← Product Code [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON) · K211759

# Selux AST System; Model AST Gen 1.0 (K211759)

_Selux Diagnostics, Inc. · LON · Jan 18, 2023 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K211759

## Device Facts

- **Applicant:** Selux Diagnostics, Inc.
- **Product Code:** [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON.md)
- **Decision Date:** Jan 18, 2023
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1645
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Intended Use

The Selux AST System is intended to be used for the automated quantitative or qualitative susceptibility testing for most clinically significant aerobic microorganisms. The Selux AST System does not provide organism identification. The Selux Gram-Positive Panel is intended for use with the Selux AST System as an in vitro test to determine the susceptibility of isolated colonies of specific Staphylococcus species and Enterococcus species to specific antimicrobial agents when used as instructed.

## Device Story

The Selux AST System performs automated antimicrobial susceptibility testing (AST) on isolated bacterial colonies. The system comprises a Sample Prep Station, an Inoculator, and an Analyzer. Users prepare a concentrated inoculum using a densitometer; the Inoculator then transfers the inoculum into 384-well polystyrene panels containing dehydrated antimicrobials. The Analyzer uses orbital shaking incubators and a multimode microplate reader to monitor growth via fluorescence and absorbance, utilizing viability (resazurin/methylene blue) and surface area assays. An MIC-determining algorithm processes these data to report minimum inhibitory concentrations (MIC) or qualitative results. The system is used in clinical laboratories; it requires Gram stain information to select the appropriate panel but does not perform organism identification. Results assist clinicians in selecting appropriate antimicrobial therapy for patients with bacterial infections.

## Clinical Evidence

Performance evaluated using 706 clinical and 159 challenge isolates of Staphylococcus spp. and Enterococcus spp. across three U.S. sites. Comparison against broth microdilution reference method. Primary endpoints: Essential Agreement (EA) and Categorical Agreement (CA) ≥90%, major error rate ≤3%, very major error rate ≤2%. Results showed acceptable performance for most antimicrobial/organism combinations, with specific limitations and alternative testing requirements noted for combinations failing acceptance criteria.

## Technological Characteristics

System uses 384-well polystyrene microplates with dehydrated antimicrobials. Sensing principle: automated growth-based detection using metabolic indicators (resazurin/methylene blue) and optical absorbance/fluorescence. Energy source: electrical (automated liquid handler, robotic grippers, microplate reader). Connectivity: LIS integration for organism ID. Software: algorithm-based MIC determination. Sterilization: not specified (consumables are sterile).

## Regulatory Identification

A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.

## Special Controls

*Classification.* Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”

## Predicate Devices

- Bd Phoenix Automated Microbiology System - Vancomycin ([K131331](/device/K131331.md))

## Submission Summary (Full Text)

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>
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FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number

K211759

B Applicant

Selux Diagnostics, Inc.

C Proprietary and Established Names

Selux AST System; Model AST Gen 1.0

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  LON | Class II | 21 CFR 866.1645 - Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System | MI - Microbiology  |
|  LTT | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology  |
|  LTW | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology  |

## II Submission/Device Overview:

### A Purpose for Submission:

To obtain substantial equivalence determination for Gram-positive organisms tested with the Selux AST System to determine the minimum inhibitory concentration of specific antimicrobials with specific Gram-positive organisms.

### B Measurand:

Antimicrobial Reporting Range

Ampicillin  ≤0.25 to ≥128 μg/mL

Ceftaroline  ≤0.06 to ≥32 μg/mL

Clindamycin  ≤0.03 to ≥16 μg/mL

Daptomycin  ≤0.06 to ≥32 μg/mL

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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K211759 - Page 2 of 30

|  Antimicrobial | Reporting Range  |
| --- | --- |
|  Delafloxacin | ≤0.008 to ≥8 μg/mL  |
|  Eravacycline | ≤0.002 to ≥0.5 μg/mL  |
|  Erythromycin | ≤0.06 to ≥32 μg/mL  |
|  Linezolid | ≤0.25 to ≥32 μg/mL  |
|  Levofloxacin | ≤0.06 to ≥32 μg/mL  |
|  Minocycline | ≤0.12 to ≥64 μg/mL  |
|  Oxacillin | ≤0.03 to ≥32 μg/mL  |
|  Penicillin | ≤0.03 to ≥64 μg/mL  |
|  Trimethoprim | ≤0.25 to ≥64 μg/mL  |
|  Vancomycin | ≤0.12 to ≥128 μg/mL  |
|  Cefoxitin Screen | SN or SP  |

## C Type of Test:

Quantitative and qualitative antimicrobial susceptibility test (AST) system that utilizes colorimetric, oxidation-reduction and growth-based techniques to determine the minimum inhibitory concentration (MIC) of specific antimicrobials to specific organisms.

## III Intended Use/Indications for Use:

### A Intended Use(s):

The Selux AST System is intended to be used for the automated quantitative or qualitative susceptibility testing for most clinically significant aerobic microorganisms. The Selux AST System does not provide organism identification.

### B Indication(s) for Use:

The Selux Gram-Positive Panel is intended for use with the Selux AST System as an *in vitro* test to determine the susceptibility of isolated colonies of specific *Staphylococcus* species and *Enterococcus* species to specific antimicrobial agents when used as instructed.

The Selux Gram-Positive Panel is a quantitative test for the following antimicrobial agents with the specific organisms identified below:

- Ampicillin: *Enterococcus faecium*, *Enterococcus faecalis*
- Clindamycin: *Staphylococcus aureus*, *Staphylococcus epidermidis*
- Ceftaroline: *Staphylococcus aureus*
- Daptomycin: *Staphylococcus aureus*, *Enterococcus faecalis*
- Delafloxacin: *Staphylococcus aureus*, *Staphylococcus haemolyticus*, *Enterococcus faecalis*
- Eravacycline: *Staphylococcus aureus*, *Enterococcus faecalis*
- Erythromycin: *Staphylococcus aureus*
- Linezolid: *Staphylococcus aureus*, *Staphylococcus epidermidis*, *Staphylococcus haemolyticus*, *Enterococcus faecium*, *Enterococcus faecalis*
- Levofloxacin: *Enterococcus faecium*, *Enterococcus faecalis*, methicillin-susceptible *Staphylococcus aureus*
- Minocycline: *Staphylococcus aureus*
- Oxacillin: *Staphylococcus aureus*, *Staphylococcus lugdunensis*

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Penicillin: Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus
Trimethoprim: Staphylococcus aureus, Coagulase-Negative Staphylococci (including S. capitus, S. haemolyticus, S. saprophyticus, S. simulans)
Vancomycin: Staphylococcus aureus, Coagulase-Negative Staphylococci (CoNS) (including S. capitus, S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. intermedius group, S. lugdunensis, S. saprophyticus, S. schleiferi, S. simulans) Enterococcus faecium, Enterococcus faecalis

The Selux Gram-Positive Panel is a qualitative test for the following antimicrobial agents with the specific target organisms identified below:

- Cefoxitin Screen to predict mecA-mediated oxacillin resistance: Staphylococcus aureus, Staphylococcus lugdunensis

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

The following limitations were added to the device labeling based on performance demonstrated in the current submission:

- The ability of the Selux AST system to detect resistance in the following antimicrobial/organism combinations is unknown because an insufficient number of resistant isolates were available at the time of comparative testing.
- Ampicillin: Enterococcus faecalis
- Cefoxitin Screen: Staphylococcus lugdunensis
- Ceftaroline: Staphylococcus aureus
- Eravacycline: Enterococcus spp.
- Linezolid: Enterococcus spp., Staphylococcus spp.
- Minocycline: Staphylococcus spp.
- Vancomycin: Staphylococcus spp.

- The current absence of daptomycin-resistant isolates precludes defining any results other than "Susceptible". Isolates yielding results other than "Susceptible" should be submitted to a reference laboratory for further testing. A single non-susceptible strain of S. aureus provided a potential very major error during the comparative testing.

- Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Clindamycin: Staphylococcus epidermidis when the Selux MIC is 4 µg/mL due to the occurrence of two major errors
- Delafloxacin: Staphylococcus haemolyticus when the Selux MIC is 0.25 µg/mL or 0.5 µg/mL due to the <90% CA caused by six minor errors
- Eravacycline: Enterococcus faecium
- Erythromycin: Enterococcus spp.
- Levofloxacin: Enterococcus faecium when the Selux MIC is 2 µg/mL due to two very major errors

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- Oxacillin: Staphylococcus spp., except S. aureus and S. lugdunensis; Staphylococcus aureus when the Selux MIC is ≤0.12 μg/mL; Staphylococcus lugdunensis when the Selux MIC is 8 μg/mL
- Penicillin: Enterococcus faecium when the Selux MIC is ≥32 μg/mL due to three major errors; Staphylococcus aureus when the Selux MIC is ≥4 μg/mL
- Trimethoprim: Coagulase-Negative staphylococci (S. epidermidis, S. hominis, S. intermedius group, S. lugdunensis, and S. schleiferi)
- Vancomycin: Enterococcus faecium when the Selux MIC is >64 μg/mL due to two major errors

D Special Instrument Requirements:

Selux AST System, Software version 1, subversion 8.165

IV Device/System Characteristics:

A Device Description:

The Selux AST System is an antimicrobial susceptibility test (AST) system that consists of a Sample Prep Station, an Inoculator, an Analyzer, a computer workstation, and the reagents and consumables required to perform AST testing. The system is operated via software that guides users through the manual sample preparation process and operates the automated Inoculator and Analyzer. The software includes an algorithm that enables the system to determine the susceptibility of an organism to the variety of antimicrobials provided in the Selux AST panels. The system is designed so that only Gram stain information is required to initiate testing to select the gram-negative or gram-positive antimicrobial panel. While complete system testing can be performed without species-level identification, this information is required for the system to report susceptibility results. Species identification information can be either manually input to the Selux system or automatically downloaded from the laboratory information system (LIS) at any time, once the sample ID is entered into the LIS.

The Selux AST Systems provides the following consumables: AST panels, panel lids, tubes and caps for sample prep, troughs for inoculator, McFarland Standards for densitometer performance checks, inoculator pipette tips, inoculator waste bins, inoculator growth media, inoculator cleaning solution, analyzer reagent packs, analyzer liquid waste disinfectant tablets, analyzer absorbent waste pads, and an analyzer solid waste bag.

The Selux AST System is divided into three primary AST steps performed at three different stations: workbench (for sample preparation), inoculator (for inoculation), and analyzer (for antimicrobial susceptibility testing).

Workbench (sample preparation)

The Workbench's graphical user interface (GUI) is accessed via a web application to guide users through the concentrated inoculum solution preparation (using the densitometer), panel selection, and carrier loading. The barcode scanner is used to register each carrier and panel, as well as associate them with each sample. During sample preparation, panels on the carriers are exposed to an ionizer to remove any latent ionic charge which may interfere with the

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assay. The saline pump is used to dispense saline aliquots for concentrated inoculum preparation and McFarland standards used for densitometer calibration.

Selux panels are 384-well polystyrene microplates that contain dehydrated antimicrobials and are sealed with a desiccant in air-impermeable foil pouches to provide room-temperature stability.

The Selux AST System provides two types of carriers: standard carriers which hold up to four panels and can be used to test 1 - 4 samples at a time and multiplex carriers which are used when two or more different quality control (QC) organisms are being tested.

# Panel inoculator

The Selux panel is inoculated by the Selux benchtop inoculator, an automated liquid handler. The inoculator dilutes and transfers the concentrated inoculum solution into each panel. The user interacts with the system through a GUI that runs on the built-in, touch screen monitor. The inoculator ensures proper inoculation for each panel by reading the panel barcodes prior to initiating its filling sequence. Further, the inoculator creates sterile assay control wells as well as special test wells by directly pipetting microorganisms from the concentrated inoculum solution into specific resistance detection wells on each panel that require high microorganism concentrations.

# AST Analyzer

The analyzer fully automates antimicrobial susceptibility testing requiring no user intervention after the inoculated carrier is loaded. The analyzer is divided into three levels: upper floor, lower floor, and reagent/waste. The upper floor contains the carrier loading bays. A robotic panel gripper picks panels and moves them between positions. A multi-channel bulk solution dispenser adds reagents to specified wells on each panel. The panels are placed into orbital shaking incubators and read by a multimode microplate reader to record absorbance and fluorescence measurements. When ready, the panels are moved to the lower floor by an elevator gantry. The lower floor also contains a robotic panel gripper. It contains a fluid handling station that dispenses and aspirates reagents. It also contains orbital shaker mixing stations, for use in the assay binding steps, and a plate reader with time-resolved fluorescence detection capabilities. The reagent/waste level contains drawers users can open to replace the liquid analyzer reagent pack consumables and to access waste.

The Selux AST System with the Gram-Positive Panel can determine the MIC of various antimicrobials when tested against specific organisms (Table 1).

Table 1. Reportable MIC Ranges and Organism-Specific Breakpoints for Antimicrobials included in the Selux AST System, Gram-Positive Panel

|  Antimicrobial | Indicated Organism | Selux AST System Reportable Range (μg/mL) | FDA-Recognized/Approved Breakpoints (μg/mL)  |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |   |  S | I | R  |
|  Ampicillin | E. faecium, E. faecalis | ≤0.25 to ≥128 | ≤8 | - | ≥16  |
|  Ceftaroline | S. aureus | ≤0.06 to ≥32 | ≤1 | 2 | ≥4  |
|  Clindamycin | S. aureus, S. epidermidis | ≤0.03 to ≥16 | ≤0.5 | 1-2 | ≥4  |

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|  Antimicrobial | Indicated Organism | Selux AST System Reportable Range (μg/mL) | FDA-Recognized/Approved Breakpoints (μg/mL)  |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |   |  S | I | R  |
|  Daptomycin | E. faecalis | ≤0.06 to ≥32 | ≤2 | 4 | ≥8  |
|   |  S. aureus | ≤0.06 to ≥32 | ≤1 | - | -  |
|  Delafloxacin | E. faecalis | ≤0.008 to ≥8 | ≤0.12 | 0.25 | ≥0.5  |
|   |  S. aureus, S. haemolyticus | ≤0.008 to ≥8 | ≤0.25 | 0.5 | ≥1  |
|  Eravacycline | E. faecalis | ≤0.002 to ≥0.5 | ≤0.06 | - | ≥0.12  |
|   |  S. aureus | ≤0.002 to ≥0.5 | ≤0.06 | - | ≥0.12  |
|  Erythromycin | S. aureus | ≤0.06 to ≥32 | ≤0.5 | 1-4 | ≥8  |
|  Linezolid | E. faecium, E. faecalis | ≤0.25 to ≥32 | ≤2 | 4 | ≥8  |
|   |  S. aureus, S. epidermidis, S. haemolyticus | ≤0.25 to ≥32 | ≤4 | - | ≥8  |
|  Levofloxacin | E. faecium, E. faecalis | ≤0.06 to ≥32 | ≤2 | 4 | ≥8  |
|   |  Methicillin-susceptible S. aureus | ≤0.06 to ≥32 | ≤2 | 4 | ≥8  |
|  Minocycline | S. aureus | ≤0.12 to ≥64 | ≤4 | 8 | ≥16  |
|  Oxacillin | S. aureus | ≤0.03 to ≥32 | ≤2 | - | ≥4  |
|   |  S. lugdunensis | ≤0.03 to ≥32 | ≤2 | - | ≥4  |
|  Penicillin | E. faecium, E. faecalis | ≤0.03 to ≥64 | ≤8 | - | ≥16  |
|   |  S. aureus | ≤0.03 to ≥64 | ≤0.12 | - | ≥0.25  |
|  Trimethoprim | Staphylococcus spp. | ≤0.25 to ≥64 | ≤8 | - | ≥16  |
|  Vancomycin | E. faecium, E. faecalis | ≤0.12 to ≥128 | ≤4 | 8-16 | ≥32  |
|   |  S. aureus | ≤0.12 to ≥128 | ≤2 | 4-8, | ≥16  |
|   |  Staphylococcus spp. other than S. aureus | ≤0.12 to ≥128 | ≤4 | 8-16 | ≥32  |
|  Cefoxitin Screen | S. aureus | SN (negative) / SP (positive) | n/a  |   |   |
|   |  S. lugdunensis | SN (negative) / SP (positive) | n/a  |   |   |

n/a: FDA breakpoints not applicable because Cefoxitin Screen is a qualitative test based on an MIC value of 4 μg/mL with results reported either as SN (screen negative) or SP (screen positive)
(-) Indicates that a corresponding MIC is not defined for that category.

## B Principle of Operation:

The Selux AST test requires that the Gram type of the organism be known prior to testing as the information is necessary to select the proper AST panel to use (i.e., gram-positive or gram-negative). The organism identification (ID) is not needed for Selux AST processing to be performed; however, the organism ID is necessary for a final result to be reported.

The Selux AST System performs antimicrobial susceptibility testing similar to the gold-standard broth microdilution method. To get an accurate reading of microbial growth, the sufficient growth assay monitors growth in dedicated AST panel wells that contain organisms and cation-adjusted Mueller-Hinton Broth but no antimicrobials or probes. Sufficient growth assay wells are monitored by fluorescence to those wells which the standard metabolism-based viability assay pair resazurin/methylene blue have been added and/or by optical absorbance. Two probe-based assays, a viability assay and a surface area assay, commence across all wells in the panel after the threshold in the sufficient growth well has been met. The viability and surface area assays are performed in each AST panel well, providing two complementary datasets for each well.

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These data are input to an MIC-determining algorithm that provides results when organism IDs are available.

## C Instrument Description Information:

1. Instrument Name:
Selux AST System

2. Specimen (Organism/Colony) Identification:
An order request is sent from the Laboratory Identification System (LIS), and the accession identifiers and other information related to the specimen are received and stored by the Site Service into the Site Database. A medical technologist will prepare one or more samples and insert them into the Selux carrier under the guidance of the Sample Preparation web interface. For the inoculator, users use the Sample Prep GUI to select the sample(s) to test and determine the appropriate Carrier to use. The user utilizes an included barcode scanner to scan Carrier Barcodes, accession information from barcoded agar plates, or concentrated inoculum tubes, depending on the laboratory workflow. The user then selects the appropriate panel type and loads it into the appropriate sample number on the carrier. The inoculator ensures proper inoculation for each panel by reading the panel barcodes prior to initiating its filler sequence. If the Selux AST system is connected to a LIS, it will attempt to obtain the organism identification if it was part of an LIS order during the user-entered sample accession. If no matching order request is found or the system is not connected to an LIS, the user can enter the organism identification in the results page any time after sample preparation. If an accession enters the Selux AST System through the LIS, the Selux AST System will check that accession against the one the user provided. The user will be alerted during Results Review of any organism identification discrepancies that must be manually resolved.

3. Specimen (Organism/Colony) Sampling and Handling:
Samples are prepared using the Selux Workbench. The user prepares a concentrated inoculum solution and uses the Selux-provided densitometer to ensure the proper microorganism turbidity has been achieved. After preparing the concentrated inoculum and placing in the Inoculator, the remaining steps are carried out by automated Selux processes. The user is required to move inoculated panels from the Inoculator to the Analyzer.

4. Calibration:
The Selux AST System is setup and installed exclusively by trained service personnel. No changes or modifications are to be made to the System configuration after service personnel have completed setup procedures unless those activities and procedures are performed by Selux Service personnel.

In addition, the densitometer should be calibrated weekly by the users to verify accuracy using Selux-provided McFarland standards.

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# 5. Quality Control:

The Selux AST System software contains Quality Control (QC) Sets (A, B, C) so that when selected, specific QC strains for testing are listed (Table 2). Concentrated inocula are prepared by the user similar as for clinical samples. The QC report lists several descriptors, including the expected QC range, actual MIC value and result status (pass/fail) for each tested antimicrobial agent. Pass/fail status is determined by the whether the actual MIC result falls within the expected QC range (pass) or outside of the expected QC range (fail).

Table 2. CLSI-Recommended QC Organisms for Gram-Positive Antimicrobials

|  Antimicrobial | Abbreviation | QC Set | QC Strain | Expected QC Range/Result  |
| --- | --- | --- | --- | --- |
|  Ampicillin | AMP | A | ATCC-29212 | 0.5-2 μg/mL  |
|  Clindamycin | CLI | A | ATCC-29213 | 0.06-0.25 μg/mL  |
|  Ceftaroline | CPT | A | ATCC-29213 | 0.12-0.5 μg/mL  |
|  Daptomycin | DAP | A | ATCC-29212 | 1-4 μg/mL  |
|  Delafloxacin | DFX | A | ATCC-29212 | 0.016-0.06 μg/mL  |
|  Eravacycline | ERV | A | ATCC-29212 | 0.016-0.06 μg/mL  |
|  Erythromycin | ERY | A | ATCC-29212 | 1-4 μg/mL  |
|  Linezolid | LNZ | A | ATCC-29213 | 1-4 μg/mL  |
|  Levofloxacin | LVX | A | ATCC-29212 | 0.25-2 μg/mL  |
|  Minocycline | MIN | A | ATCC-29212 | 1-4 μg/mL  |
|  Oxacillin | OXA | A | ATCC-29213 | 0.12-0.5 μg/mL  |
|  Penicillin | PEN | A | ATCC-29213 | 0.25-2 μg/mL  |
|  Trimethoprim | TMP | A | ATCC-29213 | 1-4 μg/mL  |
|  Vancomycin | VAN | A | ATCC-29213 | 0.5-2 μg/mL  |
|  Cefoxitin Screen | FOX SCN | A | ATCC-29213 | Negative  |
|   |   |  C | ATCC-43300 | Positive  |

# V Substantial Equivalence Information:

# A Predicate Device Name(s):

Bd Phoenix Automated Microbiology System - Vancomycin  $(0.5 - 32\mu \mathrm{g / mL})$

# B Predicate 510(k) Number(s):

K131331

C Comparison with Predicate(s):

|  Device & Predicate Device(s): | Device: K211759 | Predicate: K131331  |
| --- | --- | --- |
|  Device Trade Name | Selux AST System | BD Phoenix Automated Microbiology System- Vancomycin 0.5-32 μg/mL  |
|  General Device Characteristic Similarities  |   |   |
|  Intended Use / Indications for Use | The Selux AST System is intended to be used for the automated quantitative | The BD Phoenix Automated Microbiology System is intended for the  |
|   | system is intended to be used for the automated quantitative | system is intended for the  |
|  Product | VAN | VAN  |

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|  Device & Predicate Device(s): | Device: K211759 | Predicate: K131331  |
| --- | --- | --- |
|   | or qualitative susceptibility testing for most clinically significant aerobic microorganisms. The Selux AST System does not provide organism identification. | in vitro rapid identification (ID) of gram positive bacteria from pure culture belonging to the genera Staphylococcus, Enterococcus, other gram positive cocci and gram positive bacilli. The BD Phoenix Automated Microbiology System is also intended for the quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most gram positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.  |
|   |  The Selux Gram-Positive Panel is intended for use with the Selux AST System as an in vitro test to determine the susceptibility of isolated colonies of specific Staphylococcus species and Enterococcus species to specific antimicrobial agents when used as instructed. |   |
|  Sample | Bacterial colonies isolated from culture | Same  |
|  Technology | Automated growth-based detection using metabolic indicators to detect organism growth | Automated growth based enhanced by use of a redox indicator (colorimetric oxidation-reduction) to detect organism growth  |
|  Panel Type | Gram-positive | Same  |
|  Read Method | Automated | Same  |
|  Inoculation Method | Automated | Same  |
|  Result Reported | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (S, I, R, NS) | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (S, I, R)  |
|  Indicated Species | Specific Staphylococcus spp. and Enterococcus spp. | Staphylococcus spp. and Enterococcus spp.  |
|  General Device Characteristic Differences  |   |   |
|  Antimicrobial Agent and Reporting Range | Ampicillin ≤0.25 to ≥128 μg/mL
Ceftaroline ≤0.06 to ≥32 μg/mL
Clindamycin ≤0.03 to ≥16 μg/mL
Daptomycin ≤0.06 to ≥32 μg/mL
Delafloxacin ≤0.008 to ≥8 μg/mL
Eravacycline ≤0.002 to ≥0.5 μg/mL
Erythromycin ≤0.06 to ≥32 μg/mL
Linezolid ≤0.25 to ≥32 μg/mL
Levofloxacin ≤0.06 to ≥32 μg/mL
Minocycline ≤0.12 to ≥64 μg/mL
Oxacillin ≤0.03 to ≥32 μg/mL
Penicillin ≤0.03 to ≥64 μg/mL | Vancomycin 0.5-32μg/mL  |

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|  Device & Predicate Device(s): | Device: K211759 | Predicate: K131331  |
| --- | --- | --- |
|   | Trimethoprim ≤0.25 to ≥64 μg/mL
Vancomycin ≤0.12 to ≥128 μg/mL
Cefoxitin Screen S/R |   |
|  IVD Functions | AST | ID and AST  |
|  Instrument | Selux AST System | BD Phoenix Automated Microbiology System  |

VI Standards/Guidance Documents Referenced:

- FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)
- CLSI M100-M30, “Performance Standards for Antimicrobial Susceptibility Testing”; Thirtieth Edition (January 2020)

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

Reproducibility testing for the Selux AST System with the Gram-Positive Panel was conducted at 3 testing sites (2 external and 1 internal site). Panel members generally consisted of species indicated for use with each respective antimicrobial. To accommodate the numerous antimicrobial/organism combinations being tested concurrently, up to three non-indicated species, within an indicated genus or family, were considered acceptable for testing. Reproducibility was determined from the total number (and percent) of results that fell within one dilution (+/- one doubling dilution) of the modal MIC result for quantitative assays or the number of results that were in category agreement for qualitative assays divided by the total number of results. Reproducibility was evaluated between sites (inter-site) and within sites (intra-site). Both best-case (assumes that off-scale results are within one dilution of the mode) and worst-case (assumes that off-scale results are more than one dilution of the mode) performance was determined for each antimicrobial, as outlined in the AST Special Controls Guidance.

In the initial study, inter-site reproducibility was evaluated at three sites by testing at least 25 isolates with on-scale MIC values for each antimicrobial, for a minimum of 75 results per antimicrobial (25 isolates x 3 sites = 75 results/antimicrobial). In general, best-case inter-site reproducibility was acceptable (≥95%) and a sufficient number of results obtained (≥75 results). However, antimicrobials with inter-site worst-case reproducibility of <89% or an insufficient number of results generated (i.e., <75) in the initial study were further evaluated in a supplemental study in which testing was performed with three instruments. Data from both studies are collated and summarized in Table 3. Performance is summarized for each antimicrobial tested with all organisms as well as indicated organisms only. Inter-site reproducibility was determined to be acceptable.

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Table 3. Inter-site Reproducibility of Selux AST System

|   | All organisms (combined) |   | Indicated organisms only  |   |
| --- | --- | --- | --- | --- |
|  Antimicrobial | Best-case (%) | Worst-case (%) | Best-case (%) | Worst-case (%)  |
|  Ampicillin^{a} | 72/75 (96) | 72/75 (96) | 68/69 (98.6) | 68/69 (98.6)  |
|  Cefoxitin screen | 74/75 (98.7) | 74/75 (98.7) | 74/75 (98.7) | 74/75 (98.7)  |
|  Ceftaroline^{a} | 74/75 (98.7) | 74/75 (98.7) | 74/75 (98.7) | 74/75 (98.7)  |
|  Clindamycin | 78/81 (96.3) | 78/81 (96.3) | 63/66 (95.5) | 63/66 (95.5)  |
|  Daptomycin | 77/78 (98.7) | 77/78 (98.7) | 77/78 (98.6) | 77/78 (98.6)  |
|  Delafloxacin | 144/144 (100) | 144/144 (100) | 144/144 (100) | 144/144 (100)  |
|  Eravacycline | 78/78 (100) | 78/78 (100) | 78/78 (100) | 78/78 (100)  |
|  Erythromycin | 141/144 (97.9) | 136/144 (94.4) | 141/144 (97.9) | 136/144 (94.4)  |
|  Levofloxacin | 76/78 (97.4) | 76/78 (97.4) | 76/78 (97.4) | 76/78 (97.4)  |
|  Linezolid | 77/78 (98.7) | 77/78 (98.7) | 56/57 (98.2) | 56/57 (98.2)  |
|  Minocycline^{a} | 73/75 (97.3) | 73/75 (97.3) | 64/66 (97.0) | 64/66 (97.0)  |
|  Oxacillin | 76/78 (97.4) | 75/78 (96.2) | 76/78 (97.4) | 75/78 (96.2)  |
|  Penicillin | 74/78 (94.9) | 70/78 (89.7) | 74/78 (94.9) | 70/78 (89.7)  |
|  Trimethoprim | 77/81 (95.1) | 74/81 (91.4) | 77/81 (95.1) | 74/81 (91.4)  |
|  Vancomycin | 79/80 (98.8) | 75/80 (93.8) | 79/80 (98.8) | 75/80 (93.8)  |

a In instances where the original study had lower than the required number, supplemental testing was conducted and data collated with original data.

Intra-site reproducibility was evaluated by testing a minimum of five isolates in triplicate on three days at one internal site for each antimicrobial to generate a minimum of 45 results per antimicrobial (5 isolates x 3 replicates x 3 days = 45 results/antimicrobial). In general, best-case intra-site reproducibility was acceptable (≥95%) and a sufficient number of results obtained (≥45 results). However, antimicrobials with worst-case reproducibility <89% or an insufficient number of results generated (i.e., <45) in the initial study were further evaluated in a supplemental study. Data from both studies are collated and summarized in Table 4. Performance is summarized for each antimicrobial tested with all organisms as well as indicated organisms only. Intra-site reproducibility was determined to be acceptable.

Table 4. Intra-site Reproducibility of Selux AST System

|   | All organisms (combined) |   | Indicated organisms only  |   |
| --- | --- | --- | --- | --- |
|  Antimicrobial | Best-case (%) | Worst-case (%) | Best-case (%) | Worst-case (%)  |
|  Ampicillin | 45/45 (100) | 45/45 (100) | 45/45 (100) | 45/45 (100)  |
|  Cefoxitin screen | 47/47 (100) | 47/47 (100) | 47/47 (100) | 47/47 (100)  |
|  Ceftaroline^{a} | 48/49 (98.0) | 48/49 (98.0) | 48/49 (98.0) | 48/49 (98.0)  |
|  Clindamycin | 54/54 (100) | 54/54 (100) | 36/36 (100) | 36/36 (100)  |
|  Daptomycin | 74/74 (100) | 74/74 (100) | 65/65 (100) | 65/65 (100)  |
|  Eravacycline | 103/103 (100) | 99/103 (96.1) | 103/103 (100) | 99/103 (96.1)  |
|  Erythromycin^{b} | 44/47 (93.6) | 42/47 (89.4) | 44/47 (93.6) | 42/47 (89.4)  |
|  Linezolid | 62/63 (98.4) | 62/63 (98.4) | 53/54 (98.1) | 53/54 (98.1)  |
|  Oxacillin | 62/65 (95.4) | 62/65 (95.4) | 62/65 (95.4) | 62/65 (95.4)  |
|  Vancomycin | 83/83 (100) | 79/83 (95.2) | 83/83 (100) | 79/83 (95.2)  |

a In instances where the original study had lower than the required number, supplemental testing was conducted and data collated with original data.

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b The best-case intra-site reproducibility for erythromycin is 93.6%, which is <95%; however, reproducibility testing at two other sites were 100%, which is acceptable.

2. Linearity:

Not applicable

3. Analytical Specificity/Interference:

Not applicable

4. Assay Reportable Range:

Not applicable

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Quality Control Testing. Quality control testing was performed each day that testing was conducted. CLSI recommended QC strains for each antimicrobial were tested a sufficient number of times (i.e., at least 20 times/site) at each testing site using the Selux AST System as well as the reference site using the broth microdilution reference method.

QC expected ranges and results for the quantitative Selux AST System assays are summarized in Table 5. For all antimicrobials, greater than 95% of results were within the expected range, which is acceptable.

Table 5. QC Expected Ranges and Results for the Quantitative Selux AST System Assays

|  Antimicrobial | QC Organism | Expected Range (μg/mL) | No. in Range (%)  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  Reference | Selux  |
|  Ampicillin | E. faecalis ATCC 29212 | 0.5 – 2 | 31/31 (100) | 190/191 (99.5)  |
|  Ceftaroline | S. aureus ATCC 29213 | 0.12 – 0.5 | 26/26 (100) | 190/191 (99.5)  |
|  Clindamycin | S. aureus ATCC 29213 | 0.06 – 0.25 | 26/26 (100) | 190/191 (99.5)  |
|  Daptomycin | E. faecalis ATCC 29212 | 1 – 4 | 16/16 (100) | 81/82 (98.8)  |
|  Delafloxacin | E. faecalis ATCC 29212 | 0.016 – 0.12 | 31/31 (100) | 190/191 (99.5)  |
|  Eravacycline | E. faecalis ATCC 29212 | 0.016 – 0.06 | 31/31 (100) | 187/191 (97.9)  |
|  Erythromycin | E. faecalis ATCC 29212 | 1 – 4 | 30/31 (96.8) | 187/191 (97.9)  |
|  Levofloxacin | E. faecalis ATCC 29212 | 0.25 – 2 | 31/31 (100) | 191/191 (100)  |
|  Linezolid | S. aureus ATCC 29213 | 1 – 4 | 31/31 (100) | 189/191 (99.0)  |
|  Minocycline | E. faecalis ATCC 29212 | 1 – 4 | 16/16 (100) | 82/82 (100)  |
|  Oxacillin | S. aureus ATCC 29213 | 0.12 – 0.5 | 28/28 (100) | 189/191 (99.0)  |
|  Penicillin | S. aureus ATCC 29213 | 0.25 – 2 | 30/30 (100) | 191/191 (100)  |
|  Trimethoprim | S. aureus ATCC 29213 | 1 – 4 | 11/11 (100) | 82/82 (100)  |
|  Vancomycin | S. aureus ATCC 29213 | 0.5 – 2 | 31/31 (100) | 189/191 (99.0)  |

QC expected and actual results with Cefoxitin Screen are summarized in Table 6. The Selux AST System reported nine false positive results when testing cefoxitin with the negative QC organism, S. aureus ATCC 29213. The false positive results occurred at a single testing site

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(six of the nine failures occurred on successive days of testing). Data from samples tested on days in which QC failed were excluded from the clinical analysis. Failures with this organism could not be replicated during investigative testing which comprised of 48 individual runs, each with a separate McFarland inoculum preparation, as performance was 100% (48/48). Overall, QC was determined to be acceptable.

Table 6. QC Expected and Actual Results for the Selux AST System with Cefoxitin Screen

|  Antimicrobial | QC Organism | Expected Result | No. Correct (%)  |   |
| --- | --- | --- | --- | --- |
|   |  |  | Reference | Selux  |
|  Cefoxitin Screen | S. aureus ATCC 29213 | Negative | 10/11 (90.9) | 73/82 (89.0)  |
|  Cefoxitin Screen | S. aureus ATCC 43300 | Positive | 11/11 (100) | 83/83 (100)  |

Inoculum Density Check: The Selux AST System has an onboard densitometer and liquid handler that prepares and transfers a McFarland inoculum preparation into each panel. To verify the microorganism turbidity, quantitative culture was performed to determine the inoculum densities of all QC and reproducibility samples as well as a minimum of 10% of the clinical and challenge isolates. The microorganism concentrations for samples tested with the Selux AST System ranged from 5.0 x 10⁴ to 4.5 x 10⁶ CFU/mL and with the reference method ranged from 3.5 x 10⁴ to 1.2 x 10⁶ CFU/mL which are equivalent to an 0.5 McFarland suspension (E. coli ATCC 25922 approximately 5 x 10⁵ CFU/mL).

Device Failure: There were no device failures encountered during initial testing with the Selux AST System. However, three device failures were observed in the supplemental and additional independent validation studies. All were detected at the time of failure by the system and resulted in faulted panels, thus had no impact on results. Two failures were due to an issue with the controller board of an off-the-shelf Inoculator component, a dual pressure/vacuum source, that was resolved by replacing the controller board. A software update was released to correct the issue. The third failure was a damaged cable supplying signal and power to a z-axis motor in the Selux Analyzer. No failures were observed in subsequent processing after the cable was replaced.

Growth Failure Rate: There were no growth failures on the Selux AST System. All samples that generated reference method results also generated Selux results.

Purity Check: Purity plates were prepared from the inoculum suspensions of every sample tested. AST results were only reported for pure isolates; data generated from plates that generated multiple colony morphologies was excluded from analyses.

6. Detection Limit:
Not applicable

7. Assay Cut-Off:
Not applicable

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8. Accuracy (Instrument):

Not applicable

9. Carry-Over/Cross-Contamination:

Cross-contamination with the Selux AST System was evaluated by testing first with the Selux Inoculator and then with the entire Selux AST System (Inoculator and Analyzer).

Cross-Contamination Study for Selux Inoculator. The purpose of this study was to evaluate the possible occurrence of cross-contamination of the Selux Inoculator during Selux multiplex testing with various organisms. The Selux AST System instructions for use and user interface were followed to inoculate individual panels using one QC isolate (E. faecalis ATCC 2922, K. pneumoniae ATCC BAA-2814, S. aureus ATCC 29213 or E. coli ATCC 25922) and one sterile saline sample (media only) in adjacent panels. Inoculated panels were incubated overnight under standard growth-promoting conditions and the presence/absence of growth was visually evaluated in wells inoculated with sterile saline.

The first set of testing included 12 total inoculator runs, with 2 gram-positive isolates/saline samples and 2 gram-negative isolates/saline samples over three days. Purity plates were conducted for all samples. This set of testing yielded growth in two wells on the saline plate (2/1920 wells) and the cross-contamination study protocol was repeated for two additional sets of testing. No additional growth occurred in any of the saline wells during the final testing. MALDI-TOF species identification of the two wells with growth indicated that the contaminants were S. epidermidis and S. aureus. Even though a root cause of the S. epidermidis contamination was not determined, it was likely caused by user contamination whereas S. aureus could have been due to cross contamination during sample preparation or the inoculation process. The final contamination rate across all three rounds of testing was determined to be 2/5760 wells (0.03%) which was determined to be acceptable.

Cross-Contamination Study for Selux AST System (Inoculator and Analyzer). The purpose of this study was to evaluate the potential for cross-contamination during testing with the entire Selux AST system (Inoculator and Analyzer). Two representative clinical samples, E. coli and S. aureus, were used for testing. Testing comprised of 10 panels; five panels with E. coli and five panels with S. aureus. The strains were processed to allow the gram-negative and gram-positive samples to be alternated during inoculator processing. Purity plates were prepared from the diluted troughs in the Selux inoculator. The MIC results from the AST testing were compared to reference results from the Selux reference database. Performance was evaluated by reviewing purity plates and AST results. The criteria to evaluate the performance was set as acceptable for zero purity plate contamination caused by the other species and >90% essential agreement (EA) compared with BMD results.

The purity plates did not show evidence of cross-contamination between E. coli and S. aureus (i.e., single morphology colonies on each representative plate) and MIC results from each species demonstrated 100% EA to the reference result. Additionally, the system did not report any faults due to high background or viability contamination.

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# B Comparison Studies:

1. Method Comparison with Predicate Device:

Clinical performance testing on the Selux AST System was initially performed at three U.S. test sites (2 external, 1 internal). For instances in which testing was required to supplement existing data from the original study and support specific claims, testing was performed on three Selux AST System instruments at two testing sites.

Performance was evaluated using contemporary and stock frozen clinical isolates as well as challenge isolates, which were selected for their resistance profiles. Clinical isolates of non-fastidious bacteria were recovered from cultures of clinical specimens (e.g., blood, stool, urine, respiratory, wound, aspirates) from diverse geographic locations across the U.S.

Contemporary frozen isolates were defined as isolates that had been collected and frozen within six months of testing while stock frozen isolates were tested six or more months after collection.

A total of 706 clinical (193 contemporary and 513 stock) and 159 challenge Staphylococcus spp. and Enterococcus spp. isolates were tested to evaluate the Selux AST System performance for 14 antimicrobials and one screening test using the Selux Gram-Positive panel. Depending on the spectrum of activity, breakpoints and the claimed organisms (species/group) for each antimicrobial on the panel, the number of datapoints for the various antimicrobial-organisms tested varied and ranged from 39 (e.g. S. lugdunensis/Oxacillin) to 311 (e.g. Staphylococcus/Clindamycin). Selux results were compared to the modal value of triplicate broth microdilution reference results performed at an independent reference laboratory.

Performance was determined generally based on criteria outlined in the Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems including essential agreement (EA), categorical agreement (CA), and categorical errors (minor, major and very major errors). EA was calculated as the percentage of Selux MIC results that were within plus or minus one serial two-fold dilution of the reference result. CA was calculated as the percentage of Selux interpretive results (S/I/R) that were identical to the interpretive results of the reference result. EA of evaluable results (on-scale Selux and reference results or results in which an off-scale result was at least two doubling dilutions from the on-scale result) were also calculated. Performance was considered acceptable if the EA and CA were ≥90%, major error rate was ≤3%, and very major error rate was ≤2%.

A trending analysis using combined clinical and challenge isolate results was also conducted to evaluate antimicrobial-organism combinations for which Selux MIC results were determined to be one or more doubling dilutions lower or higher than the reference result. MIC results that were off-scale for both the reference and Selux were not considered in the trending analysis. Antimicrobial-organism combinations for which the difference between the percentage of isolates with higher or lower MIC values was ≥ 30% with a statistically significant confidence interval were considered to have evidence of trending and is addressed in the labeling.

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A high level summary of the performance of the Selux AST System is described below for each antimicrobial and indicated species. Complete details and results including EA, CA and error rate analyses are summarized in Tables 7 and 8 and trending analyses are summarized in Table 9.

## Ampicillin

A total of 299 *Enterococcus* spp. (115 *E. faecalis* and 184 *E. faecium*) isolates were evaluated with ampicillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 98.3% and CA of 100%, which is acceptable. There were no minor, major or very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant *E. faecalis* isolates.

Analysis of trending indicated that MIC values for *Enterococcus* spp. tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:
- Ampicillin: *Enterococcus* spp.

## Cefoxitin Screen

A total of 151 *S. aureus* isolates were evaluated with the cefoxitin screen. The combined results from clinical and challenge isolate testing demonstrated an CA of 98.7%, which is acceptable. There was one major error (1/71 = 1.4%) and one very major error (1/80 = 1.3%), which is acceptable.

A total of 24 *S. lugdunensis* isolates were evaluated with the cefoxitin screen. The combined results from clinical and challenge isolate testing demonstrated an CA of 95.8%, which is acceptable. There were no very major errors; however, there was one major error (1/23 = 4.3%), which was considered a random error. The following footnote to the performance table is included in the device labeling to address the major error:

When evaluating Selux AST System performance, there was a single major error (MAJ) that resulted in an unacceptable MAJ rate of 4.3% (1/23) when cefoxitin screen was tested with *Staphylococcus lugdunensis*.

In addition, a limitation statement is included in the device labeling to address the lack of testing with resistant *S. lugdunensis* isolates.

## Ceftaroline

A total of 138 *S. aureus* isolates were evaluated with the ceftaroline. The combined results from clinical and challenge isolate testing demonstrated an EA and CA of 98.6%, which is acceptable. There was one major error (1/134 = 0.7%), one minor error and no very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant *S. aureus* isolates.

There was no evidence of trending observed for *S. aureus* with ceftaroline.

## Clindamycin

A total of 311 *Staphylococcus* spp. isolates (including 145 *S. aureus* and 55 *S. epidermidis*) were evaluated with clindamycin. The combined results from clinical and

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challenge isolate testing demonstrated an EA of 95.8% and an CA of 97.1%, which is acceptable. When evaluating results by individual species, S. aureus had one minor error and one major error (1/118 = 0.8%), which is acceptable. S. epidermidis had two minor errors and two major errors (2/31 = 6.5%) at a Selux MIC value of 4 µg/mL, which is not acceptable. The following limitation is included in the device labeling to restrict reporting of S. epidermidis due to the observed major errors:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Clindamycin: Staphylococcus epidermidis when the Selux MIC is 4 µg/mL due to the occurrence of two major errors

There was no evidence of trending observed for S. aureus or S. epidermidis with clindamycin.

**Daptomycin.** A total of 116 E. faecalis isolates were evaluated with daptomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.0% and an CA of 100%. There were no minor, major or very major errors. Overall, performance is acceptable.

A total of 134 S. aureus isolates were evaluated with daptomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 98.5% and an CA of 99.3%. There was one very major error (1/1 = 100%) and no major or minor errors. The following limitation is included in the device labeling to address the single non-susceptible isolate that was found to be susceptible by Selux (potential very major error since no other category is defined other than "susceptible only"):

The current absence of daptomycin-resistant isolates precludes defining any results other than "Susceptible". Isolates yielding results other than "Susceptible" should be submitted to a reference laboratory for further testing. A single non-susceptible strain of S. aureus provided a potential very major error during the comparative testing.

There was no evidence of trending observed for E. faecalis or S. aureus with daptomycin.

**Delafloxacin.** A total of 180 E. faecalis isolates were evaluated with delafloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.2% and CA of 91.1%. There were two major errors (2/128 = 1.6%) and no very major or minor errors. Overall, performance is acceptable.

A total of 229 Staphylococcus spp. isolates (218 S. aureus and 11 S. haemolyticus) were evaluated with delafloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 99.1% and CA of 94.2%. There were no major, very major or minor errors, which is acceptable. When evaluating results by individual species, S. haemolyticus had a CA of 45.5% due to six minor errors at Selux MIC values of 0.25 µg/mL and 0.5 µg/mL. The following limitation is included in the device labeling to restrict reporting of S. haemolyticus due to the observed low CA:

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Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Delafloxacin: *Staphylococcus haemolyticus* when the Selux MIC is 0.25 µg/mL or 0.5 µg/mL due to the <90% CA caused by six minor errors

Analysis of trending indicated that MIC values for *S. haemolyticus* tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:

- Delafloxacin: *Staphylococcus haemolyticus*

**Eravacycline.** A total of 287 *Enterococcus* spp. (114 *E. faecalis* and 173 *E. faecium*) isolates were evaluated with eravacycline. The combined results from clinical and challenge isolate testing demonstrated a CA of 97.6% but an EA of 86.4% due to *E. faecium* which had an EA of 81.5%. In addition, *E. faecium* had five major errors (5/168 = 3.0%) and two very major errors (2/5 = 40%), which is not acceptable. In addition to a limitation to address the lack of testing with resistant *Enterococcus* spp. isolates, the following limitation is included in the device labeling to restrict reporting of *E. faecium* due to unacceptable performance:

- Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):
- Eravacycline: *Enterococcus faecium*

A total of 118 *S. aureus* isolates were evaluated with eravacycline. The combined results from clinical and challenge isolate testing demonstrated an EA and CA of 100%. There were no major or very major errors. Overall, performance is acceptable.

Analysis of trending indicated that MIC values for *Enterococcus faecalis* tended to be one doubling dilution lower than the reference MIC value while MIC values for *S. aureus* tended to be one doubling dilution higher than the reference MIC value. The following statements are included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:

- Eravacycline: *Enterococcus* spp.

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution higher than the reference MIC value:

- Eravacycline: *Staphylococcus aureus*

**Erythromycin.** A total of 280 *Enterococcus* spp. (182 *E. faecalis* and 98 *E. faecium*) isolates were evaluated with erythromycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 83.9% and CA of 85.4%, which is not acceptable. When evaluating results by individual species, *E. faecalis* had an EA of 81.3% and CA of 83.5% with 28 minor errors and two major errors (2/26 = 7.6%), which is not acceptable. *E. faecium* had an EA and CA of 88.8% with 11 minor errors, which is not acceptable. The following

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limitation is included in the device labeling to restrict reporting of Enterococcus spp. due to the observed low EA and CA:

- Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):
- Erythromycin: Enterococcus spp.

A total of 220 Staphylococcus spp. (including 145 S. aureus) isolates were evaluated with erythromycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 92.7% and CA of 94.6%. There were seven minor errors, five major errors (5/92 = 5.4%), and no very major errors. Since all five major errors were from non-indicated Staphylococcus spp. (i.e., non-S. aureus isolates), performance with erythromycin is acceptable.

Analysis of trending indicated that MIC values for S. aureus tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

- Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:
- Erythromycin: Staphylococcus aureus

Levofloxacin. A total of 281 Enterococcus spp. (184 E. faecalis and 97 E. faecium) isolates were evaluated with levofloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.8% and CA of 96.8%. When evaluating results by individual species, E. faecalis had one minor error and two major errors (2/141 = 1.4%), and no very major errors, which is acceptable. E. faecium had four minor errors and two very major errors (2/86 = 2.3%) at a Selux MIC value of 2 µg/mL, which is not acceptable. The following limitation is included in the device labeling to restrict reporting of E. faecium due to the observed very major errors:

- Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):
- Levofloxacin: Enterococcus faecium when the Selux MIC is 2 µg/mL due to two very major errors

A total of 135 methicillin-susceptible S. aureus isolates were evaluated with levofloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.8% and CA of 96.3%. There was one major error (1/82 = 1.2%), four minor errors, and no very major errors, which is acceptable.

Analysis of trending indicated that MIC values for E. faecalis, E. faecium and S. aureus tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

- Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:

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- Levofloxacin: Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus

Linezolid. A total of 228 Staphylococcus spp. (including 127 S. aureus, 26 S. epidermidis and 12 S. haemolyticus) isolates were evaluated with linezolid. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.8% and CA of 99.6%. When evaluating results by individual species, S. aureus had one major error (1/125 = 0.8%) and no minor or very major errors, which is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant Staphylococcus spp. isolates.

A total of 299 Enterococcus spp. (117 E. faecalis and 182 E. faecium) isolates were evaluated with linezolid. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.0% and CA of 98.3%. When evaluating results by individual species, E. faecium had three major errors (3/180 = 1.7%), two minor errors and no very major errors, which is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant Enterococcus spp. isolates.

Analysis of trending indicated that MIC values for S. haemolyticus tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:
- Linezolid: Staphylococcus haemolyticus

Minocycline. A total of 217 Staphylococcus spp. (including 113 S. aureus) isolates were evaluated with minocycline. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.7% and CA of 98.6%. When evaluating results by individual species, S. lugdunensis, a non-indicated species, had one very major error (1/1 = 100%). Since this species is not indicated for use with minocycline, performance with minocycline is acceptable.

A limitation statement is included in the device labeling to address the lack of testing with resistant Staphylococcus spp. isolates.

Analysis of trending indicated that MIC values for Staphylococcus spp. tended to be one doubling dilution higher than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution higher than the reference MIC value:
- Minocycline: Staphylococcus spp.

Oxacillin. A total of 124 CoNS isolates [including S. capitus, S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. intermedius group, S. saprophyticus, S. schleiferi, S. simulans, and Coagulase-negative Staphylococcus (not speciated)] were evaluated with oxacillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 83.9% and CA of 93.6%, which is not acceptable. There were a total of four major errors (4/44 =

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9.1%) and four very major errors (4/80 = 5.0%) for the entire reporting group, which is not acceptable. The following limitation is included in the device labeling to restrict reporting of certain Staphylococcus spp. due to unacceptable performance:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Oxacillin: Staphylococcus spp., except S. aureus and S. lugdunensis

A total of 122 S. aureus isolates were evaluated with oxacillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 85.3% and CA of 99.2%. There was one very major error (1/49 = 2.0%) and no minor or major errors. Analysis of performance using truncated reporting ranges (down to ≤0.12μg/mL) improved the EA to 93.4%. The following limitation statement is included in the device labeling to restrict reporting of S. aureus due to the low EA:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combinations:

- Oxacillin: Staphylococcus aureus when the Selux MIC is ≤0.12 μg/mL

In addition, the following footnote to the performance table is included in the device labeling to describe the truncation and limitation statement for S. aureus with oxacillin:

Using the full reporting range resulted in an unacceptable EA of 85.3% when oxacillin was tested with Staphylococcus aureus. Performance analysis using a truncated reporting range with a minimum MIC of 0.25 μg/mL improved EA to 93.4%.

A total of 39 S. lugdunensis isolates were evaluated with oxacillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 89.7% and CA of 94.9. There were two major errors (2/36 = 5.6%) at Selux MIC values of 8 and 16 μg/mL and no minor or very major errors. The following limitation statement is included in the device labeling to restrict reporting of S. lugdunensis due to the observed major errors:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combinations:

- Oxacillin: Staphylococcus lugdunensis when the Selux MIC is ≥8 μg/mL

There was no evidence of trending observed for S. aureus or S. lugdunensis with oxacillin.

Penicillin. A total of 238 Enterococcus spp. (117 E. faecalis and 121 E. faecium) isolates were evaluated with penicillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 93.7% and CA of 98.3%. When evaluating results by individual species, E. faecalis had one major (1/116 =0.9%), which is acceptable. E. faecium had three major errors (3/17 = 17.6%) at Selux MIC values ≥32 μg/mL, which is not acceptable. The following limitation is included in the device labeling to restrict reporting of E. faecium due to the observed major errors:

K211759 - Page 21 of 30

{21}

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Penicillin: Enterococcus faecium when the Selux MIC is ≥32 μg/mL due to three major errors

A total of 204 Staphylococcus spp. (all S. aureus) isolates were evaluated with penicillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 84.3% and CA of 98.0%, which is not acceptable. Analysis of performance using truncated reporting ranges (up to ≥4 μg/mL) improved the EA to 91.2%. There were no major errors but four very major errors (4/163 = 2.5%). The following limitation is included in the device labeling to restrict reporting of S. aureus due to the low EA:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Penicillin: Staphylococcus aureus when the Selux MIC is ≥4 μg/mL

In addition, the following footnote to the performance table is included in the device labeling to describe the truncation and limitation statement for S. aureus with penicillin:

Using the full reporting range resulted in an unacceptable EA of 84.3% when penicillin was tested with Staphylococcus aureus. Performance analysis using a truncated reporting range with a maximum MIC of 2 μg/mL improved EA to 91.2%.

Analysis of trending indicated that MIC values for E. faecium tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:

- Penicillin: Enterococcus faecium

Trimethoprim. A total of 215 Staphylococcus spp. [including 127 S. aureus and 88 CoNS: S. capitus (3), S. epidermidis (23), S. haemolyticus (11), S. hominis (6), S. intermedius (4), S. lugdunensis (23), S. saprophyticus (8), S. schleiferi (3), and S. simulans (7)] isolates were evaluated with trimethoprim. The combined results from clinical and challenge isolate testing demonstrated an EA of 91.1% and CA of 98.1%. When evaluating results by individual species, S. epidermidis and S. hominis each had one very major error (1/13 = 7.7% and 1/4 = 25%) and S. intermedius had two major errors (2/3 = 66.6%) while S. lugdunensis and S. schleiferi each had EA <90%, which are not acceptable. The following limitation is included in the device labeling to restrict reporting of specific CoNS species due to unacceptable performance:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Trimethoprim: Coagulase-Negative Staphylococci (S. epidermidis, S. hominis, S. intermedius group, S. lugdunensis, and S. schleiferi)

K211759 - Page 22 of 30

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Analysis of trending indicated that MIC values for S. capitus and S. haemolyticus tended to be one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:

- Trimethoprim: S. capitus, S. haemolyticus

Vancomycin. A total of 199 Enterococcus spp. (101 E. faecalis and 98 E. faecium) isolates were evaluated with vancomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.0% and CA of 98.0%. When evaluating results by individual species, E. faecalis had two minor errors, which is acceptable. E. faecium had two major errors (2/39 = 5.1%) at Selux MIC values >64 µg/mL, which is not acceptable. The following limitation is included in the device labeling to restrict reporting of E. faecium due to the observed major errors:

Perform an alternative method of testing prior to reporting results for the following antibiotic/organism combination(s):

- Vancomycin: Enterococcus faecium when the Selux MIC is >64 µg/mL due to two major errors

A total of 349 Staphylococcus spp. (including 238 S. aureus and 111 CoNS: S. capitus (7), S. cohnii (3), S. epidermidis (31), S. haemolyticus (14), S. hominis (7), S. intermedius (5), S. lugdunensis (24), S. saprophyticus (8), S. schleiferi (5), S. simulans (6) and one non-specified CoNS) isolates were evaluated with vancomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 98.9% and CA of 99.4%. When evaluating results by individual species, S. aureus had one major error (1/235 = 0.4%) and one minor error, which is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant Staphylococcus spp.

Analysis of trending indicated that MIC values for Staphylococcus spp. and E. faecalis tended to be one doubling dilution higher than the reference MIC value. The following statement is included as a footnote to the AST performance table:

Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution higher than the reference MIC value:

- Vancomycin: Staphylococcus spp. and Enterococcus faecalis

Table 7. Selux AST System – Gram-Positive Panel Performance of Quantitative Assays

|  Sample Type | Total | No.EA | EA % | Eval EA Tot | No. Eval EA | Eval EA % | No. CA | CA % | No. R/NS | No. S | min | major | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Ampicillin – Enterococcus spp. [Breakpoints (μg/mL): 8 (S), -, 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 284 | 279 | 98.2 | 164 | 159 | 97.0 | 284 | 100 | 152 | 132 | 0 | 0 | 0  |
|  Challenge | 15 | 15 | 100 | 10 | 10 | 100 | 15 | 100 | 11 | 4 | 0 | 0 | 0  |
|  Combined | 299 | 294 | 98.3 | 174 | 169 | 97.1 | 299 | 100 | 163 | 136 | 0 | 0 | 0  |
|  Ceftaroline – S. aureus [Breakpoints (μg/mL): 1 (S), 2 (I), 4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 107 | 105 | 98.1 | 107 | 105 | 98.1 | 105 | 98.1 | 1 | 103 | 1 | 1 | 0  |
|  Challenge | 31 | 31 | 100 | 31 | 31 | 100 | 31 | 100 | 0 | 31 | 0 | 0 | 0  |

K211759 - Page 23 of 30

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K211759 - Page 24 of 30
|  Sample Type | Total | No.EA | EA % | Eval EA Tot | No. Eval EA | Eval EA % | No. CA | CA % | No. R/NS | No. S | min | major | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Combined | 138 | 136 | 98.6 | 138 | 136 | 98.6 | 136 | 98.6 | 1 | 134 | 1 | 1 | 0  |
|  Clindamycin – Staphylococcus spp. [Breakpoints (μg/mL): 0.5 (S), 1-2 (I), 4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 260 | 247 | 95 | 165 | 152 | 92.1 | 252 | 96.9 | 51 | 207 | 4 | 3 | 1  |
|  Challenge | 51 | 51 | 100 | 23 | 23 | 100 | 50 | 98.0 | 22 | 28 | 1 | 0 | 0  |
|  Combined | 311 | 298 | 95.8 | 188 | 175 | 93.1 | 302 | 97.1 | 73 | 235 | 5 | 3 | 1  |
|  Daptomycin – E. faecalis [Breakpoints (μg/mL): 2 (S), 4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 111 | 104 | 93.7 | 111 | 104 | 93.7 | 111 | 100 | 0 | 111 | 0 | 0 | 0  |
|  Challenge | 5 | 5 | 100 | 5 | 5 | 100 | 5 | 100 | 0 | 5 | 0 | 0 | 0  |
|  Combined | 116 | 109 | 94.0 | 116 | 109 | 94.0 | 116 | 100 | 0 | 116 | 0 | 0 | 0  |
|  Daptomycin – S. aureus [Breakpoints (μg/mL): 1 (S), -, -]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 107 | 105 | 98.1 | 107 | 105 | 98.1 | 106 | 99.1 | 1 | 106 | NA | 0 | 1  |
|  Challenge | 27 | 27 | 100 | 27 | 27 | 100 | 27 | 100 | 0 | 27 | NA | 0 | 0  |
|  Combined | 134 | 132 | 98.5 | 134 | 132 | 98.5 | 133 | 99.3 | 1 | 133 | NA | 0 | 1  |
|  Delafloxacin – E. faecalis [Breakpoints (μg/mL): 0.125 (S), 0.25 (I), 0.5 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 175 | 170 | 97.1 | 175 | 170 | 97.1 | 159 | 90.9 | 35 | 126 | 14 | 2 | 0  |
|  Challenge | 5 | 5 | 100 | 5 | 5 | 100 | 5 | 100 | 3 | 2 | 0 | 0 | 0  |
|  Combined | 180 | 175 | 97.2 | 180 | 175 | 97.2 | 164 | 91.1 | 38 | 128 | 14 | 2 | 0  |
|  Delafloxacin – S. aureus and S. haemolyticus [Breakpoints (μg/mL): 0.25 (S), 0.5 (I), 1 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 209 | 207 | 99.0 | 60 | 58 | 96.7 | 196 | 93.8 | 8 | 181 | 13 | 0 | 0  |
|  Challenge | 20 | 20 | 100 | 17 | 17 | 100 | 20 | 100 | 6 | 10 | 0 | 0 | 0  |
|  Combined | 229 | 227 | 99.1 | 77 | 75 | 97.4 | 216 | 94.3 | 14 | 191 | 13 | 0 | 0  |
|  Eravacycline – E. faecalis and E. faecium [Breakpoints (μg/mL): 0.0625 (S), -, 0.125 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 284 | 245 | 86.3 | 283 | 244 | 86.2 | 277 | 97.5 | 6 | 278 | 0 | 5 | 2  |
|  Challenge | 3 | 3 | 100 | 3 | 3 | 100 | 3 | 100 | 0 | 3 | 0 | 0 | 0  |
|  Combined | 287 | 248 | 86.4¹ | 286 | 247 | 86.4 | 280 | 97.6 | 6 | 281 | 0 | 5 | 2  |
|  Eravacycline – S. aureus [Breakpoints (μg/mL): 0.0625 (S), -, 0.125 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 106 | 106 | 100 | 106 | 106 | 100 | 106 | 100 | 2 | 104 | 0 | 0 | 0  |
|  Challenge | 12 | 12 | 100 | 12 | 12 | 100 | 12 | 100 | 0 | 12 | 0 | 0 | 0  |
|  Combined | 118 | 118 | 100 | 118 | 118 | 100 | 118 | 100 | 2 | 116 | 0 | 0 | 0  |
|  Erythromycin – Enterococcus spp. [Breakpoints (μg/mL): 0.5 (S), 1-4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 249 | 207 | 83.1 | 116 | 74 | 63.8 | 211 | 84.7 | 151 | 29 | 36 | 2 | 0  |
|  Challenge | 31 | 28 | 90.3 | 8 | 5 | 62.5 | 28 | 90.3 | 25 | 1 | 3 | 0 | 0  |
|  Combined | 280 | 235 | 83.9¹ | 124 | 79 | 63.7 | 239 | 85.4 | 176 | 30 | 39 | 2 | 0  |
|  Erythromycin – Staphylococcus spp. [Breakpoints (μg/mL): 0.5 (S), 1-4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 181 | 165 | 91.2 | 94 | 78 | 83.0 | 169 | 93.4 | 84 | 92 | 7 | 5 | 0  |
|  Challenge | 39 | 39 | 100 | 4 | 4 | 100 | 39 | 100 | 39 | 0 | 0 | 0 | 0  |
|  Combined | 220 | 204 | 92.7 | 98 | 82 | 83.7 | 208 | 94.6 | 123 | 92 | 7 | 5 | 0  |
|  Levofloxacin – Enterococcus spp. [Breakpoints (μg/mL): 2 (S), 4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 249 | 241 | 96.8 | 151 | 143 | 94.7 | 242 | 97.2 | 104 | 143 | 4 | 2 | 1  |
|  Challenge | 32 | 31 | 96.9 | 8 | 7 | 87.5 | 30 | 93.8 | 25 | 6 | 1 | 0 | 1  |
|  Combined | 281 | 272 | 96.8 | 159 | 150 | 94.3 | 272 | 96.8 | 129 | 149 | 5 | 2 | 2  |
|  Levofloxacin – methicillin-susceptible S. aureus [Breakpoints (μg/mL): 2 (S), 4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 107 | 104 | 97.2 | 95 | 92 | 96.84 | 103 | 96.26 | 18 | 80 | 3 | 1 | 0  |
|  Challenge | 28 | 28 | 100 | 9 | 9 | 100 | 27 | 96.43 | 25 | 2 | 1 | 0 | 0  |
|  Combined | 135 | 132 | 97.78 | 104 | 101 | 97.12 | 130 | 96.3 | 43 | 82 | 4 | 1 | 0  |
|  Linezolid – Enterococcus spp. [Breakpoints (μg/mL): 2 (S), 4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 284 | 272 | 95.8 | 284 | 272 | 95.8 | 279 | 98.2 | 0 | 283 | 2 | 3 | 0  |
|  Challenge | 15 | 15 | 100 | 14 | 14 | 100 | 15 | 100 | 1 | 14 | 0 | 0 | 0  |

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K211759 - Page 25 of 30

|  Sample Type | Total | No.EA | EA % | Eval EA Tot | No. Eval EA | Eval EA % | No. CA | CA % | No. R/NS | No. S | min | major | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Combined | 299 | 287 | 96.0 | 298 | 286 | 96.0 | 294 | 98.3 | 1 | 297 | 2 | 3 | 0  |
|  **Linezolid – Staphylococcus** spp. [Breakpoints (μg/mL): 4 (S), -, 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 202 | 197 | 97.5 | 192 | 187 | 97.4 | 201 | 99.5 | 3 | 199 | 0 | 1 | 0  |
|  Challenge | 26 | 26 | 100 | 26 | 26 | 100 | 26 | 100 | 0 | 26 | 0 | 0 | 0  |
|  Combined | 228 | 223 | 97.8 | 218 | 213 | 97.7 | 227 | 99.6 | 3 | 225 | 0 | 1 | 0  |
|  **Minocycline – Staphylococcus** spp. [Breakpoints (μg/mL): 4 (S), 8 (I), 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 206 | 199 | 96.6 | 19 | 12 | 63.2 | 203 | 98.5 | 2 | 202 | 2 | 0 | 1  |
|  Challenge | 11 | 11 | 100 | 6 | 6 | 100 | 11 | 100 | 0 | 11 | 0 | 0 | 0  |
|  Combined | 217 | 210 | 96.8 | 25 | 18 | 72 | 214 | 98.6 | 2 | 213 | 2 | 0 | 1  |
|  **Oxacillin –S. aureus** [Breakpoints (μg/mL): 2 (S), -, 4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 97 | 83 | 85.6 | 63 | 49 | 77.8 | 96 | 99.0 | 38 | 59 | 0 | 0 | 1  |
|  Challenge | 25 | 21 | 84 | 16 | 12 | 75 | 25 | 100 | 11 | 14 | 0 | 0 | 0  |
|  Combined | 122 | 104 | 85.3¹ | 79 | 61 | 77.2 | 121 | 99.2 | 49 | 73 | 0 | 0 | 1  |
|  **Oxacillin – S. lugdunensis** [Breakpoints (μg/mL): 2 (S), -, 4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 38 | 34 | 89.5 | 37 | 33 | 89.2 | 36 | 94.7 | 3 | 35 | 0 | 2 | 0  |
|  Challenge | 1 | 1 | 100 | 1 | 1 | 100 | 1 | 100 | 0 | 1 | 0 | 0 | 0  |
|  Combined | 39 | 35 | 89.7 | 38 | 34 | 89.5 | 37 | 94.9 | 3 | 36 | 0 | 2 | 0  |
|  **Oxacillin – Coagulase-negative Staphylococci** except S. lugdunensis [Breakpoints (μg/mL): 0.25 (S), -, 0.5 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 115 | 96 | 83.5 | 72 | 53 | 73.6 | 107 | 93.0 | 72 | 43 | 0 | 4 | 4  |
|  Challenge | 9 | 8 | 88.9 | 2 | 1 | 50 | 9 | 100 | 8 | 1 | 0 | 0 | 0  |
|  Combined | 124 | 104 | 83.9¹ | 74 | 54 | 73.0 | 116 | 93.6 | 80 | 44 | 0 | 4 | 4  |
|  **Penicillin – Enterococcus** spp. [Breakpoints (μg/mL): 8 (S), -, 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 220 | 205 | 93.2 | 140 | 125 | 89.3 | 216 | 98.2 | 93 | 127 | 0 | 4 | 0  |
|  Challenge | 18 | 18 | 100 | 8 | 8 | 100 | 18 | 100 | 12 | 6 | 0 | 0 | 0  |
|  Combined | 238 | 223 | 93.7 | 148 | 133 | 89.9 | 234 | 98.3 | 105 | 133 | 0 | 4 | 0  |
|  **Penicillin – Staphylococcus** spp. [Breakpoints (μg/mL): 0.125 (S), -, 0.25 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 198 | 166 | 83.8 | 156 | 124 | 79.5 | 194 | 98.0 | 157 | 41 | 0 | 0 | 4  |
|  Challenge | 6 | 6 | 100 | 4 | 4 | 100 | 6 | 100 | 6 | 0 | 0 | 0 | 0  |
|  Combined | 204 | 172 | 84.3¹ | 160 | 128 | 80 | 200 | 98.0 | 163 | 41 | 0 | 0 | 4  |
|  **Trimethoprim – Staphylococcus** spp. [Breakpoints (μg/mL): 8 (S), -, 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 185 | 167 | 90.3 | 154 | 136 | 88.3 | 182 | 98.4 | 21 | 164 | 0 | 2 | 1  |
|  Challenge | 30 | 29 | 96.7 | 19 | 18 | 94.7 | 29 | 96.7 | 12 | 18 | 0 | 0 | 1  |
|  Combined | 215 | 196 | 91.2 | 173 | 154 | 89.0 | 211 | 98.1 | 33 | 182 | 0 | 2 | 2  |
|  **Vancomycin – Enterococcus** spp. [Breakpoints (μg/mL): 4 (S), 8-16 (I), 32 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 149 | 141 | 94.6 | 105 | 97 | 92.4 | 145 | 97.3 | 47 | 100 | 2 | 2 | 0  |
|  Challenge | 50 | 46 | 92 | 33 | 29 | 87.9 | 50 | 100 | 17 | 33 | 0 | 0 | 0  |
|  Combined | 199 | 187 | 94.0 | 138 | 126 | 91.3 | 195 | 98.0 | 64 | 133 | 2 | 2 | 0  |
|  **Vancomycin –S. aureus** [Breakpoints (μg/mL): 2 (S), 4-8 (I), 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 199 | 197 | 99.0 | 199 | 197 | 99.0 | 197 | 99.0 | 0 | 199 | 1 | 1 | 0  |
|  Challenge | 39 | 39 | 100.0 | 39 | 39 | 100.0 | 39 | 100.0 | 0 | 36 | 0 | 0 | 0  |
|  Combined | 238 | 236 | 99.2 | 238 | 236 | 99.2 | 236 | 99.2 | 0 | 235 | 1 | 1 | 0  |
|  **Vancomycin – Coagulase-negative Staphylococci** [Breakpoints (μg/mL): 4 (S), 8-16 (I), 32 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 99 | 97 | 98.0 | 99 | 97 | 98.0 | 99 | 100.0 | 0 | 99 | 0 | 0 | 0  |
|  Challenge | 12 | 12 | 100.0 | 12 | 12 | 100.0 | 12 | 100.0 | 0 | 12 | 0 | 0 | 0  |
|  Combined | 111 | 109 | 98.2 | 111 | 109 | 98.2 | 111 | 100.0 | 0 | 111 | 0 | 0 | 0  |

EA – Essential Agreement
CA – Category Agreement
EVAL – Evaluable isolates
R – Resistant isolates
N – Non-susceptible isolates
S – Susceptible isolates
min – minor errors
maj – major errors
vmj – very major errors

{25}

Essential Agreement (EA) occurs when there is agreement between the reference method and Selux MIC results within plus or minus one serial two-fold dilution of the antibiotic. Evaluable results are those that are on-scale for both the Selux and the reference method or those in which an off-scale result is at least two doubling dilutions from the on-scale result. Category Agreement (CA) occurs when the interpretation of the reference method and Selux result are in exact agreement.

$^{1}$ EA performance (<90%) is addressed in limitation statements, described above, and in the device labeling.

Table 8. Selux AST System - Gram-Positive Panel Performance of Cefoxitin Screen

|  Sample Type | Total | No. CA | CA % | No. R | No. S | major | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Cefoxitin Screen - S. aureus and S. lugdunensis [Breakpoints (μg/mL): 8 (S), -, 16 (R)]  |   |   |   |   |   |   |   |
|  Clinical | 130 | 127 | 97.7% | 40 | 90 | 2 | 1  |
|  Challenge | 45 | 45 | 100% | 41 | 4 | 0 | 0  |
|  Combined | 175 | 172 | 98.3% | 81 | 94 | 2 | 1  |

Table 9. Selux AST System - Gram-Positive Panel Trending

|  Drug | Organism Name | Total On Scale for Trending | ≥1 Dilution Lower # (%) | Exact # | ≥1 Dilution Higher # (%) | Percent Difference (95% CI) | Statistically Significant Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Ampicillin | Enterococcus faecalis | 115 | 83 (72.17) | 24 | 8 (6.96) | -65% (-73% to -54%) | Yes  |
|  Ampicillin | Enterococcus faecium | 184 | 120 (65.22) | 36 | 28 (15.22) | -50% (-58% to -41%) | Yes  |
|  Ceftaroline | Staphylococcus aureus | 138 | 38 (27.54) | 89 | 11 (7.97) | -20% (-28% to -11%) | No  |
|  Clindamycin | Staphylococcus aureus | 144 | 35 (24.3) | 61 | 48 (33.3) | 9% (-1% to 19%) | No  |
|  Clindamycin | Staphylococcus epidermidis | 55 | 22 (40) | 14 | 19 (34.6) | -5% (-23% to 12%) | No  |
|  Daptomycin | E. faecalis | 116 | 23 (19.8) | 49 | 44 (37.9) | 18% (% to 29%) | No  |
|  Daptomycin | S. aureus | 134 | 12 (9.0) | 111 | 11 (8.2) | -1% (-8% to 6%) | No  |
|  Delafloxacin | Enterococcus faecalis | 180 | 45 (25) | 114 | 21 (11.67) | -13% (-21% to -5%) | No  |
|  Delafloxacin | Staphylococcus aureus | 75 | 9 (12) | 38 | 28 (37.33) | 25% (12% to 38%) | No  |
|  Delafloxacin | Staphylococcus haemolyticus | 8 | 7 (87.5) | 1 | 0 (0) | -88% (-98% to -40%) | Yes  |
|  Eravacycline | Enterococcus faecalis | 114 | 64 (56.14) | 46 | 4 (3.51) | -53% (-62% to -42%) | Yes  |
|  Eravacycline | Staphylococcus aureus | 118 | 10 (8.47) | 56 | 52 (44.07) | 36% (25% to 45%) | Yes  |
|  Erythromycin | Staphylococcus aureus | 114 | 58 (50.88) | 40 | 16 (14.04) | -37% (-47% to -25%) | Yes  |
|  Levofloxacin | Enterococcus faecalis | 184 | 79 (42.93) | 88 | 17 (9.24) | -34% (-42% to -25%) | Yes  |
|  Levofloxacin | Enterococcus faecium | 97 | 87 (89.69) | 5 | 5 (5.15) | -85% (-90% to -75%) | Yes  |
|  Levofloxacin | Staphylococcus aureus | 108 | 45 (41.67) | 57 | 6 (5.56) | -36% (-46% to -25%) | Yes  |

K211759 - Page 26 of 30

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|  Drug | Organism Name | Total On Scale for Trending | ≥1 Dilution Lower # (%) | Exact # | ≥1 Dilution Higher # (%) | Percent Difference (95% CI) | Statistically Significant Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Linezolid | Enterococcus faecalis | 117 | 37 (31.62) | 72 | 8 (6.84) | -25% (-34% to -15%) | No  |
|  Linezolid | Enterococcus faecium | 182 | 51 (28.02) | 88 | 43 (23.63) | -4% (-13% to 5%) | No  |
|  Linezolid | Staphylococcus aureus | 127 | 29 (22.83) | 89 | 9 (7.09) | -16% (-24% to -7%) | No  |
|  Linezolid | Staphylococcus epidermidis | 26 | 6 (23.08) | 16 | 4 (15.38) | -8% (-29% to 14%) | No  |
|  Linezolid | Staphylococcus haemolyticus | 12 | 7 (58.33) | 4 | 1 (8.33) | -50% (-73% to -12%) | Yes  |
|  Minocycline | Staphylococcus aureus | 108 | 1 (0.93) | 7 | 100 (92.59) | 92% (84% to 95%) | Yes  |
|  Oxacillin | Staphylococcus aureus | 114 | 51 (44.74) | 30 | 33 (28.95) | -16% (-28% to -3%) | No  |
|  Oxacillin | Staphylococcus lugdunensis | 39 | 7 (17.95) | 15 | 17 (43.59) | 26% (5% to 43%) | No  |
|  Penicillin | Enterococcus faecalis | 117 | 31 (26.5) | 80 | 6 (5.13) | -21% (-30% to -12%) | No  |
|  Penicillin | Enterococcus faecium | 114 | 82 (71.93) | 14 | 18 (15.79) | -56% (-65% to -44%) | Yes  |
|  Penicillin | Staphylococcus aureus | 191 | 58 (30.37) | 67 | 66 (34.55) | 4% (-5% to 13%) | No  |
|  Trimethoprim | Staphylococcus aureus | 127 | 27 (21.26) | 74 | 26 (20.47) | -1% (-11% to 9%) | No  |
|  Trimethoprim | Staphylococcus capitus | 3 | 3 (100) | 0 | 0 (0) | -100% (-100% to -21%) | Yes  |
|  Trimethoprim | Staphylococcus haemolyticus | 7 | 5 (71.43) | 1 | 1 (14.29) | -57% (-81% to -6%) | Yes  |
|  Trimethoprim | Staphylococcus saprophyticus | 7 | 0 (0) | 6 | 1 (14.29) | 14% (-23% to 51%) | No  |
|  Trimethoprim | Staphylococcus simulans | 6 | 3 (50) | 2 | 1 (16.67) | -33% (-67% to 17%) | No  |
|  Vancomycin | Staphylococcus aureus | 238 | 12 (5.04) | 127 | 99 (41.6) | 37% (30% to 43%) | Y…

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K211759](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K211759)

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