VITEK MS

DEN130013 · bioMerieux, Inc. · PEX · Aug 21, 2013 · Microbiology

Device Facts

• Record ID: DEN130013
• Device Name: VITEK MS
• Applicant: bioMerieux, Inc.
• Product Code: PEX · Microbiology
• Decision Date: Aug 21, 2013
• Decision: DENG
• Submission Type: Direct
• Regulation: 21 CFR 866.3361
• Device Class: Class 2
• Attributes: AI/ML, Pediatric

Intended Use

VITEK MS is a mass spectrometer system using matrix-assisted laser desorption/ionization time to flight (MALDI-TOF) for the identification of microorganisms cultured from human specimens. The VITEK®MS is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and yeast infections.

Device Story

VITEK MS is a MALDI-TOF mass spectrometer system for clinical microbiology. Input: microbial colonies from culture media applied to disposable target slides with matrix solution (CHCA) and formic acid (for yeast). Operation: pulsed laser ionizes sample; high-voltage fields accelerate ions through vacuum flight tube; detector records mass-to-charge ratio spectra. Software processes spectra via baseline correction, de-noising, and peak detection; proprietary algorithm compares peaks against a reference Knowledge Base of species-specific protein profiles. Output: species or genus-level identification, low-discrimination alternatives, or no identification. Used in clinical microbiology labs by trained technicians. Results aid clinicians in diagnosing infections and guiding antibiotic therapy. Benefits include rapid identification compared to traditional biochemical methods, potentially enabling faster clinical decision-making.

Clinical Evidence

Prospective clinical study across five US laboratories compared VITEK MS identification to molecular sequencing/biochemical reference methods. Total of 7,068 isolates (Gram-positive, Gram-negative, yeast). Overall correct identification (single choice + low discrimination) was 93.6% (95% CI: 93.0-94.1%). Reproducibility study (3 sites, 10 organisms, 20 replicates each) showed 99.7% correct identification. Analytical specificity study evaluated 43 organism pairs; no significant cross-reactivity trends noted.

Technological Characteristics

MALDI-TOF mass spectrometer (Shimadzu AXIMA Assurance). Components: ionization source, vacuum flight tube, linear detector. Materials: VITEK MS-DS single-use target slides, VITEK MS-CHCA matrix, VITEK MS-FA reagent. Connectivity: USB/serial/camera to Acquisition Station; Myla middleware interfaces with LIS. Software: VITEK MS Acquisition Station, VITEK MS Analysis Server, Myla. Laser: 337 nm nitrogen laser (Class 1 product with Class 3b internal laser).

Indications for Use

Indicated for the identification of microorganisms cultured from human specimens to aid in the diagnosis of bacterial and fungal infections in patients of all ages.

Regulatory Classification

Identification

A mass spectrometer system for clinical use for the identification of microorganisms is a qualitative in vitro diagnostic device intended for the identification of microorganisms cultured from human specimens. The device is comprised of an ionization source, a mass analyzer, and a spectral database. The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (2) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols. (3) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (4) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. (5) Premarket notification submissions must include details on the appropriate end user device training program that will be offered while marketing the device.

Submission Summary (Full Text)

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## 510(k) DECISION SUMMARY

#### A. 510(k) Number:

K124067

#### B. Purpose for Submission:

De novo request for evaluation of automatic class III designation for the VITEK®MS.

#### C. Measurand:

| Abiotrophia defectiva | Campylobacter coli | Clostridium perfringens |
|------------------------------------------|-------------------------------|-----------------------------------|
| Achromobacter denitrificans1 | Campylobacter jejuni | Clostridium ramosum |
| Achromobacter xylosoxidans1 | Candida albicans | Corynebacterium jeikeium |
| Acinetobacter baumannii<br>complex | Candida dubliniensis | Cronobacter sakazakii |
| Acinetobacter haemolyticus | Candida famata | Cryptococcus neoformans |
| Acinetobacter junii | Candida glabrata | Edwardsiella hoshinae |
| Acinetobacter lwoffii | Candida guilliermondii | Edwardsiella tarda |
| Actinomyces meyeri | Candida haemulonii | Eikenella corrodens |
| Actinomyces neuii | Candida inconspicua | Elizabethkingia<br>meningoseptica |
| Actinomyces odontolyticus | Candida intermedia | Enterobacter aerogenes |
| Aerococcus viridans | Candida kefyr | Enterobacter asburiae4 |
| Aeromonashydrophila/caviae2 | Candida krusei | Enterobacter cloacae4 |
| Aeromonas sobria2 | Candida lambica | Enterobacter cancerogenus |
| Aggregatibacter<br>actinomycetemcomitans | Candida lipolytica | Enterobacter gergoviae |
| Aggregatibacter aphrophilus | Candida lusitaniae | Enterococcus avium |
| Aggregatibacter segnis | Candida norvegensis | Enterococcus casseliflavus |
| Alcaligenes faecalis ssp<br>faecalis | Candida parapsilosis | Enterococcus durans |
| Bacteroides caccae | Candida pelliculosa | Enterococcus faecalis |
| Bacteroides fragilis | Candida rugosa | Enterococcus faecium |
| Bacteroides ovatus | Candida tropicalis | Enterococcus gallinarum |
| Bacteroides thetaiotaomicron | Candida utilis | Escherichia coli5 |
| Bacteroides uniformis | Candida zeylanoides | Escherichia fergusonii |
| Bacteroides vulgatus | Chryseobacterium indologenes | Escherichia hermannii |
| Bordetella parapertussis | Citrobacter amalonaticus | Ewingella americana |
| Bordetella pertussis | Citrobacter braakii3 | Finegoldia magna |
| Brevundimonas diminuta | Citrobacter freundi3 | Fusobacterium necrophorum |
| Burkholderia multivorans | Citrobacter youngae3 | Fusobacterium nucleatum |
| | Citrobacter koseri | Gardnerella vaginalis |
| | Clostridium clostridioforme | Gemella haemolysans |
| | Clostridium difficile | |
| | | |
| Gemella morbillorum | Prevotella buccae | Staphylococcus |
| Geotrichum capitatum | Prevotella denticola | saprophyticus |
| Granulicatella adiacens | Prevotella intermedia | Staphylococcus schleiferi |
| Haemophilus influenzae | Prevotella melaninogenica | Staphylococcus sciuri |
| Haemophilus parahaemolyticus | Propionibacterium acnes | Staphylococcus simulans |
| Haemophilus parainfluenzae | Proteus mirabilis | Staphylococcus warneri |
| Hafnia alvei | Proteus penneri7 | Stenotrophomonas |
| Kingella denitrificans | Proteus vulgaris7 | maltophilia |
| Kingella kingae | Providencia rettgeri | Streptococcus agalactiae |
| Klebsiella oxytoca | Providencia stuartii | Streptococcus anginosus |
| Klebsiella pneumoniae | Pseudomonas aeruginosa | Streptococcus constellatus |
| Kodamaea ohmeri | Pseudomonas fluorescens | Streptococcus |
| Lactococcus garvieae | Pseudomonas putida | dysgalactiae |
| Lactococcus lactis ssp lactis | Pseudomonas stutzeri | Streptococcus gallolyticus |
| Leclercia adecarboxylata | Ralstonia pickettii | ssp gallolyticus |
| Legionella pneumophila | Raoultella ornithinolytica | Streptococcus infantarius |
| Leuconostoc mesenteroides | Raoultella planticola | ssp coli |
| Leuconostoc pseudomesenteroides | Rhizobium radiobacter | Streptococcus infantarius |
| Listeria monocytogenes | Rhodotorula mucilaginosa | ssp infantarius |
| Malassezia furfur | Rothia mucilaginosa | Streptococcus intermedius |
| Malassezia pachydermatis | Saccharomyces cerevisiae | Streptococcus |
| Micrococcus luteus/lylae | Salmonella group6 | mitis/Streptococcus oralis |
| Mobiluncus curtisii | Serratia fonticola | Streptococcus mutans |
| Moraxella (Branhamella) | Serratia liquefaciens | Streptococcus pneumoniae |
| catarrhalis | Serratia marcescens | Streptococcus pyogenes |
| Morganella morganii | Serratia odorifera | Streptococcus salivarius |
| Neisseria cinerea | Sphingobacterium multivorum | ssp salivarius |
| Neisseria gonorrhoeae6 | Sphingobacterium spiritivorum | Streptococcus sanguinis |
| Neisseria meningitidis | Sphingomonas paucimobilis | Trichosporon asahii |
| Neisseria mucosa | Staphylococcus aureus | Trichosporon inkin |
| Ochrobactrum anthropi | Staphylococcus capitis | Trichosporon mucoides |
| Oligella ureolytica | Staphylococcus cohnii ssp | Vibrio cholerae |
| Oligella urethralis | cohnii | Vibrio parahaemolyticus |
| Pantoea agglomerans | Staphylococcus cohnii ssp | Vibrio vulnificus |
| Parvimonas micra | urealyticus | Yersinia enterocolitica |
| Pasteurella multocida | Staphylococcus epidermidis | Yersinia frederiksenii |
| Pediococcus acidilactici | Staphylococcus haemolyticus | Yersinia intermedia |
| Peptoniphilus asaccharolyticus | Staphylococcus hominis ssp | Yersinia kristensenii |
| Peptostreptococcus anaerobius | hominis | Yersinia |
| Prevotella bivia | Staphylococcus lugdunensis | pseudotuberculosis |
| | | |

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- 1. Achromobacter denitrificans and Achromobacter xylosoxidans identifications should be considered as a slashline result, Achromobacter denitrificans/ Achromobacter xylosoxidans.
- 2. Aeromonas hydrophila/caviae and Aeromonas sobria should be considered as an Aeromonas species group identification.

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- 3. Citrobacter freundii. Citrobacter braakii and Citrobacter youngae should be considered as Citrobacter freundii complex.
- 4. Enterobacter cloacae and Enterobacter asburiae identifications should be considered as a slashline result, Enterobacter cloacae/ Enterobacter asburiae.
- 5. Shigella species and E. coli O157 are identified as Escherichia coli. Confirmatory tests are required to differentiate Escherichia coli from Shigella species or E. coli 0157.
- 6. Confirmatory tests recommended for Neisseria gonorrhea and Salmonella species.
- 7. Proteus penneri and Proteus vulgaris identifications should be considered as a slashline result, Proteus penneri/ Proteus vulgaris.

#### D. Type of Test:

A mass spectrometer system for clinical use for the identification of microorganisms is a qualitative in vitro diagnostic device intended for the identification of microorganisms cultured from human specimens. The device is comprised of an ionization source, a mass analyzer and a spectral database. The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.

#### E. Applicant:

bioMérieux, Inc.

#### F. Proprietary and Established Names:

Trade Name: VITEK®MS

Common Name: VITEK MS

#### G. Regulatory Information:

- 1. Regulation Number: 21 CFR 866. 3361
- 2. Classification: Class II (special controls)
- 3. Product code: PEX
- 4. Panel: Microbiology (83)

#### H. Intended Use:

- 1. Intended use(s):
VITEK MS is a mass spectrometer system using matrix-assisted laser desorption/ionization time to flight (MALDI-TOF) for the identification of microorganisms cultured from human specimens.

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The VITEK®MS is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and yeast infections.

The following organisms are claimed:

| Abiotrophia defectiva | Candida inconspicua | Enterococcus casseliflavus |
|------------------------------|--------------------------------|------------------------------------|
| Achromobacter denitrificans1 | Candida intermedia | Enterococcus durans |
| Achromobacter xylosoxidans1 | Candida kefyr | Enterococcus faecalis |
| Acinetobacter baumannii | Candida krusei | Enterococcus faecium |
| complex | Candida lambica | Enterococcus gallinarum |
| Acinetobacter haemolyticus | Candida lipolytica | Escherichia coli5 |
| Acinetobacter junii | Candida lusitaniae | Escherichia fergusonii |
| Acinetobacter lwoffii | Candida norvegensis | Escherichia hermannii |
| Actinomyces meyeri | Candida parapsilosis | Ewingella americana |
| Actinomyces neuii | Candida pelliculosa | Finegoldia magna |
| Actinomyces odontolyticus | Candida rugosa | Fusobacterium necrophorum |
| Aerococcus viridans | Candida tropicalis | Fusobacterium nucleatum |
| Aeromonashydrophila/caviae2 | Candida utilis | Gardnerella vaginalis |
| Aeromonas sobria2 | Candida zeylanoides | Gemella haemolysans |
| Aggregatibacter | Chryseobacterium indologenes | Gemella morbillorum |
| actinomycetemcomitans | Citrobacter amalonaticus | Geotrichum capitatum |
| Aggregatibacter aphrophilus | Citrobacter braakii3 | Granulicatella adiacens |
| Aggregatibacter segnis | Citrobacter freundi3 | Haemophilus influenzae |
| Alcaligenes faecalis ssp | Citrobacter koseri | Haemophilus<br>parahaemolyticus |
| faecalis | Citrobacter youngae3 | Haemophilus parainfluenzae |
| Bacteroides caccae | Clostridium clostridioforme | Hafnia alvei |
| Bacteroides fragilis | Clostridium difficile | Kingella denitrificans |
| Bacteroides ovatus | Clostridium perfringens | Kingella kingae |
| Bacteroides thetaiotaomicron | Clostridium ramosum | Klebsiella oxytoca |
| Bacteroides uniformis | Corynebacterium jeikeium | Klebsiella pneumoniae |
| Bacteroides vulgatus | Cronobacter sakazakii | Kodamaea ohmeri |
| Bordetella parapertussis | Cryptococcus neoformans | Lactococcus garvieae |
| Bordetella pertussis | Edwardsiella hoshinae | Lactococcus lactis ssp lactis |
| Brevundimonas diminuta | Edwardsiella tarda | Leclercia adecarboxylata |
| Burkholderia multivorans | Eikenella corrodens | Legionella pneumophila |
| Campylobacter coli | Elizabethkingia meningoseptica | Leuconostoc mesenteroides |
| Campylobacter jejuni | Enterobacter aerogenes | Leuconostoc<br>pseudomesenteroides |
| Candida albicans | Enterobacter asburiae4 | Listeria monocytogenes |
| Candida dubliniensis | Enterobacter cancerogenus | Malassezia furfur |
| Candida famata | Enterobacter cloacae4 | Malassezia pachydermatis |
| Candida glabrata | Enterobacter gergoviae | |
| Candida guilliermondii | Enterococcus avium | |
| Candida haemulonii | | |
| | | |
| Micrococcus luteus/lylae | Pseudomonas putida | Stenotrophomonas |
| Mobiluncus curtisii | Pseudomonas stutzeri | maltophilia |
| Moraxella (Branhamella) | Ralstonia pickettii | Streptococcus agalactiae |
| catarrhalis | Raoultella ornithinolytica | Streptococcus anginosus |
| Morganella morganii | Raoultella planticola | Streptococcus constellatus |
| Neisseria cinerea | Rhizobium radiobacter | Streptococcus |
| Neisseria gonorrhoeae6 | Rhodotorula mucilaginosa | dysgalactiae |
| Neisseria meningitidis | Rothia mucilaginosa | Streptococcus gallolyticus |
| Neisseria mucosa | Saccharomyces cerevisiae | ssp gallolyticus |
| Ochrobactrum anthropi | Salmonella group6 | Streptococcus infantarius |
| Oligella ureolyticaOligella | Serratia fonticola | ssp coli |
| urethralis | Serratia liquefaciens | Streptococcus infantarius |
| Pantoea agglomerans | Serratia marcescens | ssp infantarius |
| Parvimonas micra | Serratia odorifera | Streptococcus intermedius |
| Pasteurella multocida | Sphingobacterium multivorum | Streptococcus |
| Pediococcus acidilactici | Sphingobacterium spiritivorum | mitis/Streptococcus oralis |
| Peptoniphilus | Sphingomonas paucimobilis | Streptococcus mutans |
| asaccharolyticus | Staphylococcus aureus | Streptococcus pneumoniae |
| Peptostreptococcus | Staphylococcus capitis | Streptococcus pyogenes |
| anaerobius | Staphylococcus cohnii ssp | Streptococcus salivarius |
| Prevotella bivia | cohnii | ssp salivarius |
| Prevotella buccae | Staphylococcus cohnii ssp | Streptococcus sanguinis |
| Prevotella denticola | urealyticus | Trichosporon asahii |
| Prevotella intermedia | Staphylococcus epidermidis | Trichosporon inkin |
| Prevotella melaninogenica | Staphylococcus haemolyticus | Trichosporon mucoides |
| Propionibacterium acnes | Staphylococcus hominis ssp | Vibrio cholerae |
| Proteus mirabilis7 | hominis | Vibrio parahaemolyticus |
| Proteus penneri7 | Staphylococcus lugdunensis | Vibrio vulnificus |
| Proteus vulgaris | Staphylococcus saprophyticus | Yersinia enterocolitica |
| Providencia rettgeri | Staphylococcus schleiferi | Yersinia frederiksenii |
| Providencia stuartii | Staphylococcus sciuri | Yersinia intermedia |
| Pseudomonas aeruginosa | Staphylococcus simulans | Yersinia kristensenii |
| Pseudomonas fluorescens | Staphylococcus warneri | Yersinia |
| | | pseudotuberculosis |

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- 1. Achromobacter denitrificans and Achromobacter xylosoxidans identifications should be considered as a slashline result, Achromobacter denitrificans/ Achromobacter xylosoxidans.
- 2. Aeromonas hydrophila/caviae and Aeromonas sobria should be considered as an Aeromonas species group identification.
- 3. Citrobacter freundii, Citrobacter braakii and Citrobacter youngae should be considered as Citrobacter freundii complex.
- 4. Enterobacter cloacae and Enterobacter asburiae identifications should be considered as a slashline result, Enterobacter cloacae/ Enterobacter asburiae.
- 5. Shigella species and E. coli 0157 are identified as Escherichia coli. Confirmatory tests are required to differentiate Escherichia coli from Shigella species or E. coli 0157.

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- 6. Confirmatory tests recommended for Neisseria gonorrhea and Salmonella species.
- 7. Proteus penneri and Proteus vulgaris identifications should be considered as a slashline result, Proteus penneri/ Proteus vulgaris.
- 2. Indication(s) for use: Same as intended use.
- 3. Special conditions for use statement(s):

The VITEK®MS is for prescription use only in accordance with 21 CFR 801.109.

- 4. Special instrument requirements:
VITEK® MS: Shimadzu AXIMA® Assurance mass spectrometer

VITEK®MS Prep Station

VITEK MS-DS Target Slides

Reagents:

- VITEK MS-CHCA (Alpha-cyano-4-hydroxy-cinnamic acid) solution ●
- VITEK MS-FA (Formic acid) reagent ●

Database: VITEK® MS V2.0 Knowledge Base

Software:

- VITEK®MS Acquisition Station ●
- VITEK® MS Prep Station ●
- Myla™ ●

#### I. Device Description:

The VITEK® MS v2.0 system is a system consisting of kit reagents (VITEK MS-CHCA, VITEK MS-FA), VITEK MS-DS target slides, VITEK® MS Prep Station, Knowledge Base, software, and the VITEK®MS (original equipment manufacturer (OEM)-labeled Shimadzu AXIMA® Assurance mass spectrometer).

The VITEK® MS v2.0 system includes an OEM-labeled Shimadzu AXIMA® Assurance mass spectrometer linked to a reference database, referred to as Knowledge Base. Matrix assisted laser desorption ionization (MALDI) is the process used to ionize a sample in to the gas phase. A pulsed laser beam is directed on to the sample. Energy from the laser beam desorbs and ionizes the sample. Extraction plates provide high-voltage electrical fields to accelerate the ionized particles upwards through the time-of-flight (TOF) vacuum tube. An ion lens focuses the ions. Deflector plates steer the ions on a path towards the linear detector at the flight-tube. An ion gate blanks out low mass ions (for example, derived from the matrix). The detector detects the ions directly from the sample (lower-molecular weight ions followed by highermolecular weight ions). Ions hitting the detector cause an electrical signal which is recorded. The

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recorded signal is processed by the software and presented as a spectrum of intensity versus mass, in Daltons (Da).

During target ionization, mass spectra within a range of 2,000-20,000 Daltons are recorded in linear positive mode at a laser frequency of 50 Hz. For each interrogation, laser shots at different positions within the target well produce up to 100 mass profiles that are summed into a single, raw mass spectrum. The spectrum is then processed by baseline correction, de-noising, and peak detection to identify well-defined peaks. The list of these significant peaks is subjected to a proprietary process called "mass binning". The processed (binned) data are used to query the Knowledge Base to determine the unknown's taxonomic identity. These results are then provided in the form of a single, species-level (and sometimes subspecies-level) identification, a split (low discrimination) identification with up to four species-level alternatives displayed, or no identification.

VITEK MS-CHCA (Alpha-cyano-4-hydroxy-cinnamic acid) is the solution that serves as a matrix which will crystalize with the microbial sample on the target slide spot. 1.0 µl of the matrix is added to the spot with the sample and allowed to dry forming crystals.

The VITEK MS-FA (Formic acid) reagent is used to pre-treat yeast in order to extract protein before the VITEK MS-CHCA matrix is added to the spot containing the sample.

VITEK MS-DS target slides are single-use disposables which contain 3 acquisition groups of 16 sample spots. Each group includes 1 calibration spot. Target slides are for single use only.

The VITEK® MS Prep Station is used to prepare VITEK MS-DS target slides. It consists of a computer workstation equipped with a barcode reader, Touch Screen and Virtual Keyboard.

bioMérieux's VITEK®MS, is the same instrument as the Shimadzu Axima Assurance MALDI-TOF spectrometer. The VITEK®MS is manufactured for bioMérieux by Kratos Analytical (a Shimadzu subsidiary) in Manchester, UK. The VITEK®MS contains a Class 1 laser product containing a Class 3b invisible-light laser. The laser is a 337 nm nitrogen laser, fixed focus.

The Acquisition Station software operates the VITEK®MS instrument to acquire spectral data from each sample. Calibration is an automatic first step in the sample acquisition process. The Acquisition Station consists of a computer workstation equipped with a barcode reader and the Acquisition Station Software v1.4.2. The VITEK®MS is connected to the VITEK® MS Acquisition Station via USB, serial and camera ports. The recorded signal is processed by the Acquisition Station software and presented as a spectrum of intensity versus mass in Daltons (Da). After spectra have been acquired from each sample spot in an acquisition group, the calibration spot is checked again.

The VITEK® MS Analysis Server is the software that manages the VITEK®MS workflow ● and computes VITEK®MS identification results. It is a software component that resides on theMyla™ Server (PC).

Myla™ is a computer application ("Middleware"), based on Web technology, which allows data

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related to the laboratory workflow, laboratory instruments, Laboratory Information System (LIS), analysis results, etc. to be grouped together. Myla™ interfaces between the bioMérieux instruments connected to the application (e.g., VITEK®MS) and the Laboratory Information System (LIS). Myla™ manages the VITEK®MS workflow and computes the identification results with the use of a computation engine and organism knowledge bases.

Knowledge Base: The reference database for the VITEK®MS system includes data representing 755 taxa, including 645 bacteria and 110 fungi. Each species group is represented by an average of 10 isolates (range 2 - 475). In order to capture the degree of acceptable variation within spectra from the same species, each reference isolate was grown on multiple media types under several growth conditions. The raw spectra were then acquired by more than one technician using multiple instruments. This process resulted in an average of 40 reference spectra per species.

### J. Standard/Guidance Document Referenced (if applicable):

| | Standards | Recognition | Standards Title | Date |
|---|-----------|-------------|----------------------------------------------|------------|
| | No. | Number | | |
| | | (FDA) | | |
| 1 | C50-A | | Mass Spectrometry in the Clinical | 10/29/2007 |
| | | | Laboratory: General Principles and Guidance; | |
| | | | Approved Guideline, 1st Edition | |
| 2 | MM09A | 7-123 | Nucleic Acid Sequencing Methods in | 12/20/2004 |
| | | | Diagnostic Laboratory Medicine; Approved | |
| | | | Guideline, 1st Edition | |
| 3 | MM-18A | 7-192 | Criteria for Identification of Bacteria and | 4/28/2008 |
| | | | Fungi by DNA Target Sequencing: Approved | |
| | | | Guideline, 1st Edition | |
| 4 | M35-A2 | 7-197 | Abbreviated Identification of Bacteria and | 11/24/2008 |
| | | | Yeast; Approved Guideline, 2nd Edition | |
| ನ | EP9-A2-IR | 7-92 | Method Comparison and Bias Estimation | 7/30/2010 |
| | | | Using Patient Samples; Approved Guideline; | |
| | | | 2" Edition (Interim Revision) | |
| 6 | EP12-A2 | 7-152 | User Protocol for Evaluation f Qualitative | 09/09/2008 |
| | | | Test Performance (2nd edition) | |

Standards References

Guidance Documents Referenced

| | Title | Date |
|---|--------------------------------------------------------------------------------------------------------|-----------|
| 1 | FDA/CDRH/ODE Evaluation of Automatic<br>Class III Designation, Guidance for Industry<br>and CDRH Staff | 4/19/1998 |
| 2 | Statistical Guidance on Reporting Results From<br>Studies Evaluating Diagnostic Tests | 3/13/2007 |

### K. Test Principle:

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The VITEK®MS system is based on a matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF MS). The colony is mixed with a saturated matrix solution and forms crystals. The ionization of this mixture by the laser induces the desorption and transfer of protons from photo-excited matrix to analyte to form a protonated molecule. During the analysis process, proteins are ionized without fragmentation by the coordinated action of the laser and the small organic acids of the matrix and separated on the basis of their mass-to-charge ratios, a process which results in a characteristic mass spectral profile. Microbial identification is based on the comparison of the protein spectrum generated from intact whole bacterial cells to the knowledge database of species-specific reference protein profiles using a particular algorithm.

### L. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

### a. Reproducibility

A reproducibility study was conducted at three external sites with a panel of 10 organisms. Each organism was tested in duplicate in each of two runs on the VITEK®MS, on five separate days, at each trial site for a total of 20 replicates per reproducibility organism. Samples were tested in both sequential and randomized order. Three different lots of VITEK MS-CHCA, VITEK MS-FA and VITEK MS-DS target slides were included in the study.

For all sites combined, the reproducibility of the VITEK®MS organism specific and overall rate of correct identification was 99.7% (598/600) with a CI of [98.8 ; 99.9 %].

### b. Linearity/assay reportable range:

Not applicable, qualitative assay.

### c. Traceability, Stability, Expected values (controls, calibrators, or methods):

### Calibrator:

E. coli ATCC 8739 is used to as a calibrator. This organism is deposited with VITEK MS-CHCA matrix on positions: xA1, xB1, xC1, of the VITEK MS-DS target slides depending on the number of samples tested (one calibrator per acquisition group of 16 spots). The VITEK "MS goes to the calibration spot in an acquisition group and performs a calibration. If the calibration passes, the instrument goes to the first spot in the acquisition group. If the calibration fails, an error is reported and VITEK®MS proceeds to the next acquisition group without collecting sample spectra. After spectra have been acquired from each sample spot in an acquisition group, the calibration spot is checked again. The calibration sample should provide E. coli identification at 99.9% in Myla™ software.

### Controls:

Two organisms are used for positive quality control. Matrix alone is used for the negative

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control. The quality control strains are as follows:

| | Expected Result |
|------------------------------------|------------------------|
| Enterobacter aerogenes ATCC® 13048 | Enterobacter aerogenes |
| Candida glabrata ATCC MYA-2950 | Candida glabrata |
| Negative Control (matrix) | No Identification |

NOTE: If the negative control does not give the expected result, users need to visually inspect the surface of the VITEK MS-DS target slides to ensure the slides are clean and repeat testing with new slide.

- d. Assay cut-off:
After the calibration is accepted for an acquisition group, the VITEK®MS acquires the spectra for the samples in that group. The instrument then scans the sample to acquire data. As the spectrum is acquired for each target spot, it is visible in the Spectrum Display on the Acquisition Screen with the number of profiles increasing as they are collected. A single profile is generated by 5 laser shots. The goal is to achieve 100 acceptable profiles, while 30 is the minimum number of acceptable profiles. When sufficient data has been acquired, the spectrum data is passed to the Analysis Server for analysis and the VITEK®MS goes to the next spot in the acquisition group.

A perfect match between the spectrum and the unique spectrum of a single organism or organism group would provide a percent probability of 99.9. Results are displayed as follows:

- . A single identification is displayed with confidence value of 60 to 99.9 when one significant organism or organism group is retained.
- Low Discrimination identifications are displayed when more than one significant . organism or organism group are retained, but not for more than 4 organisms. In this case, the sum of confidence values is equal to 100.
- . When more than 4 organisms or organism groups are found, the organism is considered as non-identified. In this case, a list of possible organisms is displayed and the sum of confidence values is less than 100.
- . When no match is found, the organism is considered as non-identified Uunclaimed identification

A symbol 'U' may appear next to some organism identifications. This VITEK MS identification indicates that the VITEK®MS result is a non-clinically validated organism. In the interest of public health, these organisms are displayed in the VITEK MS report as a means of directing the required additional laboratory testing. Identification of nonclinically validated organisms must be performed with an alternate laboratory method. Results for non-clinically validated organisms cannot be transmitted from the VITEK MS to the laboratory information system.

{10}------------------------------------------------

Non-clinically validated organisms include:

- · Organisms with insufficient clinical performance data.
- · Organisms not found in human clinical samples as reported in the scientific literature.
- e. Detection limit (LoD)

For the VITEK®MS System, the LoD study demonstrated that the LoD is different in terms of McFarland (McF) measurement depending of the tested species (i.e., S.aureus, P. aeruginosa, E.coli, C.jeikeium, and C. glabrata). The minimum LoD is from 2 to 6 McF S. aureus and C. jeikeium respectively and 7 McF for yeast (C. glabrata). The LoD study demonstrated that applying an insufficient quantity of colony usually results in no spectra being acquired. In terms of colony forming units (CFU)/spot (1 ul), the limit of detection is 10° CFU/spot for bacteria and 10+ CFU/spot for yeast. Applying too much colony may cause suboptimal performance of the system. If an excessive quantity of colony is applied, the cells may not suspend well in the matrix suspension and may impact the extraction process and the subsequent crystal formation by the matrix. A 1 ul loop should be used to pick up part of a suitable colony (i.e., approximately 3 mm in size).

- f. Analytical specificity:
Analytical specificity was assessed using two processes:

- 1. Database development: For each reference species spectrum in the database, signal preprocessing and peak detection was performed to identify peaks. Peaks in the mass spectrum between 3,000 and 17,000 Daltons were divided into 1300 pre-defined intervals called "bins". This process was replicated for each of the reference species thus creating a matrix with a species-specific weight for each of the 1300 bins. Bin scores from organism spectra are classified based on a supervised machine learning algorithm, known as the "Advanced Spectrum Classifier" (ASC), which is derived from the distribution of weighted bin scores from all spectra for a given species. By examining the ASC scores for all claimed species, it was determined that a threshold of 60% indicates that an unknown isolate's overall score is within the range of scores generated by known examples of that species, but is outside the range of scores generated by every other species in the database.
Once an unknown organism's raw spectrum is acquired by the mass spectrometer it goes through pre-processing and mass binning as described above. The bin scores then go through an iterative process whereby the score within each bin is multiplied by the weighted bin value for each reference species in the Knowledge Base. The sum of the weighted bin scores is then calculated and used to determine the confidence value of the unknown relative to each reference species. After confidence values are obtained, the list of possible organisms is reduced using a decision analysis protocol

{11}------------------------------------------------

which is performed in order to retain only organism confidence values with scores above the predefined cut-off of a 60% confidence level and within a pre-defined ASC score tolerance. Finally, the resulting organism list is reported. In the event that there are more than four species on this list or if no species are on the list, a result of "no identification" is reported.

- 2. Analytical Specificity Study: To determine the discriminatory power of the VITEK "MS was evaluated with organisms that are closely related within a group and multiple strains of the same organism. Forty-three organism pairs representing 18 organism groups were evaluated in the study. This data set included 359 individual results. Overall, there were no specific trends or remarkable cross-reactivity to be noted in these results. Of the 18 organism groups evaluated, 12 groups had no unexpected results, with the VITEK®MS identification matching the reference identification. In the remaining six organism groups, the majority of the results matched the expected results. Exceptions are described below:
- For the Cronobacter/Enterobacter group, there were six discrepant results in the ● set of 36 tests.
- For the Enterococcus group, there was one discrepant result in the set of 21 tests. ●
- For the Klebsiella/Raoultella group, there were two discrepant results in the set of ● 19 tests.
- For the Moraxella group, there was one discrepant result in the set of six tests.
- For the Morganella/Proteus group, there were three discrepant results in the set of 23 tests.
- For the Staphylococcus group, there were four discrepant results in the set of 58 tests.

### g. Sample stability studies

Sample stability studies of prepared slides were conducted using VITEK MS-DS target slides. Slides were tested at time zero and 24, 48, 72 and 96 hours after initial spotting. (Time zero means that slides were tested in the VITEK "MS directly after the spotting.) For each time tested, 48 strains (bacteria and yeast) were tested in duplicate. Prepared VITEK MS-DS target slides must be tested within 48 hours. Prepared slides should be stored at room temperature until they are tested.

### h. Stability studies (reagents, slides)

Reagents - Shelf life and storage conditions:

- 1. VITEK MS-CHCA matrix (Ref. 411071) has a shelf-life of 365 days at 2-8° C in the packaging box. The VITEK MS-CHCA matrix is stable:
- For one week after opening and storage at 2-8 ° C protected from light (in their ● original boxes).
- . For one week at ambient temperature (on the worktop, without protection from light) having opened the tube for up to 5 hours.

Note: The tube should be resealed after each series of CHCA matrix depositions.

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

- 2. The VITEK MS-FA (Ref. 411072) reagent has a shelf-life of 365 days at 2-8° C in the packaging box. The VITEK MS-FA reagent is stable for two weeks after opening with recommended storage at 2-8 ℃.
- 3. VITEK MS-DS target slides have a shelf life of 9 months at 15-25 ° C temperature.
- i. Carry-over Contamination

A study to evaluate cross contamination and carry-over was conducted with a panel of 11 strains belonging to 11 species. High positive, moderate positive and negative (matrix) samples were evaluated over multiple test runs alternating sample types. No cross contamination or carry-over was observed as all negative spots remained negative after the run.

- j. Media Requirements:
VITEK®MS identification performance obtained on different media from three suppliers was evaluated. Organisms were inoculated onto different media according to their growth requirements and incubated in appropriate growth conditions. The media listed below have been validated and are included in the certificate of compatibility.

| Culture<br>Media | bioMérieux<br>Reference |
|-----------------------------------------------------|-------------------------|
| Columbia blood agar with 5% sheep blood | 43041 / 43049 |
| Trypticase soy agar with 5% sheep blood | 43001 / 43009 |
| Trypticase soy agar | 43011 / 43019 |
| Chocolate polyvitex agar | 43101 / 43109 |
| Campylosel agar | 43361 |
| MacConkey agar* | 43141 / 43149 |
| Modified Sabouraud dextrose agar (glucose: 20 g/l ) | 42066 |
| chromID CPS | 43541 / 43549 |

* Use of this medium from some suppliers may show less than optimal performance.

### k. Culture Age:

The recommended culture incubation time for testing bacteria and yeast with the VITEK MS organisms was generated during the building of the VITEK®MS knowledge base. Organisms were inoculated onto different media from three suppliers according to their growth requirements and incubated in appropriate conditions for 24 to 72 hours. For measurement in the VITEK MS, bactiera and yeast growth must between 24 to 72 hours.

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

### 2. Comparison studies:

- a. Method comparison with predicate device:
Not applicable. Refer to the Clinical Studies section of this document.

- b. Matrix comparison:
Not applicable.

- 3. Clinical studies:
- Clinical Sensitivity a.

#### Proficiency:

Prior to initiation of the clinical study, operators at each site were trained in target slide preparation, instrument use, and result review. Each operator was required to demonstrate proficiency by successfully analyzing a masked panel of organisms consisting of 10 isolates representing common aerobic and anaerobic Gram-positive and Gram-negative bacteria and yeasts.

### Challenge:

A challenge study was conducted as part of the clinical trial. Three challenge panels consisting of 100 stains each were assembled; each of the panels was tested at three of the clinical trial sites.

| Total<br>Performance | Number<br>of<br>Isolates | Correct Identification (ID) | | | Discordant1 | No<br>Identification2 |
|----------------------|--------------------------|-------------------------------------------------|-------------------------------------------------|---------------------------------------------------------|---------------|-----------------------|
| | | Correct for<br>Genus &<br>Species<br>(1 choice) | Low<br>Discrim.<br>(>1 choice in<br>same genus) | Combined<br>(1 choice +<br>> 1 choice in<br>same genus) | | |
| | 300 | 91.7%<br>825/900 | 4.4%<br>40/900 | 96.1%<br>865/900 | 0.2%<br>2/900 | 3.7%<br>33/900 |

### Prospective Clinical Study:

The following performance characteristics were obtained by testing from patient cultures, including Gram-positive bacteria, Gram- negative bacteria and yeasts, in five clinical microbiology laboratories in the United States, comparing VITEK®MS identification to a reference identification determined by molecular sequencing supplemented as needed by additional molecular sequencing and/or biochemical testing.

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

| Correction Identification (ID) | | | | | | | |
|--------------------------------|----------------------------------------------|-------------------------------------------------------|--------------------------------------------------------------------------------------|-------------------------------------------------------|-----------------------------------------------------------|--------------------------------------------------------|-------------------------|
| Organism<br>Group | Correct<br>Single<br>Choice<br>(no. results) | Low<br>Discrim.*<br>Correct<br>Genus<br>(no. results) | Combined Correct<br>Single Choice and Low<br>Discrim. Correct Genus<br>(no. results) | Single<br>Choice<br>Incorrect<br>ID (no.<br>results)1 | Low<br>Discrim.<br>Incorrect<br>Genus<br>(no.<br>results) | Low<br>Discrim.<br>Multiple<br>Genera<br>(no. results) | No ID2<br>(no. results) |
| Gram-<br>positive<br>bacteria | 89.5%<br>(2020/2256) | 4.0%<br>(90/2256) | 93.5% (2110/2256)<br>95% CI [92.4 ; 94.5]% | 0.6%<br>(13/2256) | 0.04%<br>(1/2256) | 2.1%<br>(48/2256) | 3.7% (84/2256) |
| Gram-<br>negative<br>bacteria | 83.8%<br>(3062/3656) | 9.0%<br>(329/3656) | 92.8% (3391/3656)<br>95% CI [91.9 ; 93.6]% | 1.1%<br>(39/3656) | 0.3%<br>(11/3656) | 2.8%<br>(104/3656) | 3.0% (111/3656) |
| Yeasts | 95.3%<br>(1102/1156) | 1.0%<br>(11/1156) | 96.3% (1113/1156)<br>95% CI [95.0 ; 97.3]% | 0.2%<br>(2/1156) | 0.0%<br>(0/1156) | 0.6%<br>(7/1156) | 2.9% (34/1156) |
| Total | 87.5%<br>(6184/7068) | 6.1%<br>(430/7068) | 93.6% (6614/7068)<br>95% CI [93.0 ; 94.1]% | 0.8%<br>(54/7068) | 0.2%<br>(12/7068) | 2.2%<br>(159/7068) | 3.2% (229/7068) |

Key:

- 1 = A table of single choice incorrect identifications is included after the Performance Characteristics by Species table.
- 2 = Includes No ID (i.e. Bad Spectra, Not Enough Peaks, Too Many Peaks (Bad spectrum), or No ID (Good spectrum).
- 3 = Of the 430 low discrimination same genus results, 426 (99.1%) had the correct species present and 4 (0.9%) did not have the correct species present.
- 4 = Of the 159 low discrimination multiple genera results, 140 (88.0%) had the correct species present and 19 (12.0%) did not have the correct species present.

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

| Species | Number<br>of<br>isolates | Correct Identification (ID) | Discordant1 | No identification2 | | |
|--------------------------------------------------|--------------------------|-------------------------------------------------|----------------------------------------------|---------------------------------------------------------|-----------|-------------|
| | | Correct for<br>Genus &<br>Species<br>(1 choice) | Low Discrim.<br>(>1 choice in<br>same genus) | Combined<br>(1 choice +<br>> 1 choice in same<br>genus) | | |
| <i>Abiotrophia defective</i> | 9 | 96.9% 31/32 | 0% 0/32 | 96.9% 31/32 | 0% 0/32 | 3.1% 1/32 |
| <i>Achromobacter denitrificans</i> 3 | 17 | 0% 0/37 | 91.9% 34/37 | 91.9% 34/37 | 0% 0/37 | 8.1% 3/37 |
| <i>Achromobacter xylosoxidans</i> 3 | 24 | 0% 0/24 | 91.7% 22/24 | 91.7% 22/24 | 0% 0/24 | 8.3% 2/24 |
| <i>Acinetobacter baumannii</i><br>complex | 65 | 87.9% 80/91 | 0% 0/91 | 87.9% 80/91 | 0% 0/91 | 12.1% 11/91 |
| <i>Acinetobacter haemolyticus</i> | 6 | 93.3% 28/30 | 3.3% 1/30 | 96.7% 29/30 | 0% 0/30 | 3.3% 1/30 |
| <i>Acinetobacter junii</i> | 11 | 50.0% 14/28 | 17.9% 5/28 | 67.9% 19/28 | 7.1% 2/28 | 25.0% 7/28 |
| <i>Acinetobacter lwoffii</i> | 26 | 84.6% 22/26 | 3.8% 1/26 | 88.5% 23/26 | 0% 0/26 | 11.5% 3/26 |
| <i>Actinomyces meyeri</i> | 8 | 70.0% 21/30 | 6.7% 2/30 | 76.7% 23/30 | 6.7% 2/30 | 16.7% 5/30 |
| <i>Actinomyces neuii</i> | 12 | 64.7% 33/51 | 0% 0/51 | 64.7% 33/51 | 2.0% 1/51 | 33.3% 17/51 |
| <i>Actinomyces odontolyticus</i> | 7 | 68.8% 22/32 | 9.4% 3/32 | 78.1% 25/32 | 0% 0/32 | 21.9% 7/32 |
| <i>Aerococcus viridans</i> | 15 | 97.2% 35/36 | 0% 0/36 | 97.2% 35/36 | 0% 0/36 | 2.8% 1/36 |
| <i>Aeromonas hydrophila/caviae</i> 4 | 25 | 64.0% 16/25 | 24.0% 6/25 | 88.0% 22/25 | 8.0% 2/25 | 4.0% 1/25 |
| <i>Aeromonas sobria</i> 4 | 10 | 37.9% 11/29 | 51.7% 15/29 | 89.7% 26/29 | 3.4% 1/29 | 6.9% 2/29 |
| <i>Aggregatibacter<br/>actinomycetemcomitans</i> | 7 | 83.9% 26/31 | 0% 0/31 | 83.9% 26/31 | 6.5% 2/31 | 9.7% 3/31 |
| <i>Aggregatibacter aphrophilus</i> | 6 | 83.9% 26/31 | 0% 0/31 | 83.9% 26/31 | 0% 0/31 | 16.1% 5/31 |
| <i>Aggregatibacter segnis</i> | 4 | 63.3% 19/30 | 6.7% 2/30 | 70.0% 21/30 | 0% 0/30 | 30.0% 9/30 |
| <i>Alcaligenes faecalis ssp faecalis</i> | 12 | 97.1% 33/34 | 0% 0/34 | 97.1% 33/34 | 2.9% 1/34 | 0% 0/34 |
| <i>Bacteroides caccae</i> | 30 | 95.9% 47/49 | 2.0% 1/49 | 98.0% 48/49 | 0% 0/49 | 2.0% 1/49 |
| <i>Bacteroides fragilis</i> | 71 | 98.6% 70/71 | 0.0% 0/71 | 98.6% 70/71 | 0% 0/71 | 1.4% 1/71 |

{16}------------------------------------------------

| Species | Number of<br>isolates | Correct Identification (ID) | | | | | | Discordant 1 | | No identification2 | |
|------------------------------|-----------------------|-------------------------------------------------|-------|----------------------------------------------|------|---------------------------------------------------------|-------|--------------|------|--------------------|-------|
| | | Correct for<br>Genus &<br>Species<br>(1 choice) | | Low Discrim.<br>(>1 choice in<br>same genus) | | Combined<br>(1 choice +<br>> 1 choice in same<br>genus) | | | | | |
| Bacteroides ovatus | 40 | 85.0% | 34/40 | 2.5% | 1/40 | 87.5% | 35/40 | 0% | 0/40 | 12.5% | 5/40 |
| Bacteroides thetaiotaomicron | 51 | 94.1% | 48/51 | 2.0% | 1/51 | 96.1% | 49/51 | 0% | 0/51 | 3.9% | 2/51 |
| Bacteroides uniformis | 30 | 80.4% | 41/51 | 0% | 0/51 | 80.4% | 41/51 | 0% | 0/51 | 19.6% | 10/51 |
| Bacteroides vulgatus | 41 | 97.6% | 40/41 | 0% | 0/41 | 97.6% | 40/41 | 0% | 0/41 | 2.4% | 1/41 |
| Bordetella parapertussis | 6 | 96.7% | 29/30 | 3.3% | 1/30 | 100% | 30/30 | 0% | 0/30 | 0% | 0/30 |
| Bordetella pertussis | 9 | 46.7% | 14/30 | 26.7% | 8/30 | 73.3% | 22/30 | 3.3% | 1/30 | 23.3% | 7/30 |
| Brevundimonas diminuta | 7 | 93.3% | 28/30 | 0% | 0/30 | 93.3% | 28/30 | 0% | 0/30 | 6.7% | 2/30 |
| Burkholderia multivorans | 25 | 91.3% | 42/46 | 4.3% | 2/46 | 95.7% | 44/46 | 2.2% | 1/46 | 2.2% | 1/46 |
| Campylobacter coli | 12 | 96.9% | 31/32 | 0% | 0/32 | 96.9% | 31/32 | 3.1% | 1/32 | 0% | 0/32 |
| Campylobacter jejuni | 33 | 93.9% | 31/33 | 0% | 0/33 | 93.9% | 31/33 | 3.0% | 1/33 | 3.0% | 1/33 |
| Candida albicans | 58 | 98.3% | 57/58 | 0% | 0/58 | 98.3% | 57/58 | 1.7% | 1/58 | 0% | 0/58 |
| Candida dubliniensis | 34 | 100% | 34/34 | 0% | 0/34 | 100% | 34/34 | 0% | 0/34 | 0% | 0/34 |
| Candida famata | 29 | 91.8% | 45/49 | 6.1% | 3/49 | 98.0% | 48/49 | 0% | 0/49 | 2.0% | 1/49 |
| Candida glabrata | 62 | 100% | 62/62 | 0% | 0/62 | 100% | 62/62 | 0% | 0/62 | 0% | 0/62 |
| Candida guilliermondii | 36 | 97.2% | 35/36 | 0% | 0/36 | 97.2% | 35/36 | 0% | 0/36 | 2.8% | 1/36 |
| Candida haemulonii | 12 | 100% | 34/34 | 0% | 0/34 | 100% | 34/34 | 0% | 0/34 | 0% | 0/34 |
| Candida inconspicua | 23 | 93.0% | 40/43 | 2.3% | 1/43 | 95.3% | 41/43 | 0% | 0/43 | 4.7% | 2/43 |
| Candida intermedia | 7 | 92.6% | 25/27 | 3.7% | 1/27 | 96.3% | 26/27 | 0% | 0/27 | 3.7% | 1/27 |
| Candida kefyr | 30 | 100% | 30/30 | 0% | 0/30 | 100% | 30/30 | 0% | 0/30 | 0% | 0/30 |

{17}------------------------------------------------

| Species | Number<br>of<br>isolates | Correct Identification (ID) | | Discordant1 | No identification2 | | |
|--------------------------------|--------------------------|-------------------------------------------------|----------------------------------------------|---------------------------------------------------------|--------------------|-------------|--------------------|
| | | Correct for<br>Genus &<br>Species<br>(1 choice) | Low Discrim.<br>(>1 choice in<br>same genus) | Combined<br>(1 choice +<br>> 1 choice in same<br>genus) | | | |
| Candida krusei | 53 | 100% | 0% | 100% | 0% | 0% | |
| Candida lambica | 9 | 96.8% | 3.2% | 100% | 0% | 0% | |
| Candida lipolytica | 28 | 100% | 0% | 100% | 0% | 0% | |
| Candida lusitaniae | 33 | 87.9% | 3.0% | 90.9% | 0% | 9.1% | |
| Candida norvegensis | 30 | 90.0% | 2.0% | 92.0% | 0% | 8.0% | |
| Candida parapsilosis | 73 | 98.6% | 0% | 98.6% | 1.4% | 0% | |
| Candida pelliculosa | 33 | 100% | 0% | 100% | 0% | 0% | |
| Candida rugosa | 6 | 100% | 0% | 100% | 0% | 0% | |
| Candida tropicalis | 54 | 90.7% | 3.7% | 94.4% | 0% | 5.6% | |
| Candida utilis | 8 | 96.7% | 0% | 96.7% | 0% | 3.3% | |
| Candida zeylanoides | 8 | 96.7% | 3.3% | 100% | 0% | 0% | |
| Chryseobacterium indologenes | 8 | 87.9% | 0% | 87.9% | 0% | 12.1% | |
| Citrobacter amalonaticus | 29 | 93.1% | 3.4% | 96.6% | 0% | 3.4% | |
| Citrobacter braakii5 | 18 | 56.4% | 30.8% | 87 2% | 5.1% | 7.7% | |
| Citrobacter freundii5 | 58 | 65.5% | 27.6% | 93.1% | 6 9% | 0% | |
| Citrobacter koseri | 31 | 100% | 0% | 100% | 0% | 0% | |
| Citrobacter youngae5 | 13 | 44.1% | 52 9% | 97.1% | 0% | 2 9% | |
| Clostridium clostridioforme | 7 | 91.7% | 0% | 91.7% | 8 3% | 0% | |
| Clostridium difficile | 30 | 90.0% | 0% | 90.0% | 0% | 10.0% | |
| Species | Number<br>of<br>isolates | Correct Identification (ID) | | | | Discordant1 | No identification2 |
| | | Correct for<br>Genus &<br>Species<br>(1 choice) | Low Discrim.<br>(>1 choice in<br>same genus) | Combined<br>(1 choice +<br>> 1 choice in same<br>genus) | | | |
| Clostridium perfringens | 61 | 98.4% | 0% | 98.4% | 0% 0/61 | 1.6% 1/61 | |
| Clostridium ramosum | 10 | 90.3% | 0% | 90.3% | 3.2% 1/31 | 6.5% 2/31 | |
| Corynebacterium jeikeium | 8 | 100% | 0% | 100% | 0% 0/31 | 0% 0/31 | |
| Cronobacter sakazakii | 10 | 73.3% | 26.7% | 100% | 0% 0/30 | 0% 0/30 | |
| Cryptococcus neoformans | 35 | 100% | 0% | 100% | 0% 0/35 | 0% 0/35 | |
| Edwardsiella hoshinae | 11 | 93.9% | 6.1% | 100% | 0% 0/33 | 0% 0/33 | |
| Edwardsiella tarda | 9 | 93.1% | 6.9% | 100% | 0% 0/29 | 0% 0/29 | |
| Eikenella corrodens | 14 | 100% | 0% | 100% | 0% 0/34 | 0% 0/34 | |
| Elizabethkingia meningoseptica | 10 | 100% | 0% | 100% | 0% 0/32 | 0% 0/32 | |
| Enterobacter aerogenes | 52 | 100% | 0% | 100% | 0% 0/52 | 0% 0/52 | |
| Enterobacter asburiae6 | 12 | 0% | 87.9% | 87.9% | 0% 0/33 | 12.1% 4/33 | |
| Enterobacter cancerogenus | 6 | 61.3% | 29.0% | 90.3% | 3.2% 1/31 | 6.5% 2/31 | |
| Enterobacter cloacae6 | 28 | 0% | 92.9% | 92.9% | 3.6% 1/28 | 3.6% 1/28 | |
| Enterobacter gergoviae | 10 | 90.6% | 0% | 90.6% | 3.1% 1/32 | 6.3% 2/32 | |
| Enterococcus avium | 33 | 90.9% | 3.0% | 93.9% | 0% 0/33 | 6.1% 2/33 | |
| Enterococcus casseliflavus | 37 | 100% | 0% | 100% | 0% 0/37 | 0% 0/37 | |
| Enterococcus durans | 30 | 96.7% | 0% | 96.7% | 3.3% 1/30 | 0% 0/30 | |
| Enterococcus faecalis | 68 | 97.1% | 0% | 97.1% | 0% 0/68 | 2.9% 2/68 | |
| Enterococcus faecium | 57 | 100% | 0% | 100% | 0% 0/57 | 0% 0/57 | |

{18}------------------------------------------------

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

| Species | Number<br>of<br>isolates | Correct for<br>Genus &<br>Species<br>(1 choice) | | Low Discrim.<br>(>1 choice in<br>same genus) | | Combined<br>(1 choice +<br>> 1 choice in same<br>genus) | Discordant¹ | | No identification² | | |
|------------------------------|--------------------------|-------------------------------------------------|-------|----------------------------------------------|-------|---------------------------------------------------------|-------------|------|--------------------|-------|------|
| Enterococcus gallinarum | 34 | 100% | 34/34 | 0% | 0/34 | 100% | 34/34 | 0% | 0/34 | 0% | 0/34 |
| Escherichia coli | 65 | 100% | 65/65 | 0% | 0/65 | 100% | 65/65 | 0% | 0/65 | 0% | 0/65 |
| Escherichia fergusonii | 6 | 48.1% | 13/27 | 22.2% | 6/27 | 70.4% | 19/27 | 7.4% | 2/27 | 22.2% | 6/27 |
| Escherichia hermannii | 7 | 78.1% | 25/32 | 0% | 0/32 | 78.1% | 25/32 | 3.1% | 1/32 | 18.8% | 6/32 |
| Ewingella americana | 6 | 90.0% | 27/30 | 0% | 0/30 | 90.0% | 27/30 | 3.3% | 1/30 | 6.7% | 2/30 |
| Finegoldia magna | 24 | 97.7% | 43/44 | 0% | 0/44 | 97.7% | 43/44 | 0% | 0/44 | 2.3% | 1/44 |
| Fusobacterium necrophorum | 26 | 88.9% | 40/45 | 0% | 0/45 | 88.9% | 40/45 | 0% | 0/45 | 11.1% | 5/45 |
| Fusobacterium nucleatum | 7 | 59.1% | 13/22 | 4.5% | 1/22 | 63.6% | 14/22 | 9.1% | 2/22 | 27.3% | 6/22 |
| Gardnerella vaginalis | 27 | 88.4% | 38/43 | 0% | 0/43 | 88.4% | 38/43 | 0% | 0/43 | 11.6% | 5/43 |
| Gemella haemolysans | 11 | 78.8% | 26/33 | 18.2% | 6/33 | 97.0% | 32/33 | 0% | 0/33 | 3.0% | 1/33 |
| Gemella morbillorum | 5 | 46.7% | 14/30 | 40.0% | 12/30 | 86.7% | 26/30 | 0% | 0/30 | 13.3% | 4/30 |
| Geotrichum capitatum | 32 | 93.8% | 30/32 | 0% | 0/32 | 93.8% | 30/32 | 0% | 0/32 | 6.3% | 2/32 |
| Granulicatella adiacens | 6 | 100% | 31/31 | 0% | 0/31 | 100% | 31/31 | 0% | 0/31 | 0% | 0/31 |
| Haemophilus influenzae | 55 | 96.4% | 53/55 | 0% | 0/55 | 96.4% | 53/55 | 0% | 0/55 | 3.6% | 2/55 |
| Haemophilus parahaemolyticus | 8 | 100% | 31/31 | 0% | 0/31 | 100% | 31/31 | 0% | 0/31 | 0% | 0/31 |
| Haemophilus parainfluenzae | 37 | 91.9% | 34/37 | 2.7% | 1/37 | 94.6% | 35/37 | 0% | 0/37 | 5.4% | 2/37 |
| Hafnia alvei | 19 | 84.2% | 16/19 | 0% | 0/19 | 84.2% | 16/19 | 5.3% | 1/19 | 10.5% | 2/19 |
| Kingella denitrificans | 3 | 95.8% | 23/24 | 0% | 0/24 | 95.8% | 23/24 | 0% | 0/24 | 4.2% | 1/24 |
| Kingella kingae | 4 | 83.3% | 25/30 | 0% | 0/30 | 83.3% | 25/30 | 0% | 0/30 | 16.7% | 5/30 |

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

| Species | Number<br>of<br>isolates | Correct Identification (ID) | | | Discordant1 | No identification2 |
|----------------------------------------------------------------------------------------|--------------------------|-------------------------------------------------|----------------------------------------------|---------------------------------------------------------|--------------------|--------------------|
| | | Correct for<br>Genus &<br>Species<br>(1 choice) | Low Discrim.<br>(>1 choice in<br>same genus) | Combined<br>(1 choice +<br>> 1 choice in same<br>genus) | | |
| Klebsiella oxytoca | 49 | 100% 49/49 | 0% 0/49 | 100% 49/49 | 0% 0/49 | 0% 0/49 |
| Klebsiella pneumoniae | 58 | 100% 58/58 | 0% 0/58 | 100% 58/58 | 0% 0/58 | 0% 0/58 |
| Kodamaea ohmeri | 11 | 93.5% 29/31 | 0% 0/31 | 93.5% 29/31 | 0% 0/31 | 6.5% 2/31 |
| Lactococcus garvieae | 9 | 100% 31/31 | 0% 0/31 | 100% 31/31 | 0% 0/31 | 0% 0/31 |
| Lactococcus lactis ssp lactis | 10…