 0 (0.0) | 0 (0.0) |
| Candida lusitaniae | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida parapsilosis | 2 (9.5) | 0 (0.0) | 1 (50.0) | 0 (0.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) |
| Candida tropicalis | 2 (9.5) | 0 (0.0) | 0 (0.0) | 1 (25.0) | 1 (9.1) | 0 (0.0) | 0 (0.0) |
| Cryptococcus gattii | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Cryptococcus neoformans | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Fusarium | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Rhodotorula | 1 (4.8) | 0 (0.0) | 0 (0.0) | 1 (25.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Table 1: Expected Value by Age Group (Prospective Samples)
#### Table 2: Expected Value by Collection Site (Prospective Samples)
| | All Sites<br>(N=21) | Site 1<br>(N=1) | Site 2<br>(N=8) | Site 3<br>(N=2) | Site 4<br>(N=4) | Site 5<br>(N=4) | Site 6<br>(N=2) |
|-------------------------|---------------------|-----------------|-----------------|-----------------|-----------------|-----------------|-----------------|
| Target | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) |
| Candida albicans | 4 (19.0) | 1 (100) | 0 (0.0) | 2 (100) | 1 (25.0) | 0 (0.0) | 0 (0.0) |
| Candida auris | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida dubliniensis | 1 (4.8) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (25.0) | 0 (0.0) | 0 (0.0) |
| Candida famata | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida glabrata | 6 (28.6) | 0 (0.0) | 2 (25.0) | 0 (0.0) | 1 (25.0) | 2 (50.0) | 1 (50.0) |
| Candida guilliermondii | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida kefyr | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida krusei | 2 (9.5) | 0 (0.0) | 2 (25.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida lusitaniae | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Candida parapsilosis | 2 (9.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (25.0) | 1 (50.0) |
| Candida tropicalis | 2 (9.5) | 0 (0.0) | 2 (25.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Cryptococcus gattii | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Cryptococcus neoformans | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Fusarium | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Rhodotorula | 1 (4.8) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (25.0) | 0 (0.0) |
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# PERFORMANCE CHARACTERISTICS
#### Clinical Performance
Samples with a Gram stain result indicating fungal organism, a final, valid investigational test result, 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 11 prospective fresh and 10 prospective frozen samples as well as 120 retrospective samples and 725 contrived samples.
#### Comparator Method
The performance of the ePlex BCID-FP Panel was compared to standard laboratory procedures, including traditional and automated culture, MALDI-TOF IVD, and microbiological and biochemical techniques. In addition, all prospective samples were tested with analytically validated PCR assays followed by bi-directional sequencing to determine the presence or absence of Candida auris, Fusarium, and Rhodotorula. Identification for samples with Candida parapsilosis identified by standard laboratory procedures was confirmed using analytically validated PCR assays followed by bi-directional sequencing.
The comparator method(s) results were used to determine the Detected / Not Detected status for each target organism on the ePlex BCID-FP Panel. The comparator methods for each target are summarized in Table 3.
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| Target | Comparator Method |
|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------|
| Candida albicans | |
| Candida dubliniensis | |
| Candida famata | |
| Candida glabrata | |
| Candida guilliermondii | |
| Candida kefyr | Standard laboratory procedures for organism identification. |
| Candida krusei | |
| Candida lusitaniae | |
| Candida tropicalis | |
| Cryptococcus gattii | |
| Cryptococcus neoformans | |
| Candida parapsilosis | Standard laboratory procedures for organism ID. PCR/sequencing to<br>confirm C. parapsilosis or identify C. metapsilosis, C. orthopsilosis. |
| Candida auris, Fusarium, and<br>Rhodotorula | Standard laboratory procedures for organism identification.<br>PCR/sequencing in prospective samples. |
#### Table 3: Comparator Method(s) by ePlex BCID-FP Panel Target
#### Demographics of Clinical Samples
Clinical performance was evaluated in samples prospectively and retrospectively collected. Prospective samples were collected at 6 clinical sites, with 21 evaluable samples. Sample with final, valid, ePlex BCID-FP Panel results and valid comparator results were considered 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 results of the prospective collection, 120 samples were collected retrospectively from a total of 9 sites, and 725 evaluable samples were contrived for organisms with low prevalence. Demographic information for retrospectively-collected samples is described in Table 5.
{13}------------------------------------------------
| | All Sites<br>(N=21) | Site 1<br>(N=1) | Site 2<br>(N=8) | Site 3<br>(N=2) | Site 4<br>(N=4 | Site 5<br>(N=4) | Site 6<br>(N=2) |
|-------------|---------------------|-----------------|-----------------|-----------------|----------------|-----------------|-----------------|
| | n (%) | n (%) | n (%) | n (%) | n (%)) | n (%) | n (%) |
| Sex, n (%) | | | | | | | |
| Male | 14<br>(66.7) | 1<br>(100) | 7<br>(87.5) | 1<br>(50.0) | 3<br>(75.0) | 1<br>(25.0) | 1<br>(50.0) |
| Female | 7<br>(33.3) | 0<br>(0.0) | 1<br>(12.5) | 1<br>(50.0) | 1<br>(25.0) | 3<br>(75.0) | 1<br>(50.0) |
| Age (years) | | | | | | | |
| <1 yr | 1<br>(4.8) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 1<br>(25.0) | 0<br>(0.0) | 0<br>(0.0) |
| 1-17 yrs | 2<br>(9.5) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 2<br>(50.0) | 0<br>(0.0) |
| 18-44 yrs | 4<br>(19.0) | 0<br>(0.0) | 2<br>(25.0) | 0<br>(0.0) | 1<br>(25.0) | 1<br>(25.0) | 0<br>(0.0) |
| 45-64 yrs | 11<br>(52.4) | 1<br>(100) | 4<br>(50.0) | 1<br>(50.0) | 2<br>(50.0) | 1<br>(25.0) | 2<br>(100) |
| 65-84 yrs | 2<br>(9.5) | 0<br>(0.0) | 1<br>(12.5) | 1<br>(50.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) |
| 85+ yrs | 1<br>(4.8) | 0<br>(0.0) | 1<br>(12.5) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) |
# Table 4: Demographic Data for Clinical Samples by Collection Site (Prospective Collection)
{14}------------------------------------------------
| | All Sites<br>(N=120) | Site 1<br>(N=13) | Site 2<br>(N=14) | Site 3<br>(N=17) | Site 4<br>(N=4) | Site 5<br>(N=3) | Site 6<br>(N=13) | Site 7<br>(N=16) | Site 8<br>(N=5) | Site 9<br>(N=35) |
|-------------|----------------------|------------------|------------------|------------------|-----------------|-----------------|------------------|------------------|-----------------|------------------|
| | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | n (%) |
| Sex, n (%) | | | | | | | | | | |
| Male | 68<br>(56.7) | 10<br>(76.9) | 8<br>(57.1) | 8<br>(47.1) | 1<br>(25.0) | 2<br>(66.7) | 8<br>(61.5) | 9<br>(56.3) | 3<br>(60.0) | 19<br>(54.3) |
| Female | 52<br>(43.3) | 3<br>(23.1) | 6<br>(42.9) | 9<br>(52.9) | 3<br>(75.0) | 1<br>(33.3) | 5<br>(38.5) | 7<br>(43.8) | 2<br>(40.0) | 16<br>(45.7) |
| Age (years) | | | | | | | | | | |
| <1 yr | 2<br>(1.7) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 2<br>(5.7) |
| 1-17 yrs | 8<br>(6.7) | 1<br>(7.7) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 0<br>(0.0) | 5<br>(38.5) | 0<br>(0.0) | 0<br>(0.0) | 2<br>(5.7) |
| 18-44 yrs | 27<br>(22.5) | 4<br>(30.8) | 2<br>(14.3) | 2<br>(11.8) | 1<br>(25.0) | 0<br>(0.0) | 3<br>(23.1) | 3<br>(18.8) | 1<br>(20.0) | 11<br>(31.4) |
| 45-64 yrs | 39<br>(32.5) | 2<br>(15.4) | 6<br>(42.9) | 6<br>(35.3) | 1<br>(25.0) | 2<br>(66.7) | 2<br>(15.4) | 7<br>(43.8) | 1<br>(20.0) | 12<br>(34.3) |
| 65-84 yrs | 39<br>(32.5) | 6<br>(46.2) | 6<br>(42.9) | 8<br>(47.1) | 2<br>(50.0) | 0<br>(0.0) | 2<br>(15.4) | 5<br>(31.3) | 2<br>(40.0) | 8<br>(22.9) |
| 85+ yrs | 5<br>(4.2) | 0<br>(0.0) | 0<br>(0.0) | 1<br>(5.9) | 0<br>(0.0) | 1<br>(33.3) | 1<br>(7.7) | 1<br>(6.3) | 1<br>(20.0) | 0<br>(0.0) |
# Table 5: Demographic Data for Clinical Samples by Collection Site (Retrospective Collection)
{15}------------------------------------------------
#### 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-FP Panel result matched the detected comparator method result, while a TN result was one where a negative ePlex BCID-FP Panel result matched a negative comparator method result. The two-sided 95% confidence interval was also calculated.
A total of 866 positive blood culture samples with a Gram stain result indicating fungal organism consisting of 11 fresh prospective, 10 frozen prospective, 120 retrospective, and 725 contrived samples were evaluated for the ePlex BCID-FP 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 6-20 below and the strains used to contrive samples are summarized in Table 21.
{16}------------------------------------------------
| Target | Sample Type | TP/TP+FN | Sensitivity/PPA<br>% (95% CI) | TN/TN+F<br>P | Specificity/NPA<br>% (95% CI) |
|------------------|---------------------------|----------|-------------------------------|--------------|-------------------------------|
| Candida albicans | Prospective (Fresh) | 2/2 | 100 (34.2-100) | 9/9 | 100 (70.1-100) |
| | Prospective (Frozen) | 2/2 | 100 (34.2-100) | 8/8 | 100 (67.6-100) |
| | Prospective (All) | 4/4 | 100 (51.0-100) | 17/17 | 100 (81.6-100) |
| | Retrospective | 49/50 | 98.0 (89.5-99.6) | 70/70 | 100 (94.8-100) |
| | Prospective/Retrospective | 53/54 | 98.1 (90.2-99.7) | 87/87 | 100 (95.8-100) |
| | Contrived | 13/14 | 92.9 (68.5-98.7) | 710/711 | 99.9 (99.2-100) |
| | Overall | 66/68 | 97.1 (89.9-99.2) | 797/798 | 99.9 (99.3-100) |
Table 6: Clinical Performance for Candida albicans
CI= Confidence Interval
| | | | Table 7: Clinical Performance for Candida auris | | | |
|--|--|--|-------------------------------------------------|--|--|--|
|--|--|--|-------------------------------------------------|--|--|--|
| Target | Sample Type | TP/TP+FN | Sensitivity/PPA<br>% (95% CI) | TN/TN+F<br>P | Specificity/NPA<br>% (95% CI) |
|---------------|---------------------------|----------|-------------------------------|--------------|-------------------------------|
| Candida auris | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 0/0 | --- | 120/120 | 100 (96.9-100) |
| | Prospective/Retrospective | 0/0 | --- | 141/141 | 100 (97.3-100) |
| | Contrived | 49/49 | 100 (92.7-100) | 676/676 | 100 (99.4-100) |
| | Overall | 49/49 | 100 (92.7-100) | 817/817 | 100 (99.5-100) |
{17}------------------------------------------------
| Target | Sample Type | TP/TP+FN | Sensitivity/PPA<br>% (95% CI) | TN/TN+F<br>P | Specificity/NPA<br>% (95% CI) |
|-------------------------|---------------------------|----------|-------------------------------|--------------|-------------------------------|
| Candida<br>dubliniensis | Prospective (Fresh) | 1/1 | 100 (20.7-100) | 10/10 | 100 (72.2-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 1/1 | 100 (20.7-100) | 20/20 | 100 (83.9-100) |
| | Retrospective | 3/3 | 100 (43.9-100) | 117/117 | 100 (96.8-100) |
| | Prospective/Retrospective | 4/4 | 100 (51.0-100) | 137/137 | 100 (97.3-100) |
| | Contrived | 48/48 | 100 (92.6-100) | 677/677 | 100 (99.4-100) |
| | Overall | 52/52 | 100 (93.1-100) | 814/814 | 100 (99.5-100) |
Table 8: Clinical Performance for Candida dubliniensis
# Table 9: Clinical Performance for Candida famata
| Target | Sample Type | | Sensitivity/PPA | Specificity/NPA | |
|----------------|---------------------------|----------|-----------------|-----------------|----------------|
| | | TP/TP+FN | % (95% CI) | TN/TN+F<br>P | % (95% CI) |
| Candida famata | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 0/0 | --- | 120/120 | 100 (96.9-100) |
| | Prospective/Retrospective | 0/0 | --- | 141/141 | 100 (97.3-100) |
| | Contrived | 51/51 | 100 (93.0-100) | 674/674 | 100 (99.4-100) |
| | Overall | 51/51 | 100 (93.0-100) | 815/815 | 100 (99.5-100) |
{18}------------------------------------------------
| Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | |
|------------------|---------------------------|-----------------|------------------|-----------------|------------------|
| | | TP/TP+FN | % (95% CI) | TN/TN+F<br>P | % (95% CI) |
| Candida glabrata | Prospective (Fresh) | 4/4 | 100 (51.0-100) | 7/7 | 100 (64.6-100) |
| | Prospective (Frozen) | 2/2 | 100 (34.2-100) | 8/8 | 100 (67.6-100) |
| | Prospective (All) | 6/6 | 100 (61.0-100) | 15/15 | 100 (79.6-100) |
| | Retrospective | 37/38 | 97.4 (86.5-99.5) | 80/82 | 97.6 (91.5-99.3) |
| | Prospective/Retrospective | 43/44 | 97.7 (88.2-99.6) | 95/97A | 97.9 (92.8-99.4) |
| | Contrived | 16/16 | 100 (80.6-100) | 709/709 | 100 (99.5-100) |
| | Overall | 59/60 | 98.3 (91.1-99.7) | 804/806 | 99.8 (99.1-99.9) |
Table 10: Clinical Performance for Candida glabrata
A. C. glabrata was detected in 2/2 false positive clinical samples using PCR/sequencing.
| | | | | | Table 11: Clinical Performance for Candida guilliermondii | |
|--|--|--|--|--|-----------------------------------------------------------|--|
|--|--|--|--|--|-----------------------------------------------------------|--|
| Target | Sample Type | TP/TP+FN | Sensitivity/PPA<br>% (95% CI) | TN/TN+F<br>P | Specificity/NPA<br>% (95% CI) |
|---------------------------|---------------------------|----------|-------------------------------|--------------|-------------------------------|
| Candida<br>guilliermondii | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| Candida<br>guilliermondii | Retrospective | 0/0 | --- | 120/120 | 100 (96.9-100) |
| Candida<br>guilliermondii | Prospective/Retrospective | 0/0 | --- | 141/141 | 100 (97.3-100) |
| Candida<br>guilliermondii | Contrived | 49/50 | 98.0 (89.5-99.6) | 675/675 | 100 (99.4-100) |
| Candida<br>guilliermondii | Overall | 49/50 | 98.0 (89.5-99.6) | 816/816 | 100 (99.5-100) |
{19}------------------------------------------------
| Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | |
|---------------|---------------------------|-----------------|----------------|-----------------|------------------|
| | | TP/TP+FN | % (95% CI) | TN/TN+F P | % (95% CI) |
| Candida kefyr | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 0/0 | --- | 120/120 | 100 (96.9-100) |
| | Prospective/Retrospective | 0/0 | --- | 141/141 | 100 (97.3-100) |
| | Contrived | 51/51 | 100 (93.0-100) | 672/674 | 99.7 (98.9-99.9) |
| | Overall | 51/51 | 100 (93.0-100) | 813/815 | 99.8 (99.1-99.9) |
Table 12: Clinical Performance for Candida kefyr
# Table 13: Clinical Performance for Candida krusei
| Target | Sample Type | | Sensitivity/PPA | Specificity/NPA | |
|----------------|---------------------------|----------|-----------------|-----------------|----------------|
| | | TP/TP+FN | % (95% CI) | TN/TN+F<br>P | % (95% CI) |
| Candida krusei | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 2/2 | 100 (34.2-100) | 8/8 | 100 (67.6-100) |
| | Prospective (All) | 2/2 | 100 (34.2-100) | 19/19 | 100 (83.2-100) |
| | Retrospective | 2/2 | 100 (34.2-100) | 118/118 | 100 (96.8-100) |
| | Prospective/Retrospective | 4/4 | 100 (51.0-100) | 137/137 | 100 (97.3-100) |
| | Contrived | 46/46 | 100 (92.3-100) | 679/679 | 100 (99.4-100) |
| | Overall | 50/50 | 100 (92.9-100) | 816/816 | 100 (99.5-100) |
{20}------------------------------------------------
| Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | |
|--------------------|---------------------------|-----------------|------------------|-----------------|-----------------|
| | | TP/TP+FN | % (95% CI) | TN/TN+F P | % (95% CI) |
| Candida lusitaniae | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 3/4 | 75.0 (30.1-95.4) | 116/116 | 100 (96.8-100) |
| | Prospective/Retrospective | 3/4 | 75.0 (30.1-95.4) | 137/137 | 100 (97.3-100) |
| | Contrived | 45/45 | 100 (92.1-100) | 679/680 | 99.9 (99.2-100) |
| | Overall | 48/49 | 98.0 (89.3-99.6) | 816/817 | 99.9 (99.3-100) |
Table 14: Clinical Performance for Candida lusitaniae
# Table 15: Clinical Performance for Candida parapsilosis
| Target | Sample Type | TP/TP+FN | % (95% CI) | TN/TN+F<br>P | % (95% CI) |
|-------------------------|---------------------------|----------|------------------|--------------|------------------|
| Candida<br>parapsilosis | Prospective (Fresh) | 2/2 | 100 (34.2-100) | 9/9 | 100 (70.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 2/2 | 100 (34.2-100) | 19/19 | 100 (83.2-100) |
| | Retrospective | 16/17 | 94.1 (73.0-99.0) | 102/103 | 99.0 (94.7-99.8) |
| | Prospective/Retrospective | 18/19 | 94.7 (75.4-99.1) | 121/122A | 99.2 (95.5-99.9) |
| | Contrived | 41/41 | 100 (91.4-100) | 684/684 | 100 (99.4-100) |
| | Overall | 59/60 | 98.3 (91.1-99.7) | 805/806 | 99.9 (99.3-100) |
C. parapsilosis was detected in 1/1 false positive clinical sample using PCR/sequencing. A.
{21}------------------------------------------------
| Target | Sample Type | TP/TP+FN | Sensitivity/PPA<br>% (95% CI) | Specificity/NPA<br>TN/TN+F<br>P | % (95% CI) |
|--------------------|---------------------------|----------|-------------------------------|---------------------------------|------------------|
| Candida tropicalis | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 2/2 | 100 (34.2-100) | 8/8 | 100 (67.6-100) |
| | Prospective (All) | 2/2 | 100 (34.2-100) | 19/19 | 100 (83.2-100) |
| | Retrospective | 3/3 | 100 (43.9-100) | 116/117 | 99.1 (95.3-99.8) |
| | Prospective/Retrospective | 5/5 | 100 (56.6-100) | 135/136A | 99.3 (96.0-99.9) |
| | Contrived | 45/45 | 100 (92.1-100) | 680/680 | 100 (99.4-100) |
| | Overall | 50/50 | 100 (92.9-100) | 815/816 | 99.9 (99.3-100) |
Table 16: Clinical Performance for Candida tropicalis
A. C. tropicalis was detected in 1/1 false positive clinical sample using PCR/sequencing.
| | | Table 17: Clinical Performance for Cryptococcus gattii | | | |
|--|--|--------------------------------------------------------|--|--|--|
|--|--|--------------------------------------------------------|--|--|--|
| Target | Sample Type | TP/TP+FN | % (95% CI) | TN/TN+F P | % (95% CI) |
|---------------------|---------------------------|----------|----------------|-----------|----------------|
| Cryptococcus gattii | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 0/0 | --- | 120/120 | 100 (96.9-100) |
| | Prospective/Retrospective | 0/0 | --- | 141/141 | 100 (97.3-100) |
| | Contrived | 50/50 | 100 (92.9-100) | 675/675 | 100 (99.4-100) |
| | Overall | 50/50 | 100 (92.9-100) | 816/816 | 100 (99.5-100) |
{22}------------------------------------------------
| Target | Sample Type | TP/TP+FN | Sensitivity/PPA<br>% (95% CI) | TN/TN+F<br>P | Specificity/NPA<br>% (95% CI) |
|----------------------------|---------------------------|----------|-------------------------------|--------------|-------------------------------|
| Cryptococcus<br>neoformans | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 5/5 | 100 (56.6-100) | 115/115 | 100 (96.8-100) |
| | Prospective/Retrospective | 5/5 | 100 (56.6-100) | 136/136 | 100 (97.3-100) |
| | Contrived | 52/52 | 100 (93.1-100) | 673/673 | 100 (99.4-100) |
| | Overall | 57/57 | 100 (93.7-100) | 809/809 | 100 (99.5-100) |
Table 18: Clinical Performance for Cryptococcus neoformans
# Table 19: Clinical Performance for Fusarium
| | | Sensitivity/PPA | | Specificity/NPA | |
|----------|---------------------------|-----------------|------------------|-----------------|----------------|
| Target | Sample Type | TP/TP+FN | % (95% CI) | TN/TN+F<br>P | % (95% CI) |
| Fusarium | Prospective (Fresh) | 0/0 | --- | 11/11 | 100 (74.1-100) |
| | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 0/0 | --- | 21/21 | 100 (84.5-100) |
| | Retrospective | 0/0 | --- | 120/120 | 100 (96.9-100) |
| | Prospective/Retrospective | 0/0 | --- | 141/141 | 100 (97.3-100) |
| | Contrived | 69/70 | 98.6 (92.3-99.7) | 655/655 | 100 (99.4-100) |
| | Overall | 69/70 | 98.6 (92.3-99.7) | 796/796 | 100 (99.5-100) |
{23}------------------------------------------------
| Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | |
|-------------|---------------------------|-----------------|------------------|-----------------|-----------------|
| | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) |
| | Prospective (Fresh) | 1/1 | 100 (20.7-100) | 10/10 | 100 (72.2-100) |
| Rhodotorula | Prospective (Frozen) | 0/0 | --- | 10/10 | 100 (72.2-100) |
| | Prospective (All) | 1/1 | 100 (20.7-100) | 20/20 | 100 (83.9-100) |
| | Retrospective | 1/1 | 100 (20.7-100) | 119/119 | 100 (96.9-100) |
| | Prospective/Retrospective | 2/2 | 100 (34.2-100) | 139/139 | 100 (97.3-100) |
| | Contrived | 48/50 | 96.0 (86.5-98.9) | 674/675 | 99.9 (99.2-100) |
| | Overall | 50/52 | 96.2 (87.0-98.9) | 813/814 | 99.9 (99.3-100) |
Table 20: Clinical Performance for Rhodotorula
# Table 21: Contrived Sample Summary
| Target | Organism | Strain | Independent<br>Contrived Samples<br>Tested |
|---------------------------|------------------------------|---------------------|--------------------------------------------|
| Candida albicans | Candida albicans | ATCC 10231 | 2 |
| | | ATCC 14053 | 2 |
| | | ATCC 24433 | 2 |
| | | ATCC 90028 | 5 |
| | | ATCC MYA-4441 | 3 |
| | Candida albicans total | | 14 |
| Candida auris | Candida auris | ATCC 10913 | 1 |
| | | ATCC 12372 | 1 |
| | | ATCC 12766 | 1 |
| | | CBS 10913 | 3 |
| | | CBS 12372 | 3 |
| | | CBS 12373 | 2 |
| | | CBS 12766 | 3 |
| | | CBS 12767 | 3 |
| | | CBS 12768 | 2 |
| | | CDC#0385 | 5 |
| | | CDC#0386 | 5 |
| | | CDC#0387 | 5 |
| | | CDC#0388 | 5 |
| | | CDC#0389 | 5 |
| | | CDC#0390 | 5 |
| | | Candida auris total | |
| | | ATCC MYA-577 | 6 |
| Target | Organism | Strain | Independent<br>Contrived Samples<br>Tested |
| Candida<br>dubliniensis | Candida dubliniensis | ATCC MYA-578 | 12 |
| | Candida dubliniensis | ATCC MYA-579 | 12 |
| | Candida dubliniensis | ATCC MYA-582 | 13 |
| | Candida dubliniensis | NCPF3949 | 5 |
| | Candida dubliniensis total | | 48 |
| Candida famata | Debaryomyces fabryi | CBS 789 | 21 |
| | Debaryomyces hansenii | CBS 1961 | 3 |
| | Debaryomyces subglobosus | CBS 1796 | 27 |
| | Candida famata total | | 51 |
| Candida glabrata | Candida glabrata | 128-4058 | 1 |
| | | 128-4072 | 1 |
| | | ATCC 15126 | 2 |
| | | ATCC 15545 | 2 |
| | | ATCC 2001 | 1 |
| | | ATCC 66032 | 4 |
| | | ATCC 90030 | 2 |
| | Candida glabrata | ATCC MYA-2950 | 3 |
| | Candida glabrata total | | 16 |
| Candida<br>guilliermondii | Candida guilliermondii | ATCC 22017 | 13 |
| | | ATCC 6260 | 12 |
| | Meyerozyma guilliermondii | ATCC 90197 | 10 |
| | | ATCC 90198 | 9 |
| | | ATCC 90199 | 6 |
| | Candida guilliermondii total | | 50 |
| Candida kefyr | Candida kefyr | ATCC 204093 | 4 |
| | | ATCC 2512 | 10 |
| | | ATCC 4135 | 13 |
| | | ATCC 66028 | 12 |
| | | ATCC 8553 | 12 |
| | Candida kefyr total | | 51 |
| Candida krusei | Candida krusei | ATCC 14243 | 8 |
| | | ATCC 22985 | 9 |
| | | ATCC 28870 | 9 |
| | | ATCC 32196 | 10 |
| | | ATCC 34135 | 10 |
| | Candida krusei total | | 46 |
| Target | Organism | Strain | Independent<br>Contrived Samples<br>Tested |
| Candida<br>lusitaniae | Candida lusitaniae | ATCC 26287 | 5 |
| | | ATCC 34449 | 10 |
| | | ATCC 42720 | 9 |
| | | ATCC 66035 | 11 |
| | | ATCC MYA-766 | 10 |
| | Candida lusitaniae total | | 45 |
| Candida<br>parapsilosis | Candida parapsilosis | ATCC 22019 | 11 |
| | | ATCC 28474 | 5 |
| | | ATCC 28475 | 10 |
| | | ATCC 58895 | 7 |
| | | ATCC 90018 | 8 |
| | Candida parapsilosis total | | 41 |
{24}------------------------------------------------
{25}------------------------------------------------
| Candida tropicalis | Candida tropicalis | ATCC 1369 | 9 |
|----------------------------|-----------------------------------------------------------------------------------------------------------------|-------------------------------|---------------------|
| | | ATCC 13803 | 12 |
| | | ATCC 201380 | 9 |
| | | ATCC 201381 | 7 |
| | | ATCC 750 | 8 |
| | | Candida tropicalis total | 45 |
| Cryptococcus<br>gattii | Cryptococcus gattii | ATCC 14248 | 11 |
| | | | ATCC 76108 |
| | | | ATCC MYA-4138 |
| | | | ATCC MYA-4560 |
| | | ATCC MYA-4877 | 9 |
| |…
