BioFire Joint Infection (JI) Panel

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol on the left is a stylized representation of a caduceus, a symbol often associated with medicine and healthcare. The text on the right is in a blue font, with "FDA" in a larger, bolder font than the rest of the text. # EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR BioFire Joint Infection (JI) Panel DECISION SUMMARY #### I Background Information: #### A De Novo Number DEN200066 ### B Applicant BioFire Diagnostics, LLC ### C Proprietary and Established Names BioFire Joint Infection (JI) Panel ### D Regulatory Information | Product<br>Code(s) | Classification | Regulation<br>Section | Panel | |--------------------|----------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------| | QSN | Class II | 21 CFR 866.3988 - Device<br>to detect and identify<br>microorganism nucleic<br>acids and resistance<br>markers from patients with<br>suspected orthopedic<br>infection | MI - Microbiology | #### II Submission/Device Overview: #### A Purpose for Submission: De Novo request for evaluation of automatic class III designation for BioFire Joint Infection (JI) Panel #### B Measurand: Anaerococcus prevotii/vaginalis, Bacteroides fragilis, Candida spp., Candida albicans, Citrobacter, Clostridium perfringens, Cutibacterium avidum/granulosum, Enterobacter cloacae complex, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Fingoldia magna, Haemophilus influenzae, Kingella kingae, Klebsiella aerogenes, Klebsiella pneumoniae group, Morganella morganii, Neisseria gonorrhoeae, Parvimonas micra, Peptoniphilus, Peptostreptococcus anaerobius, Proteus spp., Pseudomonas aeruginosa, Salmonella spp., Serratia marcescens, {1}------------------------------------------------ Staphylococcus aureus, Staphylococcus lugdunensis, Streptococcus spp., Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, CTX-M. IMP. KPC. NDM. OXA-48-like. VIM. mecA/C and MREJ. #### C Type of Test: Qualitative nucleic acid amplification assay #### III Indications for Use: #### A Indication(s) for Use: The BioFire Joint Infection (JI) Panel is a multiplexed nucleic-acid-based, in vitro diagnostic test intended for use with BioFire FilmArray 2.0 and BioFire FilmArray Torch Systems for the simultaneous qualitative detection and identification of multiple bacterial and yeast nucleic acids and select antimicrobial resistance genes from synovial fluid obtained from individuals suspected to have a joint infection. The following organisms are identified using the BioFire JI Panel: Anaerococcus prevotii/vaginalis, Bacteroides fragilis, Candida spp., Candida albicans, Citrobacter, Clostridium perfringens, Cutibacterium avidum/granulosum, Enterobacter cloacae complex, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Fingoldia magna, Haemophilus influenzae, Kingella kingae, Klebsiella aerogenes, Klebsiella pneumoniae group, Morganella morganii. Neisseria gonorrhoeae, Parvimonas micra, Peptoniphilus, Peptostreptococcus anaerobius, Proteus spp., Pseudomonas aeruginosa, Salmonella spp., Serratia marcescens, Staphylococcus aureus, Staphylococcus lugdunensis, Streptococcus spp., Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes. The BioFire JI Panel contains assays for the detection of genetic determinants associated with S. aureus resistance to methicillin (mecA/C) in conjunction with the SCCmec right extremity junction (MREJ), enterococcal resistance to vancomycin (vanA and vanB), and some mechanisms of gram-negative bacterial resistance ß-lactams including penicillins, cephalosporins, monobactams, and carbapenems (blactx.M, blakec, blaNDM, blaOXA-48-like; blavin). Detection of these genetic determinants can aid in the identification of potentially antimicrobial-resistant organisms in synovial fluid samples. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene assays do not indicate susceptibility, as multiple mechanisms of resistance to methicillin, vancomycin, and ß-lactams exist. The BioFire JI Panel is indicated as an aid in the diagnosis of specific agents of joint infection and results should be used in conjunction with other clinical and laboratory findings. Negative results may be due to infection with pathogens that are not detected by this test, pathogens present below the limit of detection of the assay, or infection that may not be detected in a synovial fluid specimen. Positive results do not rule out co-infection with other organisms. The BioFire JI Panel is not intended to monitor treatment for joint infections. {2}------------------------------------------------ Culture of synovial fluid is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the synovial fluid that are not detected by the BioFire JI Panel, and to further identify species in the genus, complex or group results. #### B Special Conditions for Use Statement(s): Rx - For Prescription Use Only #### C Special Instrument Requirements: The BioFire JI Panel is performed on the FilmArray 2.0 or FilmArray Torch systems. #### IV Device/System Characteristics: #### A Device Description: The BioFire Joint Infection (JI) Panel is designed to simultaneously identify 39 different bacteria, yeast, and select genetic determinants of antimicrobial resistance from synovial fluid specimens. The BioFire JI Panel is compatible with BioFire's PCR-based in vitro diagnostic BioFire FilmArray 2.0 and BioFire FilmArray Torch Systems for infectious disease testing. A panel-specific software module (i.e., BioFire JI Panel pouch module software) is used to perform BioFire JI Panel testing on these systems. A test is initiated by loading Hydration Solution into one port of the BioFire JI Panel pouch and the synovial fluid sample mixed with the provided Sample Buffer into the other port of the BioFire JI Panel pouch and placing it in a FilmArray instrument. The pouch contains all of the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the BioFire Software guides the user through the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run. The FilmArray instrument contains a coordinated system of inflatable bladders and seal points. which act on the pouch to control the movement of liguid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically-controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis. Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the Film Array performs a nested multiplex PCR that is executed in two stages. During the first stage, the FilmArray performs a single, large volume, highly {3}------------------------------------------------ multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LC Green Plus, BioFire Diagnostics). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the end of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data. The FilmArray Software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel. #### Materials provided in each BioFire Joint Infection Panel kit: Each kit contains sufficient reagents to test 30 samples (30-test kit; RFIT-ASY-0138): - . Individually-packaged BioFire JI Panel pouches - Single-use (1.0 mL) Sample Buffer ampoules . - Single-use pre-filled (1.5 mL) Hydration Injection Vials (blue) . - Single-use Sample Injection Vials (red) . - Individually-packaged Transfer Pipettes . #### Materials required but not provided: - . FilmArray system including: - FilmArray 2.0 or FilmArray Torch and accompanying software - FilmArray Pouch Loading Station - · 10% bleach solution #### Interpretation of Results When PCR2 is complete, the FilmArray instrument performs a DNA melting analysis on the PCR products and measures the fluorescence signal generated in each well (for more information see appropriate FilmArray Operator's Manual). The FilmArray Software then performs several analyses and assigns a final assay result. The steps in the analyses are described below. #### Analysis of Melt Curves The FilmArray Software evaluates the DNA melt curve for each well of the PCR2 array to determine if a PCR product was present in that well. If the melt profile indicates the presence of a PCR product, then the analysis software calculates the melting temperature (Tm) of the curve and compares it against the expected Tm range for the assay. If the software {4}------------------------------------------------ determines that the Tm of the curve is within the assay-specific Tm range. the melt curve is called positive. If the software determines that the Tm of the curve is not in the appropriate Tm range, the melt curve is called negative. #### Analysis of Replicates Once positive melt curves have been identified, the software evaluates the replicates for each assay to determine the assay result. For an assay to be called positive, two associated melt curves must be called positive, and both Tms must be similar. Assays that do not meet these criteria are called negative. #### Organism and Antimicrobial Resistance Gene Interpretation Each positive and negative assay result is interpreted by the FilmArray Software to provide results for the identification of specific bacteria and antimicrobial resistance (AMR) genes. For most analytes detected by the BioFire JI Panel, interpretations are based on the result of a single assay. However, results for the AMR genes require interpretation based on more than one assay result, as discussed in the relevant sections below. #### Interpretations for Gram-positive Bacteria The BioFire Joint Infection Panel provides a Detected or Not Detected result for most gram-positive bacteria based on one corresponding assay result. If the assay is positive, the test result will be Detected, and if the assay is negative, the test result will be Not Detected. Detection of organisms for which results are based on the interpretation of more than one assay are described below. #### Cutibacterium avidum/granulosum The BioFire JI Panel contains two assays (Cutibacterium1 and Cutibacterium 2) for the detection of these two Curibacterium species. A positive result for one or both assays will generate a Cutibacterium avidum/granulosum Detected test result. Cutibacterium avidum/granulosum will be reported as Not Detected when both assays are negative. #### Staphylococcus aureus The BioFire JI Panel contains two different assays (Saureus1 and Saureus2) for the detection of Staphylococcus aureus. The FilmArray Software interprets each of these assays independently (as described above) and if one or a combination of the assays is positive, the result will be Staphylococcus aureus Detected. If both assays are negative the result will be Staphylococcus aureus Not Detected. {5}------------------------------------------------ Streptococcus spp. The BioFire JI Panel contains four assays for the detection of Streptococcus species. Species-specific assays are included for the detection of Streptococcus pyogenes (Spyogenes), Streptococcus agalactiae (Sagalactiae), and Streptococcus pneumoniae (Spneumoniae). The fourth assay is a genus level assay (Streptococcus) designed to react with most Viridans group and other Streptococcus species that are not specifically identified by one of the other assays on the panel. The software integrates the results of all four Streptococcus assays into a Streptococcus spp. result as shown in the table below. | BioFire JI Panel Results | Streptococcus | Sagalactiae | Spneumoniae | Spyogenes | Description | |---------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------|-------------|-------------|-----------|-----------------------------------------------------------------------------------------------------------------------------------------------------------| | | Assay | Assay | Assay | Assay | | | Streptococcus spp Not<br>Detected<br>Streptococcus agalactiae<br>Not Detected<br>Streptococcus pneumoniae<br>Not Detected<br>Streptococcus pyogenes<br>Not Detected | Negative | Negative | Negative | Negative | No Streptococcus species<br>detected in the sample | | Streptococcus spp Detected<br>Streptococcus agalactiae<br>Not Detected<br>Streptococcus pneumoniae<br>Not Detected<br>Streptococcus pyogenes<br>Not Detected | Positive | Negative | Negative | Negative | One or more Streptococcus<br>species detected in the sample<br>(not S. agalactiae, S.<br>pneumoniae, or S. pyogenes) | | Streptococcus spp Detected<br>Streptococcus agalactiae<br>Detected<br>Streptococcus pneumoniae<br>Not Detected<br>Streptococcus pyogenes<br>Not Detected | Any Result | Positive | Negative | Negative | S. agalactiae detected in the<br>sample.<br>Note: additional Streptococcus<br>species (not S. pneumoniae or<br>S. pyogenes) may also be in<br>the sample. | | Streptococcus spp Detected<br>Streptococcus agalactiae<br>Not Detected<br>Streptococcus pneumoniae<br>Detected<br>Streptococcus pyogenes<br>Not Detected | Any Result | Negative | Positive | Negative | S. pneumoniae detected in the<br>sample.<br>Note: additional Streptococcus<br>species (not S. agalactiae or S.<br>pyogenes) may also be in the<br>sample. | | Streptococcus spp Detected<br>Streptococcus agalactiae<br>Not Detected<br>Streptococcus pneumoniae<br>Not Detected<br>Streptococcus pyogenes<br>Detected | Any Result | Negative | Negative | Positive | S. pyogenes detected in the<br>sample.<br>Note: additional Streptococcus<br>species (not S. agalactiae or S.<br>pneumoniae) may also be in<br>the sample. | #### Table 1. Streptococcus Species Results Reporting {6}------------------------------------------------ #### Interpretations for Gram-negative Bacteria The BioFire JI Panel contains assays for the specific detection of several gram-negative aerobic and anaerobic species associated with bone and joint infections. Species are identified individually (Bacteroides fragilis, Escherichia coli, Haemophilus influenzae, Kingella kingae, Klebsiella aerogenes, Morganella morganii, Neisseria gonorrhoeae, Pseudomonas aeruginosa. Serratia marcescens), or as multi-species complex, group, or genus results (Enterobacter cloacae complex, Klebsiella pneumoniae group, Citrobacter, Proteus spp., and Salmonella spp.). Each species, complex, group, or genus result is reported as Detected or Not Detected based on an individual corresponding assay result. If the assay is positive, the result will be Detected; if the assay is negative, the result will be Not Detected. #### Interpretations for Antimicrobial Resistance (AMR) Genes The BioFire JI Panel contains assays for the specific detection of several genetic determinants of resistance to multiple classes of antibiotics found in select gram-positive bacteria (mecA/C and MREJ [MRSA] and vanA/B) or gram-negative bacteria (CTX-M, IMP, KPC, NDM, OXA-48-like, and VIM). Results for the AMR genes are not reported unless an applicable bacterium (Table 2) is also detected, therefore the results are based on multiple assays, as described below. The results for each of the antimicrobial resistance genes will be listed as either: - i Detected - when an applicable bacterium is detected AND the antimicrobial resistance gene assay(s) are positive. - i Not Detected - when an applicable bacterium is detected AND the antimicrobial resistance gene assay(s) are negative. - i N/A - when all applicable bacteria are Not Detected, regardless of the result for the antimicrobial resistance gene assay(s). #### Table 2: Antimicrobial Resistance (AMR) Genes and Applicable Organisms | AMR Gene Result | Applicable Bacteria | |-----------------|-----------------------------------------------| | mecA/C and MREJ | Staphylococcus aureus | | vanA/B | Enterococcus faecalis<br>Enterococcus faecium | {7}------------------------------------------------ | AMR Gene Result | Applicable Bacteria | |-----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | CTX-M | Citrobacter<br>Enterobacter cloacae complex<br>Escherichia coli<br>Klebsiella aerogenes<br>Klebsiella pneumoniae group<br>Morganella morganii<br>Proteus spp.<br>Pseudomonas aeruginosa<br>Salmonella spp.<br>Serratia marcescens | | IMP | Citrobacter<br>Enterobacter cloacae complex<br>Escherichia coli<br>Klebsiella aerogenes<br>Klebsiella pneumoniae group<br>Morganella morganii<br>Proteus spp.<br>Pseudomonas aeruginosa<br>Salmonella spp.<br>Serratia marcescens | | KPC | Citrobacter<br>Enterobacter cloacae complex<br>Escherichia coli<br>Klebsiella aerogenes<br>Klebsiella pneumoniae group<br>Morganella morganii<br>Proteus spp.<br>Pseudomonas aeruginosa<br>Salmonella spp.<br>Serratia marcescens | | NDM | Citrobacter<br>Enterobacter cloacae complex<br>Escherichia coli<br>Klebsiella aerogenes<br>Klebsiella pneumoniae group<br>Morganella morganii<br>Proteus spp.<br>Pseudomonas aeruginosa<br>Salmonella spp.<br>Serratia marcescens | | VIM | Citrobacter<br>Enterobacter cloacae complex<br>Escherichia coli<br>Klebsiella aerogenes<br>Klebsiella pneumoniae group<br>Morganella morganii<br>Proteus spp.<br>Pseudomonas aeruginosa<br>Salmonella spp.<br>Serratia marcescens | | OXA-48-like | Citrobacter<br>Enterobacter cloacae complex<br>Escherichia coli<br>Klebsiella aerogenes<br>Klebsiella pneumoniae group<br>Morganella morganii<br>Proteus spp.<br>Salmonella spp.<br>Serratia marcescens | Each AMR gene result is associated with a single corresponding assay except for the mecA/C and MREJ result, which is dependent on both the mecA/C assay and the MREJ assay. Detection of both Staphylococcus aureus and the mecA/C and MREJ markers is indicative of Methicillin Resistant Staphylococcus Aureus (MRSA). # Run Summary The Run Summary section of the test report provides information about the sample and the run including: Sample ID, time and date of run, control results, and an overall summary of the test results. Control results are reported as Passed, Failed, or Invalid. The Table 3 below provides additional information for each of the possible control field results. | Table 3: Interpretation of Controls Field on the BioFire JI Panel Test Report | | | | | |-------------------------------------------------------------------------------|--|--|--|--| | | | | | | | Control<br>Result | Explanation | Action | |-------------------|--------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------| | Passed | The run was successfully completed<br>AND<br>Both pouch controls were<br>successful. | None<br>Report the results provided on the test report. | | Failed | The run was completed<br>BUT<br>At least one of the pouch controls<br>(RNA Process Control and/or<br>PCR2) failed. | Repeat the test using a new pouch.<br>If the error persists, contact Customer<br>Technical Support for further instruction. | {8}------------------------------------------------ | Control<br>Result | Explanation | Action | |-------------------|------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Invalid | The controls are invalid because the<br>run did not complete.<br>(Typically this indicates a software<br>or hardware error). | Note the Run Status field in the Run Details<br>section of the report. Refer to the appropriate<br>BioFire operator's manual or contact<br>Technical Support for further instruction.<br>Once the error is resolved, repeat the test or<br>repeat the test using another module, if<br>available. | # Result Summary The Results Summary section of the test report lists the result for each target tested by the panel. Possible results for each organism are Detected, Not Detected, or Invalid. Possible results for each antimicrobial resistance gene are Detected, Not Detected, N/A, or Invalid. Table 4 below provides an explanation for each interpretation and any follow-up necessary to obtain a final result. | Result | Explanation | Action | |----------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------| | Detected | The run was successfully completed<br>AND<br>The pouch controls were successful (Passed)<br>AND<br>The assay(s) for the organism were POSITIVE | Report<br>results. | | Not Detected | The run was successfully completed<br>AND<br>The pouch controls were successful (Passed)<br>AND<br>The assay(s) for the organism were NEGATIVE | Report<br>results. | | Invalid | The pouch controls were not successful (Failed)<br>OR<br>The run was not successful<br>(Run Status displayed as: Aborted, Incomplete, Instrument<br>Error or Software Error) | See Table<br>3 for<br>instruction. | | N/A<br>(Antimicrobial<br>Resistance<br>Genes only) | The run was successfully completed<br>AND<br>The pouch controls were successful (Passed)<br>AND<br>The assay(s) for the organism(s) associated with the<br>antimicrobial resistance gene were NEGATIVE so the<br>results of the antimicrobial resistance gene are not<br>applicable to the test results. | Report<br>results. | ## Table 4: Reporting of Results and Required Actions # B Principle of Operation {9}------------------------------------------------ The BioFire JI Panel pouch is a closed system disposable that stores all the necessary reagents for sample preparation, reverse transcription, polymerase chain reaction (PCR), and detection in order to isolate, amplify, and detect nucleic acid from multiple bacterial and/or fungal pathogens within a single synovial fluid specimen. After sample collection, the user injects hydration solution and sample combined with sample buffer into the pouch, places the pouch into a FilmArray instrument, and starts a run. The entire run process takes about one hour. Additional detail can be found in the appropriate FilmArray Operator's Manual. During a run, the FilmArray system: - . Lyses the sample by agitation (bead beading). - . Extracts and purifies all nucleic acids from the sample using magnetic bead technology. - Performs nested multiplex PCR bv: . - · First performing reverse transcription and a single, large volume. massively-multiplexed reaction (PCR1) - · Then performing multiple singleplex second-stage PCR reactions (PCR2) to amplify sequences within the PCR1 products - . Uses endpoint melting curve data to detect and generate a result for each target on the BioFire Joint Infection Panel array. #### C Instrument Description Information - 1. Instrument Name: FilmArray 2.0 or FilmArray Torch - 2. Specimen Identification: Synovial fluid specimens - 3. Specimen Sampling and Handling: Synovial fluid specimens should be tested as soon as possible after collection. If transport or storage is required, specimens can be held refrigerated for up to 7 days (2-8°C), - 4. Calibration: N/A - 5. Quality Control: See section VI.5 for information on internal and external controls. {10}------------------------------------------------ #### V Standards/Guidance Documents Referenced: - . ISO 14971:2019 Medical devices - Applications of risk management to medical devices - IEC 62366-1:2015, Medical device Application of usability . engineering to medical devices - ISO 62304:2006. Medical device software Software life-cycle . processes - IEC 62304:2006, November 27, 2008 - . ISO 15223-1:2016 Medical Devices - Symbols to be used with medical devie labels, labeling and information to be supplied - Part 1: General requirements - . ISO13485:2016/EN ISO 13485:2016. Medical devices - Quality Management System - Requirements for regulatory purposes - ISO 20916:2019 In vitro diagnostic medical devices Clinical . performance studies using specimens from human subjects - Good study practice - . EN 13612:20002, Performance evaluation of in vitro diagnostic medical devices (European Commission) - EN ISO 18113-1:2011. In vitro diagnostic medical devices -. Information supplied by the manufacturer (labeling) - Part 1: Terms, definition, and general requirements - . EN ISO 18113-2:2011, In vitro diagnostic medical devices -Information supplied by the manufacturer (labeling) - Part 2: In vitro diagnostic reagents for professional use - EN ISO 23640: 2015. In vitro diagnostic medical devices -. Evaluation of stability of in vitro diagnostic reagents #### Performance Characteristics: VI #### A Analytical Performance: #### 1. Precision/Reproducibility: A multi-site reproducibility study of the BioFire JI Panel was performed with contrived synovial fluid samples over multiple days at three laboratory locations (sites) on a combination of FilmArray 2.0 and FilmArray Torch systems. Reproducibility represents the run-to-run variability of results under actual use conditions over time and is measured as agreement with the expected result. The study evaluated contrived samples containing a subset of representative organisms and AMR genes at two concentrations (and negative). The study incorporated potential variation introduced by site (three), day (five), operator (at least two per site), instrument module/system, and reagent kit lot (three). Negative results were obtained from samples that were not spiked with the organism or AMR gene. {11}------------------------------------------------ Each of the three sites tested 20 replicates per sample and system for a total of 120 valid runs per sample and 480 valid runs overall. A summary of results (percent (%) agreement with the expected Detected or Not Detected result) for each atypical bacterium and virus (by site and system) is provided Table 5 below. | | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | | | |----------------------------------------------------------------------------|----------------------------------------------------------------------|--------------------------------------------|--------------------------------|--------------------------------|------------------------------------------|-------------------------------------| | Analyte | | | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | | | Gram Positive Bacteria | | | | | | Anaerococcus<br>prevotii/vaginalis | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Clostridium perfringens | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Cutibacterium<br>avidum/granulosum | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Enterococcus faecalis | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 238/240<br>99.2% | 478/480<br>99.6%<br>[98.5%-<br>99.9%] | | | | Moderate Positive<br>3× LoD<br>3.6E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | Enterococcus faecium<br>(ATCC 700221) | Low Positive<br>1× LoD<br>1.2E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Finegoldia magna | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Parvimonas micra | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Peptoniphilus | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Peptostreptococcus<br>anaerobius<br>(ATCC 27337) | Moderate Positive<br>3× LoD<br>4.8E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | | | | Analyte | | | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | | Low Positive<br>1× LoD<br>1.6E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | | Moderate Positive<br>3× LoD<br>1.3E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | Staphylococcus aureus<br>(ATCC 43300) | Low Positive<br>1× LoD<br>4.2E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 119/120<br>99.2% | 239/240<br>99.6%<br>[97.7%-<br>99.9%] | | | Staphylococcus<br>lugdunensis | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | | Moderate Positive<br>3× LoD<br>1.6E+03 copies/mL | Detected | 58/60<br>96.7% | 60/60<br>100% | 118/120<br>98.3%<br>[94.1%-<br>99.8%] | | | Streptococcus spp.<br>(Streptococcus pneumoniae;<br>ATCC 6303) | Low Positive<br>1× LoD<br>5.3E+02 copies/mL | Detected | 59/60<br>98.3% | 59/60<br>98.3% | 118/120<br>98.3%<br>[94.1%-<br>99.8%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Streptococcus agalactiae | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Streptococcus pneumoniae<br>(ATCC 6303) | Moderate Positive<br>3× LoD<br>1.6E+03 copies/mL | Detected | 58/60<br>96.7% | 60/60<br>100% | 118/120<br>98.3%<br>[94.1%-<br>99.8%] | | | Analyte | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | | | | | | | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | | Low Positive<br>1x LoD<br>5.3E+02 copies/mL | Detected | 59/60<br>98.3% | 59/60<br>98.3% | 118/120<br>98.3%<br>[94.1%-<br>99.8%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Streptococcus pyogenes | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | | | | Analyte | | | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | Bacteroides fragilis<br>(ATCC 25285) | Moderate Positive<br>3× LoD<br>3.3E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Low Positive<br>1× LoD<br>1.1E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Citrobacter<br>(Citrobacter freundii;<br>ATCC 8090) | Moderate Positive<br>3× LoD<br>1.4E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Low Positive<br>1× LoD<br>4.7E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Enterobacter cloacae<br>complex | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Eschericia coli<br>AR-Bank#0150 | High Positive<br>30× LoD<br>1.8E+05 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | High Positive<br>10× LoD<br>6.0E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Haemophilus influenzae<br>ATCC 10211 | Moderate Positive<br>3× LoD<br>2.1E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Low Positive<br>1× LoD<br>6.9E+02 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Analyte | Concentration<br>Tested | Expected<br>Result | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | Kingella kingae | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Klebsiella aerogenes | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Klebsiella pneumoniae<br>group<br>(Klebsiella pneumoniae;<br>AR-Bank#0097) | Moderate Positive<br>3x LoD<br>4.8E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | Klebsiella pneumoniae<br>group<br>(Klebsiella pneumoniae;<br>AR-Bank#0097) | Low Positive<br>1x LoD<br>1.6E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | Klebsiella pneumoniae<br>group<br>(Klebsiella pneumoniae;<br>AR-Bank#0097) | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Morganella morganii | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Neisseria gonorrhoeae<br>ATCC 19424 | Moderate Positive<br>3x LoD<br>6.6E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | Neisseria gonorrhoeae<br>ATCC 19424 | Low Positive<br>1x LoD<br>2.2E+03 copies/mL | Detected | 59/60<br>98.3% | 60/60<br>100% | 119/120<br>99.2%<br>[95.4%-<br>99.9%] | | | Neisseria gonorrhoeae<br>ATCC 19424 | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Proteus spp. | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Pseudomonas aeruginosa | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Salmonella spp. | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Serratia marcescens | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Yeast | | | | | | | | Analyte | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | | | | | | | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | <i>Candida krusei</i><br>(ATCC 6258) | Moderate Positive<br>3× LoD<br>3.0E+03 CFU/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | <i>Candida krusei</i><br>(ATCC 6258) | Low Positive<br>1× LoD<br>1.0E+03 CFU/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | <i>Candida krusei</i><br>(ATCC 6258) | None<br>(No Analyte) | Not Detected | N/A | | | | | <i>Candida albicans</i><br>(ATCC 90028) | Moderate Positive<br>3× LoD<br>1.5E+03 CFU/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | <i>Candida albicans</i><br>(ATCC 90028) | Low Positive<br>1× LoD<br>5.0E+02 CFU/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | <i>Candida albicans</i><br>(ATCC 90028) | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | Analyte | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | All Sites<br>[95% CI] | | | CTX-M | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | IMP | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | KPC<br>(Klebsiella pneumoniae;<br>AR-Bank#0097) | Moderate Positive<br>3× LoD<br>4.8E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Low Positive<br>1× LoD<br>1.6E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | mecA/C and MREJ<br>(MRSA)<br>(Staphylococcus aureus;<br>ATCC 43300) | Moderate Positive<br>3× LoD<br>1.3E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Low Positive<br>1× LoD<br>4.2E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | NDM<br>(E. coli;<br>AR-Bank#0150) | High Positive<br>30× LoD<br>1.8E+05 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | High Positive<br>10× LoD<br>6.0E+04 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | OXA-48-like | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | vanA/B<br>(Enterococcus faecium;<br>ATCC 700221) | Moderate Positive<br>3× LoD<br>3.6E+03 copies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | Analyte | Concentration<br>Tested | Expected<br>Result | Agreement with Expected Result | | | | | | | | FilmArray<br>2.0 | FilmArray<br>Torch | All Sites<br>[95% CI] | | | | Low Positive<br>1× LoD<br>1.2E+03 opies/mL | Detected | 60/60<br>100% | 60/60<br>100% | 120/120<br>100%<br>[97.0%-<br>100%] | | | | None<br>(No Analyte) | Not Detected | 120/120<br>100% | 120/120<br>100% | 240/240<br>100%<br>[98.5%-<br>100%] | | | VIM | None<br>(No Analyte) | Not Detected | 240/240<br>100% | 240/240<br>100% | 480/480<br>100%<br>[99.2%-<br>100%] | | | Overall Agreement with Expected Results<br>[95% Confidence Interval] | | | | 18,468/18,480<br>99.94%<br>[99.89-99.97] | | Table 5: Reproducibility of BioFire Joint Infection Panel Results {12}------------------------------------------------ {13}------------------------------------------------ {14}------------------------------------------------ {15}------------------------------------------------ {16}------------------------------------------------ {17}------------------------------------------------ {18}------------------------------------------------ # 2. Linearity: Not applicable. # 3. Analytical Specificity/Interference: # Analytical Reactivity Analytical reactivity of the BioFire JI Panel assays was evaluated using a combination of in silico analysis of sequences available in public databases and testing of over 350 different isolates representing various species, subspecies, strains, serotypes, AMR gene types, and other characterized variants. Each isolate was tested in triplicate at concentrations near LoD or the lowest reportable level for the analyte. Limitations on assay reactivity (observed and/or predicted by in silico analysis) with specific bacterial and yeast isolates or sequences and specific AMR gene types or sequences are noted (Table 6). Most limitations are associated with single-base sequence variants under one or more assay primers. # Table 6. Limitations on Analytical Reactivity of BioFire JI Panel Assays | Limitation | Analyte | Strain/Isolate Variant | |-----------------------------------------------------|-----------------------------------|----------------------------------------------------------------------------------------------------------------------| | Minor<br>(Detected at <30X LoD) | Anaerococcus prevottii/vaginalisª | clinical isolates (private<br>collection) with variant sequencesa | | | Enterobacter cloacae complexb | Enterobacter hormaechei ATCC<br>49162b | | | Pseudomonas aeruginosa | Pseudomonas aeruginosa ATCC 9027 | | | Candida albicansc | 'petite' strains (altered or no mitochondrial DNA)c | | | Cutibacterium granulosum | clinical isolate (private collection with variant sequence | | | Enterobacter cloacae complexb | Enterobacter asburiae ATCC 35953, ATCC35954, and ATCC 35957b | | | Haemophilus influenzae | clinical isolate (private collection USA 2012) with gene target deletion | | | Klebsiella aerogenes | Klebsiella (Enterobacter) aerogenes ATCC 29751 | | | Neisseria gonorrhoeae | Neisseria gonorrhoeae NCTC 13817 (strain WHO-U) | | Major<br>(Detected at ≥100X LoD<br>Or Not Detected) | Pseudomonas aeruginosa | Pseudomonas aeruginosa ATCC 25619 | | | Streptococcus pyogenes | clinical isolate (private collection USA 2019) with gene target deletion or re-arrangement | | | AMR Gene Types | | | | CTX-M | CTX-M types 74, 75, 113, 151 | | | IMP | IMP types 31, 35, 46 | | | <i>mecA/C</i> and MREJd,e | MREJ type xvd, xviiie, xixe, xxe | | | VIM | VIM types 7, 39, 45, 46, 61, 65, 67 | | | Rare or Non-relevant Species | | | | Candida spp. | several Candida species; see Error! Reference source not found. | | | Citrobacter | Citrobacter almonaticus, C. farmeri, C.gillenii, C. rodentium, C. sedlakii | | | Peptoniphilus spp. | Peptoniphilus coxii, P. duerdenii, P. ivorii, P. koenoeneniae, P. massiliensisf, P. porci, P. olsenii, P. tyrelliase | | | Streptococcus spp. | Streptococcus entericus, S.halitosis, S. hyovaginalis, S. pantholopis | {19}------------------------------------------------ 3 Detection near LoD was impaired for four isolates of A. vaginalis. Sequencing revealed primer mismatches predicted to impar detection. Comparable sequence variants were observed in two A. vaginalis sequences retrieved from public databases. A limitation on reactivity is predicted for approximately 25% of A. prevotii/vaginalis sequences and isolates evaluated. b Reactivity limitations observed or predicted for sequence variants identified for E. hormacchei ATCC 49162, E. asburiae ATCC 35953 (tested), ATCC 35954 (not tested), ATCC 35955 (not tested), and a small subset of database sequences for E. cloacae, E. hormaechei, E. ludwigii and E. mori with similar or less impactful variants under assay primers. Variant sequences with major or minor reactivity limitations represent less than 2% of sequences for ECC species. · Petite strains of Candida albicans will not be detected by the Candida albicans-specific assay but will be amplified by the multi-species Candida assay and reported as Candida Detected. 4 Sequence analysis predicts that approximately 40% of MREJ type xv-like sequences will not be detected due to a variant base at the 3' end of an assay primer. € MREJ types xviii, xix and xx will not be described in association with methicillin-sensitive isolates, so the meca/C and MREJ (MRSA) Not Detected result with the methicillin-sensitive phenotype of isolates with these MREJ types. f Not a validly published Peptoniphilus species. {20}------------------------------------------------ | Organism | Isolate ID<br>(Strain) | Test<br>Concentration<br>(copies/mL) | xLoD | Result | |-----------------------------------------|----------------------------|--------------------------------------|------|--------------------------------------------------| | <i>Anaerococcus</i><br><i>prevotii</i> | ATCC 9321<br>(PC 1) | 4.8E+03 | 1x | <i>Anaerococcus prevotii/vaginalis</i> Detecteda | | | ATCC 14952<br>(M3) | 1.4E+05 | 3x | | | | CCUG 72601 | 1.4E+05 | 3x | | | | VTK 400239 | 1.4E+05 | 3x | | | | ATCC 51170<br>(GIFU 12669) | 4.8E+04 | 1x | | | | DSM 25446<br>(ph9) | 1.4E+05 | 3x | | | <i>Anaerococcus</i><br><i>vaginalis</i> | GRE 1654021 | 1.4E+05 | 3x | | | | GRE 1554051a | 1.4E+06 | 30x | | | | GRE 1653021 | 4.8E+05 | 10x | | | | GRE 1757298a | 4.8E+05 | 10x | | | | VTK 401665a | 1.4E+06 | 30x | | | | VTK 401672a | 4.8E+05 | 10x | | Table 7: Angerococcus prevotii/vaginalis Isolates Tested aVariant sequence with 3' base mismatch to a primer that may impair detection near LoD (10 to 30-fold). Variant sequences with minor detection impairment represent ~25% of total A. prevotii/vaginalis sequences evaluated. ### Table 8: Clostridium perfringens Isolates Tested | Organism | Toxinotype | Isolate ID | Test Concentration | | Result | |----------------------------|------------|-----------------------|--------------------|-------|----------------------------| | | | | (copies/mL) | X LoD | | | Clostridium<br>perfringens | A | ATCC 13124 (S 107) | 1.3E+03 | 1x | Clostridium<br>perfringens | | | A | ATCC 27059 (814) | 3.9E+03 | 3x | Clostridium<br>perfringens | | | C | ATCC 3628 (Strain 51) | 3.9E+03 | 3x | Clostridium<br>perfringens | | | E | ATCC 8009 | 3.9E+03 | 3x | Detected | | | - | ATCC 9081 (13942) | 3.9E+03 | 3x | | | | | Test Concentration | | | |-----------------------------|------------------------------|--------------------|-------|-------------------------------| | Organism | Isolate ID | (copies/mL) | X LoD | Result | | Cutibacterium<br>avidum | ATCC 25577 (1689B, VPI 0179) | 5.0E+04 | 1x | Cutibacterium<br>Detected | | | ATCC 49753 (VPI 0575) | 1.5E+05 | 3x | | | | ATCC 49754 (VPI 0576) | 5E+05 | 10x | | | | ATCC 49755 (VPI 0589) | 1.5E+05 | 3x | | | | ATCC 49769 (VPI 0670) | 5E+05 | 10x | | | | ATCC 25564 (VPI 0507) | 5.0E+04 | 1x | | | | ATCC 11829 (VPI 0210) | 1.5E+05 | 3x | | | Cutibacterium<br>granulosum | ATCC 25746 (D-34) | 1.5E+05 | 3x | Cutibacterium<br>Detected | | | CCUB 14831 (Serovar 3) | 1.5E+05 | 3x | | | | GRE 1554046 | 1.5E+05 | 3x | | | | GRE 1951015a | 5E+05 | 10x | | | | GRE 1760015a | 5.0E+06 | 100x | Cutibacterium<br>Not Detected | #### Table 9: Cutibacterium avidum/granulosum Isolates Tested aSequences with predicted impacts on reactivity by in silico analysis {21}------------------------------------------------ | Organism | Isolate ID (Strain) | Test Concentration | | Result | |--------------------------|-----------------------------|--------------------|-------|--------------------------------------| | | | (copies/mL) | X LoD | | | Enterococcus<br>faecalis | ATCC 51299 (NJ-3) | 5.0E+03 | 1x | Enterococcus<br>faecalis<br>Detected | | | ATCC 19433 (Tissier) | 1.5E+04 | 3x | | | | ATCC 49533 (UWH 1936) | 1.5E+04 | 3x | | | | ATCC 700802 (V583) | 1.5E+04 | 3x | | | | ATCC BAA-2573 (bMx 0502240) | 1.5E+04 | 3x | | | | JMI 12536 | 1.5E+04 | 3x | | #### Table 10: Enterococcus faecalis Isolates Tested ## Table 11: Enterococcus faecium Isolates Tested | Organism | Isolate ID (Strain) | Test Concentration | | Result | |---------------------------------------|--------------------------------------|--------------------|------|---------------------------------------| | | | (copies/mL) | xLoD | | | <i>Enterococcus</i><br><i>faecium</i> | ATCC 700221 | 1.2E+03 | 1x | | | | ATCC 19434 (Grumbach serotype 11) | 3.6E+03 | 3x | <i>Enterococcus</i><br><i>faecium</i> | | | ATCC 27270 (X3) | 3.6E+03 | 3x | | | | ATCC 51858 (Vancomycin-dependent #4) | 3.6E+03 | 3x | Detected | | | ATCC BAA-2318 | 3.6E+03 | 3x | | | | JMI 475 | 3.6E+03 | 3x | | ### Table 12: Finegoldia magna Isolates Tested | Organism | Isolate ID (Strain) | Test Concentration<br>(copies/mL) X LoD | Reported Result | |-----------------------------|----------------------|-----------------------------------------|--------------------------------------| | <i>Finegoldia<br/>magna</i> | ATCC 15794 (2974) | 3.1E+05 1x | <i>Finegoldia magna<br/>Detected</i> | | | ATCC 14955 (BU) | 9.3E+05 3x | | | | ATCC 29328 (WAL2508) | 9.3E+05 3x | | | | ATCC 53516 (312) | 9.3E+05 3x | | | | DSM 20362 (168) | 9.3E+05 3x |…