Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate A Virtual Midday Symposium conducted at the Home Study Available 2020 ASHP Midyear Clinical Meeting and January 20, 2021 – May 31, 2022 Exhibition Tuesday, December 8, 2020 1:00 – 2:30 pm ET FACULTY Kevin W. Garey, Pharm.D., M.S., FASHP, Activity Chair ACCREDITATION Professor and Chair The American Society of Health‐System University of Houston College of Pharmacy Pharmacists is accredited by the Houston, Texas Accreditation Council for Pharmacy Education as a provider of continuing Krishna Rao, M.D., M.S. pharmacy education. Assistant Professor ACPE #: 0204‐0000‐20‐438‐L01‐P University of Michigan 0204‐0000‐20‐438‐H01‐P Ann Arbor, Michigan 1.5 hour, application‐based Erik R. Dubberke, M.D., MSPH Professor of Medicine The American Society of Health System Clinical Director, Transplant Infectious Diseases Pharmacists is accredited by the Washington University School of Medicine Accreditation Council for Continuing St. Louis, Missouri Medical Education to provide continuing medical education for physicians. View faculty bios at ashpadvantage.com/highriskcdiff The American Society of Health‐System Pharmacists CE PROCESSING designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should Participants will process CE credit online at claim only the credit commensurate with the extent http://elearning.ashp.org/my‐activities. CE credit will be of their participation in the activity. reported directly to CPE Monitor. Per ACPE, CE credit for live Midyear activities must be claimed by February 1, 2021. CE credit for this archived activity must be claimed no later than 60 days from the date of completion. ASHP FINANCIAL RELATIONSHIP DISCLOSURE STATEMENT Planners, presenters, reviewers, ASHP staff, and others with an opportunity to control CE content are required to disclose relevant financial relationships with ACCME‐defined commercial interests. All actual conflicts of interest have been resolved prior to the continuing education activity taking place. ASHP will disclose financial relationship information prior to the beginning of the activity. A relevant financial relationship is defined as a financial relationship between an individual (or spouse/partner) in control of content and a commercial interest, in any amount, in the past 12 months, and products and/or services of the commercial interest (with which they have the financial relationship) are related to the continuing education activity. An ACCME‐defined commercial interest is any entity producing, marketing re‐selling, or distributing healthcare goods or services consumed by, or used on, patients. The ACCME does not consider providers of clinical service directly to patients to be commercial interests—unless the provider of clinical service is owned, or controlled by, an ACCME‐defined commercial interest. Provided by ASHP Supported by an educational grant from Merck 1 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate Kevin W. Garey, Pharm.D., M.S., FASHP, Activity Chair Professor and Chair, University of Houston College of Pharmacy Houston, Texas Krishna Rao, M.D., M.S. Assistant Professor, University of Michigan Ann Arbor, Michigan Erik R. Dubberke, M.D., MSPH Professor of Medicine, Washington University School of Medicine St. Louis, Missouri Provided by ASHP Supported by an educational grant from Merck Financial Relationship Disclosure • Kevin Garey: Research grants from Acurx Pharmaceuticals, Paratek Pharmaceuticals, Summit Pharmaceuticals, and Tetraphase Pharmaceuticals • Erik Dubberke: Research grants from Pfizer, Rebiotix/Ferring Pharmaceuticals, and Synthetic Biologics; Consulting for BioK+ International, Inc., Merck and Co, Inc, Pfizer, Rebiotix/Ferring Pharmaceuticals, Seres Therapeutics, and Summit Therapeutics • Krishna Rao: Research grant from Merck and Co, Inc.; Consulting for Bio‐K+ International, Inc. and Roche Molecular Systems, Inc. All other planners, presenters, reviewers, ASHP staff, and others with an opportunity to control content report no financial relationships relevant* to this activity. *As defined by the ACCME definition of commercial entity. © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 2 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate Learning Objectives • Distinguish how current Clostridioides difficile infection (CDI) therapies prevent CDI recurrence. • Identify patients that would benefit from fidaxomicin or vancomycin with another anti‐CDI recurrence strategy. • Identify patient populations in which an anti‐CDI recurrence strategy would be most cost effective in practice. • Develop an interprofessional treatment plan for recurrent CDI for special populations. Abbreviations • C. difficile‐ Clostridioides difficile • OR‐ overall response • CI‐ confidence interval • PCR‐ polymerase chain reaction • EIA‐ enzyme‐linked immunosorbent assay • PICO‐ population, intervention, comparison, • ESBL‐ extended‐spectrum beta‐lactamase and outcomes • FDX‐ fidaxomicin • PK/PD‐ pharmacokinetic/pharmacodynamic • FMT‐ fecal microbiota transplant • Q3D‐ every 3rd day •HR‐hazard ratio •QOD‐every other day • IBD‐ inflammatory bowel disease • RCT‐ randomized controlled trial • IV – intravenous • SCr‐ serum creatinine • mITT‐ modified intention‐to‐treat • SOC‐ standard of care • MRT‐ microbiota restoration therapy • VAN‐ vancomycin • NNT‐ number needed to treat • WBC‐ white blood cell count © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 3 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate The Great Debates in C. difficile Infection Kevin W. Garey, Pharm.D., M.S., FASHP Krishna Rao, M.D., M.S. Erik R. Dubberke, M.D., MSPH Professor and Chair Assistant Professor Professor of Medicine University of Houston College of Pharmacy Division of Infectious Diseases Clinical Director, Transplant Houston, Texas Department of Internal Medicine Infectious Diseases University of Michigan Medical School Washington University School of Medicine Ann Arbor, Michigan Saint Louis, Missouri Today’s Objectives • Overview: Vancomycin is still commonly used but causes dysbiosis and a high recurrence rate? – Pro‐Con debate: Can vancomycin be used as part of an anti‐CDI recurrence strategy? • Overview: What are the currently available anti‐CDI recurrence strategies? – Pro‐Con debate: What is the best anti‐CDI recurrence strategy? • Overview: Choosing an anti‐CDI recurrence strategy reduced recurrence but has higher drug acquisition costs? – Pro‐Con debate: When is an anti‐CDI recurrence strategy cost‐effective? © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 4 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate A little bit about CDI to get everyone up and running Antibody response Britton RA, Young VB. Gastroenterology. 2014;146:1547-53. DEBATE 1: How do I kill C. difficile without causing more dysbiosis? Antibody response Britton RA, Young VB. Gastroenterology. 2014;146:1547-53. © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 5 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate DEBATE 2: Should I focus on the microbiome or pharmacology in my C. difficile treatment? Antibody response Britton RA, Young VB. Gastroenterology. 2014;146:1547-53. Antibody response DEBATE 3: What is the most cost effective way to save the microbiome?! Britton RA, Young VB. Gastroenterology. 2014;146:1547-53. © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 6 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate DEBATE 1: Can vancomycin be used as part of an anti‐CDI recurrence strategy? • Moderator: Erik R. Dubberke, M.D., MSPH • No, start with a narrower spectrum antibiotic: Krishna Rao, M.D., M.S. • Yes, vancomycin combined with another anti‐CDI recurrence strategy makes sense: Kevin Garey, Pharm.D., M.S. Vancomycin Is Still Commonly Used But Causes Dysbiosis and a High Recurrence Rate Erik R. Dubberke, M.D., MSPH Professor of Medicine Clinical Director, Transplant Infectious Diseases Washington University School of Medicine St. Louis, Missouri © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 7 Preventing and Treating Recurrent Clostridioides difficile Infection in High‐Risk Populations: A Pro/Con Debate Current Pathogenesis Model for CDI C. difficile C. difficile exposure exposure Antimicrobial(s) Asymptomatic C. difficile colonization CDI Acquisition of a toxigenic strain of C. difficile and failure to mount an anamnestic antibody response results in CDI. Johnson S, Gerding DN. Clin Infect Dis. 1998; 26:1027-34. Kyne L et al. N Engl J Med. 2000; 342:390-7. Current Pathogenesis Model for CDI C. difficile C. difficile exposure exposure Antimicrobial(s) Asymptomatic C. difficile colonization CDI Acquisition of a toxigenic strain of C. difficile and failure to mount an anamnestic antibody response results in CDI. Johnson S, Gerding DN. Clin Infect Dis. 1998; 26:1027-34. Kyne L et al. N Engl J Med. 2000; 342:390-7. © 2020 American Society of Health-System Pharmacists, Inc. All rights reserved. 8 Preventing and Treating