Expert Discussion:

What’s New and Noteworthy in C. difficile?

Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Provided by ProCE, LLC and supported by educational grants from Ferring

Pharmaceuticals and Merck Sharp & Dohme Corp.
About the Faculty

Christopher M. Bland, PharmD, FIDSA, FCCP, BCPS

Christopher M. Bland, PharmD, is a Clinical Professor at the
University of Georgia College of Pharmacy in Savannah, Georgia at
the Southeast Georgia campus. He has over 20 years of clinical
experience in a number of different practice areas with infectious
diseases as his primary passion. He has been named both the
Preceptor of the Year and Teacher of the Year at the University of
Georgia College of Pharmacy and is a Fellow of IDSA and ACCP. He
co-founded SERGE-45, a practice-based infectious diseases research
network across the Southeastern United States with currently over
80 members across 14 states and Washington, D.C.

Lindsay Daniels, PharmD, MPH, BCIDP

Dr. Lindsay Daniels is a Clinical Pharmacy Specialist in Infectious
Diseases at the University of North Carolina Medical Center in Chapel
Hill, North Carolina. She received her Doctor of Pharmacy degree
from the Virginia Commonwealth University in 2006 and Master of
Public Health degree from the University of North Carolina Gillings
School of Public Health in 2020. Dr. Daniels has more than 10 years of
experience providing clinical pharmacy services on inpatient
infectious diseases medicine and consult services. She has led several
stewardship initiatives, and currently serves as Lead Pharmacist for
the Carolina Antimicrobial Stewardship Program at the University of
North Carolina Medical Center.
About the Faculty

Kevin W. Garey, PharmD, MS, FASHP, FIDSA

Kevin Garey, PharmD, MS, FASHP is a Professor at the University of
Houston College of Pharmacy and Chair of the Department of
Pharmacy Practice and Translational Research. He is an Adjunct
Professor at the University of Texas School of Public Health and a
Clinical Specialist and Researcher at Baylor St. Luke’s Medical Center,
Houston, Texas. He received a Bachelor of Science in Pharmacy
degree from Dalhousie University in Halifax, Nova Scotia, Canada, a
Doctor of Pharmacy from SUNY Buffalo in Buffalo, New York, and a
Masters of Science in Biometry from the University of Texas School of
Public Health. Postdoctoral training includes a pharmacy practice
residency at Bassett Healthcare, Cooperstown, New York and
infectious disease specialty residency and fellowship training at the
University of Illinois at Chicago, Chicago, Illinois.
Dr. Garey is a member of the Infectious Diseases Society of American (IDSA) Standards and
Practice Guidelines Committee and is a member of the IDSA-Society of Healthcare Epidemiology
of America (SHEA) practice guidelines for C. difficile infection. He is an active member of the
Society of Infectious Diseases Pharmacists (SIDP) and the American Society of Health-system
Pharmacists (ASHP). He has been awarded several national awards including the ASHP Best
Practice Award in Health-system Pharmacy Administration (2010), the ASHP Drug Therapy
Research Award (2007), and the SIDP Impact Paper in Infectious Diseases Pharmacotherapy
Research Award (2007, 2012). He received the University of Houston PLS leadership award in
2013.
Dr. Garey's research is supported by the National Institute of Health, the Centers for Disease
Control and Prevention, and the biotechnology industry. He has published over 220 manuscripts
centered on clinical and translational research in healthcare associated infections including
healthcare-related infections, candidemia, and Clostridium difficile infection.
Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Expert Discussion:
What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Provided by ProCE, LLC and supported by educational grants from Ferring

Pharmaceuticals and Merck Sharp & Dohme Corp.

CE Activity Information and Accreditation

This activity is jointly provided by ProCE, LLC and the Society of Infectious
Diseases Pharmacists. ProCE, LLC is accredited by the Accreditation Council for
Pharmacy Education as a provider of continuing pharmacy education. ACPE
Universal Activity Number 0221-9999-21-256-L01-P has been assigned to this
live knowledge-based activity (initial release date 10-12-21). This activity is
approved for 0.5 contact hour (0.05 CEU) in states that recognize ACPE
providers. The activity is provided at no cost to learners. Learners must
complete the online posttest and activity evaluation within 30 days of the
activity to receive pharmacy CE credit. No partial credit will be given.
Statements of completion will be issued online at www.ProCE.com, and proof
of completion will be posted in NABP CPE Monitor profiles.

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

CE Activity Information and Accreditation

Target Audience
The target audience for this activity is pharmacists, including those specializing in infectious diseases,
gastroenterology, internal medicine, and family medicine, and other healthcare professionals who care for
patients with CDI.

Learning Objectives
At the conclusion of this activity, learners should be able to:
 Discuss the guideline-recommended treatment algorithms for Clostridioides difficile infection (CDI)
 Determine treatment strategies for reducing CDI recurrence, including patient education, and ensuring
medication access during transitions of care

Funding
This activity is supported by educational grants from Ferring Pharmaceuticals and Merck Sharp & Dohme Corp.

Disclosure of Conflicts of Interest

ProCE requires instructors, planners, managers, and other individuals
who are in a position to control the content of this activity to disclose any
relevant conflict of interest (COI) they may have as related to the content
of this activity. All identified COI are thoroughly vetted and resolved
according to ProCE policy.
ProCE is committed to providing its learners with high-quality CME/CE
activities and related materials that promote improvements or quality in
healthcare and not a specific proprietary business interest of a
commercial interest.

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Disclosures
The faculty reported the following relevant financial relationships or relationships to
products or devices they have with ineligible companies related to the content of this
CME/CE activity:
Christopher M. Bland, PharmD, FIDSA, FCCP, BCPS, has disclosed that he has received fees
for non-CME/CE services from Baudax Bio, Merck, and Tetraphase, performed contract
research for Merck, and received consulting fees from Merck.
Lindsay Daniels, PharmD, MPH, BCIDP, has no relevant conflicts of interest to report.
Kevin W. Garey, PharmD, MS, FASHP, FIDSA, has disclosed that he has performed contract
research for Acurx Pharmaceuticals, Paratek Pharmaceuticals, and Summit Pharmaceuticals.
The planners/managers reported the following relationships:
Zachary Schwartz, MSc, ELS, and Petra Cravens, PhD; have no relevant conflicts of interest to
report.
ProCE staff members have no relevant conflicts of interest to report. 5

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that
are not indicated by the FDA. The planners of this activity do not recommend the use of any agent
outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily
represent the views of the planners. Please refer to the official prescribing information for each
product for discussion of approved indications, contraindications, and warnings.

Disclaimer
Learners have an implied responsibility to use the newly acquired information to enhance patient
outcomes and their own professional development. The information presented in this activity is not
meant to serve as a guideline for patient management. Any procedures, medications, or other courses
of diagnosis or treatment discussed or suggested in this activity should not be used by healthcare
professionals without evaluation of their patient’s conditions and possible contraindications and/or
dangers in use, review of any applicable manufacturer’s product information, and comparison with
recommendations of other authorities.
6

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Expert Discussion:
What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Provided by ProCE, LLC and supported by educational grants from Ferring

Pharmaceuticals and Merck Sharp & Dohme Corp.

Faculty
Christopher M. Bland, PharmD, FIDSA, FCCP, BCPS
Clinical Professor
Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy
Infectious Diseases Pharmacist
St. Joseph’s/Candler Health System, Inc.
Savannah, Georgia

Lindsay Daniels, PharmD, MPH, BCIDP

Clinical Pharmacy Specialist, Infectious Diseases
Department of Pharmacy, UNC Medical Center
Adjunct Assistant Professor of Clinical Education
University of North Carolina
Chapel Hill, North Carolina

Kevin W. Garey, PharmD, MS, FASHP, FIDSA

Professor and Chair
Pharmacy Practice and Translational Research
University of Houston College of Pharmacy
Houston, Texas
8

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Christopher M. Bland, PharmD, FIDSA, FCCP, BCPS

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Audience
Which statement regarding C difficile infection is TRUE? Response

A. Rates of community-associated infections are decreasing

B. Previous antibiotic use is noted in all cases
C. Proton pump inhibitors are associated with recurrence
D. Resistance is more common than recurrence

10

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

State of Union: C difficile Infection in 2021

 Leading cause of antibiotic-associated diarrhea
 Urgent threat per CDC Resistance Threat Report
 More than 450,000 cases annually in the US
 Nearly 225,000 cases in hospitalized patients annually
‒ Most common healthcare-associated infection in the US
 Community-acquired cases not decreasing
 Cost: $1 billion annually
‒ Not including community-acquired cases
CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: US. DHHS, CDC, 2019. Guh. NEJM. 2020;382:1320.
Slide credit: ProCE.com 11

State of Union: C difficile Infection in 2021

 Risk reduction  Treatment options
‒ Avoiding antibiotics for viral ‒ Antibiotics
illnesses
‒ Regular vs pulse/taper
‒ COVID-19 challenges
‒ First vs recurrent
‒ De-escalation through stewardship
‒ Severity
‒ Shortening of therapy
‒ Antibodies
‒ Bacteremia
‒ Gut flora re-establishment
‒ UTIs
‒ Diagnostic interpretation
Slide credit: ProCE.com 12

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

C difficile
 Risk factors  Clinical presentation
‒ Antibiotic therapy* ‒ Wide range of presentations
‒ But not everyone ‒ Asymptomatic colonization to
‒ Immunosuppression life-threatening infection

‒ Advanced age* ‒ 3 or more unformed/loose

stools in 24-hr period plus
‒ Acid suppressing therapy* testing results
‒ Chronic renal disease
‒ Treatment decisions
‒ Chronic hepatic disease
‒ Severity of illness
‒ Malnutrition ‒ Initial vs recurrent
*Associated with recurrence

Khanafer. Anaerobe. 2017;44:117.

Slide credit: ProCE.com 13

Lindsay Daniels, PharmD, MPH, BCIDP

ProCE.com 14

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Which treatment strategy has been shown to Audience

Response
reduce CDI recurrence?
A. Metronidazole
B. Vancomycin
C. Fidaxomicin
D. Vancomycin + bezlotoxumab
E. Both C and D

15

CDI Guideline 2021 Updates

CDI Episode IDSA/SHEA 2021 ACG 2021

-Vancomycin (strong/low) , OR
-Preferred: fidaxomicin (conditional/moderate)
Initial -Fidaxomicin (strong/moderate)
-Alternative: vancomycin
(non-severe) -Metronidazole may be considered in low-risk patients
-Metronidazole if above agents are unavailable
(strong/moderate)

Initial -Preferred: fidaxomicin (conditional/moderate) -Vancomycin (strong/low), OR

(severe) -Alternative: vancomycin -Fidaxomicin (conditional/very low)

-High dose vancomycin + metronidazole IV

-High dose vancomycin + metronidazole IV
Fulminant (conditional/very low)
-Add vancomycin rectally if ileus
-Add vancomycin rectally if ileus (conditional/very low)

Severe CDI: WBC ≥15,000 cells/mm3 or serum creatinine >1.5 mg/dL.

Fulminant CDI: hypotension, shock, ileus, or megacolon.

Johnson. Clin Infect Dis. 2021;73:755.

Kelly. Am J Gastroenterol. 2021;116:1124.
Slide credit: ProCE.com 16

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

CDI Guideline 2021 Updates

IDSA/SHEA 2021 ACG 2021

-Preferred: fidaxomicin standard or extended-pulsed

-Vancomycin tapered or pulsed regimen
regimen (conditional/low)
(strong/very low), OR
First recurrence -Alternative: vancomycin tapered or pulsed regimen
-Fidaxomicin (if initially treated with vancomycin or
-Alternative: vancomycin standard regimen (if
metronidazole) (conditional, moderate)
initially treated with metronidazole)

-Fidaxomicin standard or extended-pulsed regimen

Second
-Vancomycin tapered or pulsed regimen
recurrence and -Emphasis on FMT
-Vancomycin standard regimen followed by rifaximin
beyond
-FMT (for third recurrence and beyond)

-Patients with a recurrent CDI episode within the -Patients at high risk of recurrence
Bezlotoxumab
past 6 mo (conditional/very low) (conditional/moderate)

Johnson. Clin Infect Dis. 2021; 73(5):755.

Kelly. Am J Gastroenterol 2021;116:1124.
Slide credit: ProCE.com 17

IDSA/SHEA Guidelines:
Fidaxomicin vs Vancomycin for Initial CDI Episode
CDI Initial Clinical Cure
Fidaxomicin Vancomycin Risk Ratio Risk Ratio

Study or Events Total Events Total Weight M-H, Random, Yr M-H, Random, 95% CI
Subgroup 95% CI
Louie 253 287 265 309 39.2% 1.03 (0.97-1.09) 2011

Cornely 221 252 223 257 34.3% 1.01 (0.95-1.08) 2012

Guery 138 177 147 179 14.0% 0.95 (0.86-1.05) 2018

Mikamo 87 104 95 108 12.5% 0.95 (0.85-1.06) 2018

Total (95% CI) 820 853 100.0% 1.00 (0.96-1.04)

Total events 699 730

Heterogeneity: TauZ = 0.00; ChiZ = 2.66, df = 3 (P = .45); IZ = 0% 0.5 0.7 1 1.5 2

Test for overall effect: Z = 0.04 (P = .97)
Favors Vancomycin Favors Fidaxomicin

Johnson. Clin Infect Dis. 2021;73:e1029.

Slide credit: ProCE.com 18

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

IDSA/SHEA Guidelines:
Fidaxomicin vs Vancomycin for Initial CDI Episode
CDI Sustained Response (Follow-up: 4 Wk)
Fidaxomicin Vancomycin Risk Ratio Risk Ratio

Study or Events Total Events Total Weight M-H, Random, Yr M-H, Random, 95% CI
Subgroup 95% CI
Louie 214 287 198 309 37.5% 1.16 (1.05-1.30) 2011

Cornely 193 252 163 257 32.6% 1.21 (1.08-1.36) 2012

Guery 124 177 106 179 18.0% 1.18 (1.01-1.38) 2018

Mikamo 70 104 71 108 11.9% 1.02 (0.85-1.24) 2018

Total (95% CI) 820 853 100.0% 1.16 (1.09-1.24)

Total events 601 538

Heterogeneity: TauZ = 0.00; ChiZ = 2.17, df = 3 (P = .54); IZ = 0% 0.5 0.7 1 1.5 2

Test for overall effect: Z = 4.51 (P <.00001)
Favors Vancomycin Favors Fidaxomicin

Johnson. Clin Infect Dis. 2021;73:e1029.

Slide credit: ProCE.com 19

ACG 2021 Guidelines: Role of Fidaxomicin

 Vancomycin and fidaxomicin remain first-line options
‒ Comparable cure rates
‒ Higher costs and access challenges with fidaxomicin
 Severe CDI: low certainty evidence for fidaxomicin
‒ Gentry et al: retrospective cohort study, severe CDI
‒ No difference in combined primary outcome of clinical failure or recurrence
‒ Rajasingham et al: cost-effective analysis stratified by severity
‒ Vancomycin shown to be optimal cost-effective treatment for severe CDI

Kelly. Am J Gastroenterol. 2021;116:1124. Gentry. Clin Microbiol Infect. 2019;25:987. Rajasingham. Clin Infect Dis. 2020;70:754. Slide credit: ProCE.com 20

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Bezlotoxumab
 Monoclonal antibody targeting C difficile toxin B
 Single 60-min infusion (10 mg/kg), given during course of CDI treatment
 MODIFY 1 and MODIFY 2
‒ Bezlotoxumab, actoxumab (MODIFY 1 only), bezlotoxumab plus
actoxumab, or placebo
‒ All patients received standard-of-care antibiotics
‒ Bezlotoxumab reduced CDI recurrence at 12 wk compared with placebo
 Patients at high risk of recurrence most likely to benefit
Wilcox. NEJM. 2017;376:305. Gerding. Cin Infect Dis. 2018;67:649.
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Putting the CDI Guidelines into Practice

 Emphasis placed on preventing recurrence as an important
component of treatment
 Questions remain regarding optimal strategy to reduce recurrence
 Cost considerations
‒ More expensive treatments, but potentially cost-effective
‒ Cost to the patient
 Logistical and feasibility considerations

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Expert Discussion: What’s New and Noteworthy in C. difficile?
Roundtable #1: Overview of C. difficile Infection Management and Effect on Health Systems

Question and Answer Session

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