Selux AST System; Model AST Gen 1.0

K211748 · Selux Diagnostics, Inc. · LON · Apr 19, 2023 · Microbiology

Device Facts

• Record ID: K211748
• Device Name: Selux AST System; Model AST Gen 1.0
• Applicant: Selux Diagnostics, Inc.
• Product Code: LON · Microbiology
• Decision Date: Apr 19, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Indications for 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-Negative Panel is intended for use with the Selux AST System as an in vitro test to determine the susceptibility of isolated colonies of specific gram-negative bacilli to specific antimicrobial agents when used as instructed.

Device Story

System performs automated antimicrobial susceptibility testing (AST) on isolated bacterial colonies. Components: Sample Prep Station, Inoculator, Analyzer, workstation. Workflow: User prepares sample; system inoculates 384-well panels; analyzer monitors growth via fluorescence/absorbance. Principle: Growth-based detection using serial two-fold dilution; metabolic assays (viability/surface binding) quantify growth after sufficient replication threshold. Algorithm: Species-specific MIC determination; requires organism ID (manual or LIS download) for result reporting. Output: MIC values and categorical interpretations (S, I, R, NS). Used in clinical laboratories to guide antimicrobial therapy; benefits patient by providing rapid susceptibility results (<6 hours) to inform treatment decisions.

Clinical Evidence

Performance evaluated using 1401 clinical and 222 challenge isolates across 24 antimicrobials. Compared to modal MIC of triplicate broth microdilution reference method. Metrics: Essential Agreement (EA) and Categorical Agreement (CA) ≥90%, major error ≤3%, very major error ≤2%. Results varied by drug-organism combination; specific limitations and alternative testing requirements were established for combinations failing acceptance criteria. Trending analysis performed for all combinations.

Technological Characteristics

Automated growth-based detection system using 384-well panels. Methodology: Serial two-fold dilution. Sensing: Fluorescence and optical absorbance for metabolic assays (viability/surface binding). Connectivity: LIS integration for ID download. Software: Algorithm-based MIC determination. Sterilization: Not specified.

Indications for Use

Indicated for determining susceptibility of isolated colonies of specific gram-negative bacilli (Enterobacterales, Acinetobacter baumannii complex, Pseudomonas aeruginosa) to specific antimicrobial agents. Rx only.

Regulatory Classification

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- Ceftaroline 0.0156-4 µg/mL (K190905)

Submission Summary (Full Text)

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**FDA** U.S. FOOD & DRUG
ADMINISTRATION

# **510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY**

# **I Background Information:**

# **A 510(k) Number**

K211748

# **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-negative organisms tested with the Selux AST System to determine the minimum inhibitory concentration of specific antimicrobials with specific Gram-negative organisms.

# **B Measurand:**

# **Antimicrobial**

Amikacin
Amoxicillin-Clavulanate
Ampicillin
Ampicillin-Sulbactam

# **Reportable Range**

$\leq 0.12$ to $\geq 256$ $\mu\text{g/mL}$
$\leq 0.5$ to $\geq 128$ $\mu\text{g/mL}$
$\leq 0.25$ to $\geq 128$ $\mu\text{g/mL}$
$\leq 0.5$ to $\geq 128$ $\mu\text{g/mL}$

Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

Updated: 5/30/2023

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| Antimicrobial | Reportable Range |
| --- | --- |
| Aztreonam | ≤0.03 to ≥128 µg/mL |
| Cefazolin | ≤0.12 to ≥128 µg/mL |
| Cefepime | ≤0.25 to ≥128 µg/mL |
| Cefoxitin | ≤1 to ≥128 µg/mL |
| Ceftazidime | ≤0.25 to ≥64 µg/mL |
| Ceftazidime-Avibactam | ≤0.12 to ≥64 µg/mL |
| Ceftriaxone | ≤0.25 to ≥32 µg/mL |
| Ciprofloxacin | ≤0.03 to ≥16 µg/mL |
| Eravacycline | ≤0.016 to ≥4 µg/mL |
| Ertapenem | ≤0.03 to ≥16 µg/mL |
| Gentamicin | ≤0.06 to ≥64 µg/mL |
| Imipenem-Relebactam | ≤0.03 to ≥128 µg/mL |
| Levofloxacin | ≤0.06 to ≥32 µg/mL |
| Meropenem | ≤0.12 to ≥64 µg/mL |
| Meropenem-Vaborbactam | ≤0.06 to ≥64 µg/mL |
| Minocycline | ≤0.25 to ≥64 µg/mL |
| Piperacillin-Tazobactam | ≤0.25 to ≥512 µg/mL |
| Tobramycin | ≤0.12 to ≥128 µg/mL |
| Trimethoprim-Sulfamethoxazole | ≤0.12 to ≥32 µg/mL |

### C Type of Test:

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

### 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-Negative Panel is intended for use with the Selux AST System as an *in vitro* test to determine the susceptibility of isolated colonies of specific gram-negative bacilli to specific antimicrobial agents when used as instructed.

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

- Amikacin: *Pseudomonas aeruginosa*
- Amoxicillin-Clavulanate: *Escherichia coli*, *Klebsiella* species (including *K. oxytoca*, *K. pneumoniae*), *Proteus mirabilis*
- Ampicillin: *Escherichia coli*, *Proteus mirabilis*
- Ampicillin-Sulbactam: *Acinetobacter baumannii* complex, *Escherichia coli*, *Klebsiella* species (including *K. oxytoca*, *K. pneumoniae*), *Proteus mirabilis*, *Proteus vulgaris*
- Aztreonam: *Escherichia coli*

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- Cefazolin: Escherichia coli, Klebsiella pneumoniae
- Cefepime: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
- Cefoxitin: Escherichia coli, Klebsiella species (including K. oxytoca, K. pneumoniae), Morganella morganii
- Ceftazidime: Citrobacter species (including C. freundii complex, C. koseri), Enterobacter cloacae complex, Escherichia coli, Klebsiella species (including K. aerogenes, K. oxytoca, K. pneumoniae), Proteus mirabilis, Proteus vulgaris, Serratia marcescens
- Ceftazidime-Avibactam: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
- Ceftriaxone: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis
- Ciprofloxacin: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa
- Eravacycline: Citrobacter freundii complex, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca
- Ertapenem: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
- Gentamicin: Citrobacter species (including C. freundii complex, C. koseri), Enterobacter cloacae complex, Escherichia coli, Klebsiella species (including K. aerogenes, K. oxytoca, K. pneumoniae), Proteus species (including P. mirabilis, P. vulgaris), Pseudomonas aeruginosa, Serratia marcescens
- Imipenem-Relebactam: Citrobacter freundii complex, Citrobacter koseri, Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa
- Levofloxacin: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
- Meropenem: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens
- Meropenem-Vaborbactam: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Serratia marcescens
- Minocycline: Escherichia coli, Klebsiella species (including K. aerogenes, K. oxytoca, K. pneumoniae)
- Piperacillin-Tazobactam: Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris
- Tobramycin: Pseudomonas aeruginosa
- Trimethoprim-Sulfamethoxazole: Enterobacter cloacae complex, Klebsiella species (including K. aerogenes, K. oxytoca, K. pneumoniae)

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# 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-Sulbactam: Proteus vulgaris
- Cefepime: Klebsiella aerogenes, Morganella morganii, Proteus vulgaris, Serratia marcescens
- Cefoxitin: Klebsiella oxytoca
- Ceftazidime-avibactam: Citrobacter koseri, Klebsiella aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
- Ciprofloxacin: Citrobacter koseri, Proteus vulgaris
- Eravacycline: Escherichia coli, Klebsiella oxytoca
- Ertapenem: Citrobacter koseri, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus vulgaris
- Gentamicin: Klebsiella aerogenes, Morganella morganii, Proteus vulgaris, Serratia marcescens
- Imipenem-Relebactam: Citrobacter koseri, Klebsiella aerogenes, Klebsiella oxytoca
- Levofloxacin: Citrobacter koseri
- Meropenem: Citrobacter koseri, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris
- Meropenem-vaborbactam: Citrobacter koseri, Klebsiella aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens
- Minocycline: Klebsiella oxytoca
- Piperacillin-tazobactam: Citrobacter koseri, Proteus mirabilis, Proteus vulgaris

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

- Amikacin: Acinetobacter baumannii
- Ampicillin: Proteus mirabilis when the Selux MIC is 2 μg/mL due to one very major error
- Ampicillin-Sulbactam: Proteus vulgaris when the Selux MIC is 32 μg/mL due to 3 major errors
- Aztreonam: Pseudomonas aeruginosa
- Cefazolin: Proteus mirabilis
- Cefepime: Klebsiella aerogenes when the Selux MIC is ≥64 μg/mL due to 2 major errors, Pseudomonas aeruginosa
- Cefoxitin: Proteus mirabilis, Proteus vulgaris
- Ceftazidime: Acinetobacter baumannii, Pseudomonas aeruginosa
- Ceftriaxone: Enterobacter cloacae, Serratia marcescens
- Ciprofloxacin: Serratia marcescens
- Eravacycline: Klebsiella pneumoniae
- Ertapenem: Citrobacter freundii complex when the Selux MIC is 2, 4, or 8 μg/mL due to 3 major errors, Enterobacter cloacae, Klebsiella aerogenes
- Gentamicin: Pseudomonas aeruginosa when the Selux MIC is ≤0.06 μg/mL

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- Imipenem: Acinetobacter baumannii
- Imipenem-Relebactam: Klebsiella oxytoca when the Selux MIC is 4 µg/mL due to one major error, Klebsiella aerogenes, Klebsiella pneumoniae
- Levofloxacin: Citrobacter freundii complex when the Selux MIC is 2 µg/mL due to 2 major errors, Klebsiella aerogenes when the Selux MIC is 2 µg/mL due to one major error, Pseudomonas aeruginosa
- Meropenem: Acinetobacter baumannii, Citrobacter freundii complex when the Selux MIC is 16 or 32 µg/mL due to 3 major errors, Serratia marcescens when the Selux MIC is 16 or 32 µg/mL due to 4 major errors
- Meropenem-Vaborbactam: Proteus mirabilis, Proteus vulgaris
- Minocycline: Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae when the Selux MIC is 4 µg/mL due to 2 very major errors
- Piperacillin-Tazobactam: Acinetobacter baumannii, Citrobacter freundii, Enterobacter cloacae, Klebsiella aerogenes, Pseudomonas aeruginosa, Serratia marcescens
- Trimethoprim-Sulfamethoxazole: Citrobacter freundii, Escherichia coli

# D Special Instrument Requirements:

Selux AST System, Software version 1, subversion 8.168

# 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), panel inoculator (for inoculation), and AST analyzer (for antimicrobial susceptibility testing), as described in detail in the Device Description section of K211759.

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

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

| Antimicrobial | Organism Group | Selux AST System Reportable Range (μg/mL) | FDA-Recognized/ Approved Breakpoints (μg/mL) | | |
| --- | --- | --- | --- | --- | --- |
| | | | S | I | R |
| Amikacin | *Pseudomonas aeruginosa* | ≤0.12 to ≥256 | ≤16 | 32 | ≥64 |
| Amoxicillin-Clavulanate | Enterobacterales | ≤0.5 to ≥128 | ≤8 | 16 | ≥32 |
| Ampicillin | Enterobacterales | ≤0.25 to ≥128 | ≤8 | 16 | ≥32 |
| Ampicillin-Sulbactam | *Acinetobacter baumannii* complex Enterobacterales | ≤0.5 to ≥128 | ≤8 | 16 | ≥32 |
| Aztreonam | Enterobacterales | ≤0.03 to ≥128 | ≤4 | 8 | ≥16 |
| Cefazolin | Enterobacterales | ≤0.12 to ≥128 | ≤1 | 2 | ≥4 |
| Cefepime | Enterobacterales | ≤0.25 to ≥128 | ≤2 | 4-8 | ≥16 |
| Cefoxitin | Enterobacterales | ≤1 to ≥128 | ≤4 | 8 | ≥16 |
| Ceftazidime | Enterobacterales | ≤0.25 to ≥64 | ≤4 | 8 | ≥16 |
| Ceftazidime-Avibactam | Enterobacterales *Pseudomonas aeruginosa* | ≤0.12 to ≥64 | ≤8 | - | ≥16 |
| Ceftriaxone | Enterobacterales | ≤0.25 to ≥32 | ≤1 | 2 | ≥4 |
| Ciprofloxacin | Enterobacterales | ≤0.03 to ≥16 | ≤0.25 | 0.5 | ≥1 |
| | *Pseudomonas aeruginosa* | | ≤0.5 | 1 | ≥2 |
| Eravacycline | Enterobacterales | ≤0.016 to ≥4 | ≤0.5 | - | - |
| Ertapenem | Enterobacterales | ≤0.03 to ≥16 | ≤0.5 | 1 | ≥2 |
| Gentamicin | Enterobacterales *Pseudomonas aeruginosa* | ≤0.06 to ≥64 | ≤4 | 8 | ≥16 |
| Imipenem-Relebactam | Enterobacterales | ≤0.03 to ≥128 | ≤1 | 2 | ≥4 |
| | *Pseudomonas aeruginosa* | | ≤2 | 4 | ≥8 |
| Levofloxacin | Enterobacterales | ≤0.06 to ≥32 | ≤0.5 | 1 | ≥2 |
| Meropenem | Enterobacterales | ≤0.12 to ≥64 | ≤1 | 2 | ≥4 |
| | *Pseudomonas aeruginosa* | | ≤2 | 4 | ≥8 |
| Meropenem-Vaborbactam | Enterobacterales | ≤0.06 to ≥64 | ≤4 | 8 | ≥16 |
| Minocycline | Enterobacterales | ≤0.25 to ≥64 | ≤4 | 8 | ≥16 |
| Piperacillin-Tazobactam | Enterobacterales | ≤0.25 to ≥512 | ≤16 | 32-64 | ≥128 |
| Tobramycin | *Pseudomonas aeruginosa* | ≤0.12 to ≥128 | ≤4 | 8 | ≥16 |
| Trimethoprim-Sulfamethoxazole | Enterobacterales | ≤0.12 to ≥32 | ≤2 | - | ≥4 |

S, Susceptible; I, Intermediate; R, Resistant; -, no breakpoint (interpretive criterion) recognized

### 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.

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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 commence across all wells in the panel after the threshold in the sufficient growth well has been met. The “viability assay” uses a fluorescent metabolic probe as an indicator of cellular activity and the “surface area assay” uses a fluorescent cationic probe that binds microorganism surfaces as a proxy for cellular surface area. The viability and surface area assays are performed in each AST panel well, providing two complementary datasets for each well. These data are input to an MIC-determining algorithm that provides results when organism IDs are available.

Refer to the K211759 Decision Summary for additional information on the Selux AST System.

## V Substantial Equivalence Information:

### A Predicate Device Name(s):

BD Phoenix Automated Microbiology System - GN Ceftaroline (0.0156-4 µg/mL)

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

K190905

### C Comparison with Predicate(s):

| Device & Predicate Device(s): | Device: K211748 | Predicate: K190905 |
| --- | --- | --- |
| Device Trade Name | Selux AST System | BD Phoenix Automated Microbiology System – GN Ceftaroline (0.0156-4 µg/mL) |
| **General Device Characteristic Similarities** | | |
| Intended Use/Indications For 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-Negative Panel is intended for use with the Selux AST System as an *in vitro* test to determine the susceptibility of isolated colonies of specific gram-negative bacilli to specific antimicrobial agents when used as instructed.* | The BD Phoenix Automated Microbiology System is intended for *in vitro* quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most Gram-negative aerobic and facultative anaerobic bacteria isolates from pure culture for *Enterobacteriaceae* and Non-*Enterobacteriaceae* and most Gram-positive bacteria isolates from pure culture belonging to the genera *Staphylococcus*, *Enterococcus* and *Streptococcus*. |
| Source of Microorganisms | 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-negative | Same |

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| Device & Predicate Device(s): | Device: K211748 | Predicate: K190905 |
| --- | --- | --- |
| 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 | *Acinetobacter baumannii* complex, specific Enterobacterales species, and *Pseudomonas aeruginosa* | Specific Enterobacterales species |
| **General Device Characteristic Differences** | | |
| Antimicrobial Agent and Reporting Range | Amikacin ≤0.12 to ≥256 µg/mL Amoxicillin-Clavulanate ≤0.5 to ≥128 µg/mL Ampicillin ≤0.25 to ≥128 µg/mL Ampicillin-Sulbactam ≤0.5 to ≥128 µg/mL Aztreonam ≤0.03 to ≥128 µg/mL Cefazolin ≤0.12 to ≥128 µg/mL Cefepime ≤0.25 to ≥128 µg/mL Cefoxitin ≤1 to ≥128 µg/mL Ceftazidime ≤0.25 to ≥64 µg/mL Ceftazidime-Avibactam ≤0.12 to ≥64 µg/mL Ceftriaxone ≤0.25 to ≥32 µg/mL Ciprofloxacin ≤0.03 to ≥16 µg/mL Eravacycline ≤0.016 to ≥4 µg/mL Ertapenem ≤0.03 to ≥16 µg/mL Gentamicin ≤0.06 to ≥64 µg/mL Imipenem ≤0.016 to ≥64 µg/mL Imipenem-Relebactam ≤0.03 to ≥128 µg/mL Levofloxacin ≤0.06 to ≥32 µg/mL Meropenem ≤0.12 to ≥64 µg/mL Meropenem-Vaborbactam ≤0.06 to ≥64 µg/mL Minocycline ≤0.25 to ≥64 µg/mL Piperacillin-Tazobactam ≤0.25 to ≥512 µg/mL Tobramycin ≤0.12 to ≥128 µg/mL Trimethoprim-Sulfamethoxazole ≤0.12 to ≥32 µg/mL | Ceftaroline 0.0156-4 µg/mL |
| IVD Functions | AST | ID and AST |
| Instrument | Selux AST System | BD Phoenix Automated Microbiology System |

* The Selux Gram-Negative Panel is a quantitative test for the antimicrobial agents with the specific organisms listed in section III.B (Indications for Use Statement).

## 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:

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Reproducibility testing for the Selux AST System with the Gram-Negative 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 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 ($\geq 95\%$) and a sufficient number of results obtained ($\geq 75$ 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 2**. Performance is summarized for each antimicrobial tested with all organisms as well as indicated organisms only. Inter-site reproducibility was determined to be acceptable.

**Table 2.** Inter-site Reproducibility of Selux AST System (Gram Negative Panel)

| Antimicrobial | All organisms (combined) | | Indicated organisms only | |
| --- | --- | --- | --- | --- |
| | Best-case (%) | Worst-case (%) | Best-case (%) | Worst-case (%) |
| Amikacin | 98/104 (94.2%) | 98/104 (94.2%) | 92/98 (93.9%) | 92/98 (93.9%) |
| Amoxicillin-Clavulanate | 77/78 (98.7%) | 76/78 (97.4%) | 71/72 (98.6%) | 70/72 (97.2%) |
| Ampicillin | 72/75 (96%) | 72/75 (96%) | 68/69 (98.6%) | 68/69 (98.6%) |
| Ampicillin-Sulbactam | 74/75 (98.7%) | 74/75 (98.7%) | 69/69 (100%) | 69/69 (100%) |
| Aztreonam | 77/78 (98.7%) | 75/78 (96.2%) | 77/78 (98.7%) | 75/78 (96.2%) |
| Cefazolin^{a} | 77/81 (95.1%) | 76/81 (93.8%) | 68/72 (94.4%) | 67/72 (93.1%) |
| Cefepime | 77/78 (98.7%) | 76/78 (97.4%) | 77/78 (98.7%) | 76/78 (97.4%) |
| Cefoxitin | 73/75 (97.3%) | 72/75 (96.0%) | 70/72 (97.2%) | 69/72 (95.8%) |
| Ceftazidime | 77/81 (95.1%) | 76/81 (93.8%) | 77/81 (95.1%) | 76/81 (93.8%) |
| Ceftazidime-Avibactam | 140/144 (97.2%) | 139/144 (96.5%) | 140/144 (97.2%) | 139/144 (96.5%) |
| Ceftriaxone | 140/141 (99.3%) | 140/141 (99.3%) | 140/141 (99.3%) | 140/141 (99.3%) |
| Ciprofloxacin^{a} | 74/75 (98.7%) | 71/75 (94.7%) | 74/75 (98.7%) | 71/75 (94.7%) |
| Eravacycline | 78/78 (100%) | 78/78 (100%) | 78/78 (100%) | 78/78 (100%) |
| Ertapenem | 143/145 (98.6%) | 143/145 (98.6%) | 143/145 (98.6%) | 143/145 (98.6%) |
| Gentamicin^{a} | 77/80 (96.3%) | 77/80 (96.3%) | 77/80 (96.3%) | 77/80 (96.3%) |
| Imipenem | 145/149 (97.3%) | 140/149 (94.0%) | 145/149 (97.3%) | 140/149 (94.0%) |
| Imipenem-Relebactam | 71/75 (94.7%) | 71/75 (94.7%) | 71/75 (94.7%) | 71/75 (94.7%) |
| Levofloxacin | 76/78 (97.4%) | 76/78 (97.4%) | 73/75 (97.3%) | 73/75 (97.3%) |
| Meropenem | 75/78 (96.2%) | 73/78 (93.6%) | 70/72 (97.2%) | 68/72 (94.4%) |
| Meropenem-Vaborbactam | 142/145 (97.9%) | 132/145 (91.0%) | 142/145 (97.9%) | 132/145 (91.0%) |

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| | All organisms (combined) | | Indicated organisms only | |
| --- | --- | --- | --- | --- |
| Antimicrobial | Best-case (%) | Worst-case (%) | Best-case (%) | Worst-case (%) |
| Minocycline^{a} | 73/75 (97.3%) | 73/75 (97.3%) | 64/66 (97.3%) | 64/66 (97.3%) |
| Piperacillin-Tazobactam^{a} | 72/75 (96.0%) | 69/75 (92.0%) | 63/66 (95.5%) | 60/66 (90.9%) |
| Tobramycin | 74/78 (94.9%) | 73/78 (93.6%) | 74/78 (94.9%) | 73/78 (93.6%) |
| Trimethoprim-Sulfamethoxazole | 143/148 (96.6%) | 142/148 (95.9%) | 143/148 (96.6%) | 142/148 (95.9%) |

$^{a}$ 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 3. 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 3. Intra-site Reproducibility of Selux AST System (Gram Negative Panel)

| | All organisms (combined) | | Indicated organisms only | |
| --- | --- | --- | --- | --- |
| Antimicrobial | Best-case (%) | Worst-case (%) | Best-case (%) | Worst-case (%) |
| Amoxicillin-Clavulanate | 63/63 (100%) | 63/63 (100%) | 63/63 (100%) | 63/63 (100%) |
| Ampicillin | 45/45 (100%) | 45/45 (100%) | 45/45 (100%) | 45/45 (100%) |
| Ampicillin-Sulbactam | 72/72 (100%) | 72/72 (100%) | 72/72 (100%) | 72/72 (100%) |
| Aztreonam | 71/74 (95.9%) | 68/74 (91.9%) | 71/74 (95.9%) | 68/74 (91.9%) |
| Cefazolin | 61/63 (96.8%) | 61/63 (96.8%) | 61/63 (96.8%) | 61/63 (96.8%) |
| Cefepime | 45/47 (95.7%) | 45/47 (95.7%) | 45/47 (95.7%) | 45/47 (95.7%) |
| Cefoxitin | 54/54 (100%) | 54/54 (100%) | 54/54 (100%) | 54/54 (100%) |
| Ceftazidime | 92/93 (98.9%) | 91/93 (97.8%) | 92/93 (98.9%) | 91/93 (97.8%) |
| Ceftazidime-Avibactam | 47/47 (100%) | 43/47 (91.5%) | 47/47 (100%) | 43/47 (91.5%) |
| Eravacycline | 103/103 (100%) | 99/103 (96.1%) | 103/103 (100%) | 99/103 (96.1%) |
| Gentamicin | 116/121 (95.9%) | 116/121 (95.9%) | 116/121 (95.9%) | 116/121 (95.9%) |
| Imipenem-Relebactam | 72/76 (94.7%) | 72/76 (94.7%) | 72/76 (94.7%) | 72/76 (94.7%) |
| Levofloxacin | 179/181 (98.9%) | 174/181 (96.1%) | 179/181 (98.9%) | 174/181 (96.1%) |
| Meropenem | 57/58 (98.3%) | 56/58 (96.6%) | 57/58 (98.3%) | 56/58 (96.6%) |
| Meropenem-Vaborbactam | 45/47 (95.7%) | 43/47 (91.5%) | 45/47 (95.7%) | 43/47 (91.5%) |
| Piperacillin-Tazobactam | 54/56 (96.4%) | 54/56 (96.4%) | 54/56 (96.4%) | 54/56 (96.4%) |
| Trimethoprim-Sulfamethoxazole | 62/65 (95.4%) | 61/65 (93.8%) | 62/65 (95.4%) | 61/65 (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.

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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.** The Selux AST System software contains QC Sets (A, B, C) such that when the Gram-Negative Panel is selected, the system will indicate the appropriate QC strains to be prepared for testing. CLSI-recommended QC strains and expected QC ranges for use with the Gram-Negative Panel are summarized in **Table 4**, which also includes the designation of the QC set as appropriate for each antimicrobial. Notably, QC Set A comprises gram-positive ATCC QC organisms which is acceptable to use for QC testing of the Gram-Negative Panel provided that QC is run concurrently with Set B and/or C, which comprise gram-negative ATCC QC organisms. This is necessary because the metabolic assay in the Selux AST System utilizes an additional biochemical reagent, an electron transfer agent, exclusively with gram-negative organisms. The following QC reporting scheme is included in the device labeling (and is supported by software information) to ensure that gram-negative organisms will be processed correctly by the Selux AST System:

- *Gram-Negative Panel QC failure when testing gram-positive QC organisms:* clinical results should not be reported for the antimicrobial(s) in which QC failed but may be reported for the antimicrobials for which QC passed.
- *Gram-Negative Panel QC failure when testing gram-negative QC organisms:*
- If all gram-negative organisms fail QC: all QC results (including those when testing gram-positive organisms) should be considered failed and clinical results should not be reported for any antimicrobial.
- If one (or fewer than all) gram-negative organisms fail QC: clinical results should not be reported for the antimicrobial(s) in which QC failed but may be reported for the antimicrobials for which QC passed (including those when testing gram-positive organisms).

**Table 4.** CLSI-Recommended QC Organisms for Gram-Negative Panel

| Antimicrobial | Abbreviation | QC Set | QC Strain | Expected QC Range (μg/mL) |
| --- | --- | --- | --- | --- |
| Amikacin | AMK | A | ATCC 29213^{a} | 1-4 |
| Amoxicillin-Clavulanate | AMC | B | ATCC 700603 | 4-16 |
| Ampicillin | AMP | C | ATCC 25922 | 2-8 |
| Ampicillin-Sulbactam | SAM | B | ATCC 700603 | 8-32 |
| Aztreonam | ATM | C | ATCC 25922 | 0.06-0.25 |
| Cefazolin | CFZ | C | ATCC 25922 | 1-4 |
| Cefepime | FEP | A | ATCC 29213^{a} | 1-4 |
| Cefoxitin | FOX | C | ATCC 25922 | 2-8 |
| Ceftazidime | CAZ | A | ATCC 29213^{a} | 4-16 |
| Ceftazidime-Avibactam | CZA | B | ATCC 700603 | 0.25-2 |

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| Antimicrobial | Abbreviation | QC Set | QC Strain | Expected QC Range (μg/mL) |
| --- | --- | --- | --- | --- |
| Ceftriaxone | CRO | A | ATCC 29213^{a} | 1-8 |
| Ciprofloxacin | CIP | A | ATCC 29213^{a} | 0.12-0.5 |
| Eravacycline | ERV | C | ATCC 25922 | 0.016-0.12 |
| Ertapenem | ETP | A | ATCC 29213^{a} | 0.06-0.25 |
| Gentamicin | GEN | A | ATCC 29212^{a} | 4-16 |
| Imipenem | IMP | B | ATCC 700603 | 0.06-0.5 |
| Imipenem-Relebactam | IMR | C | ATCC BAA-2814 | 0.06-0.5 |
| Levofloxacin | LVX | A | ATCC 29212^{a} | 0.25-2 |
| Meropenem | MEM | A | ATCC 29212^{a} | 2-8 |
| Meropenem-Vaborbactam | MEV | C | ATCC BAA-2814 | 0.12-0.5 |
| Minocycline | MIN | A | ATCC 29212^{a} | 1-4 |
| Piperacillin-Tazobactam | TZP | B | ATCC 700603 | 8-32 |
| Tobramycin | TOB | A | ATCC 29212^{a} | 8-32 |
| Trimethoprim-Sulfamethoxazole | SXT | C | ATCC 25922 | 0.12-0.5^{b} |

$^{a}$ Set A comprises gram-positive ATCC QC organisms which is acceptable to use for QC testing of the Gram-Negative Comprehensive panel provided that QC is run concurrently with Set B and/or C, which comprise gram-negative ATCC QC organisms. This is necessary because the metabolic assay in the Selux AST System utilizes an additional biochemical reagent, an electron transfer agent, exclusively with gram-negative organisms. This ensures that gram-negative organisms will be processed correctly by the Selux AST System.

$^{b}$ Expected QC range for SXT in CLSI M100 is ≤0.5; Selux AST reporting range for SXT is ≤0.12 to ≥32 μg/mL. Selux MIC results of ≤0.5 μg/mL were considered acceptable.

Quality control testing was performed each day that testing was conducted. CLSI-recommended QC strains for each antimicrobial (described in Table 4) were tested a sufficient number of times (i.e., at least 20 times/site) at each testing site using the Selux AST System. QC testing of the broth microdilution reference method was performed at a single, central site. In some cases, the site used CLSI-recommended QC organisms that were different from QC organisms tested with the Selux AST System. This is noted in Table 5.

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

Due to an administrative error, reference data for minocycline and tobramycin was not previously included in Table 5. This data is included in the updated table for both minocycline and tobramycin testing of E. coli ATCC 25922.

Table 5. QC Results for the Selux AST System Assay with Gram Negative Panel

| Antimicrobial | QC Strain | Expected Range (μg/mL) | No. in Range (%) | |
| --- | --- | --- | --- | --- |
| | | | Reference | Selux |
| Amikacin | S. aureus ATCC 29213 | 1-4 | 56/56 (100) | 218/219 (99.5) |
| Amoxicillin | K. pneumoniae ATCC 700603^{a} | ≥128^{c} | 47/47 (100) | 219/221 (99.1) |
| Amoxicillin-Clavulanate | K. pneumoniae ATCC 700603 | 4-16 | 49/50 (98.0) | 211/221 (95.5) |
| Ampicillin | E. coli ATCC 25922 | 2-8 | 47/48 (97.9) | 210/210 (100) |
| | K. pneumoniae ATCC 700603^{a} | ≥128^{c} | 50/50 (100) | 219/221 (99.1) |
| Ampicillin-Sulbactam | K. pneumoniae ATCC 700603 | 8-32 | 46/47 (97.9) | 221/221 (100) |
| Aztreonam | E. coli ATCC 25922 | 0.06-0.25 | 56/57 (98.2) | 210/210 (100) |

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| Antimicrobial | QC Strain | Expected Range (μg/mL) | No. in Range (%) | |
| --- | --- | --- | --- | --- |
| | | | Reference | Selux |
| Cefazolin | *E. coli* ATCC 25922 | 1-4 | 53/53 (100) | 210/210 (100) |
| Cefepime | *S. aureus* ATCC 29213 | 1-4 | 54/55 (98.2) | 218/219 (99.5) |
| Cefoxitin | *E. coli* ATCC 25922 | 2-8 | 45/46 (97.8) | 209/210 (99.5) |
| Ceftazidime | *S. aureus* ATCC 29213 | 4-16 | NT | 217/219 (99.1) |
| | *E. coli* ATCC 25922^{b} | 0.06-0.5 | 56/57 (98.2) | NT |
| | *K. pneumoniae* ATCC 700603^{a} | 16-64 | 66/66 (100) | 218/221 (98.6) |
| Ceftazidime-Avibactam | *K. pneumoniae* ATCC 700603 | 0.25-2 | 59/59 (100) | 221/221 (100) |
| Ceftriaxone | *S. aureus* ATCC 29213 | 1-8 | 45/49 (97.8) | 218/219 (99.5) |
| Ciprofloxacin | *S. aureus* ATCC 29213 | 0.12-0.5 | 57/58 (98.3) | 218/219 (99.5) |
| Eravacycline | *E. coli* ATCC 25922 | 0.016-0.12 | 49/49 (100) | 210/210 (100) |
| Ertapenem | *S. aureus* ATCC 29213 | 0.06-0.25 | 51/51 (100) | 217/219 (99.1) |
| Gentamicin | *E. faecalis* ATCC 29212 | 4-16 | 51/53 (96.2) | 216/217 (99.5) |
| Imipenem | *K. pneumoniae* ATCC 700603 | 0.06-0.5 | 64/64 (100) | 221/221 (100) |
| | *K. pneumoniae* ATCC BAA-2814^{a} | 16-64 | 65/65 (100) | 210/210 (100) |
| Imipenem-Relebactam | *K. pneumoniae* ATCC BAA-2814 | 0.06-0.5 | 65/65 (100) | 207/210 (98.6) |
| Levofloxacin | *E. faecalis* ATCC 29212 | 0.25-2 | 38/40 (95.0) | 89/90 (98.9) |
| Meropenem | *E. faecalis* ATCC 29212 | 2-8 | 55/56 (98.2) | 217/217 (100) |
| Meropenem-Vaborbactam | *K. pneumoniae* ATCC BAA-2814 | 0.12-0.5 | 48/49 (98.0) | 204/210 (97.1) |
| Minocycline | *E. faecalis* ATCC 29212 | 1-4 | NT | 216/217 (99.5) |
| | *E. coli* ATCC 25922^{b} | 0.25-1 | 43/44 (97.7) | NT |
| Piperacillin-Tazobactam | *K. pneumoniae* ATCC 700603 | 8-32 | 66/66 (100) | 221/221 (100) |
| Tobramycin | *E. faecalis* ATCC 29212 | 8-32 | NT | 211/217 (97.2) |
| | *E. coli* ATCC 25922^{b} | 0.25-1 | 52/53 (98.1) | NT |
| Trimethoprim-Sulfamethoxazole | *E. coli* ATCC 25922 | 0.12-0.5^{b} | 44/100 (100) | 208/210 (99.0) |

NT: Not tested

$^{a}$ Tested to confirm the integrity of the QC strain for testing with the beta-lactam/beta-lactam-inhibitor combination antimicrobial.

$^{b}$ BMD reference method testing was performed at a single, central site which utilized their standard, CLSI-recommended QC organisms.

$^{c}$ Expected QC range in CLSI M100 is >128; highest concentration of Amoxicillin and Ampicillin on the Selux AST result panel is 128 μg/mL. Selux MIC results of ≥128 μg/mL were considered acceptable.

**Inoculum Density Check:** Refer to the K211759 decision summary for description and results since studies were performed concurrently.

**Device Failure:** Refer to the K211759 decision summary for description and results since studies were performed concurrently.

**Growth Failure Rate:** There were 13 growth failures (13/1401 tests = 0.93%) when using the Gram-Negative Panel on the Selux AST System. All samples that generated Selux results also generated reference method 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:

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Not Applicable

7. Assay Cut-Off:

## **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 1401 clinical (426 contemporary and 975 stock) and 222 challenge isolates from 12 Enterobacterales species, *Acinetobacter baumannii* complex, and *Pseudomonas aeruginosa* were tested to evaluate the Selux AST System performance for 24 antimicrobials using the Selux Gram-Negative 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 165 (e.g. *P. aeruginosa*/Imipenem-Relebactam) to 977 (e.g. Enterobacterales/Ertapenem). 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 $\geq 90\%$, major error rate was $\leq 3\%$, and very major error rate was $\leq 2\%$.

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 $\geq 30\%$ with a statistically

K211748 - Page 14 of 43

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significant confidence interval were considered to have evidence of trending and is addressed in the labeling.

A high-level summary of the Selux AST System performance using the Gram-Negative Panel is described below for each antimicrobial and indicated species. Complete details and results including EA, CA and error rate analyses are summarized in **Table 6** and trending analyses are summarized in **Table 7**.

**Amikacin.** A total of 111 *A. baumannii* isolates were evaluated with amikacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 55.0% and CA of 86.5%, which is not acceptable. There were 6 minor, 8 major (8/80 = 10%) and 1 very major (1/25 = 4%) errors, which is not acceptable. Due to the unacceptable performance for *A. baumannii*, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of *A. baumannii* due to unacceptable performance:

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

- Amikacin: *Acinetobacter baumannii*

A total of 165 *P. aeruginosa* isolates were evaluated with amikacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 90.9% and CA of 98.2%. There were 3 minor, 0 major and 0 very major errors. Overall, performance is acceptable.

Analysis of trending indicated that MIC values for *P. aeruginosa* tended to be one doubling dilution lower than the reference MIC value. The following statement is included in the device labeling 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:

- Amikacin: *Pseudomonas aeruginosa*

**Amoxicillin-Clavulanate.** A total of 593 Enterobacterales isolates (indicated species: 179 *E. coli*, 48 *K. oxytoca*, 142 *K. pneumoniae*, 88 *P. mirabilis*; non-indicated species: 74 *C. koseri*, 62 *P. vulgaris*) were evaluated with amoxicillin-clavulanate. The combined results from clinical and challenge isolate testing demonstrated an EA of 93.3% and CA of 92.8%. There were 37 minor, 5 major and 1 very major errors. When evaluating results by individual species, *E. coli* had a CA of 88.7% due to 17 minor, 1 major and 0 very major errors which was determined to be acceptable since the majority of categorical errors were minor and the EA of evaluable results was good (96.5%). *P. mirabilis* had one very major error (1/8 = 16.7%), which was considered a random error due to the limited number of resistant isolates tested.

Analysis of trending indicated that MIC values for *K. pneumoniae* 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:

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

- Amoxicillin-Clavulanate: Klebsiella pneumoniae

Ampicillin. A total of 254 Enterobacterales isolates (165 E. coli, 89 P. mirabilis) were evaluated with ampicillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.9% and CA of 98.8%. There was 1 minor, 1 major and 1 very major error. When evaluating results by individual species, P. mirabilis had 1 major error (1/60 = 1.7%) and 1 very major error (1/26 = 3.8%) at a Selux MIC value of 2 μg/mL which represents 4.5% (4/89) of results with this drug/organism combination. The following limitation is included in the device labeling to address the very major error:

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

- Ampicillin: Proteus mirabilis when the Selux MIC is 2 μg/mL due to one very major error

Analysis of trending indicated that MIC values for E. coli 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: Escherichia coli

Ampicillin-Sulbactam. A total of 123 A. baumannii isolates were evaluated with ampicillin-sulbactam. The combined results from clinical and challenge isolate testing demonstrated an EA of 91.9% and CA of 92.7%. There were 6 minor, 2 major and 1 very major error. Overall, performance is acceptable.

A total of 574 Enterobacterales isolates (204 E. coli, 29 K. oxytoca, 116 K. pneumoniae, 75 M. morganii, 88 P. mirabilis, 62 P. vulgaris) were evaluated with ampicillin-sulbactam. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.9% and CA of 83.5%. There were 90 minor, 5 major and 0 very major errors. When evaluating results by individual species, K. oxytoca and P. mirabilis each had CA <90% which was considered acceptable since all of the categorical errors were minor and the EA of evaluable results was good (>95%). P. vulgaris had a CA of 45.2% due to 31 minor errors as well as 3 major errors (3/43 = 7.0%) at a Selux MIC value of 32 μg/mL which represents 9.7% (6/62) of results with this drug/organism combination. M. morganii had a CA of 72% due to 19 minor and 2 major errors (2/4 = 50%), which is not acceptable. Due to the unacceptable performance for M. morganii, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling address the P. vulgaris major errors and restrict reporting of M. morganii due to unacceptable performance:

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

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- Ampicillin-Sulbactam: Morganella morganii; Proteus vulgaris when the Selux MIC is 32 μg/mL due to 3 major errors

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

Analysis of trending indicated that MIC values for K. oxytoca tended to be one doubling dilution lower than the reference MIC value while MIC values for P. vulgaris 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:

- Ampicillin-Sulbactam: Klebsiella oxytoca

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

- Ampicillin-Sulbactam: Proteus vulgaris

Aztreonam. A total of 183 Enterobacterales isolates (183 E. coli) were evaluated with aztreonam. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.8% and CA of 97.3%. There were 5 minor, 0 major and 0 very major errors. Overall, performance is acceptable.

A total of 219 P. aeruginosa isolates were evaluated with aztreonam. The combined results from clinical and challenge isolate testing demonstrated an EA of 91.3% and CA of 87.7%. There were 20 minor, 3 major (3/158 = 1.9%) and 4 very major (4/48 = 8.3%) errors. Due to the unacceptable performance for P. aeruginosa, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of P. aeruginosa due to unacceptable performance:

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

- Aztreonam: Pseudomonas aeruginosa

Cefazolin. A total of 412 Enterobacterales isolates (indicated species: 177 E. coli, 115 K. pneumoniae, 66 P. mirabilis; non-indicated species: 54 C. koseri) were evaluated with cefazolin. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.2% and CA of 74.8%. There were 102 minor, 1 major and 1 very major errors. When evaluating results by individual species, E. coli and K. pneumoniae each had CA <90% which was considered acceptable since most of the categorical errors were minor and the EA of evaluable results was good (>90%). P. mirabilis had an EA of 86.4% and an EA of evaluable results of 84.8% (50/59), which is not acceptable. Due to the unacceptable performance for P. mirabilis, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation statement is included in the device labeling to restrict reporting of P. mirabilis due to unacceptable performance:

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

- Cefazolin: *Proteus mirabilis*

Analysis of trending indicated that MIC values for *C. koseri*, *E. coli* and *K. pneumoniae* 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:

- Cefazolin: *Citrobacter koseri*, *Escherichia coli*, *Klebsiella pneumoniae*

**Cefepime.** A total of 956 Enterobacterales isolates (77 *C. freundii* complex, 74 *C. koseri*, 77 *E. cloacae* complex, 170 *E. coli*, 52 *K. aerogenes*, 29 *K. oxytoca*, 111 *K. pneumoniae*, 75 *M. morganii*, 88 *P. mirabilis*, 100 *P. vulgaris*, 103 *S. marcescens*) were evaluated with cefepime. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.8% and CA of 96.0%. There were 26 minor, 10 major and 2 very major errors. When evaluating results by individual species, *M. morganii* had 1 very major error (1/1 = 100%) and *P. vulgaris* had 1 very major error (1/2 = 50%), which were considered random errors due to the insufficient number of resistant isolates tested. *K. aerogenes* had 2 major errors (2/51 = 3.9%) at Selux MIC values of ≥64 μg/mL which represents 5.8% (3/52) of results with this drug/organism combination. The following limitation is included in the device labeling to address the major errors:

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

- Cefepime: *Klebsiella aerogenes* when the Selux MIC is to ≥64 μg/mL due to two major errors

A total of 215 *P. aeruginosa* isolates were evaluated with cefepime. The combined results from clinical and challenge isolate testing demonstrated an EA of 87.4% and CA of 86.8%. There were 0 minor, 13 major (13/178 = 7.3%) and 7 very major (7/37 = 18.9%) errors. Due to the lack of an intermediate interpretive criterion, further analysis of the errors was performed and adjustments were made by considering the MIC values of the errors compared to the reference MIC value. Nine of the 13 major errors and 6 of the 7 very major errors had an MIC value that was in essential agreement with the reference MIC value. Therefore, the adjusted major error rate is 2.2% (4/178), which is acceptable. However, the adjusted very major error rate is 2.7% (1/37) which is not acceptable. Due to the unacceptable performance for *P. aeruginosa*, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of *P. aeruginosa* due to unacceptable performance:

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

- Cefepime: *Pseudomonas aeruginosa*

A limitation statement is included in the device labeling to address the lack of testing with resistant *K. aerogenes*, *M. morganii*, *P. vulgaris* and *S. marcescens* isolates.

K211748 - Page 18 of 43

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Analysis of trending indicated that MIC values for C. freundii, C. koseri, E. cloacae, E. coli, K. aerogenes, K. oxytoca, M. morganii, P. mirabilis, P. vulgaris, S. marcescens 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:

- Cefepime: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Cefoxitin. A total of 637 Enterobacterales isolates (indicated species: 168 E. coli, 29 K. oxytoca, 133 K. pneumoniae, 64 M. morganii, 89 P. mirabilis, 100 P. vulgaris; non-indicated species: 54 C. koseri) were evaluated with cefoxitin. The combined results from clinical and challenge isolate testing demonstrated an EA of 92.3% and CA of 80.2%. There were 114 minor, 9 major and 3 very major errors. When evaluating results by individual species, K. oxytoca and M. morganii had CA of <90% which was considered acceptable since most of the categorical errors were minor and the EA of evaluable results was good (>90%). P. mirabilis had a CA of 88.8% due to 6 minor, 2 major (2/75 = 2.7%) and 2 very major (2/7 = 28.6%) errors, which is not acceptable. P. vulgaris had an EA of 86% and a CA of 53% due to 46 minor errors and 1 major error (1/53 = 1.9%), which is not acceptable. Due to the unacceptable performance for P. mirabilis and P. vulgaris, these drug/organism combinations are not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of P. mirabilis and P. vulgaris due to unacceptable performance:

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

- Cefoxitin: Proteus mirabilis, Proteus vulgaris

A limitation statement is included in the device labeling to address the lack of testing with resistant K. oxytoca and P. vulgaris isolates.

There was no evidence of trending observed with any indicated species with cefoxitin.

Ceftazidime. A total of 127 A. baumannii isolates were evaluated with ceftazidime. The combined results from clinical and challenge isolate testing demonstrated an EA of 86.6% and CA of 94.5%. There were 7 minor, 0 major and 0 very major error. In addition, the EA of evaluable results was 81.5% (75/92). Due to the unacceptable performance for A. baumannii, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of A. baumannii due to unacceptable performance:

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

- Ceftazidime: Acinetobacter baumannii

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A total of 787 Enterobacterales isolates (64 C. freundii, 55 C. koseri, 84 E. cloacae, 186 E. coli, 36 K. aerogenes, 29 K. oxytoca, 145 K. pneumoniae, 66 P. mirabilis, 55 P. vulgaris, 67 S. marcescens) were evaluated with ceftazidime. The combined results from clinical and challenge isolate testing demonstrated an EA of 95.6% and CA of 96.4%. There were 26 minor, 1 major and 1 very major errors. Overall, performance is acceptable.

A total of 224 P. aeruginosa isolates were evaluated with ceftazidime. The combined results from clinical and challenge isolate testing demonstrated an EA of 88.0% and CA of 93.3%. There were 9 major (9/178 = 5.1%) and 6 very major (6/46 = 13%) errors. Due to the lack of an intermediate interpretive criterion, further analysis of the errors was performed and adjustments were made by considering the MIC values of the errors compared to the reference MIC value. One of the 9 major errors and 1 of the 6 very major errors had an MIC value that was in essential agreement with the reference MIC value. Therefore, the adjusted major error rate is 4.5% (8/177) and the adjusted very major error rate is 10.9% (5/46), which is not acceptable. Due to the unacceptable performance for P. aeruginosa, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of P. aeruginosa due to unacceptable performance:

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

- Ceftazidime: Pseudomonas aeruginosa

Analysis of trending indicated that MIC values for C. freundii complex, C. koseri, E. cloacae, K. aerogenes, K. oxytoca, K. pneumoniae, P. mirabilis, P. vulgaris, and S. marcescens 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:

- Ceftazidime: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Ceftazidime-avibactam. A total of 815 Enterobacterales isolates (61 C. freundii, 54 C. koseri, 75 E. cloacae, 170 E. coli, 52 K. aerogenes, 28 K. oxytoca, 126 K. pneumoniae, 62 M. morganii, 66 P. mirabilis, 55 P. vulgaris, 66 S. marcescens) were evaluated with ceftazidime-avibactam. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.3% and CA of 99.4%. There were 5 major and 0 very major errors. Overall, performance is acceptable.

A total of 163 P. aeruginosa isolates were evaluated with ceftazidime-avibactam. The combined results from clinical and challenge isolate testing demonstrated an EA of 89.6% and CA of 96.9%. There were 4 major errors (4/153 = 2.6%) and 1 very major error (1/10 = 10%). Due to the lack of an intermediate interpretive criterion, further analysis of the errors was performed and adjustments were made by considering the MIC values of the errors compared to the reference MIC value. Two of the 4 major errors and 1 of the 1 very major errors had an MIC value that was in essential agreement with the reference MIC value.

K211748 - Page 20 of 43

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Therefore, the adjusted major error rate is 1.3% (2/153) and the adjusted very major error rate is 0% (0/10), which is acceptable.

A limitation statement is included in the device labeling to address the lack of testing with resistant *C. koseri*, *K. aerogenes*, *K. oxytoca*, *M. morganii*, *P. mirabilis*, *P. vulgaris* and *S. marcescens* isolates.

Analysis of trending indicated that MIC values for *C. freundii*, *C. koseri*, *E. coli*, *K. aerogenes*, *K. oxytoca*, *M. morganii*, *P. mirabilis*, and *P. vulgaris* 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:

- Ceftazidime-avibactam: *Citrobacter freundii*, *Citrobacter koseri*, *Escherichia coli*, *Klebsiella aerogenes*, *Klebsiella oxytoca*, *Morganella morganii*, *Proteus mirabilis*, *Proteus vulgaris*

**Ceftriaxone.** A total of 722 Enterobacterales isolates (64 *C. freundii*, 54 *C. koseri*, 84 *E. cloacae*, 175 *E. coli*, 35 *K. aerogenes*, 29 *K. oxytoca*, 109 *K. pneumoniae*, 67 *P. mirabilis*, 105 *S. marcescens*) were evaluated with ceftriaxone. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.5% and CA of 98.5%. There were 3 minor, 4 major and 4 very major errors. When evaluating results by individual species, *E. cloacae* had 3 very major errors (3/34 = 8.8%) and *S. marcescens* had 1 very major error (1/12 = 8.3%), which are not acceptable. Due to the unacceptable performance for *E. cloacae* and *S. marcescens*, these drug/organism combinations are not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of *E. cloacae* and *S. marcescens* due to unacceptable performance:

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

- Ceftriaxone: *Enterobacter cloacae*, *Serratia marcescens*

Analysis of trending indicated that MIC values for *C. freundii*, *C. koseri*, *E. coli*, *K. aerogenes*, *K. oxytoca*, and *P. mirabilis* 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:

- Ceftriaxone: *Citrobacter freundii*, *Citrobacter koseri*, *Escherichia coli*, *Klebsiella aerogenes*, *Klebsiella oxytoca*, *Proteus mirabilis*

**Ciprofloxacin.** A total of 818 Enterobacterales isolates (62 *C. freundii*, 55 *C. koseri*, 76 *E. cloacae*, 170 *E. coli*, 32 *K. aerogenes*, 29 *K. oxytoca*, 105 *K. pneumoniae*, 63 *M. morganii*, 67 *P. mirabilis*, 55 *P. vulgaris*, 104 *S. marcescens*) were evaluated with ciprofloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.7% and CA of 96.2%. There were 26 minor, 3 major and 2 very major errors. When evaluating

K211748 - Page 21 of 43

{21}

results by individual species, S. marcescens had 2 very major errors (2/12 = 16.7%), which is not acceptable. Due to the unacceptable performance for S. marcescens, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of S. marcescens due to unacceptable performance:

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

- Ciprofloxacin: Serratia marcescens

A total of 169 P. aeruginosa isolates were evaluated with ciprofloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 95.9% and CA of 94.7%. There were 5 minor, 4 major and 0 very major errors. Overall, performance is acceptable.

A limitation statement is included in the device labeling to address the lack of testing with resistant C. koseri and P. vulgaris isolates.

Analysis of trending indicated that MIC values for P. aeruginosa tended to be one doubling dilution lower than the reference MIC value while MIC values for C. freundii, C. koseri, E. cloacae, E. coli, K. aerogenes, K. oxytoca, M. morganii, and P. vulgaris 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:

- Ciprofloxacin: Pseudomonas aeruginosa

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

- Ciprofloxacin: Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris

Eravacycline. A total of 487 Enterobacterales isolates (62 C. freundii, 78 E. cloacae, 167 E. coli, 47 K. oxytoca, 133 K. pneumoniae) were evaluated with eravacycline. The combined results from clinical and challenge isolate testing demonstrated an EA of 98.2% and CA of 98.6%. There were 4 major and 3 very major errors. When evaluating results by individual species, E. cloacae had 3 major errors (3/59 = 5.1%), K. oxytoca had 1 very major error (1/1 =100%), and K. pneumoniae had 2 very major errors (2/30 = 6.7%). Due to the lack of an intermediate interpretive criterion (eravacycline only has a “susceptible” category), further analysis of the errors was performed and adjustments were made by considering the MIC values of the errors compared to the reference MIC value. Two of the 3 E. cloacae major errors and 1 of the 1 K. oxytoca very major errors had an MIC value that was in essential agreement with the reference MIC value. Therefore, the adjusted major error rate for E. cloacae is 1.7% (1/59) and the adjusted very major error rate for K. oxytoca is 0% (0/1), which is acceptable. None of the 2 K. pneumoniae very major errors were in essential agreement resulting in an unacceptable very major error rate. Due to the unacceptable

K211748 - Page 22 of 43

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performance for K. pneumoniae, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of K. pneumoniae due to unacceptable performance:

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

- Eravacycline: Klebsiella pneumoniae

A limitation statement is included in the device labeling to address the lack of testing with resistant E. coli and K. oxytoca isolates.

Analysis of trending indicated that MIC values for C. freundii 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:

- Eravacycline: Citrobacter freundii

Ertapenem. A total of 977 Enterobacterales isolates (56 C. freundii, 74 C. koseri, 95 E. cloacae, 210 E. coli, 55 K. aerogenes, 28 K. oxytoca, 141 K. pneumoniae, 62 M. morganii, 88 P. mirabilis, 100 P. vulgaris, 68 S. marcescens) were evaluated with ertapenem. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.7% and CA of 97.4%. There were 11 minor, 14 major and 0 very major errors. When evaluating results by individual species, C. freundii had 3 major errors (3/53 = 5.7%) at Selux MIC values of 2, 4 and 8 μg/mL which represent 5.4% (3/56) of results from this drug/organism combination. E. cloacae had an EA of 80%, a CA of 88.4%, and 6 major errors (6/70 = 8.6%), which is not acceptable. K. aerogenes had an EA of 80% and 2 major errors (2/50 = 4%), which is not acceptable. Due to the unacceptable performance for E. cloacae and K. aerogenes, these drug/organism combinations are not indicated for use with the Selux AST System. The following limitation is included in the device labeling to address the C. freundii major errors and restrict reporting of E. cloacae and K. aerogenes due to unacceptable performance:

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

- Ertapenem: Citrobacter freundii when the Selux MIC is 2, 4 or 8 μg/mL due to 3 major errors, Enterobacter cloacae, Klebsiella aerogenes

A limitation statement is included in the device labeling to address the lack of testing with resistant C. koseri, K. oxytoca, M. morganii, P. mirabilis, and P. vulgaris isolates.

Analysis of trending indicated that MIC values for M. morganii tended to be one doubling dilution lower than the reference MIC value while MIC values for C. freundii, C. koseri, E. coli, P. mirabilis, P. vulgaris and S. marcescens tended to be one doubling dilution higher than the reference MIC value. The following statements are included as footnotes to the AST performance table:

K211748 - Page 23 of 43

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

- Ertapenem: Morganella morganii

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

- Ertapenem: Citrobacter freundii, Citrobacter koseri, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Gentamicin. A total of 817 Enterobacterales isolates (indicated species: 56 C. freundii, 74 C. koseri, 95 E. cloacae, 210 E. coli, 55 K. aerogenes, 28 K. oxytoca, 141 K. pneumoniae, 88 P. mirabilis, 100 P. vulgaris, 68 S. marcescens; non-indicated species: 62 M. morganii) were evaluated with gentamicin. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.0% and CA of 98.8%. There were 7 minor, 1 major and 2 very major errors. When evaluating results by individual species, M. morganii had 1 very major error (1/8 = 12.5%) and P. mirabilis had 1 very major error (1/6 = 16.7%), which were considered random errors due to the limited number of resistant isolates tested.

A total of 218 P. aeruginosa were evaluated with gentamicin. The combined results from clinical and challenge isolate testing demonstrated an EA of 88.5% and CA of 97.3%. There were 6 minor, 0 major and 0 very major errors. Restriction of reporting MIC values of ≤ 0.06 μg/mL (lowest reportable MIC value that represents 4.1% (9/218) of results from this drug/organism combination) improved the EA to 90.4%, which is acceptable. The following limitation statement is included in the device labeling to restrict reporting of P. aeruginosa due to the low EA:

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

- Gentamicin: Pseudomonas aeruginosa when the Selux MIC is ≤ 0.06 μg/mL

A limitation statement is included in the device labeling to address the lack of testing with resistant K. aerogenes, M. morganii, P. vulgaris, and S. marcescens isolates.

Analysis of trending indicated that MIC values for C. freundii, E. cloacae complex, E. coli, K. oxytoca, and K. pneumoniae tended to be one doubling dilution lower than the reference MIC value while MIC values for S. marcescens tended to be one doubling dilution higher than the reference MIC value. The following statements are included as footnotes 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:

- Gentamicin: Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae

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

- Gentamicin: Serratia marcescens

K211748 - Page 24 of 43

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**Imipenem.** A total of 126 *A. baumannii* isolates were evaluated with imipenem. The combined results from clinical and challenge isolate testing demonstrated an EA of 88.9% and CA of 98.4%. There were 0 minor, 0 major and 2 very major errors (2/62 = 3.2%), which is not acceptable. Due to the unacceptable performance for *A. baumannii*, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation statement is included in the device labeling to restrict reporting of *A. baumannii* due to the unacceptable performance:

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

- Imipenem: *Acinetobacter baumannii*

**Imipenem-relebactam.** A total of 471 Enterobacterales isolates (55*C. freundii*, 55 *C. koseri*, 172 *E. coli*, 31 *K. aerogenes*, 27 *K. oxytoca*, 131 *K. pneumoniae*) were evaluated with imipenem-relebactam. The combined results from clinical and challenge isolate testing demonstrated an EA of 93.4% and CA of 97.5%. There were 9 minor, 3 major and 0 very major errors. When evaluating results by individual species, *K. oxytoca* had 1 major error (1/27 = 3.7%) at a Selux MIC value of 4 µg/mL which represents 3.7% (1/27) of results from this drug/organism combination. *K. aerogenes* and *K. pneumoniae* had an EA <90%, which is not acceptable. Due to the unacceptable performance for *K. aerogenes* and *K. pneumoniae*, these drug/organism combinations are not indicated for use with the Selux AST System. The following limitation is included in the device labeling to address the *K. oxytoca* major error and restrict reporting of *K. aerogenes* and *K. pneumoniae* due to unacceptable performance:

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

- Imipenem-relebactam: *Klebsiella oxytoca* when the Selux MIC is 4 µg/mL due to one major error, *Klebsiella pneumoniae*, *Klebsiella aerogenes*

A total of 165 *P. aeruginosa* isolates were evaluated with imipenem-relebactam. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.4% and CA of 98.2%. There were 3 minor, 0 major and 0 very major errors. Overall, performance was acceptable.

A limitation statement is included in the device labeling to address the lack of testing with resistant *C. koseri*, *K. aerogenes*, and *K. oxytoca* isolates.

Analysis of trending indicated that MIC values for *C. freundii* tended to be one doubling dilution lower than the reference MIC value while MIC values for *K. oxytoca* tended to be one doubling dilution higher than the reference MIC value. The following statements are included as footnotes 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:

- Imipenem-relebactam: *Citrobacter freundii*

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

K211748 - Page 25 of 43

{25}

- Imipenem-relebactam: Klebsiella oxytoca

Levofloxacin. A total of 784 Enterobacterales isolates (63 C. freundii, 54 C. koseri, 75 E. cloacae, 171 E. coli, 32 K. aerogenes, 27 K. oxytoca, 110 K. pneumoniae, 62 M. morganii, 67 P. mirabilis, 55 P. vulgaris, 68 S. marcescens) were evaluated with levofloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.1% and CA of 94.9%. There were 33 minor, 6 major and 1 very major errors. When evaluating results by individual species, K. aerogenes had 1 major error (1/30 = 3.3%) at a Selux MIC value of 2 μg/mL, which represents 3.1% (1/32) of results from this drug/organism combination. C. freundii had 2 major errors (2/55 = 3.6%) at a Selux MIC value of 2 μg/mL which represent 4.8% (3/63) of results from this drug/organism combination, as well as 1 very major error (1/7 = 14.3%), which was considered a random error due to the limited number of resistant isolates tested. The following limitation is included in the device labeling to address the major errors:

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

- Levofloxacin: Citrobacter freundii when the Selux MIC is 2 μg/mL due to two major errors, Klebsiella aerogenes when the Selux MIC is 2 μg/mL due to one major error

A total of 171 P. aeruginosa isolates were evaluated with levofloxacin. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.2% and CA of 90.1%. There were 14 minor, 1 major and 2 very major errors (2/42 = 4.8%), which is not acceptable. Due to the unacceptable performance for P. aeruginosa, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation is included in the device labeling to restrict reporting of P. aeruginosa due to unacceptable performance:

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

- Levofloxacin: Pseudomonas aeruginosa

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

Analysis of trending indicated that MIC values for C. freundii, C. koseri, E. cloacae, E. coli, K. aerogenes, K. oxytoca, K. pneumoniae, M. morganii, P. mirabilis, and P. vulgaris 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:

- Levofloxacin: C. freundii, C. koseri, E. cloacae, E. coli, K. aerogenes, K. oxytoca, K. pneumoniae, M. morganii, P. mirabilis, P. vulgaris

Meropenem. A total of 126 A. baumannii isolates were evaluated with meropenem. The combined results from clinical and challenge isolate testing demonstrated an EA of 86.5%

K211748 - Page 26 of 43

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and CA of 98.4%. There were 0 minor, 2 major (2/63 = 3.2%) and 0 very major errors. Due to the unacceptable performance for A. baumannii, this drug/organism combination is not indicated for use with the Selux AST System. The following limitation statement is included in the device labeling to restrict reporting of A. baumannii due to the unacceptable performance:

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

- Meropenem: Acinetobacter baumannii

A total of 865 Enterobacterales isolates (indicated species: 78 C. freundii, 74 C. koseri, 74 E. cloacae, 166 E. coli, 27 K. oxytoca, 126 K. pneumoniae, 62 M. morganii, 66 P. mirabilis, 55 P. vulgaris, 105 S. marcescens; non-indicated species: 32 K. aerogenes) were evaluated with meropenem. The combined results from clinical and challenge isolate testing demonstrated an EA of 96.3% and CA of 98.0%. There were 4 minor, 12 major and 1 very major errors. When evaluating results by individual species, C. freundii has 3 major errors (3/74 = 4.1%) at Selux MIC values of 16 and 32 μg/mL, which represent 6.4% (5/78) of results from this drug/organism combination. S. marcescens had 4 major errors (4/101 = 4.0%) at Selux MIC value of 16 and 32 μg/mL, which represent 6.7% (7/105) of results from this drug/organism combination, as well as 1 very major error (1/4 = 25%) which was considered a random error due to the limited number of resistant isolates tested. The following limitations are included in the device labeling to address the major errors:

Perform an alternative method of testing prior to reporting results for the following an…