bioMérieux, Inc. 100 Rodolphe Street, Durham, NC 27712 Phone: 800-682-2666

www.biomerieux-usa.com P/N 60-00880-1

Dear bioMérieux Customer, April 2013

We are pleased to announce the launch of a new VITEK® 2 Streptococcal antibiotic susceptibility test (AST) card; AST-ST01, item# 410028. This new AST card will be available to order in the U.S. beginning March 5th, 2013.

AST-ST01 offers expanded Streptococcus species coverage that includes Streptococcus pneumoniae and viridans and beta-hemolytic streptococci. The new AST-ST01 card contains a total of 11 antibiotics plus the Inducible Clindamycin Resistance Test (ICR Test) as seen below: AST-ST01 (410028) with calling ranges:

- Ampicillin < 0.25 - > 16 - Benzylpenicillin < 0.06 - > 8 - Cefotaxime < 0.12 - > 8 - Ceftriaxone < 0.12 - > 8 - Clindamycin < 0.25 - > 1 - Erythromycin < 0.12 - > 8 - ICR Test +/- - Levofloxacin < 0.25 - > 16 - Linezolid < 2 - > 8 - Tetracycline < 0.25 - > 16 - Trimethoprim/Sulfamethoxazole < 10(0.5/9.5) - > 320(16/304) - Vancomycin < 0.12 - > 8

The new AST-ST01 card has an average mean time to call of ~11 hours, an 18-month shelf-life, and requires V2S 5.01 software or greater. In addition to the above features of the new AST-ST01 card, it is important to note two additional points:

1) The first sentence (in “bold”) below will be removed from the patient lab reports in a future VITEK 2 Systems software release as it is based on scientific literature only and not on the VITEK 2 Streptococcus ICR performance testing.

“A positive ICR test is indicative of inducible resistance to macrolides, lincosamides, and type B streptogramin.” This isolate is presumed to be resistant to clindamycin; however, clindamycin may still be effective in some patients.”

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As a reminder for your laboratory, that the first sentence in the positive ICR message is only based on scientific literature, bioMérieux suggests creating a custom bioART rule.

2) Upon using new Streptococcus AST cards containing Erythromycin, and if you are using the CLSI Interpretation Standard in the VITEK 2 Systems (V2S) software versions 05.03 and higher, you will have a one-time software configuration change to implement. Before reporting Erythromycin results for Streptococcus, you will need to manually change the breakpoints to <=0.25 S, 0.5 I, and >=1 R utilizing the “User Defined Breakpoints” feature. This change is required for the Erythromycin contained on the new AST-ST01 card because the V2S software does not contain the current FDA Erythromycin breakpoints for Streptococcus. The current FDA Erythromycin breakpoints for Streptococcus will be incorporated to the V2S software version 7.01, anticipated to be available in 1Q/2014.

See Appendix A for: Instructions to manually change the Erythromycin breakpoints for Streptococci in the V2S software

See Appendix B for: Performance characteristics of AST-ST01

See Appendix C for: Instructions to create a custom bioART rule for a positive ICR

message See Appendix D for: Instructions to manually add Benzylpenicillin breakpoints for Streptococcus pneumoniae by source in the V2S software.

bioMérieux is dedicated to ongoing product improvements in order to provide the best products for your laboratory. If you have any questions, please contact your local bioMérieux representative.

Sincerely,

Christian Coogan, MS U.S. Marketing Manager, Clinical Microbiology

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APPENDIX A

The following are the instructions for a one-time software configuration change you will need to implement if you are using one of the new Streptococcus (ST) VITEK® 2 AST cards containing Erythromycin and are using the CLSI Interpretation Standard in the VITEK® 2 Systems (V2S) software versions 05.03 and higher. Before reporting Erythromycin results for Streptococcus, you will need to manually change the breakpoints to <=0.25 S, 0.5 I, and >=1 R utilizing the “User Defined Breakpoints” feature. This change is required for the new AST-ST01 Erythromycin because the V2S software does not contain the current FDA Erythromycin breakpoints for Streptococcus. The current FDA Erythromycin breakpoints for Streptococcus will be incorporated to the V2S software version 7.01, anticipated to be available in early 2014. You should update these breakpoints in the CLSI Interpretation Standard by using the following steps.

1. Log onto the VITEK® 2 Systems software with supervisor access. 2. Access the AES configuration from the main screen

3. Unlock AES configuration

4. Click yes on the popup message.

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11. Click in the Comment column of the Erythromycin line and enter a comment of your choice.

12. Click Save.

13. Lock AES Configuration when all editing is complete.

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APPENDIX B

Performance Characteristics for Streptococcus Species Antimicrobial Susceptibility Testing

Antimicrobial Antimi-crobial Code

Bp1 Comment

Essential Agreement Category Agreement

Reproducibility % Error % Error

%EA VME ME mE %CA VME ME mE

Ampicillin

AM CLSI #, E 99.1 0.0 0.0 0.5 97.0 0.0 0.0 3.0 99.6

Cefotaxime

CTX CLSI #, E Streptococcus

species

99.0 0.0 0.2 0.2 96.5 0.0 0.2 3.3 100

#, E S. pneumoniae (non-meningitis) 4

98.6 0.0 0.3 0.9 89.7 0.0 0.3 10.0 100

Ceftriaxone

CRO FDA, CLSI

#, E Streptococcus species

98.9 0.0 0.2 0.1 97.7 0.0 0.2 2.1 100

S. pneumoniae (meningitis) 3

97.7 0.0 0.0 1.4 90.9 0.0 0.0 9.1 100

S. pneumoniae (non-meningitis) 3

97.7 0.0 1.0 0.0 93.7 0.0 1.0 5.4 100

Beta hemolytic streptococci 3

100 0.0 0.0 0.0 100 0.0 0.0 0.0 100

Viridans group streptococci 3

97.8 0.5 0.0 0.0 96.3 0.0 0.0 3.7 100

Clindamycin

CM CLSI2 #, E N/A N/A N/A N/A 97.2 1.1 1.1 1.7 100

Erythromycin

E FDA, CLSI

#, E 97.9 0.8 0.2 0.5 98.7 0.8 0.2 0.9 96.7

Inducible Clindamycin Resistance

ICR CLSI #, E N/A N/A N/A N/A 99.2 1.5 0.7 N/A 100

Levofloxacin

LEV CLSI (FDA)

#, E 99.0 0.0 0.0 0.3 97.9 0.0 0.0 2.1 100

Linezolid LNZ CLSI #, E - - - - 99.8 0.0 0.2 N/A 100

Penicillin

P CLSI2 #, E, (Include S. pneumoniae

with pneumonia breakpoint)

99.1 0.0 0.0 0.6 96.8 0.0 0.0 3.2 99.6

#, E, S. pneumoniae (pneumonia)

97.7 0.0 0.0 1.1 92.3 0.0 0.0 7.7

#, E, S. pneumoniae (meningitis)

97.7 0.6 0.5 N/A 97.7 1.2 3.2 N/A

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Tetracycline

TE FDA #, E 96.8 0.7 0.2 0.7 97.1 0.7 0.2 2.5 100

CLSI E 96.8 1.9 0.2 0.3 96.4 1.9 0.2 2.7

Trimethoprim / Sulfamethoxazole

SXT FDA, CLSI

#, E - - - - 96.1 0.0 0.0 3.9 100

Vancomycin

VA FDA- CLSI

#, E 95.8 0.0 0.0 0.0 100 0.0 0.0 0.0 100

1 Abbreviations: Bp = break point; EA = essential agreement; CA = category agreement; VME = Very Major Error (susceptible result with resistant reference result); ME = Major Error (resistant result with susceptible reference result); mE = minor Error (susceptible or resistant result with an intermediate reference result, or an intermediate result with a susceptible or resistant reference result). 2 FDA breakpoints are used in the CLSI Interpretation Standard (breakpoint committee) in the VITEK 2 Systems Software. 3 The analysis was done using the FDA/CLSI breakpoints of: S. pneumoniae (meningitis): S < 0.5, I = 1, R > 2 S. pneumoniae (non-meningitis): S < 1, I = 2, R > 4 Beta hemolytic streptococci: S < 0.5 Viridans group streptococci: S < 1, I = 2, R > 4 4 The analysis was done using the CLSI breakpoints of: S < 1, I = 2, R > 4

Key: # = US FDA 510 (k) cleared CLSI = Clinical and Laboratory Standards Institute CA-SFM = Comite de l’Antibiogramme de la Societe Francaise de Microbiologie E = External performance data I = Internal performance data

- = Not available N/A = Not applicable Ref. = Reference method for clinical performance study

= Symbol identifies the performance characteristics for a specific antimicrobial version. This symbol is also referenced in the package insert.

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APPENDIX C

The following instructions are provided for the purposes of creating a custom bioART comment as a reminder for the current positive ICR message.

Overview 1. Login to VITEK 2 Systems as a member of the Lab Supervisor group 2. Navigate to Advanced Reporting Tool 3. Create a new bioART rule which consists of two conditions and one action. Conditions

include: Test Result and Organism. Action include: Comment. 4. Save the rule and exit Advanced Reporting Tool

Details

Navigate to Advanced reporting Tool 1. Login to VITEK 2 Systems as a member of the Lab Supervisor group. 2. From the main menu, click on the “Configuration View” icon and select Advanced

Reporting Tool. 3. Unlock configuration by clicking on the Lock/Unlock icon.

Create new custom rule 1. Click on the “Create new Rule” icon. 2. Enter a name for the rule and press OK.

Create the following Condition 1. Click “Add a condition” 2. Select “Test Result” 3. Select “ICR” 4. Select “POS” for the result 5. Click OK 6. Click on the “Add Condition” again 7. Select “Organism” 8. Holding down the control key, select the following organisms: Streptococcus beta-

hemolytic group, S. pneumonia, and S. viridians group other than S. pneumonia. 9. Click OK

Create the following Action 1. Click on “Add an Action” 2. Select “Comment” 3. Enter the following text: “The first sentence of the current positive ICR message is

based on scientific literature only and not on the VITEK 2 AST performance testing.” 4. Click OK

Save and exit 1. Click on the save icon 2. Lock configuration by clicking on the Lock/Unlock icon. 3. Return to the main menu

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APPENDIX D

The following are the instructions for a one-time software configuration change you may need to implement if you are using one of the new Streptococcus (ST) VITEK® 2 AST cards containing Benzylpenicillin in the VITEK® 2 Systems (V2S) software versions 05.01 and higher.

NOTE: This change is only required for the new AST-ST01 test kit if your facility has been utilizing previous AST-GP## cards for reporting Streptococcus pneumoniae. If your facility has not used AST-GP## cards for reporting Streptococcus pneumoniae then you do not need to make this change.

Before reporting AST-ST Benzylpenicillin results for Streptococcus pneumoniae, you will need to manually change the breakpoints to include distinct sources and their respective breakpoints utilizing the “User Defined Breakpoints” feature. Breakpoints for Streptococcus pneumoniae by source:

1. Click on the + icon to create a new breakpoint.

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2. Open the Organism hierarchy to select Streptococcus pneumoniae and move the organism to the right column and click on Next.

3. Select Benzylpenicillin from the resulting dialog box and move the antibiotic to the right column and select Next.

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4. Select the source from the next dialog box and move to the right column and click OK.

5. The newly created breakpoint entry will be highlighted in yellow. You may begin to add the defined breakpoints specific to the source, antibiotic, organism and reference.

NOTE: After the defined breakpoints have been added Click Save. This action is required after each breakpoint modification is complete.

NOTE: The FDA and CLSI breakpoints are the same for sources Pneumonia and Meningitis.

6. The Streptococcus pneumoniae - Other category must remain in the parameter set, however the breakpoints must be removed. Select each breakpoint value to open the menu and highlight the blank area above the first breakpoint to remove the numerical value.

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7. Once the changes have been implemented the table will appear as seen below. All modification and additions will be tracked in your AES User Changes Report.

8. LIS Codes to be added to LIS Dictionary as needed:

Note - Pneumonia correlates to Non-meningitis breakpoints in CLSI Table 2G.