CLSI Subcommittee on Veterinary Antimicrobial Susceptibility Testing (VAST) Meeting Summary Minutes (Draft)

The information contained in these minutes represents a summary of the discussions from a CLSI committee meeting, and do not represent approved current or future CLSI document content. These summary minutes and their content are considered property of and proprietary to CLSI, and as such, are not to be quoted, reproduced, or referenced without the expressed permission of CLSI. Thank you for your cooperation. Page 1 of 33

CLSI Subcommittee on Veterinary Antimicrobial Susceptibility Testing (VAST) Meeting (Draft) Meeting Title: Subcommittee (SC) on Veterinary Antimicrobial Susceptibility Testing (VAST) Meeting Date: 12 13 January 2017 Start Time: 12 January- 1:00 PM US Mountain Time (MST) 13 January 8:00 AM MST Meeting Purpose: Requested Attendee(s): Actual Attendee(s): Mark G. Papich, DVM, MS Chairholder Contact: Lori Moon (lmoon@clsi.org) End Time: 5:00 PM MST 4:00 PM MST A meeting of the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Veterinary Antimicrobial Susceptibility Testing (VAST) was held on 12 13 January 2017 at the Mission Palms Resort Hotel in Tempe, Arizona. Subcommittee Chairholder, Vice-chairholder, Members, Advisors, and Reviewers; Guests; CLSI Staff (see subcommittee roster) North Carolina State University Brian V. Lubbers, DVM, PhD, DACVCP Vice-Chairholder Stefan Schwarz, DVM Secretary Kansas State Veterinary Diagnostic Lab Freie University of Berlin Members Present Dubraska V. Diaz-Campos, DVM, PhD Mark D. Fielder, MD Cynthia C. Knapp, MS Cory Langston, DVM, PhD Xian-Zhi Li, PhD Marilyn N. Martinez, PhD Thomas R. Shryock, PhD Virginia Sinnott-Stutzman, DVM, DACVECC Maria M. Traczewski, BS, MT(ASCP) Darren Trott, DVM, PhD Washington Animal Disease Diagnostic Laboratory Kingston University London Thermo Fisher Scientific Mississippi State University Health Canada Veterinary Drugs Directorate FDA Center for Veterinary Medicine Antimicrobial Consultants, LLC Angell Animal Medical Center (MSPCA) The Clinical Microbiology Institute University of Adelaide School of Animal and Veterinary Science Advisors Present Donald J. Bade, BS Hari P. Dwivedi, BVSc, MVSc, PhD Virginia R. Fajt, DVM, PhD, DACVCP Thomas R. Fritsche, MD, PhD, FCAP, FIDSA Joshua Hayes, PhD Adam Krull, DVM, PhD Sakurako Marchand Tomás Martin-Jimenez, DVM, DVM, PhD, DACVCP, DECVPT Ron Miller, PhD Ian Morrissey, MBA, PhD, FRSM Microbial Research, Inc. BioMerieux, Inc Texas A&M University Marshfield Clinic FDA Center for Veterinary Medicine Iowa State University Veterinary Diagnostic Laboratory BioMerieux, Inc. University of Tennessee FDA Center for Veterinary Medicine IHMA Europe Sarl Page 2 of 33

Christine Pallotta, BS, MS Stefan Schwarz, DVM Dee Shortridge, PhD Michael T. Sweeney, MS Thermo Fisher Scientific Freie University of Berlin JMI Laboratories Zoetis Reviewers Present Eden Bermingham, DVM, MS, DACVCP Robert Bowden, BS Beth Harris Nicole Holliday Lacie Johansen Scott Killian Sara Lawhon Tessa LeCuyer Maureen Mansfield Claire Miller, DVM, PhD Anil Thachil, BVSc, MVSc, PhD, Diplomate ACVM Susan Thomson Amy Trettien, DVM Jeffrey L. Watts, PhD FDA Center for Veterinary Medicine University of Florida Veterinary Diagnostic Laboratories National Centers for Animal Health Thermo Fisher Scientific Zoetis Thermo Fisher Scientific Texas A&M University Washington State University Thermo Fisher Scientific Washington Animal Disease Diagnostic Laboratory Cornell University NYS Animal Health Diagnostic Center MAST Group Zoetis Zoetis Guests Present Robert Eusebio Heike Kaspar Amanda Kreuder Karen Kryston Raymond Kwong David Paisey Jean-Yves Ressot Ronald Tessman Gregory Tyson Beckman Federal Office of Consumer Protection and Food Safety Iowa State University Veterinary Diagnostic Laboratory Beckman Beckman Coulter Thermo Fisher Scientific BioMerieux, Inc. Bayer FDA Staff Lori T. Moon, MS, MT (ASCP) CLSI Page 3 of 33

Opening PLENARY AGENDA Thursday, 12 January 2017 1:00 5:00 pm in Abbey North/South (N/S) Breakfast/Breaks Available Daily at 7:00 am (Courtyard East) Title Start End Length Category Presenter(s) Folder # (min) 1. Opening Remarks and Introductions 01:00p 01:05p 5 Opening Remarks Dr. Papich N/A 3. CLSI Updates 01:05p 01:10p 5 CLSI Updates Mr. Fine N/A CLSI Staff 4. Updates to Disclosure of Interest (DOI) Summary 01:10p 01:15p 5 DOI Updates Dr. Papich 2 5. Approval of Agenda 01:15p 01:20p 5 Approval Dr. Papich 3 6. Jan 2016 Meeting and Action s 01:20p 01:30p 10 Review Dr. Papich 4 7. AST Liaison Report 01:30p 02:00p 30 Report Dr. Thomas Shryock 5 8. USCAST Report 02:00p 02:15p 15 Report Dr. Ron Miller 5 Pirlimycin QC Presentation 02:15p 02:45p 30 Presentation/ Ms. Maria Traczewski 6 9. Pirlimycin Tier 3 Broth Disk Diffusion Quality Control vs. S. aureus ATCC 29213 Vote Break 02:45p 03:00p 15 [2.] Award Presentation 03:00p 03:15p 15 Award Presentation Mr. Glen Fine N/A 10. Generic Drug Working Group Summary/Abbreviated WG Report Presentations Cefazolin and Cephalexin for Enterobacteriaceae from Canine Urinary Tract Isolates Doxycycline in Horses Enrofloxacin in Horses Other WG discussions 03:15p 04:45p 90 Presentations/ Vote Report Dr. Papich 7 11. VET06 Working Group 04:45p 05:00p 15 Report Ms. Traczewski N/A Summary/Abbreviated WG Report Presentation 12. Adjourn 05:00p Dr. Papich N/A 5:00 6:00 PM VAST Subcommittee 25 th Anniversary Cake Reception from in Abbey N/S Page 4 of 33

# 13. 14. 15. 16. VET01 Document Development Committee Presentation of DDC progress on VET01 revision Discussion of document (VET01_20Dec2016) review and comments received Path forward and VAST SC approval Closing PLENARY AGENDA Friday, 13 January 2017 8:00 AM 4:00 PM in Abbey N/S Breakfast/Breaks Available Daily at 7:00 am (Courtyard East) Title Start End Length Category Presenter Folder (min) 08:00a 09:00a 60 Presentation/Discussion/ Mr. Sweeney 8 Vote WG on VAST Breakpoint Tables (VET08) Presentation of WG progress on VET08 supplement (formerly VET01S, 3rd edition) Discussion of document review and comments received on: VET08_20Dec2016 VET08-AppendixA_20Dec2016 VET08-AppendixB_20Dec2016) Path forward and VAST SC approval 09:00a 10:00a 60 Presentation/Discussion/ Vote Mr. Sweeney 8 Break 10:00a 10:15a 15 Aquaculture Working Group (see also #21) 10:15a 10:30a 15 Report Dr. Ron Miller 9 Summary/Abbreviated WG Report Presentation VET05/ECV Working Group 10:30a 12:00p 90 Presentation/Discussion/ Dr. Ron Miller 10 Summary WG Report Presentation and Discussion Vote Luncheon Cloister Room 12:00p 01:00p 60 17. Education Working Group 01:00p 02:00p 60 Presentation/Discussion Dr. Virginia Fajt N/A Summary/Abbreviated WG Report Presentation 18. Bovine Mastitis Interpretive Criteria (BMIC) Working Group 02:00p 02:30p 30 Report Dr. Jeff Watts 11 Summary/Abbreviated WG Report Presentation 19. Veterinary Fastidious Media (VFM) Working Group - 02:30p 03:00p 30 Report Mr. Don Bade 12 Summary/Abbreviated WG Report Presentation Break 03:00p 03:15p 15 20. VET02 and PK-PD Working Group 03:05p 03:15p 10 Report Dr. Marilyn Martinez N/A Summary/Abbreviated WG Report Presentation 21. Aquaculture Working Group 03:15p 03:30p 10 Presentation/Discussion/ Dr. Ron Miller N/A Flavobacterium psychrophilum ECVs Vote 22. Other Business 03:30p 03:35p 5 Discussion Dr. Papich N/A 23. Meeting Wrap-up/Plans for next meeting 03:35p 03:45p 10 Discussion Dr. Papich N/A 24. Adjourn 03:45p Dr. Papich N/A Page 5 of 33

Day 1: 12 January 2017 The information contained in these minutes represents a summary of the discussions from a CLSI committee meeting, and do not represent approved current or future CLSI document content. These summary minutes and their content are considered property of and proprietary to CLSI, and as such, are not to be quoted, reproduced, or referenced without the expressed permission of CLSI. Thank you for your cooperation. 1. Opening Remarks and Introductions: Dr. Mark Papich opened the plenary session of the Subcommittee on Veterinary Antimicrobial Susceptibility Testing (VAST) at 1:05 PM US Mountain Time (MST) by welcoming the attendees and thanking them for their participation and hard work. Dr. Papich thanked volunteers for serving on the various Working Groups, most of which met earlier today. He stated that the purpose of the meeting is for sponsors to present data and the working groups to address their agenda item topics and obtain input from the subcommittee. There is one sponsor scheduled to present data during this meeting: Ms. Maria Traczewski is presenting data in support of Pirlimycin QC range modification. There is also a full agenda with presentations from the working groups, including 3 breakpoint presentations from the Generic Working Group (WG). During this time, the subcommittee will make motions and vote on the agenda topics. The 2017 Subcommittee on VAST has 10 voting members who were all present at the meeting and Dr. Papich reviewed the applicable rules on voting in the January 2017 VAST Meeting Materials folder 4_References for Use (4-7_2017_Jan_VAST_Voting_Rules): 2017 Roster 10 voting members (excludes Chairholder and Vice-chairholder) Committee Status "Pass" Vote All members present and voting 10-0, 9-1, 8-2, 7-3 One member not present or abstaining 9-0, 8-1, 7-2, 6-3 Two members not present or abstaining 8-0, 7-1, 6-2, 5-3 Three members not present or abstaining 7-0, 6-1, 5-2 If more than three members not present: Chairholder s discretion to conduct vote or table until sufficient members are present or mail vote taken. Dr. Papich discussed the VAST Subcommittee succession plan and reviewed the CLSI Board of Directors (BOD) Policy for the three AST subcommittees that representatives from pharmaceutical companies and allied stakeholders are no longer included as voting members, but may continue to serve in other capacities. The only practical impact of this policy change is removal as formal voting members in final subcommitees votes due to the AST/breakpoint-setting groups being the only consensus process groups at CLSI that make decisions on specifically-named manufacturers products published in CLSI documents. Page 6 of 33

1. (cont d) Although the policy was drafted primarily for the human AST Subcommittee, the CLSI BOD did not allow exemption of the VAST Subcommittee but has allowed another extension for 2017 before full implementation (Ms. Maria Traczewski is serving a 1-year term in 2017). Dr. Papich mentioned the recent changes to the subcommittee (listed below) and then asked all subcommittee meeting participants to introduce themselves. Changes to the Subcommittee in 2017 include: New Vice-chairholder: Brian V. Lubbers, DVM, PhD, DACVCP has served as a voting member on the subcommittee from 2014 2016 (P) New Voting Members: Mark D. Fielder, MD from Kingston University London (P) Cory Langston, DVM, PhD from Mississippi State University (P) Xianzhi Li, PhD from Health Canada Veterinary Drugs Directorate (G) Virginia Sinnott, DVM, DACVECC from Angell Animal Medical Center (MSPCA) (P) Darren Trott, PhD from University of Adelaide School of Animal and Veterinary Science (P) New Advisors: Hari P. Dwivedi, BVSc, MBSc, PhD from BioMerieux, Inc. (I) Adam Krull, DVM, PhD from Iowa State University Veterinary Diagnostic Laboratory (P) Sakurado Marchand from BioMerieux, Inc. (I) Tomás Martin-Jimenez from University of Tennessee (P) Christine Pallotta, BS, MS from Thermo Fisher Scientific (I) Members who rotated to Advisors: Markus Rose, DVM, PhD has served as a member on the subcommittee from 2012 2016 and as a reviewer or observer from 2008 2011 (I) Stefan Schwarz, PhD has served as a member on the subcommittee from 2007 2016 (G,P) Shabbir Simjee, DVM, PhD has served as a member on the subcommittee from 2012 2016 (I) Page 7 of 33

1. (cont d) John Turnidge, MD has served as a member on the subcommittee from 2012 2016 and as an advisor from 2006 2011 (G) Page 8 of 33 Members and advisors who rotated to reviewers: Mike Apley, DVM, PhD has served as a member on the subcommittee from 2012 2016 (P) Luca Guardabassi, DVM, PhD has served as an advisor on the subcommittee from 2013 2016 (P) and will continue serving as a reviewer on the subcommittee from Ross University School of Veterinary Medicine (new employer) (P) Robert D. Walker, PhD has served as an advisor in 2007 and 2016 and as a voting member for many years Other rotations/changes: Dee Shortridge, PhD will continue serving as an advisor on the subcommittee from JMI Laboratories (new employer) (I) Peter Silley, PhD has made many contributions providing data used to determine breakpoints, serving as a member of the VET02 Working Group (WG) and VET05-ECV WG while serving on the subcommittee as a voting member (2006 2011 and 2014 2016) or as an advisor (2012 2013), has retired and will no longer be able to participate on the subcommittee Steven Brown, PhD, D(ABMM) has made many contributions providing data used to determine breakpoints, serving as a member of various WGs while serving on the subcommittee as a voting member (2005 2011) or as an advisor (2012 2016), has retired and will no longer be able to participate on the subcommittee 2. Award Presentation: Mr. Glen Fine welcomed everyone, thanked the VAST Subcommittee volunteers for their continued time and efforts, and explained that the John V. Bergen Excellence Award is presented annually to an outstanding volunteer in recognition of advances in CLSI organizational directives and objectives, through unique and significant contributions. He then introduced the recipient of the 2016 John V. Bergen Excellence Award, Dr. Jeffrey L. Watts, who has been an instrumental leader in VAST SC standards development activities since its inception 25 years ago and was also its first chairholder. Dr. Watts has been tirelessly providing mentorship, recruiting volunteers and overseeing from scratch the development of the two cornerstone documents (VET01 and VET02) which formed the basis for all subsequent work and expansion of the VAST Subcommittee. He has also served as Vicechairholder, Advisor, Chairholder of VAST Working Groups, and participated in several veterinary document development committees. With the dramatic rise in the awareness of the global public health importance of antimicrobial resistance, the contribution of the VAST Subcommittee s efforts to contribute to responsible antibiotic use in food and companion animals has become of major international importance. In short, because of his good work, CLSI has enjoyed a 25-year head start in this arena. In addition to all of this, Dr. Watts has been an outstanding volunteer recruiter to add essential expertise from industry and healthcare professions, academia and government into the mix. He has been instrumental in identifying the relatively small number of highly qualified people in the veterinary microbiology field and mentoring them. He has been a tireless advocate for his company s membership and encouraging others to join CLSI. Congratulations were given to the 2016 recipient of the John V. Bergen Excellence Award, Dr. Jeffrey L. Watts.

3. CLSI Updates: Ms. Lori Moon gave an update on CLSI documents and document development processes What's New: Recently Published CLSI Documents: M100-S27, Performance Standards for Antimicrobial Susceptibility Testing; Twenty Sixth Informational Supplement January 2017 CLSI Documents Publishing Soon: VET06-A, Methods for Antimicrobial Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria Isolated from Animals New CLSI Consensus Document Category: Archived Categorization for document availability: Active: Current CLSI documents that have been approved through the CLSI consensus process. Archived: an active consensus document that is technically valid and determined to not pose safety risks when implemented, but is no longer being reviewed through the CLSI consensus process; NOTE 1: Any CLSI document that is adopted as an American National Standard is not eligible for archiving per ANSI Essential Requirements; NOTE 2: An archived document is retained in the CLSI library because of its value to the laboratory community. Reaffirmed: active CLSI documents that have been reviewed and determined to be suitable for continued publication without revision to content; these documents undergo an abbreviated consensus process, and may be available in electronic format only Withdrawn: CLSI documents that have been discontinued Reaffirmed VET documents reviewed in 2016: VET03-A VET05-R Follow up with WG chairholders with more details on policy and process for reaffirmed documents (Action ). 4. Updates to Disclosure of Interests (DOI) Summary: Dr. Papich asked the members and advisors to check the DOI Summary provided in the meeting materials for any updates to the current disclosure summary. No additional disclosures were presented and Dr. Papich requested that members and advisors send any updates to Ms. Lori Moon at lmoon@clsi.org (Action ). 5. Approval of Agenda: Dr. Papich requested approval of the subcommittee meeting agenda and hearing no objections it was approved. 6. Jan 2016 Meeting and Action s: Dr. Papich reminded everyone that the summary minutes of the 7 8 January 2016 subcommittee meeting were approved by electronic vote in July August 2016 are in the January 2017 VAST Meeting Materials folder 4_References for Use (4-4_2016_Jan_VAST_SummaryMinutes-Final) and are also available for review on the CLSI website in the VAST Meeting Files (https://clsi.org/education/microbiology/subcommittee-on-vast/vast-meeting-files-resources/) in the January 2016 file. Page 9 of 33

7. AST Liaison Report: Dr. Thomas Shryock Dr. Shryock described his role as the VAST-AST Liaison, to interface between the VAST Subcommittee and the Subcommittee on Antimicrobial Susceptibility Testing (AST) and give formal subcommittee updates at each meeting in the future (Action ). As VAST-AST Liaison, he will also report back to the VAST Subcommittee via email for immediate updates and alerts following the January AST Subcommittee meetings (Action ). Dr. Shryock presented highlights from the June 2016 AST Subcommittee meeting minutes, including reports on the AST SC Breakpoint WG, the Methods Development & Standardization WG, the QC WG, the Text & Tables WG, the Methods Application and Interpretation WG, and the Outreach WG. Dr. Shryock s presentation will be posted on the CLSI website under VAST Meeting Files & Resources (https://clsi.org/education/microbiology/subcommittee-on-vast/vast-meeting-files-resources/) AST Subcommittee meeting minutes will be posted on the CLSI website under AST Meeting Files & Resources (https://clsi.org/education/microbiology/ast/ast-meeting-files-resources/). 8. USCAST Report: Dr. Ron Miller Dr. Miller updated the subcommittee with a briefing from the first meeting of the United States Committee on Antimicrobial Susceptibility Testing (USCAST), the National Antimicrobial Susceptibility Testing Committee for the United States, which he attended as an observer. He discussed the relationship between USCAST and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and described the EUCAST process, subcommittees, and implementation in Europe. He highlighted some of the differences between USCAST and EUCAST and also emphasized that USCAST has no intentions of addressing veterinary-specific breakpoints. 9. Pirlimycin QC Presentation: Ms. Maria Traczewski Ms. Traczewski presented a proposal for modification of the disk diffusion expected QC range for pirlimycin (2 g) with Staphylococcus aureus ATCC 25923, which is currently published in the VET01S_Ed3, Table 4 as 20 25 mm. In January 2016, data was presented to propose the QC range be lowered by 1 mm (to 19 25 mm). In response the Subcommittee passed a motion that Tier 3 QC studies should be performed before resubmitting the proposal to accept a new QC range. Ms. Traczewski presented the data from a Tier 3 study for disk diffusion QC using 2 g pirlimycin disks and S. aureus ATCC 25923. As a result, a proposal was made to change the QC range from 20 25 mm to 19 25 mm. A motion was made to accept the proposal for changing the range for Staphylococcus aureus ATCC 25923 by Dr. Cory Langston and seconded by Dr. Xianzhi Li. In further discussion, Dr. Thomas Shryock asked if the dataset was adequate. Ms. Traczewski reported that the testing was performed in 2 different laboratories with 3 replicates. Vote on the Motion: Passed (9-accept, 0-reject, 1-abstained [M. Traczewski, presenter]) Page 10 of 33

10. (A) Generic Drug Working Group Presentation: Cefazolin and Cephalexin for Enterobacteriaceae from Canine Urinary Tract Isolates Dr. Papich first presented the EUCAST data sets for cephalothin/escherichia coli, ampicillin/e. coli and cefpodoxime/e. coli and the corresponding CLSI breakpoints for ampicillin (applicable to urinary tract infections [UTI], E. coli and dogs) of S 8 µg/ml and amoxicillin-cluvulanate (applicable to UTI, E. coli and dogs) of S 8/4 µg/ml. Dr. Papich also explained from which datasets these urinary breakpoints were derived. He stated that urine concentrations of some antimicrobials may be 100x greater than the corresponding serum/plasma concentration. He gave examples that showed that urine concentrations after standard oral dose administration in dogs were for ampicillin 300 µg/ml, amoxicillin 200 µg/ml, cephalexin 225 µg/ml and tetracycline 138 µg/ml. Dr. Papich explained that amoxicillin is a fist-line drug option for uncomplicated UTI in dogs. CLSI has defined a urinary cefazolin breakpoint in the document M100-S25 (2015) of 16 µg/ml for susceptible and 32 µg/ml for resistant. This breakpoint is applicable to E. coli, Klebsiella pneumoniae and Proteus mirabilis from uncomplicated UTI; cefazolin is a surrogate to predict the susceptibilities of seven oral cephalosporins including cephalexin and cefpodoxime. However, cefpodoxime is an approved oral cephalosporin for dogs and should be tested individually as some isolates may be susceptible to cefpodoxime while testing resistant to cefazolin. Given the fact that oral administration of cephalexin (25 mg/kg per day) achieves concentrations in the urine of healthy dogs of 225 µg/ml, a breakpoint of ( S ) of 16 µg/ml for the cephalosporins would produce susceptible result for cephalexin for over 90% of E. coli and P. mirabilis isolates from dogs. However, the current cephalexin breakpoint of 2 µg/ml would cause all of the isolates to be considered resistant. Dr. Papich presented cephalothin MIC data from Germany for a wide range of bacteria from horses, dogs and cats of which the vast majority displayed MICs of 16 µg/ml except Pseudomonas spp. Proposal: Based on the data presented, a proposal was made to change the breakpoints for cephalexin and cefazolin applicable to E. coli, K. pneumoniae and P. mirabilis from uncomplicated UTI to S 16 µg/ml and R 32 µg/ml. In the comments box, the following comments were included: Cefazolin and cephalexin may be tested when used for treatment of uncomplicated urinary tract infections caused by E. coli, K. pneumoniae, or P. mirabilis. Cefpodoxime may be tested individually because some isolates may be susceptible to this agent while testing resistant to cefazolin or cephalexin. These breakpoints were determined from data showing that oral administration of cephalexin (25 mg/kg per day) achieves concentrations in the urine of dogs of 225 µg/ml produced clinical cures of 96% of patients. A motion was made by Dr. Marilyn Martinez and seconded by Dr. Langston to accept the proposal to change the breakpoints for cephalexin and cefazolin applicable to E. coli, K. pneumoniae and P. mirabilis from uncomplicated UTI to S 16 µg/ml and R 32 µg/ml and add the proposed comment. Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) An amendment was proposed which included the addition of urine to cefpodoxime and a change in the last sentence of the comments box to These breakpoints were determined from data derived from oral administration of cephalexin (25 mg/kg per day). A motion was made by Dr. Martinez and seconded by Dr. Langston to accept the proposed to add urine to cefpodoxime and change the last sentence of the comments box to These breakpoints were determined from data derived from oral administration of cephalexin (25 mg/kg per day) and add to VET08 Table 1A, Group A (Dogs only). Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) Page 11 of 33

10. (A) (cont d) Generic Drug Working Group Presentation: Cefazolin and Cephalexin for Enterobacteriaceae from Canine Urinary Tract Isolates Test/ Report Group Body Site Antimicrobial Agent β-lactams (Cephalosporins) Dogs Organism A UTI Cefpodoxime E. coli Proteus mirabilis A UTI Cephalexin, Cefazolin E. coli, Klebsiella pneumoniae, Proteus mirabilis MIC Interpretive Criteria (µg/ml) S I R Comments 2 4 8 See comment XX below. 16 32 (XX) Cefazolin and cephalexin may be tested when used for treatment of uncomplicated urinary tract infections caused by E. coli, K. pneumoniae, or P. mirabilis. Cefpodoxime may be tested individually because some isolates may be susceptible to this agent while testing resistant to cefazolin or cephalexin. These breakpoints were determined from data derived from oral administration of cephalexin (25 mg/kg per day). The above entry will be made to the VET08 (the VET01 informational supplement revision in progress) Table 2A: 10. (B) Generic Drug Working Group Presentation: Enrofloxacin in Horses Dr. Papich stated that interpretive categories of enrofloxacin were previously established for bacteria from dogs, cats, cattle, and swine, but not yet for bacteria from horses. He gave an overview of the currently available breakpoints for bacteria from dogs, cats, cattle, and swine. In addition, he also provided information about the formulations and routes of administration of enrofloxacin in small and large animals. In horses, no approved forms or doses of enrofloxacin exist. The dosages used in horses are extrapolated from other animals, or based on pharmacokinetic studies. Most common recommendation: 7.5 mg/kg oral administered once daily. Dr. Papich presented pharmacokinetic data for enrofloxacin in horses which were derived from a number of published studies. As a summary of 57 observations and 10 data sets, the following parameters were determined: mean T½: 8.3 hours (Std Dev 2.92) and mean Clearance (CL/F): 0.417 L/kg/hr (Std Dev 0.247). In horses the plasma protein binding is 22% for enrofloxacin (fu=0.78). MIC data of enrofloxacin from Zoetis were presented for a number of bacteria from horses in the USA and Canada, including S. aureus, P. aeruginosa, S. equi subsp. equi, and S. equi subsp. zooepidemicus Page 12 of 33

10. (B) (cont d) Generic Drug Working Group Presentation: Enrofloxacin in Horses Dr. Papich presented Monte Carlo simulations which were based on the following inputs: MIC: 0.03 8 µg/ml; two oral doses: 7.5 mg/kg every 24 h and 10 mg/kg every 24 h; CL/F: 0.417 L/kg/hr (Std Dev 0.247) and protein binding (fu=0.78). As a result, a high probability of target attainment (PTA) for free drug AUC/MIC > 100, or the lower value of > 72 can be achieved for a MIC value of 0.12 µg/ml or less, from administration of enrofloxacin in horses at an oral dose of 7.5 mg/kg every 24 hours. Thus, the proposed S breakpoint is 0.12 µg/ml. Using a higher dose of 10 mg/kg q24h, a PTA may be achieved for a MIC of 0.25 µg/ml using a target of AUC/MIC > 50. Consequently, the proposed I breakpoint is 0.25 µg/ml. As the MIC breakpoint is below the wild-type cutoff (ECOFF) for equine isolates of S. equi ssp. zooepidemicus, S. equi ssp. equi, and P. aeruginosa (COpd < COwt), these isolates are considered non-susceptible. In contrast, many (but not all) equine isolates of S. aureus and E. coli isolates are susceptible (COpd COwt). Thus, these breakpoints serve mainly the laboratories to NOT recommend the use of enrofloxacin for the therapy of streptococcal diseases in horses rather than guiding therapy with enrofloxacin. A motion was made by Dr. Martinez and seconded by Dr. Thomas Fritsche to accept the proposed breakpoints as seen in the Table entry below) and to add Enrofloxacin for horses to VET08 Table 1A, Group A. Vote on the Motion: Passed (9-accept, 0-reject, 1-abstained [Dr. Xianzhi Li, due to the inclusion of Pseudomonas aeruginosa]) Proposed entry in VET08 Table 2: Test/ Report Group Body Site Fluoroquinolones Dogs A Skin, soft tissue, respiratory, UTI Antimicrobial Agent Enrofloxacin Organism Eneterobacteriaceae, Staphylococcus spp., Streptococcus spp. MIC Interpretive Criteria (µg/ml) S I R 0.5 1 2 4 Cats A Skin, soft tissue, Eneterobacteriaceae, Staphylococcus 0.5 1 2 4 spp., Streptococcus spp. Cattle A Respiratory Enrofloxacin BRD Pathogens 0.25 0.5 1 1 Swine A Respiratory Enrofloxacin SRD Pathogens 0.25 0.5 2 Horses A Skin, soft tissue, respiratory, Enrofloxacin E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus equi ssp. zooepidemicus, Streptococcus equi ssp. equi Comments 0.12 0.25 0.5 Enrofloxacin breakpoints were determined from an examination of MIC distributions of isolates and PK/PD analysis of enrofloxacin, after administration of enrofloxacin at a dose of 7.5 mg/kg oral, every 24 hours. For inclusion in VET08, this information in this table needs to be reformatted and the respective information needs to be included in the tables for Enterobacteriaceae (Table 2A), Pseudomonas aeruginosa (Table 2B), Staphylococcus spp. (Table 2C), and Streptococcus spp. (Table 2D). 12. The meeting was adjourned at 5:15 PM MST until the following day. Page 13 of 33

Day 2: 13 January 2017 Meeting opened at 8:00 AM MST Opening remarks: Dr. Papich welcomed everyone and reviewed the updated agenda and plan to continue with the Generic WG presentation (Agenda #10C) then continue with the agenda as scheduled. He announced that some of the later presentations will likely not take as long as scheduled so the meeting is not expected to run past the scheduled time. 10 (C) Generic Drug Working Group (GWG) Presentation: Doxycycline in Horses Dr. Papich stated that interpretive categories for doxycycline have been previously established for isolates from dogs. The current breakpoints for canine S. pseudintermedius are S 0.12 µg/ml, I 0.25 µg/ml and R 0.5 µg/ml What exists and what labs would currently use for horses would be the human breakpoint ( 4 µg/ml). Dr. Papich also gave an overview about the currently available doxycycline formulations (injectable doxycycline is fatal to horses but they can be given oral formulas). For use in horses, no approved forms or doses exist. The doses used in horses are extrapolated from human, canine, and feline studies, or based on preliminary pharmacokinetic studies. The most common recommendation is 10 mg/kg oral administered either once or twice per day but most often twice daily. Dr. Papich presented an overview of the pharmacokinetic data for doxycycline in horses based on seven studies. As a summary of these studies, a Mean T½ of 9.97 h (StdDev 5.9) and a Mean Clearance (CL/F) of 2.04 L/kg/hr (StdDev 1.28) were calculated. MIC data of bacteria from horses were obtained from Zoetis (2014-2015) and included S. equi ssp. zooepidemicus, S. equi ssp. equi, S. aureus and P. aeruginosa. Further MIC data were from Texas A & M and included Enterobacteriaceae, S. aureus and P. aeruginosa. Dr. Papich asked Ms. Lacie Johansen if she could provide scattergrams of tetracycline and doxycycline from the same isolates to the GWG for analysis and decision to present to the VAST Subcommittee (Action ). Dr. Papich presented Monte Carlo simulations which were based on the following inputs: MIC: 0.03 16 µg/ml; three oral doses: 10 mg/kg every 12 h and 10 mg/kg every 24 h and 20 mg/kg every 12 h; CL/F: mean (and variance) and protein binding (fu=0.24). As a result, a high probability of target attainment (PTA) for AUC/MIC > 25 can be achieved for a MIC value of 0.12 µg/ml or less, from administration of doxycycline in horses at an oral dose of 20 mg/kg every 12 h. Thus, the proposed breakpoints for equine E. coli, S. aureus, S. equi ssp. zooepidemicus, and S. equi ssp. equi are S 0.12 µg/ml, I = 0.25 µg/ml, and R 0.5 µg/ml which corresponds exactly to the breakpoints applicable to canine S. pseudintermedius. The correlating doxycycline zone diameter breakpoints for S. pseudintermedius are S 25, I = 21-24 and R 20 mm. A motion was made by Dr. Martinez and seconded by Dr. Virginia Sinnott to accept the proposed breakpoints as seen in the Table entry below. For inclusion in VET08, the table entry will need to be re-formatted and the respective information needs to be included in the respective tables for E. coli (Table 2A), Staphylococcus spp. (Table 2C), and Streptococcus spp. (Table 2D). Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) A second motion was made by Dr. Langston and seconded by Ms. Maria Traczewski to add doxycycline to VET08 Table 1A, Group A (dogs and horses only). Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) Page 14 of 33

10. (C) (cont d) Generic Drug Working Group Presentation: Doxycycline in Horses Test/ Report Group Body Site Tetracyclines Antimicrobial Agent Organism MIC Interpretive Criteria (µg/ml) S I R Comments Dogs A Skin, soft tissue Doxycycline Staphylococcus pseudintermedius 0.12 0.25 0.5 Doxycycline breakpoints derived from microbiological and PK data using a clinical dose of 5 mg/kg, orally, twice daily, and PD data. Tetracycline Staphylococcus spp. 0.25 0.5 1 Tetracycline tested as the class representative for susceptibility to chlortetracycline, oxytetracycline, doxycycline, and minocycline. Organisms that are susceptible to tetracycline are also considered to susceptible to other members of the class. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline or minocycline or both. Horses A Doxycycline Escherichia coli, Staphylcococcus aureus, Streptococcus equi ssp. zooepidemicus, Streptococcus equi spp. equi 0.12 0.25 0.5 Doxycycline breakpoints derived from microbiological and PK-PD analysis using a clinical dose of 20 mg/kg, orally, twice daily to horses, and PD data. For inclusion in VET08, the table entries need to be re-formatted and the respective information needs to be included in the respective tables for E. coli (Table 2A), Staphylococcus spp. (Table 2C), and Streptococcus spp. (Table 2D). 10. (D) Generic Drug Working Group Update Dr. Papich suggested to determine breakpoints for the following antimicrobial agents in the future. Dr. Papich requested MIC data, pharmacokinetic data, and PK-PD targets from VAST Subcommittee member s and advisor s laboratories (Action ) for the Generic Drug WG to analyze for future breakpoint presentations: Ampicillin bacteria from cattle Chloramphenicol bacteria from dogs and horses Carbapenems (imipenem, meropenem) bacteria from companion animals (although the likely result of analysis would be to discourage their use) 3 rd generation cephalosporins bacteria from dogs, cats, and horses Rifampin bacteria from dogs and horses Florfenicol Enterobacteriaceae Page 15 of 33

11. VET06 Working Group: Ms. Traczewski (Chairholder) Page 16 of 33 Ms. Traczewski asked Ms. Moon to give an update on the status of the VET06 publication and Ms. Moon reported that the VET06 supplement was currently in the CLSI editorial process with a projected February 2017 publication date. 13. VET01 Document Development Committee: Mr. Michael Sweeney (Chairholder) Mr. Sweeney provided the subcommittee with an update of the progress and a slide showing the timeline of events from finalizing the VET01 revision project proposal in April 2016, receiving endorsement of the subcommittee and the Expert Panel on Microbiology in May 2016, and approval by the Consensus Council (CC) in June 2016. After a Call for Volunteers in June-July 2016, the document development committee (DDC) was selected, approved by the CC and appointed in August 2016. The DDC reviewed and commented on what they wanted to see in the reorganized VET01 draft document before meeting face-to-face in September and then through teleconferences continued development of the VET01 draft included in the subcommittee meeting materials for review and comment. Mr. Sweeney reviewed the DDC feedback of improvements that were needed from the VET01-A4 document (better organization, more user friendly, clearer descriptions) and some ideas to make improvements in the resision. The proposed outline has been reduced from 18 chapters to 8 chapters.other improvements include color-coding of the methods chapters (Disk Diffusion, Broth Dilution, and Agar Dilution), developing companion products, and including a table of unusual resistance phenotypes and intrinsic resistance tables which will be Appendix A and B, respectively, in the new supplement (VET08). Mr. Sweeney posed several questions from the VET01 DDC to the Subcommittee, they discussed: Proposed modification of the Test/Report Group D description, and the Subcommittee agreed with removing the list of antimicrobial agents and revising the paragraph to reference websites, if possible, and referring to VET08, Table 1. Questions about the Gram-positive MIC panel on-scale QC requirements were referred to Ms. Cindy Knapp and Ms. Traczewski who will also check with M02 and M07 revision drafts in progress (Action ). Questions about Table 6.2 were resolved in the draft document with track changes showing edits during the meeting. Where to include methods for AST of Campylobacter species, which originally started in VET01, then disk diffusion methods were added to M45- A2, then all methods and QC were added to M45-A3, and now all of this is in VET06 (projected to publish in February 2017). A motion was made by Dr. Darren Trott and seconded by Dr. Xianzhi Li to remove the Campylobacter AST methods from the VET01 draft document (and therefore also its informational supplement, VET08) and keep them (only) in the VET06 supplement. Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) The DDC requested the VAST Subcommittee approval for the DDC to proceed to the Committee Draft review and vote to submit it to be prepared for Proposed Draft vote (60 day vote). Subcommittee members were asked to review the VET01 draft document in the meeting materials (VET01_20Dec2016) and provide any additional comments as soon as possible, with a requested deadline of 23 January 2017 (Action ). A motion was made by Dr. Darren Trott and seconded by Dr. Xianzhi Li to to approve the VET01 draft document with comments and proceed. Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) 14. Working Group on Editorial/VAST Breakpoint Tables (VET08): Mr. Sweeney (Chairholder) Mr. Sweeney reviewed the VET08 WG progress since the official appointment of this standing WG in June 2016. Input from the subcommittee is needed on the current draft VET08 (fka VET01-S3). Two new tables, Appendix A and B, have been adapted from M100 tables for veterinary use to be included in VET08. Mr. Sweeney asked leaders of the Appendix A and B subgroups to present the current drafts of the new VET08 Appendix tables to the subcommittee.

14. (cont d) Page 17 of 33 Working Group on Editorial/VAST Breakpoint Tables (VET08): Mr. Sweeney (Chairholder) Dr. Sinnott presented Appendix A. Suggestions for Confirmation of Resistant (R), Intermediate (I), or Nonsusceptible (NS) Antimicrobial Susceptibility Test Results and Organism Identification and pointed out that Category I (in M100, Appendix A) was removed because there is currently no requirement to report or send organisms in the US and some of Europe, but to reserve the possibility of adding Category I back if there are requirements added in the future. Dr. Lubbers suggested adding organisms that test as susceptible but should not be. Dr. Sinnott agreed, naming E. coli vs. doxycycline as an example (Action ). Dr. Trott requested keeping Category I, as there are requirements in Australia to submit certain pathogens and a recent publication that can be cited (Action ). Dr. Stefan Schwarz suggested that florfenicol and tulathromycin should be added for Mannheimia haemolytica (Action ). Dr. Sinnott requested lots of comments from the subcommittee members, advisors, and reviewers, with any ideas, suggested additions or substractions to the draft Appendix A. Dr. Diaz-Campos reviewed the draft Appendix B circulated with the meeting materials that was adapted from M100, Appendix B, slightly modified for veterinary specificity. She requested comment from the subcommittee about what to add or remove. Dr. Papich suggested keeping as much as possible so that laboratories can tell clinicians that it is not necessary to test a particular drug-bug combination that is already known to be intrinsically resistant. Dr. Lubbers agreed with being all-inclusive, as it won t matter is something is not relevant. Mr. Sweeney then requested that the subcommittee review some of the comments on the VET08 draft submitted by Mr. Robert Bowden. Mr. Bowden presented questions and the results of the VAST Subcommitee discussions are as follows: Comment Type (ie, Chapter Number general [ge], Paragraph/ editorial [ed], Figure/Table/ Comment Resolution technical Note (justification for change provided by Proposed Change (to be completed by committee [te]) (eg, Table 1) the commenter) (provided by the commenter) and/or committee leadership) Commenter s Name # and Affiliation 3. Robert Bowden, University of Florida Veterinary Diagnostic Laboratories 4. Robert Bowden, University of Florida Veterinary Diagnostic Laboratories (continued) Table 2A Table 2A A corresponding disc diffusion breakpoint does not exist for the veterinary E. coli UTI MIC breakpoint for ampicillin but the human susceptible breakpoint is identical and does include a Susceptible disc breakpoint of 17 mm. A corresponding disc diffusion breakpoint does not exist for the veterinary E. coli UTI MIC breakpoint for amoxicillinclavulanate but the human susceptible breakpoint is identical and does include a Susceptible disc breakpoint of 18 mm. Add a Dog E. coli UTI Susceptible disc diffusion breakpoint of 17 mm for ampicillin. Add a Dog E. coli UTI Susceptible disc diffusion breakpoint of 18 mm for amoxicillin-clavulanate. Members of the Subcommittee on VAST members approved this addition during the January 2017 meeting. Members of the VAST Subcommittee approved this addition during the January 2017 meeting.

14. (cont d) Working Group on Editorial/VAST Breakpoint Tables (VET08): Mr. Sweeney (Chairholder) Commenter s Name # and Affiliation 7. Robert Bowden, University of Florida Veterinary Diagnostic Laboratories 14. Robert Bowden, University of Florida Veterinary Diagnostic Laboratories Comment Type (ie, general [ge], editorial [ed], technical [te]) Chapter Number (eg, 3.1) Paragraph/ Figure/Table/ Note (eg, Table 1) Table 2D Appendix A Comment (justification for change provided by the commenter) Within Table 2D (Streptococcus spp.) No ampicillin breakpoints exist for cats and no amoxicillinclavulanate breakpoints exist for dogs. The amoxicillin-clavulanate breakpoints for cats are modelled from amoxicillin data. The ampicillin breakpoints for dogs are modelled from amoxicillin data. As streptococci do not produce beta-lactamase, clavulanate should not be necessary. Acinetobacter baumannii and Haemophilus influenzae are not included elsewhere in VET08. I know the former is a veterinary pathogen but is Haemophilus influenzae? Proposed Change (provided by the commenter) Consider adding ampicillin breakpoints for cats to match current amoxicillinclavulanate cat breakpoints and add amoxicillinclavulanate breakpoints for dogs to match current ampicillin dog breakpoints. AND/OR Consider removal of amoxicillin-clavulanate breakpoints in favor of ampicillin breakpoints with comment The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin with or without clavulanate. Remove Haemophilus influenzae from Appendix A and consider adding a table for Acinetobacter bacumannii with human breakpoints. Resolution (to be completed by committee and/or committee leadership) During the January 2017 meeting, the VAST SC members agreed that if an isolate is susceptible to any b- lactam then it can be reported as S to all for b-hemolytic streptococci, and approved adding a comment using text from VET01 stating that Amoxicillin/clavulanate breakpoints should be used to predict ampicillin for cats (non-uti). Hemophilus influenzae will be removed from the master draft VET08. The Subcommittee was asked to review the VET08 draft document in the meeting materials and provide feedback comments by an extended deadline of 10 February 2017 (Action ). Page 18 of 33

15. WG on Aquatic Animals: Dr. Ron Miller (Chairholder) see also #21 Page 19 of 33 Dr. Miller presented a research progress report of the WG on Aquatic Animals (aka Aquaculture WG) with disk diffusion method (VET03A) and broth dilution method (VET04A) development finished for nonfastidious isolates, and broth dilution method development for Flavobacterium columnare/ Flavobacterium psychrophilium (VET04A-2) (see slide 3 in meeting materials). Research is ongoing for method development for the following: F. columnare - disk diffusion at 28C (48 hours) Edwardsiella ictaluri and streptococci - disk diffusion Francisella spp. - disk diffusion and broth microdilution Vibrionaceae (psychrophilic) disk diffusion at 18C Piscirickettsia salmonis broth microdilution Epimediological cutoff values (ECVs) for disk diffusion and broth microdilution testing have been developed and published for Aeromonas salmonicida (VET03/04-S2), with ongoing work for ECVs to be published for F. columnare, E. ictaluri, Aeromonas hydrophila, and Yersinia ruckeri. The Aquaculture WG needs: The VET05-R updated with firm recommendations of how ECVs should be set (Action ) More MIC and zone diameter data for key fish pathogens (Action ): E. ictaluri Y. ruckeri Flavobacterium spp. A. hydrophila Additional standard methods developed (Action ) for testing: Pathogens requiring NaCl supplementation Pathogens requiring blood supplementation Francisella spp. The Aquaculture WG plans for 2017 include proposing tentative ECVs for E. ictaluri, A. hydrophila, F. columnare, F. psychrophilum, and Y. ruckeri (Action ). Dr. Miller asked how the Aquaculture WG should move forward doing the work and proposing ECVs to the VAST Subcommittee) or to EUCAST. VAST Subcommittee members agreed (10-approve, 0-reject, 0-abstained) that fish pathogen ECVs should be kept within CLSI. Methods for ECVs will be included in the updated VET03 (methods guideline) and VET04S (informational supplement with breakpoints/ecvs for both disk diffusion and broth microdilution methods). 16. VET05 Epidemiologic Cutoff Values WG: Dr. Ron Miller (Vice-chairholder) Dr. Miller reviewed terminology differentiating clinical breakpoints (CBPs) from epidemiological cutoffs (called ECVs by CLSI and ECOFFs by EUCAST): For CBPs, interpretive categories are S, I, R, established for clinical application, dose dependent, and reported as %R, %S, etc. For ECVs, interpretive categories are wild type (WT) with no phenotypically detectable resistance mechanisms and non-wild type (NWT) which have the presence of resistance mechanisms, and are always reported as %R or %S, which can be misleading.

16. (cont d) VET05 Epidemiologic Cutoff Values WG: Dr. Ron Miller (Vice-chairholder) Dr. Miller presented the the following figure illustrating common incorrect reporting of ECVs: He recapped the urgent need for harmonization of definitions used for AST published in 2012 by former VAST Subcommittee member Dr. Peter Silley: Not all surveillance programs define R in the same way making comparisons across programs very difficult Trend for R to be defined by the ECOFF rather than CBP and no standard way to define the WT cutoff He reported that EUCAST plans to formally propose surveillance program reporting as %NWT and %WT and reviewed who sets/publishes ECOFFs/ECVs: EUCAST is primarily focused on human pathogens and the AST data is freely available CLSI has 3 AST subcommittees: AST SC (human pathogens) - ECVs for Shigella spp. and Neisseria gonorrhoeae in M100-S27 (plus new colistin C for some Enterobacteriaceae) Antifungal SC (AFSC) ECVs for Candida spp. and Aspergillus spp. in M57/M59 VAST SC o ECVs from Aquaculture WG published in VET03/04-S2 o No longer pursuing publication of ECVs for foodborne pathogens as of January 2017 (VET07S cancelled) Page 20 of 33

16. (cont d) VET05 Epidemiologic Cutoff Values WG: Dr. Ron Miller (Vice-chairholder) During the 12 January 2017 ECV WG meeting, the WG discussed the overall scope of ECV WG after the WG voted to abandon the ECV-setting and publishing task (aka, the VET07S project). This vote on whether to continue the effort toward setting ECVs and publishing them in a supplement was taken via email and the results were No 7, Yes 0, and No Reply 3, with the comments below: Voter # Comment # Comment 1 1 I believe that we can provide more useful information through a high-level position statement that can guide developing surveillance programs vs. the confusion that we may create given our different ECVs (from EUCAST). 2 (Question raised): Are the ECVs the same depending on the host? Dr. Miller responded that when he attempted to analyze the data by host many datasetshad off-scale MICsmaking analysis difficult. He noted, there are certainly some species-drug combinations that the data could be analyzed if someone would like to volunteer. 2 1 It seems that the EUCAST document provided by John (Turnidge) will serve as the gold-standard on how to set ECVs in the future. Even though the NARMS dataset is really large, we still don t currently meet the requirements proposed by EUCAST for ECV analysis by having the minimum of 5 labs. As an alternative, maybe FDA could consider rolling the NARMS dataset with the current EUCAST data once they begin to re-evaluate their ECVs. Also, it s not clear to me what process is in place (for either the VET05 WG or EUCAST groups) on how future susceptibility data will be merged with current data to support published ECVs. 2 I don t see value in the VET05 WG setting ECVs for zoonotic bacteria when values are already available. There continues to be inappropriate use of ECVs and misunderstanding of the terms wild-type (WT)/non-wild type (NWT) and ECV versus S, I, R only add to this confusion. Our published ECVs could add to the potential for misinterpretation of clinical relevance and outcome. Hopefully EUCAST will address this by providing some type of educational training that thoroughly explains the differences between WT/NWT and ECV vs clinical breakpoint (CBP). 3 As stated in previous meeting minutes, I still question why ceftiofur and florfenicol are included in this analysis. Since there are no ceftiofur breakpoints for Salmonella or E. coli, why not use ceftriaxone as the 3rd-gen representative. The inclusion of ceftiofur and florfenicol, as veterinary drugs, seem to stand out from the other drugs that are more human-health related. 4 It s unclear to me what visibility the human-health AST CLSI group has with our WG. My opinion is that this should be a HH-led initiative rather than vet-led. 3 1 In my opinion we should not compete with EUCAST for antibiotics that are used for human and veterinary medicine. However, I think we should attempt to calculate ECVs for antibiotics that are used only in veterinary medicine. 4 1 My preference as you know is to have a single international group setting ECOFFs. So instead we need to find a way for the EUCAST and CLSI working groups to work together. There are several people in common already as you know. 5 1 No 6 1 No 7 1 No In further discussion discussion of Voter #4 s comment, the WG agreed on the need to build a bridge between CLSI and EUCAST sharing MIC data, etc. We need consistency and better approaches to get a better understanding of EUCAST s methods. A proposal was made to include genotypic data as an approach and how we can use genotypic data to determine an ECV in a revision of the VET05R document. Page 21 of 33

16. (cont d) VET05 Epidemiologic Cutoff Values WG: Dr. Ron Miller (Vice-chairholder) The WG discussed the updates needed to the VET05R document and the need to determine whether it should be converted from a report to a guideline. The ECV WG proposes that the updated text should position the use of CLSI methods as the most appropriate for national monitoring programs. CLSI then can expand its international training and Workshops to include lower middle income countries (LMICs) or organizations such as the World Organisation for Animal Health (OIE) or the Food and Agriculture Organization of the United Nations (FAO). The ECV WG also proposes removing all references to using CBPs for foodborne surveillance, updating the ECOFFinder (available at http://clsi.org/standards/micro/rangefinder/) and the Normalised Resistance (NRI) method of Kronvall (2010) (available at http://www.bioscand.se/nri) descriptions, discussing WGS, and providing methods for setting ECVs, sampling considerations, and tips for data analysis and presentation. However, additional ECVs are needed for surveillance programs (eg, US National Antimicrobial Resistance Monitoring Surveillance [NARMS]) to detect emerging resistance mechanisms. Dr. Miller reviewed how ECV are currently set and the limitations of each method (ECOFFinder, visual inspection, WGS) and that as of yet, the following conditions for setting ECVs are not fully defined or standardized by CLSI or EUCAST: Minimum number of different WT isolates (likely to be >100) Minimum number of laboratories testing to account for interlaboratory assay variation (likely to be 5) Whether isolate data from multiple hosts (eg, human, pigs, cattle, poultry) can be merged (believed to generally be merged) Use of WGS (major role or supportive?) The VET05/ECV WG proposes submitting previously approved ECV data and conclusions to EUCAST to include in their ECOFF data determinations. Most ECVs approved by the VAST SC were in agreement with the EUCAST ECOFFs (as shown in slide 10 of the VET05/ECV WG VAST SC meeting presentation), except for a few ECVs (eg, nalidixic acid for Salmonella spp.). Dr. Miller also recommended the formation of a joint AST SC/VAST SC WG to develop an official CLSI position on how ECVs should be established, how they should and should not be used, how ECVs can be used with caution for clinical application when CBPs are unavailable, and when if ever is it appropriate to use CBPs for surveillance when ECVs are available? Dr. Miller presented some of the new tools available including Interactive Data Displays on the NARMS website (at http://www.fda.gov/ AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm416741.htm) New WGS resources are also available from the National Center for Biotechnology Information (NCBI). NCBI has released a comprehensive, centralized resistance gene database (https://www.ncbi.nlm.nih.gov/bioproject/prjna313047), including translated gene sequences. Associated analytical tools will be released. A motion was made by Dr. Shryock and seconded by Ms. Knapp to confer with CLSI leadership about sharing data with EUCAST in an ongoing effort and framing it in a positive way for promoting One Health. Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) In further discussion, VAST Subcommittee volunteers (Dr. Papich, Dr. Lubbers, Dr. Shryock, Dr. Ron Miller, Dr. Shabbir Simjee, and Dr. Watts) formed a new ECV Data Sharing Advisory Group (Action ), proposing to oversee data collection, analysis, and presentation, and CLSI vetting the data. Dr. Papich requested the group to seek reciprocal data sharing (from EUCAST) through CLSI leadership, and Dr. Martinez agreed that should be a goal. Dr. Morrissey cautioned that EUCAST has an updating mechanism in place that CLSI does not have. Dr. Watts commented that it is important to make sure that the CLSI process for setting ECVs is well-defined (Action ). Page 22 of 33

17. Education WG: Dr. Virginia Fajt (Chairholder) Dr. Fajt presented an update on the project proposal for a new document to consolidate information and provide assistance to veterinarians on how to interpret AST results using CLSI VAST-approved methods and breakpoints. The WG has identified two primary sections to be included in the document: What is in a report and what does it mean Common misconceptions The proposal had previously been submitted to the CLSI Consensus Council (CC) for consideration in 2016. They rejected the proposal (originally titled A veterinarian s guide to antibiotic therapy ) primarily due to concerns they felt it was promoting an approach to the practice of medicine (ie, a practice standard). The WG noted that this was absolutely not the intent of the publication, but rather it was to be an aid for veterinarians and veterinary students on how to interpret culture and susceptibility (C&S) reports and likewise help laboratories explain their antimicrobial susceptibility testing (AST) results to veterinarians. The WG is also considering the possibility of a future webinar as a potential companion product to the document, as well as cross-referencing with the American Society for Microbiology (ASM) and/or joint authorship. Action : Dr. Dubraska Diaz-Campos offered to provide feedback about the new veterinary project proposal from the American Association of Veterinary Laboratory Diagnosticians (AAVLD). Action : Dr. Fajt asked for any examples of common VAST-related questions to be sent to her in follow up to this meeting (All VAST meeting participants). Action : The proposal will be resubmitted (originally submitted in March 2016) with a tentative title of Application of CLSI VET01-Generated Susceptibility Test Data for Optimizing Antimicrobial Stewardship: A Report for the Veterinary Profession and a shorter, more succinct description of its purpose and contents. CLSI staff was asked to confirm deadline dates for submitting the project proposal (Action ) and provide information about bulk pricing of this document (Action ). 18. A) Bovine Mastitis Interpretive Criteria (BMIC) WG: Dr. Jeffrey Watts (Chairholder) Dr. Watts provided a description of the document prepared by the BMIC WG (included in the meeting materials. Some of the highlights include: Allows sponsors the option of presenting clinical breakpoints (CBPs) for dry cow or lactating cow products Requires bacterial identification to the species level, although the species may be able to be grouped together Written to consider the European constituency Intramammary infusion products would be allowed Some comment by the meeting participants included: Spontaneous cure rates may be considered resources are available (see Dr. Watts) The document is only 4 pages the charge of the WG was to make this a concise document Consider including a hyperlink to a template document as an example for the sponsors Action : Dr. Watts requested review and comment on the completed appendix from all meeting participants by 28 February 2017. Page 23 of 33

18. (cont d) B) WG on Topicals: Dr. Watts (presenter) Dr. Watts summarized the December teleconference meeting of the new Topicals WG for Dr. Amy Trettien, WG Chairholder. The WG discussed issues regarding setting CBPs for topical antimicrobial agents decided to limit initial efforts to single-agent products for simple pyoderma (eg, mupirocin, retapamulin). The next steps are to review past CLSI AST and EUCAST efforts on topicals, and review data available on mupirocin and retapamulin). 19. Veterinary Fastidious Media (VFM) WG: Mr. Don Bade (Chairholder) Mr. Bade presented an update which included: Reviewing the history of the WG for new members and explained why it was developed Explaining that we have not made any additional progress due to lack of funding Noting that Zoetis was interested in potentially helping to fund some of this project Following the next step in the decision tree, asking the VAST SC whether the VFM WG should keep moving forward with the MHF-Y media. Vote: VAST SC unanimously voted to proceed with the plan for testing potential substitute media for the VFM. In further discussion, the subcommittee agreed To keep this project moving forward due to the risk of supply of supplement C becoming unavailable for AST testing That no additional development should be done to include Hemophilus parasuis That the testing proposed during the Jan 2016 meeting is sufficient to allow QC and BP to be set. To work at getting funding from Pharma To discuss with Pharma that if QC results change and trending in performance between VFM and MHF-Y is noted, a BP change may be needed. However if this happens the Generic working group offered to do the analyses for the Pharma company since it is due to our methodology that this is occurring Thermo Fisher agreed that the MHF-y broth can be made to replace VFM when the time comes Action : Discuss funding needs with Pharma companies interested in funding VFM-replacement testing. 20. VET02 WG and PK-PD WG: Dr. Marilyn Martinez (Chairholder) Dr. Martinez reported that the revised VET02 document is waiting to be put through the full CLSI editorial process. In new activity of the PK-PD WG, Dr. Martinez forwarded a proposal to collaborate with the EUCAST Veterinary Subcommittee on Antimicrobial Susceptibility Testing (VetCAST), discussed during the PK-PD WG meeting on 12 January 2017. VetCAST has more funding available for research, which enables them to generate original data, and the collaboration would allow the PK-PD WG to generate PK-PD targets to include these data in the VET02 document. However, the ultimate determination of clinical breakpoints will remain solely under the purview of the CLSI VAST Subcommittee. Within the framework of this collaborative effort, the PK-PD WG will continue to function as a WG operating under the CLSI VAST Subcommittee.The PK-PD WG agreed to collaborate on a position paper that describes this VAST-VetCAST collaboration and points that the VAST considers essential components of the selection or magnitude of all PK-PD indices [For additional collaboration proposed with EUCAST, see #16 and the VET05/ECV WG motion passed by the VAST Subcommittee]. A straw vote to support the PK-PD WG proposal for collaboration with VetCAST was requested. Vote on the request was approved (9-accept, 0-reject, 1-abstained [M. Martinez abstained]) Page 24 of 33

21. WG on Aquatic Animals: Dr. Ron Miller (Chairholder) Dr. Miller requested an addition to the agenda to propose ECVs for Flavobacterium psychrophilum. Dr. Miller presented slides on behalf of Dr. Peter Smith (NUI-Galway) and the Aquaculture WG. MIC data from 5 laboratories were presented for approximately 353 isolates, with no lab providing >50% of the total data points. QC was performed per CLSI document VET04 guidelines. Following is a summary of the data presented, with the full meeting presentation (Jan2017_VAST-SC_21_AWG_Fpsychrophilum_MICs_ECV_Presentation) available on the CLSI website (https://clsi.org/education/microbiology/subcommittee-on-vast/vast-meeting-files-resources/). ECV data presented for vote for F. psychrophilum ECV for florfenicol: Page 25 of 33

21. (cont d) WG on Aquatic Animals: Dr. Ron Miller (Chairholder) ECV data presented for vote for F. psychrophilum ECV for oxolinic acid: ECV data presented for vote for F. psychrophilum ECV for flumequine: Page 26 of 33

21. (cont d) WG on Aquatic Animals: Dr. Ron Miller (Chairholder) ECV data presented for vote for F. psychrophilum ECV for Enrofloxacin: Data presented in support of oxolinic acid being a reporter agent for fluoroquinolones: Page 27 of 33

21. (cont d) WG on Aquatic Animals: Dr. Ron Miller (Chairholder) ECV data presented for vote for F. psychrophilum ECV for oxytetracycline: Page 28 of 33

21. (cont d) WG on Aquatic Animals: Dr. Ron Miller (Chairholder) ECV data presented for vote for F. psychrophilum ECV for erythromycin: ECVs presented for vote for Flavobacterium psychrophilum: Florfenicol 2 g/ml Oxolinic acid 0.25 g/ml Flumequine 0.125 g/ml Enrofloxacin 0.03 g/ml Oxytetracycline 0.125 g/ml Erythromycin 8 g/ml Comment to be added to the next revision of the VET03/04-S2: Oxolinic acid as a reporter agent for quinolone susceptibility A motion was made by Dr. Trott and seconded by Dr. Langston to approve the proposed ECVs for F. psychrophilum and the proposed comment to be included with the ECV for oxolinic acid in the next revision of the informational supplement (VET03/04-S2). Vote on the Motion: Passed (10-accept, 0-reject, 0-abstained) Page 29 of 33