IC I LE

D I FF
I DI U M D I )
O S TR O N ( C
CL E C T I
IN F
BY
DR. MARWA MAHMOUD ABDELLATIEF
GASTROENTEROLOGY SPECIALIST
 MICROBIOLOGY

 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)
 CDI RANGES FROM MILD, MODERATE, TO SEVERE AND EVEN FATAL ILLNESS
 BACKGROUND

• 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 DESTROY)
• PATHOGENESIS IS MAINLY DUE TO TOXINS PRODUCTION
• INFECTIVE DOSE IS < 10 SPORES
IMPACT
 TRANSMISSION

• 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.

Step 1-
PATHOGENESIS
Ingestion
of spores
transmitted
from other Step 2- Germination
patients into growing Step 4 . Toxin B & A
(vegetative) form production leads to colon
damage +/- pseudomembrane
Step 3 - Altered lower
intestine flora (due to
antimicrobial use)
allows proliferation of
C. difficile in colon
 Colonized
no symptoms

Antimicrobials

C Diff exposure & acquisition

Admitted to
healthcare facility Infected
Symptomatic
 RISK FACTORS
• 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 ACTIVITIES)
• TUBE FEEDS AND GI SURGERY
• EXPOSURE TO GASTRIC ACID SUPPRESSION MEDS ??
ANTIBIOTICS PREDISPOSING TO CDI

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
 CLINICAL MANIFESTATIONS

• 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
 SYMPTOMS

• WATERY DIARRHEA ( > 3 UNFORMED STOOLS IN 24 OR FEWER CONSECUTIVE

HOURS)

• LOSS OF APPETITE

• FEVER

• NAUSEA

• ABDOMINAL PAIN AND CRAMPING

TESTING
 BEST STRATEGY FOR C. DIFFICILE TESTING
• TESTING SHOULD BE PERFORMED ONLY ON DIARRHEAL STOOL

• 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
CONFIRMATION

 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)
 TREATMENT

EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTION RECOMMENDATIONS

INCLUDE THE FOLLOWING 
• NONEPIDEMIC, NONSEVERE CDI CLEARLY INDUCED BY ANTIBIOTIC USE, WITH NO
SIGNS OF SEVERE COLITIS >> IT MAY BE ACCEPTABLE TO STOP ANTIBIOTIC
TREATMENT AND OBSERVE THE CLINICAL RESPONSE FOR 48 HOURS.
• ANTIBIOTIC TREATMENT IS RECOMMENDED FOR ALL EXCEPT VERY MILD CASES
ACTUALLY TRIGGERED BY ANTIBIOTIC USE; SUITABLE TREATMENTS INCLUDE
• METRONIDAZOLE
• VANCOMYCIN
• FIDAXOMICIN.
• MILD/MODERATE DISEASE >> ORAL METRONIDAZOLE (500 MG 3 TIMES DAILY
FOR 10 DAYS) IS RECOMMENDED AS THE INITIAL TREATMENT.
• IN PATIENTS FOR WHOM ORAL TREATMENT IS INAPPROPRIATE, FIDAXOMICIN MAY BE
USED; SPECIFIC INDICATIONS INCLUDE FIRST-LINE TREATMENT IN PATIENTS WITH
RECURRENCE OR AT RISK FOR RECURRENCE.

• SEVERE CDI >> VANCOMYCIN (125 MG 4 TIMES DAILY FOR 10 DAYS; MAY BE
INCREASED TO 500 MG 4 TIMES DAILY) OR FIDAXOMICIN (200 MG TWICE DAILY
FOR 10 DAYS).
• USE OF FIDAXOMICIN IS NOT SUPPORTED IN LIFE-THREATENING CDI.
• USE OF ORAL METRONIDAZOLE IN SEVERE OR LIFE-THREATENING CDI IS
DISCOURAGED.
• FECAL TRANSPLANTATION IS RECOMMENDED FOR MULTIPLE RECURRENT CDI.
• FOR PATIENTS WITH COLONIC PERFORATION AND/OR SYSTEMIC
INFLAMMATION AND DETERIORATING CLINICAL CONDITION DESPITE
ANTIBIOTIC TREATMENT, TOTAL ABDOMINAL COLECTOMY OR DIVERTING LOOP
ILEOSTOMY COMBINED WITH COLONIC LAVAGE IS RECOMMENDED.
• ADDITIONAL MANAGEMENT MEASURES INCLUDE
• DISCONTINUING UNNECESSARY ANTIMICROBIAL THERAPY,
• ADEQUATE REPLACEMENT OF FLUIDS AND ELECTROLYTES,
• AVOIDING ANTIMOTILITY MEDICATIONS
• REVIEWING THE USE OF PROTON PUMP INHIBITORS.
 SURVEILLANCE: CASE DEFINITION

• 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
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
TIME LINE FOR SURVEILLANCE DEFINITIONS
OF CDI
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
 AGE-ADJUSTED DEATH RATE* FOR
ENTEROCOLITIS DUE TO C. DIFFICILE, 1999–
2006
2.5
Male
Female
2.0 White
Black
Entire US population
1.5
Rate

1.0

0.5

0
1999 2000 2001 2002 2003 2004 2005 2006
Year
MORTALITY DUE TO C. DIFFICILE INFECTION PER
100,000 POPULATION, MASSACHUSETTS
A 31 YO 14 WEEKS PREGNANT WITH TWINS WENT TO A LOCAL ED COMPLAINING OF 3 WEEKS OF
INTERMITTENT DIARRHEA, THEN 3 DAYS OF CRAMPING AND WATERY, BLACK STOOLS 4-5 TIMES/DA
STOOLS SPECIMENS TESTED POSITIVE FOR C. DIFFICILE TOXIN AND SHE WAS ADMITTED, TREATED
METRONIDAZOLE AND DISCHARGED
HISTORY OF TRIMETHOPRIM-SULFAMETHOXAZOLE EXPOSURE FOR A URINARY TRACT INFECTION
ABOUT 3 MONTHS BEFORE ADMISSION
READMITTED THE NEXT DAY FOR 18 DAYS WITH SEVERE COLITIS AND WAS TREATED WITH
METRONIDAZOLE, CHOLESTYRAMINE, AND ORAL VANCOMYCIN, IMPROVED AND DISCHARGED
HOME
4 DAYS LATER SHE WAS READMITTED WITH DIARRHEA AND HYPOTENSION, HAD A SPONTANEOUS
ABORTION
DESPITE AGGRESSIVE TREATMENT INCLUDING A SUBTOTAL COLECTOMY, INTUBATION, AND
INOTROPIC MEDICATION, THE PATIENT DIED ON THE THIRD HOSPITAL DAY.
HISTOPATHOLOGIC EXAMINATION OF THE COLON DEMONSTRATED MEGACOLON WITH EVIDENCE
OF PSEUDOMEMBRANOUS COLITIS.
 ANTIMICROBIAL STEWARDSHIP

• REGARDLESS OF SETTING, ~ 50% ANTIBIOTIC USE IS “INAPPROPRIATE”

• THE BEST CDI PREVENTATIVE MEASURE
• DECREASE IN NUMBER OF PATIENTS AT RISK (SUSCEPTIBLE)
• DECREASE IN NUMBER OF PATIENTS WITH CDI (RESERVOIRS)
• RECOMMENDATIONS:
MINIMIZE THE FREQUENCY AND DURATION OF ANTIMICROBIAL
THERAPY
DECREASE THE NUMBER OF ANTIMICROBIAL AGENTS PRESCRIBED,
TARGETED ANTIMICROBIALS SHOULD BE BASED ON THE LOCAL
EPIDEMIOLOGY AND THE C. DIFFICILE STRAINS
RESTRICT THE USE OF CEPHALOSPORIN AND CLINDAMYCIN
AUDIT AND FEEDBACK TARGETING BROAD-SPECTRUM ANTIBIOTICS
 PREVENTION STRATEGIES: CORE

• 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
 PREVENTION STRATEGIES: SUPPLEMENTAL

• 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 RATES
• USE SODIUM HYPOCHLORITE (BLEACH) - CONTAINING AGENTS FOR
ENVIRONMENTAL CLEANING
• IMPLEMENT AN ANTIMICROBIAL STEWARDSHIP PROGRAM
 PREVENTIVE STRATEGIES:
CONTACT PRECAUTIONS
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
 PREVENTIVE STRATEGIES:
HAND HYGIENE
CORE SUPPLEMENTAL
• HH BASED ON CDC OR WHO • SOAP AND WATER FOR HH
GUIDELINES BEFORE EXITING ROOM OF
• SOAP AND WATER A PATIENT WITH CDI
PREFERENTIALLY IN • INTENSIFY ASSESSMENT OF
OUTBREAK OR ENDEMIC COMPLIANCE
SETTINGS
• MEASURE COMPLIANCE
Conclusion: Spores may be difficult to eradicate even with HH
 PREVENTIVE STRATEGIES:
ENVIRONMENTAL CLEANING
CORE SUPPLEMENTAL
 CLEANING AND DISINFECTION  REASSESS ADEQUACY OF
OF EQUIPMENT AND ROOM CLEANING AND
ADDRESS ISSUES
ENVIRONMENT
 USE SODIUM
 CONSIDER SODIUM HYPOCHLORITE (BLEACH) –
HYPOCHLORITE IN OUTBREAK CONTAINING AGENTS
OR ENDEMIC SETTINGS
 ROUTINELY ASSESS
ADHERENCE TO PROTOCOLS
AND ADEQUACY OF CLEANING
 PREVENTIVE STRATEGIES: SUMMARY

• SURVEILLANCE
• MICROBIOLOGIC IDENTIFICATION
• CONTACT PRECAUTIONS
• HAND HYGIENE
• ENVIRONMENTAL CLEANING
• ANTIMICROBIAL STEWARDSHIP
• EDUCATION  HCWS, PATIENTS, VISITORS, FAMILIES
• ADMINISTRATIVE SUPPORT
 RESOURCES
SHEA/IDSA Compendium of Recommendations

Prevention of Clostridium difficile Infection (CDI) Massachusetts CDI Prevention

Collaborative
Carolyn Gould, MD MSCR
L. Cliff McDonald, MD
 O U
K Y
AN
T H