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Sherif Ibrahim, MD, MPH


Division of Infectious Disease Epidemiology

 Review microbiology and epidemiology of
Clostridium difficile

 Review risk factors for transmission

 Discuss testing methods and diagnosis

 Review surveillance for C. difficile

 Discuss preventive strategies

 Gram positive spore forming bacillus (rods)
 Obligate anaerobe
 Part of the GI Flora in
◦ 1-3% of healthy adult
◦ 70% of children < 12 months
 Some strains produce toxins A & B
 Toxins-producing strains cause C. diff Infection
 CDI ranges from mild, moderate, to severe and
even fatal illness

 A common cause of nosocomial antibiotic-
associated diarrhea (AAD)
 Most common infectious cause of acute diarrheal
illness in LTCFs
 The only nosocomial organism that is anaerobic
and forms spores (survive> 5 months and hard to
 Pathogenesis is mainly due to toxins production
 Infective dose is < 10 spores

 Fecal – oral route
◦ Contaminated hands of healthcare workers
◦ Contaminated environmental surfaces.
 Person to person in hospitals and LTCFs
 Reservoir:
◦ Human: colonized or infected persons
◦ Contaminated environment
 C. diff spores can survive for up 5 months on
environmental surfaces.

no symptoms


C Diff exposure & acquisition

Admitted to
healthcare facility Infected

 Exposure to antimicrobials (prior 2-3 months)
 Exposure to healthcare (prior 2-3 months)
 Infection with toxogenic strains of C. difficile
 Old age > 64 years
 Underlying illness
 Immunosuppression & HIV
 Chemotherapy (immunosuppression & antibiotic-like
 Tube feeds and GI surgery
 Exposure to gastric acid suppression meds ??

Very commonly related Less commonly related Uncommonly related

Clindamycin Sulfa Aminoglycosides

Ampicillin Macrolides Rifampin
Amoxicillin Carbapenems Tetracycline
Cephalosporins Other penicillins Chloramphincol

 Among symptomatic patients with CDI:

• 96% received antimicrobials within the 14 days before onset
•100% received an antimicrobial within the previous 3 months
 20% of hospitalized patients are colonized with C. diff

 Illness caused by toxin-producing strains of
C. difficile ranges from
◦ Asymptomatic carriers = Colonized
◦ Mild or moderate diarrhea
◦ Pseudo membranous colitis that can be fatal
 A median time between exposure to onset of
CDI symptoms is of 2–3 days
 Risk of developing CDI after exposure ranges
between 5-10 days to 10 weeks

 Watery diarrhea ( > 3 unformed stools in 24 or
fewer consecutive hours)
 Loss of appetite
 Fever
 Nausea
 Abdominal pain and cramping

Test Advantage Disadvantage
Testing Enzyme • Detects toxin A or both A & B Less sensitive
Toxins immuno-assay • Rapid (same day) 63-94%

Organism Glutamate Rapid, sensitive, may Not specific, toxin

ID Dehydrogenase prove useful as a triage or testing required to
screening tool verify diagnosis
PCR Rapid, sensitive, detects Expensive
presence of toxin gene Special equipment

Stool culture Most sensitive test False-positive

available when performed results if isolate is not
appropriately tested for toxin
labor-intensive; requires
48–96 hours

 Testing should be performed only on diarrheal
 Testing asymptomatic patients is not indicated
 Testing for cure is not recommended

 For clinical use: two-step testing uses initially EIA
detection of GDH for screening followed by
cytotoxicity assay or toxigenic culture for
 Gold standard is stool culture followed by toxigenic
culture assay
 Toxin is very unstable, degrades at room
temperature, and undetectable within 2 hours (false
negative results)

 Case definition
Clinical: presence of diarrhea AND
Laboratory: A stool test result positive for toxigenic C.
diff or its toxins OR colonoscopic / histopathologic
findings demonstrating evidence of pseudomembranes

SHEA- ADSA, 2010

 Surveillance definitions of CDI by time of onset:
 Healthcare facility (HCF)-onset, HCF-associated CDI  Onset >
48 hrs of admission
 Community-onset, HCF-associated CDI  Onset in the
community or within 48 hours of admission and within < 4 weeks
of the last discharge
 Community-associated CDI  Onset in the community but within
more that 12 weeks of last discharge

SHEA- ADSA, 2010

Admission Discharge

2d < 4 weeks 4-12 weeks > 12 weeks

HO CO-HCFA Indeterminate CA-CDI

Day 1 Day 4 Time

HO: Hospital (Healthcare)-Onset

CO-HCFA: Community-Onset , Healthcare Facility-Associated
CA: Community-Associated

* Depending upon whether patient was discharged within previous 4 weeks

Onset defined in NHSN by specimen collection date

 At minimum: conduct surveillance for HCF-
onset, HCF-associated to
 detect outbreaks
 monitor patient safety
 Rate of HCF-associated CDI (number of cases
per 10,000 patient-days
 Compare your rates with other facilities
 In outbreaks  stratify rates by patient location
in order to target control measures

2.0 White
Entire US population



1999 2000 2001 2002 2003 2004 2005 2006
*Per 100,000 US standard population
Heron et al. Natl Vital Stat Rep 2009;57(14).
Available at

 Contact Precautions for duration of diarrhea

 Hand hygiene (HH) in compliance with CDC/WHO

 Cleaning and disinfection of equipment and environment

 Laboratory-based alert system for immediate notification

of positive test results

 Educate HCP, housekeeping, admin staff, patients,

families, visitors, about CDI
Tip: Routine identification of colonized patients for infection control
purposes is not recommended and treatment of such identified patients
is not effective

 Extend contact precautions beyond duration of
diarrhea (48 hours)
 Presumptive isolation for symptomatic patients
 Implement soap and water for hand hygiene before
exiting room of a patient with CDI
 Implement universal glove use on units with high CDI
 Use sodium hypochlorite (bleach) - containing agents
for environmental cleaning
 Implement an antimicrobial stewardship program

Core Supplemental
 Gloves/gowns on room  Extend use of contact
entry precautions beyond
 Private room (preferred) or duration of diarrhea
cohort with dedicated  Presumptive isolation
commodes  Universal glove use on
 Dedicated equipment units with high CDI rates
 Maintain for duration of  Intensify assessment of
diarrhea compliance
 Measure compliance

 Identify and remove environmental sources of C. diff

 Routine environmental screening for C. diff is not


 Ensure that environmental cleaning is adequate and

high-touch surfaces are not being overlooked

 IF possible, use the environmental markers to

assess cleaning after education