← Product Code [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON) · K111599

# VITEK 2 AST-ST LINEZOLID (K111599)

_bioMerieux, Inc. · LON · Aug 12, 2011 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K111599

## Device Facts

- **Applicant:** bioMerieux, Inc.
- **Product Code:** [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON.md)
- **Decision Date:** Aug 12, 2011
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1645
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

VITEK® 2 Streptococcus Linezolid is designed for antimicrobial susceptibility testing of Streptococcus species and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 Streptococcus Linezolid is a qualitative test. Linezolid has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections Streptococcus agalactiae Streptococcus pneumoniae [including multi-drug resistant isolates (MDRSP)] Streptococcus pyogenes

## Device Story

VITEK® 2 AST-ST Linezolid is an in vitro diagnostic test for antimicrobial susceptibility; used with VITEK® 2 and VITEK® 2 Compact systems. Input: isolated bacterial colonies diluted in saline. Process: card rehydration with sample; automated filling/sealing; incubation/reading for up to 18 hours. Principle: miniaturized doubling dilution technique (MIC). Output: MIC value and interpretive category result. Used in clinical laboratories; operated by lab technicians. Results assist clinicians in selecting appropriate antibiotic therapy for Streptococcus infections.

## Clinical Evidence

Performance established via clinical study (1425 clinical isolates) and challenge set (200 isolates). Compared against CLSI broth microdilution reference method. Combined Category Agreement (CA) was 99.8% (1612/1615). Four major errors observed (0.25% error rate). No very major errors. Reproducibility demonstrated 100% CA.

## Technological Characteristics

Miniaturized card-based broth microdilution system. Automated filling, sealing, and incubation/reading. Compatible with VITEK® 2 and VITEK® 2 Compact instrument platforms. Qualitative test for MIC determination. Software-controlled incubation and growth monitoring.

## Regulatory Identification

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

## Special Controls

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

## Predicate Devices

- VITEK® 2 Gram Positive Amoxicillin for Streptococcus pneumoniae ([K063597](/device/K063597.md))

## Submission Summary (Full Text)

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

A. 510(k) Number:
k111599

B. Purpose for Submission:
To obtain a substantial equivalence determination for this premarket notification for the addition of Linezolid to the VITEK 2 and VITEK 2 Compact Antimicrobial Susceptibility Test (AST) Systems.

C. Measurand:
Linezolid concentrations of 2 and 4 µg/mL are included in the VITEK® 2 AST-ST Linezolid card.

D. Type of Test:
The minimum inhibitory concentration (MIC) is determined using qualitative growth based detection algorithm using predetermined growth threshold. The MIC reporting result range of the card is ≤ 2– ≥8 µg/mL.

E. Applicant:
bioMerieux, Inc.

F. Proprietary and Established Names:
VITEK® 2 AST-ST Linezolid

G. Regulatory Information:
|  Product Code | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  LON | Class II | 21 CFR 866.1645 | Microbiology  |

H. Intended Use:

1. Intended use(s):
VITEK® 2 Streptococcus Linezolid is designed for antimicrobial susceptibility testing of Streptococcus species and is intended for use with the VITEK® 2 and

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VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 Streptococcus Linezolid is a qualitative test. Linezolid has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

**Active in vitro and in clinical infections**

*Streptococcus agalactiae*

*Streptococcus pneumoniae* [including multi-drug resistant isolates (MDRSP)]

*Streptococcus pyogenes*

2. **Indication(s) for use:**

VITEK® 2 Streptococcus Linezolid is designed for antimicrobial susceptibility testing of *Streptococcus* species and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of *in vitro* susceptibility to antimicrobial agents. VITEK® 2 Streptococcus Linezolid is a qualitative test. Linezolid has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

**Active in vitro and in clinical infections**

*Streptococcus agalactiae*

*Streptococcus pneumoniae* (including multi-drug resistant isolates [MDRSP])

*Streptococcus pyogenes*

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems 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.

3. **Special conditions for use statement(s):**

For prescription use only.

The current absence of resistant isolates precludes defining results other than Susceptible. Isolates yielding MIC results suggestive of Nonsusceptible category should be submitted to a reference laboratory for further testing.

The ability of the VITEK 2 AST-ST to detect resistance to Linezolid in *S. pneumoniae*, *S. agalactiae*, and *S. pyogenes* is unknown because resistant organisms were not available at the time of comparative testing.

4. **Special instrument requirements:**

For use with the VITEK® 2 and VITEK® 2 Compact Systems

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I. Device Description:

The VITEK 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident 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 Linezolid has the following concentrations in the card: 2, 4 µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 2 – ≥ 8 µg/mL.

The MIC ranges, interpretive criteria and equivalent concentrations are as follows:

|  VITEK 2 AST-ST | Equivalent Standard Method Concentration by Efficacy in µg/mL | MIC Ranges and FDA/CLSI Categories MIC* in µg/mL:  |   |
| --- | --- | --- | --- |
|   |   |  S* | NS  |
|  Linezolid | 2, 4 | ≤ 2 | -  |

* Currently only a "Susceptible" category is defined for Linezolid.
NS = Non-Susceptible
S = Susceptible: Attainable levels in blood or tissue on usual usage, including oral administration when applicable.

J. Substantial Equivalence Information:

1. Predicate device name(s):

VITEK 2 AST-GP Amoxicillin for S. pneumoniae

2. Predicate K number(s):

k063597

3. Comparison with predicate:

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended Use | Determining susceptibility to antimicrobial agents | Same  |
|  Inoculation and test organism | Isolated colonies of Streptococcus species | Same  |
|  Instrument | Test are run on both the VITEK 2 and VITEK 2 Compact Systems | Same  |
|  Test Card | The VITEK 2 card, including base broth | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Test Method | Automated qualitative antimicrobial susceptibility test for use with the VITEK® 2 and VITEK® 2 Compact Systems to determine the in vitro susceptibility of Streptococcus species. | Automated quantitative antimicrobial susceptibility test for use with the VITEK® 2 and VITEK® 2 Compact Systems to determine the in vitro susceptibility of Streptococcus species.  |
|  Antibiotic | Linezolid-specific concentrations | Amoxicillin-specific concentrations  |
|  Reading algorithm | Unique to Linezolid | Unique to Amoxicillin  |

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

"Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071462.pdf

Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Approved Standard -8th Edition, Document M7-A8.

Performance Standards for Antimicrobial Susceptibility Testing - 19th Informational Supplement, M100-S19.

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L. Test Principle:

Automated growth based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. 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 on the card. The VITEK 2 AST-ST Linezolid has the following concentrations in the card: 2, 4 µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 2 – ≥ 8 µg/mL.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

A reproducibility study was conducted at three external clinical sites. Ten Streptococcus species isolates were tested at each site and testing was performed in triplicate over three days with the VITEK 2 AST-ST Linezolid card. The testing was performed using both the manual dilution method and the automated dilution mode. Testing was conducted on the VITEK 2 instrument.

Streptococci are highly susceptible to Linezolid and currently there are no resistant strains. The MIC values were below the lowest concentration on the VITEK 2 AST-ST for Linezolid and all ten isolates tested produced off scale MIC results (≤ 2 µg/mL). In absence of on scale MIC results and because of the limited (two) concentration range on the VITEK 2, a reproducibility based on +/- one dilution is not possible and only a qualitative assessment based on Category Agreement is made. All reproducibility isolates were inhibited at concentrations in the susceptible range for Linezolid. Therefore, acceptable reproducibility was demonstrated with a CA (S/NS) of 100% by both manual dilution and automated dilution.

b. Linearity/assay reportable range:

Not applicable

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

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The recommended Streptococcus pneumonia QC organism was tested on every test occasion with the reference method and the VITEK 2 System. Ancillary quality control testing was also performed. Two gram-positive organisms were tested throughout comparative testing at each study site by the reference method only. This was done to perform further quality control of the broth microdilution panels using E. faecalis ATCC 29212 and S. aureus ATCC 29213 which have a QC range of 1-4 µg/mL for Linezolid. 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 acceptable QC results.

Quality Control was performed during the studies using both the auto-dilution and the manual method of diluting the organisms on the VITEK 2 System. Results demonstrated that methods were comparable.

Quality Control Results with the VITEK 2 System for Linezolid:

|  Organism | Concentration (μg/mL) | Auto Dilution |   | Manual Dilution  |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  Reference | VITEK 2 | Reference | VITEK 2  |
|  Streptococcus pneumonia ATCC 49619 | ≤0.025 |  |  |  |   |
|   |  0.5 |  |  |  |   |
|   |  1 | 92 |  | 91 |   |
|  Acceptable MIC range: 0.5-2 μg/mL | 2* | 90 | 182 | 89 | 179  |
|   |  4* |  |  |  |   |
|   |  8* |  |  |  |   |
|   |  ≥16 |  |  |  |   |

* VITEK Card Result Range is ≤ 2 - ≥ 8

At least one Quality control organism was in control in the reference on all days. Quality Control results for the VITEK 2 System using either inoculation dilution method demonstrated that the VITEK 2 System could produce the expected quality control results.

A similar QC study was conducted to evaluate the VITEK 2 Compact System. Results were compared to the expected CLSI QC results. All results for the VITEK 2 Compact System were within the expected QC ranges 100% of the time.

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

d. Detection limit:

Not applicable.

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e. Analytical specificity:

Not applicable.

f. Assay cut-off:

Not applicable

## 2. Comparison studies:

a. Method comparison with predicate device:

Performance was established through a clinical study which was conducted at four external study sites. A total of 1425 clinical isolates were tested by VITEK® 2 AST-ST Linezolid with the VITEK® 2 System. The majority of the isolates were recently isolated from clinical specimens. Four hundred and sixty-five of the 1425 clinical isolates tested were stock isolates (32.6%). A challenge set consisting of 200 isolates was evaluated with VITEK® 2 AST-ST Linezolid. Testing of clinical isolates was performed using the automated method of inoculation and the challenge organisms were tested with both the manual dilution and automatic dilution. Each isolate was tested by the VITEK 2 AST-ST Linezolid and the CLSI broth microdilution reference method. The inoculum was prepared with direct colony suspension. A comparison was provided to the reference method with the following agreement. Four major errors were seen. No growth was observed in 9 isolates.

AutoDilution

|  Organism Group | CA N | CA % | #NS | # vmj | # maj  |
| --- | --- | --- | --- | --- | --- |
|  All Streptococcus species  |   |   |   |   |   |
|  CLINICAL | 1412 | 99.7 | 0 | 0 | 4  |
|  CHALLENGE | 200 | 100 | 0 | 0 | 0  |
|  COMBINED (CLINICAL AND CHALLENGE) | 1612 | 99.8 | 0 | 0 | 4  |

CA-Category Agreement NS-not susceptible

maj-major discrepancies

vmj-very major discrepancies

Essential agreement (EA) is when the VITEK 2 panels agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the VITEK 2 panel result interpretation agrees exactly with the reference panel result interpretation. Evaluable EA is when the MIC result is on scale for both the

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VITEK 2 and the reference and have on-scale EA. No evaluation could be made on the basis of essential agreement because the VITEK® 2 AST-ST contained only two discrete concentrations of Linezolid and is therefore considered a breakpoint panel. Performance was evaluated on the basis of CA.

A CA of 99.7% and 100% was observed for clinical and challenge isolates, respectively. Only 4 major errors were observed giving an error rate of 0.25% that is well within the acceptable range defined in the AST Guidance Document.

Performance of the VITEK® 2 and the VITEK® 2 Compact was also evaluated with the same 200 challenge organisms using the manual dilution method. Results from those two studies were identical and showed 100% CA.

Manual Dilution (Challenge only/ VITEK® 2 and the VITEK® 2 Compact)

|  Organism Group | CA N | CA % | #NS | # vmj | # maj  |
| --- | --- | --- | --- | --- | --- |
|  All Streptococcus species | 200 | 100 | 0 | 0 | 0  |

b. Matrix comparison:
Not Applicable

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):
Not Applicable

4. Clinical cut-off:
Not Applicable

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5. Expected values/Reference range:

FDA Interpretive criteria for *Streptococcus* species, including *S. pneumoniae* are:

$$
S = \leq 2 \ \mu g/mL, \ NS = *
$$

* Currently only a “Susceptible” category is defined for Linezolid. Strains yielding test results suggestive of a “nonsusceptible” category should be retested, and if the result is confirmed, the isolate should be submitted to a reference laboratory for further testing.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR section 809.10.

O. Conclusion:

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

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K111599](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K111599)

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