Evolving Challenges in

Clostridium difficile Infection (CDI):

From Risk Assessment to Innovative
Treatments
Disclosure of Conflicts of Interest
Linda M. Mundy, MD, Ph.D

Dr. Linda M. Mundy, has affiliations with
Genentech, Inc. (Patent holder - spouse) and
GlaxoSmithKline (Consultant).
Educational Objectives
Discuss the pathophysiology of Clostridium difficile
infection (CDI) as it relates to clinical disease

Identify important risk factors for initial CDI and
recurrence

Apply therapeutic strategies for improved patient
outcomes

Implement methods to prevent CDI in high-risk patients


CDI Overview: 60 Years of Research
Evolution of C. difficile knowledge over past 60
years
1950: Staphylococcus enterocolitis
1974: Clindamycin colitis
1978: C. difficile as agent of pseudomembranous colitis
1981: Vancomycin approved by FDA for CDI
1982: Metronidazole introduced for CDI
1984: Enzyme immunoassays for CDI
2000: Outbreak in Pittsburgh, PA
2003: Outbreak in Quebec
2005: Outbreaks in United States and Europe

CDI Overview
Spore-forming, anaerobic,
gram-positive bacterium
Causes gastrointestinal
infections resulting in diarrhea
and colitis
Severity ranges from mild colitis
to toxic megacolon and death
Leading cause of healthcare-associated infectious
diarrhea in US
Rivals methicillin-resistant Staphylococcus aureus
(MRSA) as the most common organism to cause
healthcare-associated infections in US

Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.
CDC. Fact Sheet, August 2004 (updated 7/22/05).
McDonald LC, et al. Emerg Infect Dis. 2006;12:409-415.
CDI Epidemiology
Incidence of CDI appears to be increasing in the US
Healthcare Cost and Utilization Project (HCUP). http://hcupnet.ahrq.gov.
138,954
348,950
CDI Epidemiology
Severity of CDI appears to be increasing
1-2

Increased morbidity and mortality
Increased infection in low-risk populations
1-3

Emergence of novel, hypervirulent strain now
reported across the US, Canada, and Europe
Increased toxin production and sporulation may
contribute to widespread disease
4,5


1. McDonald LC, et al. Emerg Infect Dis. 2006;12(3):409-415.
2. Loo VG, et al. N Engl J Med. 2005;353:2442-2449.
3. Kuijper EJ, et al. Euro Surveill. 2007;12(6):E1-E2.
4. Tucker ME. http://www.ehospitalistnews.com/news/infectious-diseases/single-article/ic-difficilei-epidemic-still-poses-clinical-
challenges/01e37c081f.html
5. Merrigan M, et al. J Bacteriol. 2010;192:4904-4911.
CDI Epidemiology
Characteristics of novel epidemic strain:
Typed BI/NAP1/027

Highly virulent
Produces 16-fold higher levels of Toxin A and
23-fold higher levels of Toxin B
Produces binary toxin CDT
Highly resistant to fluoroquinolones
Denve C, et al. Int J Antimicrob Agents. 2009;33:S24-S28.
CDI Pathophysiology
Primary virulence factors:
Toxin A (TcdA)
Toxin B (TcdB)
Toxins A and B are potent cytotoxic enzymes
that damage the human colonic mucosa
Binary toxin (CDT) was previously identified in
~6% of C. difficile isolates, but is present in all
isolates of the hypervirulent strain
May potentiate toxicity of TcdA and TcdB and lead
to more severe disease
Denve C, et al. Int J Antimicrob Agents. 2009;33:S24-S28.
Economic Burden of CDI
Study Patient
Population
Per-Episode
Costs
Increase in
Length of Stay
US Cost
Kyne 1998
1
-2 medical
wards
-40 cases
$3,669 3.6 days $1.1 billion
OBrien 2000
2
-MA discharge
database
-3,692 cases
Primary
diagnosis:
$10,212
Secondary
diagnosis:
$13,675
3.0 days $3.2 billion
Dubberke 2003
3
-Nonsurgical
patients
-439 cases
$2,454
$3,240
2.8 days $1.3 billion
1. Kyne L, et al. Clin Infect Dis. 2002;34:346-353.
2. OBrien JA, et al. Infect Control Hosp Epidemiol. 2007;28:1219-1227.
3. Dubberke ER, et al. Clin Infect Dis. 2008;46:497-504.
Economic Burden of CDI
Limitations of current data
Primarily hospitalized patients with CDI
Few studies determined costs associated with
treatment of CDI complications
Most data obtained prior to outbreak of epidemic
strain
Difficult to extrapolate and apply to current
epidemiology and management
Economic burden expected to accumulate


1. Dubberke ER, Wertheimer AI. Infect Control Hosp Epidemiol. 2009;30:57-66.
2. Ghantoji SS, et al. J Hosp Infect. 2010;74:309-318.
Pathogenesis of CDI
From Poutanen SM, Simor AE. Can Med Assoc J. 2004;171(1):51-58; with permission.
Risk Factors for Initial CDI
Classic risk factors:
Antibiotic therapy
Advanced age
Prolonged stay in healthcare facility
High severity of illness
Additional risk factors
Inflammatory bowel disease
Gastrointestinal surgery
Gastric acid suppression (PPIs)
Immunosuppression
1. Hookman P, Barkin, JS. World J Gastroenterol. 2009;15:1554-1580.
2. APIC. Guide to the Elimination of Clostridium difficile in Healthcare Settings. November 2008.
3. Makris AT, Gelone S. J Am Med Dir Assoc. 2007;8:290-299.
4. Cohen SH, et al. Infection Control and Hospital Epidemiology. 2010;31(5):431-455.
5. Goodhand JR, et al. Ailment Pharmacol Ther. 2011;33:428-441.
6. Aseeri M, et al. Am J Gastroenterol. 2008;103:2308-2313.
7. Schaier M, et al. Nephrol Dial Transplant. 2004;19:2432-2436.
Identifying Patients at Risk
for Recurrence and Poor Outcomes
Elderly
Administration of antibiotics after initial
treatment of CDI
Prolonged hospitalization or stay in long-term
care facility (LTCF)
Defective immune response to toxin A
Gastric acid suppression

1. Johnson S. J Infect. 2009;58:403-410.
2. Hookman P, Barkin JS. World J Gastroenterol. 2009;15(13):1554-1580.
3. Zilberberg M, et al. Crit Care Med. 2009;37:2583-2589.
4. Garey KW, et al. J Hosp Infect. 2008;70:298-304.
Elderly
20.4/1,000 discharges
15.2/1,000 discharges
8.29/1,000 discharges
2.97/1,000
discharges
Healthcare Cost and Utilization Project (HCUP). http://hcupnet.ahrq.gov.
Administration of Antibiotics
After Initial CDI Therapy
Continued use of non-C. difficile antibiotic after
diagnosis of CDI associated with an odds ratio of 4.23
(P<0.001) for recurrent disease
1

Phase 3 study of fidaxomicin and vancomycin linked
concomitant antibiotics with lower rates of global
cure (initial cure without recurrence at 30d):
2

P
a
t
i
e
n
t
s
,

%

P<0.001
FDX VAN Total FDX VAN Total
1. Garey KW, et al. J Hosp Infect. 2008;70:298-304. 2. Johnson S, et al. DDW 2010; Abstract 711c.
GLOBAL CURE
Prolonged Hospitalization or Stay in LTCF
Risk related to transmission of C. difficile spores
Primary source from healthcare workers
Staff may carry C. difficile spores on their hands (not likely
fecal carriers)
Environmental contamination important secondary
source
Up to 50% of LTCF residents and 40% of
hospitalized patients have been found to be
colonized with C. difficile or its toxin
Infection control and preventions strategies (ie,
hand hygiene, isolation precautions) can reduce
this risk

1. McFarland LV, et al. N Engl J Med. 1989;320:204-210. 2. Bartlett JG, Gerding DN. Clin Infect Dis. 2008;46(Suppl 1):S12-S18. 3. Simor AE, et
al. Infect Control Hosp Epidemiol. 2002;23:696-703. 4. Hookman P, Barkin JS. World J Gastroenterol. 2009;15:1554-1580.

Defective immune response to toxin A
Generation of antibody
responses to toxin A
associated with protection
from disease and
asymptomatic carriage of
C. difficile.
Following symptomatic
infection, many individuals
develop anti-toxin A and B
antibodies
Inability to acquire immunity
to toxin A increases risk for
recurrent disease
Individuals with recurrent CDI
mount poor anti-toxin
responses


1. Giannasca PJ, Warny M. Vaccine. 2004;22:848-856.
2. Kyne L, et al. Lancet. 2001;357:189-193; with permission
Median serum concentrations of
antibody against toxin A
S
e
r
u
m

I
g
M

S
e
r
u
m

I
g
G

CDI Diagnostic Challenges
Test Advantage(s) Disadvantage(s)
Toxin testing
Enzyme
immunoassay

Rapid, simple,
inexpensive

Least sensitive method, some
detect only toxin A (some strains
only produce toxin B)
Tissue culture
cytotoxicity

Organism identification
More sensitive than
enzyme immunoassay
Labor intensive; requires 2448
hours for a final result, special
equipment; not as sensitive as
generally thought
Detection of
glutamate
dehydrogenase
Rapid, sensitive, may
prove useful as a triage
or screening tool
Not specific, toxin testing required
to verify diagnosis; may not be
100% sensitive
PCR Rapid, sensitive,
detects presence of
toxin gene
Cost, special equipment, may be
too sensitive
Stool culture Most sensitive test
available when
performed
appropriately
May be associated with false-
positive results if isolate is not
tested for toxin; labor-intensive;
requires 4896 hours for results
CDI Diagnostic Challenges
Two- and three-step testing algorithms have
been proposed
Initial screen: EIA for glutamate dehydrogenase
Confirmatory: Cell cytotoxicity assay (or culture)
or polymerase chain reaction (PCR)
Results appear to differ based on the GDH kit
used
Optimal universal strategy remains continuous
source of debate

1. Hansen G, et al. Clin Laboratory News. 2010 July:10-13.
2. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
SHEA/IDSA 2010 Guidelines
for Diagnosis
Testing for C. difficile or its toxins should be
performed only on unformed stool (unless
ileus is suspected)
Testing asymptomatic patients not clinically
useful and not recommended outside of
epidemiological studies
Stool culture with confirmation of isolate
toxigenicity (toxigenic culture) provides the
standard against which other clinical test
results should be compared

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
SHEA/IDSA 2010 Guidelines
for Diagnosis (Cont.)
EIA considered a suboptimal alternative approach
for diagnosis
2-step testing can help to overcome low
sensitivity of toxin testing; this approach remains
an interim recommendation
More data on the utility of PCR testing is
necessary before it can be recommended for
routine testing
Repeat testing during same episode of diarrhea is
discouraged

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
Basic Principles of CDI Therapy
Discontinue offending antimicrobial agent (if
possible)
Send stool specimen for C. difficile testing
Initiate CDI therapy either empirically or
following confirmation of diagnosis (depending
on clinical urgency)
Pharmacotherapy
Vancomycin (only FDA-approved treatment for CDI)
Metronidazole
Other
Supportive treatment
Monitor for symptom resolution and be aware
of recurrence after treatment discontinuation

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
SHEA/IDSA Treatment
Recommendations
Severity-based management
SHEA/IDSA recommends stratification of
treatment based on disease severity
Risk-stratification method has not yet been
validated
Criteria based on expert opinion and/or
retrospective data

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
SHEA/IDSA Treatment
Recommendations
Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
Clinical scenario Supportive clinical data Recommended treatment
Mild to moderate Leukocytosis (WBC < 15,000
cells/uL) or SCr level < 1.5
times premorbid level
Metronidazole 500 mg 3
times per day PO for 10-
14 days
Severe Leukocytosis (WBC 15,000
cells/uL) or SCr level 1.5
times premorbid level
Vancomycin 125 mg 4
times per day PO for 10-
14 days
Severe, complicated Hypotension or shock, ileus,
megacolon
Vancomycin 500 mg 4
times per day PO or by
nasogastric tube plus
metronidazole 500 mg IV
q 8 hrs
Additional Management of
Severe, Complicated CDI
Prompt recognition of severe, complicated CDI and
early surgical evaluation is critical*
Indications of severe, complicated disease course:
Elevated and rising white blood cell count (WBC)
Elevated serum creatinine (SCr) level
Elevated serum lactate
Clinical and/or radiographic evidence of severe ileus,
impending toxic megacolon
Consider vancomycin per rectum if ileus is severe

*Colectomy may be lifesaving, but is associated with
increased risk of mortality if WBC is > 50,000 and lactate is
>5 mg/dL
1. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
2. Pepin J, et al. Dis Colon Rectum. 2009;52:400-405.
Management of Recurrent CDI
CDI recurrence is a significant challenge
Rates of recurrent CDI:
20% after first episode
45% after first recurrence

65% after two or more recurrences








Clinical scenario Recommended treatment
First recurrence Treat as first episode according to
disease severity
Second recurrence Treat with oral vancomycin taper
and/or pulse dosing
1. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
2. Johnson S. J Infect. 2009;58(6):403-410.

Multiple Recurrent CDI
Several empirical approaches have been advocated
but most have no controlled data
1-3

Metronidazole should not be used beyond first
recurrence or for prolonged course, ie, >14 days
(concerns for hepatotoxicity and polyneuropathy)
1-3

Best data with vancomycin taper regimen
4,5



1. Aslam S, et al. Lancet Infect Dis. 2005;5:549-557. 2. McFarland LV, et al. Am J Gastroenterol. 2002:97:1769-1775. 3. McFarland LV, et
al. JAMA. 1994;271:1913-1918. 4. Kyne L, Kelly CP. Gut. 2001;49:152-153. 5. Tedesco FJ, et al. Am J Gastroenterol. 1985;80:867-868.
Oral Vancomycin Taper
125 mg QID x 10-14 days
125 mg BID x 7 days
125 mg daily x 7 days
125 mg once every 2 days x 8 days
125 mg once every 3 days x 15 days
Alternative CDI Therapies: Probiotics
Adjunctive treatment for recurrent CDI
Randomized trials of Lactobacillus species have failed to
demonstrate benefit to prevent recurrent CDI
Saccharomyces boulardii for secondary prophylaxis
once promising
2,3

Confirmatory trial failed to confirm
Overall no effect: 44% vs 47% recurrence (RR 0.91;
95% confidence interval 0.66 to 1.27)
3
subgroup analysis showed borderline benefit with S. boulardii and
high dose vancomycin (p=0.05)
Reports of fungemia have been reported
More study needed for probiotics in primary
prevention

1. Dendukuri N, et al. CMAJ. 2005;173:167-170.
2. Tung JM, et al. Can J Gastroenterol. 2009;23:817-821.
3. Surawicz CM, et al. Clin Infect Dis. 2000;31:1012-1017.
Alternative CDI Therapies: Rifaximin
Rifaximin chaser therapy for multiple recurrent
CDI
1

Rifaximin 400 mg BID for 14 days immediately
following last course of vancomycin
Seven of eight patients had no further diarrhea
recurrence
Single case of rifaximin resistance with recurrent CDI
after a second course of rifaxmin
Follow up experience with 6 patients
2 recurred, rifaximin resistance identified in one
Issues with resistance
2

Rifampin resistance observed in 36.8% of 470
recovered isolates and 81.5% of 205 epidemic clone
isolates


1. Johnson S, et al. Clin Infect Dis. 2007;44:846-848.
2. Curry SR, et al. Clin Infect Dis. 2009;48:425-429.
3. Johnson S, et al. Anaerobe. 2009; 15:290-1
Alternative CDI Therapies: Nitazoxanide
May be effective in patients
who failed treatment with
metronidazole
1

66% cure rate in 35 patients
who failed treatment with
metronidazole
Non-inferior to vancomycin
in small study of 50 patients
(Figure)
2

Initial response:
Vancomycin: 87%
Nitazoxanide: 94%
Similar time to complete
resolution of symptoms
Time to resolution of symptoms
P=0.55
1. Musher DM, et al. J Antimicrob Chemother. 2007;59:705-710.
2. Musher DM, et al. Clin Infec Dis. 2009;48:e41-e46; with permission.
Alternative CDI Therapies: Tigecycline
Adjunctive treatment for severe CDI
Lu CL, et al. Int J Antimicrob Agents.
2010;35:311-312.
Single case study
CDI refractory to metronidazole and vancomycin successfully
treated with IV tigecycline
Herpers BL, et al. Clin Infect Dis. 2009;48:1732-1735.
4 pts with severe, refractory CDI
Successful treatment with IV tigecycline therapy
Kopterides P, et al. Anaesth Intensive Care.
2010;38:755-758.
Single case study
Treatment failure with tigecycline combined with
vancomycin, metronidazole, and intravenous
immunoglobulin (IVIG)

Alternative CDI Therapies: IVIG
Study Type N Population Potential Benefit
of IVIG?
Yes No
McPherson 2006
1
Retrospective
Review
14 Severe,
refractory,
recurrent CDI
X
Abougergi 2010
2
Observational
study and
literature review
21 Severe C. difficile
colitis
X
Wilcox 2004
3
Descriptive study 5 Intractable,
severe C. difficile
diarrhea
X
OHoro 2009
4
Systematic
review
-- CDI
inconclusive inconclusive
Hassoun 2007
5
Case review 1 Severe C. difficile
colitis
X
Inconclusive evidence regarding the benefit of
intravenous immunoglobulin (IVIG) in CDI
1. McPherson S, et al. Dis Colon Rectum. 2006;49:640-645. 2. Abougergi MS, et al. J Hosp Med. 2010;5:E1-E9. 3. Wilcox MH. J Antimicrob
Chemother. 2004;53:882-884. 4. OHoro J, Safdar N. Int J Infect Dis. 2009;13:663-667. 5. Hassoun A, Ibrahim F. Am J Geriatr Pharmacother.
2007;5:48-51.
Fecal Flora Restoration
Theory: Restoration of fecal flora and colonization
resistance
Data:
1958 to 2000: 9 reports (68 patients); cure rate ~90%.
2003: 18 patients; fecal filtrate (stool transplant); 1 of 16
survivors had a single subsequent recurrence; pre-treated
with vancomycin and omeprazole; instilled through
nasogastric tube.
Test donor: enteric pathogens, C. difficile, ova and
parasites, HAV, HBV, HCV, HIV, RPR
1. Persky SE, Brandt LJ. Am J Gastroenterol. 2000;95:3283-3285.
2. Borody TJ. Am J Gastroenterol. 2000;95:3028-3029.
3. Palmer R. Nat Med. 2011;17:150-152.
Potential Future CDI Therapies: Fidaxomicin
Rate of clinical cure with fidaxomicin non-inferior
to that of vancomycin (phase 3 trial results)
Fidaxomicin associated with significantly lower rate
of CDI recurrence
Similar adverse event profile
Louie TJ, et al. N Engl J Med. 2011;364:422-431; with permission.
Potential Future CDI Therapies: Fidaxomicin
Similar conclusions reached in second phase 3
study
Equivalent cure
rates were
achieved with
FDX and VAN
Significantly fewer
recurrences were
seen after FDX
(50% less than VAN)
resulting in higher global cures

91.7
12.8
79.6
90.6
25.3
65.5
91.1
19.1
72.3
0
10
20
30
40
50
60
70
80
90
100
Clinical Cure Recurrence Global cure
*

FDX VAN Total FDX VAN Total FDX VAN Total
198
216
213
235
411
451
23
180
46
182
69
362
172
216
154
235
326
451
FDX, fidaxomicin; VAN, vancomycin; *P = NS;

P = .002;

P < .001
Johnson S, et al. DDW 2010; Abstract 711c.


Potential Future CDI Therapies:
Nontoxigenic C. difficile
Nontoxigenic C. difficile strains
occur naturally
Natural asymptomatic C. difficile
colonization (toxigenic or
nontoxigenic) decreases risk of
infection
Nontoxigenic C. difficile can be
administered orally as spores to
provide protection against CDI
Mechanism by which nontoxigenic
C. difficile prevents colonization by
toxigenic strains not yet elucidated
Human Phase I trials completed in
early 2010
1. Gerding DN, Johnson S. Clin Infect Dis. 2010;51:1306-1313.
2. Sambol SP, et al. J Infect Dis. 2002;186:1781-1789; with permission
Non-toxigenic C. difficile
prevented CDI in 87%-97%
of hamsters
Prevention of Fatal Infection with Toxigenic C.
difficile (J9) by Prior Colonization of Hamsters
with Non-toxigenic C. difficile (M3)
M3 J9
Control
J9
XX -dead
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day..
Clindamycin
Potential Future CDI Therapies:
C. difficile Toxoid Vaccine
Seroconversion rates in young vs elderly healthy
subjects (50 g dose)
Foglia G, et al. Anarobe Society of Americas 2010; Abstract CD 1093.
Day
Study 009
65 yrs; median age = 70
Study 008
1855 yrs; median age = 26
0 10 20 30 40 50 60 70 80
0
25
50
75
100
S
e
r
o
c
o
n
v
e
r
s
i
o
n

R
a
t
e

(
%
)

Toxin A Toxin B Both toxins
S
e
r
o
c
o
n
v
e
r
s
i
o
n

R
a
t
e

(
%
)

100%
75%
75%
42%
25%
0 10 20 30 40 50 60 70 80
0
20
40
60
80
100
Day
100%
Potential Future CDI Therapies:
Monoclonal Antibodies (mAbs)
Recent study of mAbs in 200 CDI patients receiving
metronidazole or vancomycin
Recurrence rates:
7% in mAb group vs. 25% in placebo group


Lowy I, et al. N Engl J Med. 2010;362:197-205.
Time to CDI recurrence
Prevention of CDI
Transmission between patients and healthcare
professionals within hospitals represents major
source of C. difficile acquisition
Survey reports inconsistencies among infection
control measures
Hand hygiene policies
Duration of isolation
Environmental cleaning practices
Antimicrobial stewardship programs

APIC 2010 Clostridium difficile Pace of Progress Survey. Available at:
http://www.apic.org/Content/NavigationMenu/ResearchFoundation/NationalCDiffPrevalanceStudy/CDI_Pace_of_Progress_Survey_Report.pdf.
Accessed January 31, 2011.
Minimize Transmission among
Healthcare Personnel: Hand Hygiene
Appropriate hand hygiene area of
controversy
In routine settings, alcohol-based hand hygiene in
conjunction with isolation precautions using
gloves may be acceptable
In setting of outbreak or increased rates, consider
washing hands with soap and water after caring
for patients with C. difficile

HCWs = healthcare workers.
1. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31:431-455.
2. Dubberke ER, et al. Infect Control Hosp Epidemiol. 2008;29:S81-S92.
3. APIC Guide to the Elimination of Clostridium difficile in Healthcare Settings, Association for Professionals in Infection Control and
Epidemiology, Inc. November 2008.
Efficacy of Hand Hygiene Methods for Removal
of C. difficile Contamination from Hands
*
Different from AHR (P<0.05).
**
Different from AHR and AHW (P<0.05).
*
Oughton M, et al. Infect Control Hosp Epidemiol. 2009;30(10):939-944.
AHR = alcohol
hand rub
AHW = alcohol
hand wipe
CFU = colony
forming units
CWS = cold water
soap
WWA = warm
water and
antibacterial
WWS = warm
water and soap
Decrease in colony counts
compared with no wash
1.8 1.8
1.4
0.6
-0.1
-1
-0.5
0
0.5
1
1.5
2
2.5
Hand hygiene method
D
e
c
r
e
a
s
e

i
n

c
o
l
o
n
y

c
o
u
n
t
s


(
l
o
g

C
F
U
/
m
L
)

WWS CWS WWA AHW AHR
** ** *
Minimize Transmission among
Healthcare Personnel: Hand Hygiene
C. difficile spores generally resistant to
bactericidal effects of alcohol
Clinical correlation of CDI and alcohol-based
disinfectants?
Several studies have failed to demonstrate an
increase in CDI rates with alcohol-based hand
hygiene
No studies have found a decrease in CDI rates with
soap and water


1. Gordin FM, et al. Infect Control Hosp Epidemiol. 2005;26:650-653.
2. Boyce JM, et al. Infect Control Hosp Epidemiol. 2006;27:479-483.
3. Knight N, et al. Am J Infect Control 2010;38:523-528.
4. Vernaz N, et al. J Antimicrob Chemother. 2008; 62:601-607.
5. Kaier K, et al. Infect Control Hosp Epidemiol. 2009;30:346-353.
Minimize Transmission Among Healthcare
Personnel: Contact Precautions
Patients with CDI placed in private rooms
when possible
Full barrier precautions (gown and gloves) for
contact with CDI patient
Use of dedicated patient care items and
equipment
1. Dubberke ER, et al. Infect Control Hosp Epidemiol. 2008;29:S81-S92.
2. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
Minimize Transmission among
Healthcare Personnel: Use of Gloves
Four wards randomized
Intervention
Education: gloves when
handling body substances
(stool)
Gloves placed at bedside
Reduction in CDI and
colonization on glove
wards

P = 0.015
Johnson S, et al. Am J Med. 1990;88:137-140.
Minimize Transmission from
Environment: Disinfection
Use of sodium hypochlorite (at least 5,000 ppm
available chlorine) for environmental contamination,
during outbreak areas
Inconsistent efficacy in endemic settings
Areas in question:
Concentration of bleach? [Available chlorine: 5,000 ppm
(1:10), 1,000 ppm, or 500ppm]
Where to clean? [CDI rooms only, all rooms, entire ward]
How frequent? [Daily or upon discharge]
How to implement? [Mix fresh daily, premixed, or
prepackaged wipes; wipe or spray]
Perez. J, et al. Am J Infect Control. 2005;33:320-325.
Minimize Transmission by
Environment: Bleach Disinfection
Mayfield JL, et al. Clin Infect Dis. 2000;31:995-1000.
Reduce Risk of CDI Acquisition:
Antimicrobial Stewardship
Reduce use of high
risk antimicrobials
Reduce unnecessary
antimicrobial use
Effective in outbreak
and non-outbreak
settings
1. Valiquette L. Clin Infect Dis. 2007;45:S112-121; with permission.
2. Fowler S. J Antimicrob Chemother. 2007;59:990-995.
Bundles for CDI
Prevention and
treatment bundles
In response to increased
CDI incidence and
severity
Prevention bundle
stressed adherence to
existing policies
Abbett SK, et al. Infect Control Hosp Epidemiol. 2009; 30:1062-1069.
Reduction in CDI after Bundle
CDI incidence decreased from 1.10 to 0.66 cases /
1,000 patient days (P<0.001)
Data on compliance with policies before or after
bundle lacking
Unclear what parts of bundle were effective
Abbett SK, et al. Infect Control Hosp Epidemiol. 2009; 30:1062-1069.
CDI: Future Direction
Optimal diagnostic algorithm for CDI
Prompt recognition of severe CDI
Validation of risk-stratified treatment for CDI
Expanding armamentarium for CDI (both
antibiotic and non-antibiotic approaches)
Successful implementation of CDI bundle of
infection control measures