Transcript Evolving Challenges in Clostridium difficile Infection

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
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–
–
–
–
–
–
–
–
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
348,950
138,954
Healthcare Cost and Utilization Project (HCUP). http://hcupnet.ahrq.gov.
CDI Epidemiology
• Severity of CDI appears to be increasing1-2
– Increased morbidity and mortality
• Increased infection in “low-risk” populations1-3
• Emergence of novel, hypervirulent strain now
reported across the US, Canada, and Europe
– Increased toxin production and sporulation may
contribute to widespread disease4,5
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-clinicalchallenges/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
Denève 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
Denève C, et al. Int J Antimicrob Agents. 2009;33:S24-S28.
Economic Burden of CDI
Study
Patient
Population
Kyne 19981
-2 medical
wards
-40 cases
O’Brien 20002
-MA discharge
database
-3,692 cases
Dubberke 20033
-Nonsurgical
patients
-439 cases
Per-Episode
Costs
Increase in
Length of Stay
US Cost
$3,669
3.6 days
$1.1 billion
Primary
diagnosis:
$10,212
Secondary
diagnosis:
$13,675
3.0 days
$3.2 billion
$2,454 –
$3,240
2.8 days
$1.3 billion
1. Kyne L, et al. Clin Infect Dis. 2002;34:346-353.
2. O’Brien 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 disease1
• Phase 3 study of fidaxomicin and vancomycin linked
concomitant antibiotics with lower rates of global
cure (initial cure without recurrence at 30d):2
Patients, %
P<0.001
GLOBAL CURE
FDX
VAN
Total
FDX
VAN
1. Garey KW, et al. J Hosp Infect. 2008;70:298-304. 2. Johnson S, et al. DDW 2010; Abstract 711c.
Total
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
– 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
Serum IgM
Median serum concentrations of
antibody against toxin A
Serum IgG
• 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
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)
More sensitive than
enzyme immunoassay
Labor intensive; requires 24–48
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 falsepositive results if isolate is not
tested for toxin; labor-intensive;
requires 48–96 hours for results
Tissue culture
cytotoxicity
Organism identification
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
Clinical scenario
Supportive clinical data
Recommended treatment
Mild to moderate
Leukocytosis (WBC < 15,000 Metronidazole 500 mg 3
cells/uL) or SCr level < 1.5
times per day PO for 10times premorbid level
14 days
Severe
Leukocytosis (WBC ≥ 15,000 Vancomycin 125 mg 4
cells/uL) or SCr level ≥ 1.5
times per day PO for 10times premorbid level
14 days
Severe, complicated
Hypotension or shock, ileus, Vancomycin 500 mg 4
megacolon
times per day PO or by
nasogastric tube plus
metronidazole 500 mg IV
q 8 hrs
Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.
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
First recurrence
Recommended treatment
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 data1-3
• 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 regimen4,5
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
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.
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 promising2,3
– “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
CDI1
– 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 resistance2
– 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
metronidazole1
Time to resolution of symptoms
– 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
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.
P=0.55
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
• Inconclusive evidence regarding the benefit of
intravenous immunoglobulin (IVIG) in CDI
Study
Type
N
Population
Potential Benefit
of IVIG?
Yes
No
McPherson 20061
Retrospective
Review
14
Severe,
refractory,
recurrent CDI
Abougergi 20102
Observational
study and
literature review
21
Severe C. difficile
colitis
X
Wilcox 20043
Descriptive study
5
Intractable,
severe C. difficile
diarrhea
X
O’Horo 20094
Systematic
review
--
CDI
inconclusive
Hassoun 20075
Case review
1
Severe C. difficile
colitis
X
X
inconclusive
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. O’Horo 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
100
††
91.7 90.6 91.1
– Equivalent cure
80
70
rates were
60
achieved with
50
†
40
FDX and VAN
30
– Significantly fewer 2010 198 213 411
23 46 69
172 154 326
216 235 451
180 182 362
216 235 451
recurrences were 0 FDX VAN Total
FDX VAN Total
FDX VAN Total
Clinical Cure
Recurrence
Global cure
seen after FDX
FDX, fidaxomicin; VAN, vancomycin; *P = NS; P = .002; P < .001
(50% less than VAN)
resulting in higher global cures
90
79.6
72.3
65.5
25.3
19.1
12.8
†
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)
Clindamycin
Day 1
Day 2
M3
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
J9
J9
Control
XX -dead
Day..
Potential Future CDI Therapies:
C. difficile Toxoid Vaccine
• Seroconversion rates in young vs elderly healthy
subjects (50 μg dose)
100%
100
75%
75
50
25
Study 009
≥65 yrs; median age = 70
Seroconversion Rate (%)
Seroconversion Rate (%)
Study 008
18–55 yrs; median age = 26
100
80
10
20
30
40
50
60
70
75%
60
40
42%
25%
20
0
0
100%
0
80
0
10
20
30
40
Day
Toxin A
Foglia G, et al. Anarobe Society of Americas 2010; Abstract CD 1093.
50
60
70
80
Day
Toxin B
Both toxins
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
Time to CDI recurrence
Lowy I, et al. N Engl J Med. 2010;362:197-205.
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
Decrease in colony counts
compared with no wash
AHR = alcohol
hand rub
AHW = alcohol
hand wipe
Decrease in colony counts
(log CFU/mL)
2.5
2
CFU = colony
forming units
1.5
1
1.8
1.8
1.4
0.5
0
CWS = cold water
soap
** ** *
*0.6
-0.1
-0.5
-1
WWA = warm
water and
antibacterial
WWS = warm
water and soap
WWS
CWS
WWA
AHW
AHR
Hand hygiene method
* 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.
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.
2.
3.
4.
5.
Gordin FM, et al. Infect Control Hosp Epidemiol. 2005;26:650-653.
Boyce JM, et al. Infect Control Hosp Epidemiol. 2006;27:479-483.
Knight N, et al. Am J Infect Control 2010;38:523-528.
Vernaz N, et al. J Antimicrob Chemother. 2008; 62:601-607.
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
Johnson S, et al. Am J Med. 1990;88:137-140.
P = 0.015
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