VITEK(R) 2 STREPTOCOCCUS TETRACYCLINE

K111893 · bioMerieux, Inc. · LON · Feb 28, 2012 · Microbiology

Device Facts

• Record ID: K111893
• Device Name: VITEK(R) 2 STREPTOCOCCUS TETRACYCLINE
• Applicant: bioMerieux, Inc.
• Product Code: LON · Microbiology
• Decision Date: Feb 28, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Indications for Use

VITEK® 2 Streptococcus Tetracycline is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 Streptococcus Tetracycline is a quantitative test intended for use with the VITEK® 2 and the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Tetracycline has an antimicrobial activity against the microorganisms listed below, according to the FDA label for this antimicrobial. Streptococcus pneumoniae Streptococcus pyogenes Viridans group streptococci The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 System for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast.

Device Story

VITEK® 2 Streptococcus Tetracycline is an in vitro diagnostic test card used with VITEK® 2 and VITEK® 2 Compact systems; performs automated quantitative antimicrobial susceptibility testing (AST). Input: isolated bacterial colonies diluted in saline (0.45%-0.50%) to rehydrate antimicrobial medium in card. Operation: system automatically fills, seals, and incubates card; monitors growth in wells over time; calculates minimum inhibitory concentration (MIC) and interpretive category. Output: report containing MIC values and interpretive results. Used in clinical laboratories; assists healthcare providers in selecting appropriate antimicrobial therapy for Streptococcus infections. Benefits: standardized, automated susceptibility determination; facilitates timely clinical decision-making.

Clinical Evidence

Performance evaluated using 1,535 clinical and challenge isolates. Combined essential agreement (EA) was 96.8%; category agreement (CA) was 97.1% (FDA breakpoints) and 96.4% (CLSI breakpoints). Reproducibility >95%. Comparison between auto and manual dilution methods showed comparable performance. No clinical sensitivity/specificity data required for AST systems.

Technological Characteristics

Test card with 64 micro-wells containing premeasured antibiotic and culture media. Sensing principle: automated optical growth detection. Energy source: VITEK 2/Compact instrument. Connectivity: standalone/networked system. Software: automated growth-based detection algorithm. Sterilization: not specified.

Indications for Use

Indicated for antimicrobial susceptibility testing of Streptococcus species (S. pneumoniae, S. pyogenes, Viridans group streptococci) to determine in vitro susceptibility to tetracycline. For use by laboratory professionals with isolated colonies.

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

• VITEK® 2 Gram Positive Amoxicillin for Streptococcus pneumoniae (k063597)

Submission Summary (Full Text)

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

A. 510(k) Number:
k111893

B. Purpose for Submission:
The addition of Tetracycline to the VITEK® 2 and VITEK®2 Compact Systems Antimicrobial Susceptibility Test (AST) Systems

C. Measurand
VITEK® 2 Streptococcus Tetracycline (≤ 0.25- ≥ 16 μg/mL)

D. Type of Test:
Automated quantitative growth based detection algorithm using optics light detection

E. Applicant:
bioMérieux, Inc.

F. Proprietary and Established Names:
Vitek®2 Streptococcus Tetracycline (≤ 0.25- ≥ 16 μg/mL)

G. Regulatory Information:
1. Regulation section:
866.1645 Short-Term Antimicrobial Susceptibility Test System
2. Classification:
II
3. Product Code:
LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation

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4. Panel:

83 Microbiology

H. Intended Use:

1. Intended use(s):

VITEK® 2 Streptococcus Tetracycline is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 Streptococcus Tetracycline is a quantitative test intended for use with the VITEK® 2 and the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Tetracycline has an antimicrobial activity against the microorganisms listed below, according to the FDA label for this antimicrobial.

Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group streptococci

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 System for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast.

2. Indication(s) for use:

VITEK® 2 Streptococcus Tetracycline is designed for antimicrobial susceptibility testing of Streptococcus species. VITEK® 2 Streptococcus Tetracycline is a quantitative test intended for use with the VITEK® 2 and the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Tetracycline has an antimicrobial activity against the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections:
Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group streptococci

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 System for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant

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aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast.

3. Special condition for use statement(s):

Prescription Use Only

4. Special instrument Requirements:

VITEK® 2 and the VITEK® 2 Compact Systems

I. Device Description:

Each VITEK® 2 test card contains 64 micro-wells, with a control well which contains only microbiological culture media on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 – 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK 2 Compact has a manual filling, sealing and loading operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

The VITEK 2 AST-ST Tetracycline has the following concentrations in the card: 0.125, 0.5, 1, 4μg/mL (equivalent standard method concentration by efficacy in μg/mL). The MIC result range for the VITEK 2 card is ≤0.25 – ≥ 16μg/mL.

J. Substantial Equivalence Information:

1. Predicate device name(s)

VITEK® 2 Gram Positive Amoxicillin for Streptococcus pneumoniae

2. Predicate K number(s):

k063597

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# 3. Comparison with predicate

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Determine antimicrobial susceptibility to antimicrobial agents | Same |
| Test Card | VITEK® 2 card format with base broth | same |
| Instrument | VITEK® 2 and VITEK®2 Compact System | same |
| Differences | | |
| Item | Device | Predicate |
| Antibiotic | Tetracycline | Amoxicillin |
| Reading algorithm | Unique for Tetracycline | Unique for amoxicillin |
| Test organism | S. pneumoniae, S. pyogenes, viridans Streptococci | S. pneumoniae |

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

Class II Special Controls Guidance Document: "Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", issued August 28, 2009.

CLSI M7-A8 "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard"

CLSI M100-S19 "Performance Standards for Antimicrobial Susceptibility; Twenty-First Information Supplement"

# L. Test Principle:

Each VITEK® 2 test card contains 64 micro-wells. A control well which contains only microbiological culture media is on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with $0.45 - 0.5\%$ saline before being used to rehydrate the antimicrobial medium within the card. The VITEK 2 System automatically fills, seals, and places the card into the incubator/reader. The VITEK 2 Compact has a manual filling, sealing and loading operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

The VITEK 2 AST-ST Tetracycline has the following concentrations in the card: $0.125, 0.5, 1, 4\mu \mathrm{g} / \mathrm{mL}$ (equivalent standard method concentration by efficacy in $\mu \mathrm{g} / \mathrm{mL}$ ). The MIC result range for the VITEK 2 card is $\leq 0.25 - \geq 16\mu \mathrm{g} / \mathrm{mL}$ .

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In addition to the automatic dilution, there is also a manual inoculation dilution procedure described in the packager insert.

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

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Reproducibility was demonstrated using 10 isolates at three sites on three separate days in triplicates. The study included the Auto-dilution and the Manual dilution with the VITEK®2, and the Manual dilution with the VITEK®2 Compact. All results were >95% reproducible.

#### b. Linearity/assay reportable range:

Not Applicable

#### c. Traceability (controls, calibrators, or method):

The recommended QC isolates were tested on every test occasion with the reference method and the VITEK®2. The reference method QC results were in range for every day tested. The VITEK®2 was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended range.

Quality Control was performed during the studies using both the auto-dilution and the manual method of diluting the organisms. Results demonstrated that methods were comparable with the same mode.

Quality Control Summary (VITEK®2, Auto and Manual dilution

| Organism | Conc. in μg/ml | Auto-dilution | | Manual dilution | |
| --- | --- | --- | --- | --- | --- |
| S. pneumoniae | | Ref. | Test | Ref. | Test |
| ATCC 49619 | ≤0.0625 | 1 | | 1 | |
| Expected Range | 0.125 | 163 | | 165 | |
| 0.12- 0.5 μg/mL | 0.25 | 50 | 214 | 49 | 215 |
| (Card Range | 0.5 | | | | |
| ≤0.25- 0.5 μg/mL) | | | | | |

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An additional QC study was performed with the VITEK®2 Compact, the secondary option, at three sites, with the following results.

Quality Control Summary (VITEK®2 Compact, Manual dilution)

| Organism | Conc. in μg/ml | Manual-dilution | |
| --- | --- | --- | --- |
| S. pneumoniae | | Ref. | Test |
| ATCC 49619 | 0.125 | | |
| Expected Range | 0.25 | 17 | 60 |
| 0.12- 0.5 μg/ml | 0.5 | 43 | |
| (Card Range | 0.125 | | |
| ≤0.25- 0.5 μg/mL) | | | |

Inoculum density control was monitored using the DensiChek2 instrument. This was standardized weekly with all results recorded and in the expected range. Verification was performed during internal testing.

d. Detection limit:
Not Applicable

e. Analytical specificity:
Not Applicable

f. Assay cut-off:
Not Applicable

2. Comparison studies:

The reference method follows CLSI approved broth microdilution testing conditions:

- Medium: Mueller-Hinton broth supplemented with lysed blood
- Inoculum: Direct colony suspension
- Incubation: 35°C, ambient air, 20-24 hours

a. Method comparison with predicate device:

Clinical study was performed at four external sites using the VITEK2 Streptococcus Tetracycline and broth microdilution panels containing Tetracycline. A total of 1338 clinical isolates were tested at four external sites by auto inoculation. All clinical isolates grew in the VITEK®2 AST-ST Tetracycline Test. Two hundred and nine (15.6%: 209/1338) were from stock isolates. For comparison of auto and manual dilution, the challenge set of 197 isolates was included.

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Performance Summary Table (VITEK 2, Auto Dilution), using FDA Breakpoints $(\leq 4,8,\geq 16)$

| | total | EA | %EA | Eval EA Total | Eval EA | Eval %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 1338 | 1290 | 96.4 | 191 | 155 | 81.2 | 1296 | 96.9 | 475 | 36 | 2 | 4 |
| Challenge | 197 | 196 | 99.5 | 32 | 32 | 100 | 195 | 99.0 | 69 | 2 | 0 | 0 |
| Combined | 1535 | 1486 | 96.8 | 223 | 187 | 83.9 | 1491 | 97.1 | 544 | 38 | 2 | 4 |

Performance Summary Table (VITEK 2, Auto Dilution), using CLSI Breakpoints $(\leq 2,4,\geq 8)$

| | total | EA | %EA | Eval EA Total | Eval EA | Eval %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 1338 | 1290 | 96.4 | 191 | 155 | 81.2 | 1283 | 95.9 | 507 | 42 | 2 | 11 |
| Challenge | 197 | 196 | 99.5 | 32 | 32 | 100 | 197 | 100 | 71 | 0 | 0 | 0 |
| Combined | 1535 | 1486 | 96.8 | 223 | 187 | 83.9 | 1480 | 96.4 | 578 | 42 | 0 | 11 |

EA-Essential Agreement

CA-Category Agreement

R-resistant isolates

maj-major discrepancies

vmj-very major discrepancies

min-minor discrepancies

Manual Dilution:

The challenge set of 197 organisms was also tested at one site using the manual method of inoculation with the following performance.

Comparison Challenge Data - Auto vs. Manual dilution (VITEK 2), FDA Breakpoints $(\leq 4,8,\geq 16)$

| | total | EA | %EA | Eval EA Total | Eval EA | Eval %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Auto | 197 | 196 | 99.5 | 32 | 32 | 100 | 195 | 99.0 | 69 | 2 | 0 | 0 |
| Manual | 197 | 195 | 99.0 | 33 | 32 | 97.0 | 194 | 98.5 | 69 | 3 | 0 | 0 |

Comparison Challenge Data - Auto vs. Manual dilution (VITEK 2), CLSI Breakpoints $(\leq 2,4,\geq 8)$

| | total | EA | %EA | Eval EA Total | Eval EA | Eval %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Auto | 197 | 196 | 99.5 | 32 | 32 | 100 | 197 | 100 | 71 | 0 | 0 | 0 |
| Manual | 197 | 195 | 99.0 | 33 | 32 | 97.0 | 197 | 100 | 71 | 0 | 0 | 0 |

The performance of the optional VITEK®2 Compact was evaluated in the QC, challenge, and reproducibility studies with acceptable results with the FDA breakpoints.

b. Matrix comparison:

Not Applicable

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3. Clinical studies:
a. Clinical sensitivity: Not Applicable
b. Clinical specificity: Not Applicable
c. Other clinical supportive data (when a and b are not applicable):

4. Clinical cut-off: Not Applicable

5. Expected values/Reference range
$\leq 4$ (S), $8(\mathrm{I}), \geq 16$ (R)

N. Proposed Labeling:
The labeling is sufficient and satisfies the requirement of 21 CFR Part 809.10.

O. Conclusion
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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