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Clostridium difficile: An overview


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Title: Clostridium difficile: An overview

Clostridium difficile An overview
  • Lynn M. Carosella RN, BSN, MA,CIC
  • Infection Control Preventionist
  • Scottsdale Healthcare
  • October 25, 2008

  • State three risk factors for C. difficile
  • List three diagnostic tests for C. difficile
  • State two treatment options for CDAD
  • List three infection control measures of CDAD in
    the healthcare setting

Clostridium difficile
  • Anaerobic, spore-forming, gram positive rod
  • Reservoir intestinal tract
  • Transmission via the fecal-oral route

  • Most common reservoirs of C. difficile in
  • Colonized Humans
  • Environmental Surfaces
  • Contaminated Equipment
  • Outside of the Hospital
  • Environment
  • Food Supply

Risk Factors for Clostridium difficile Associated
Disease (CDAD)Antibiotics
  • Exposure to antibiotics causes disruption of
    protective intestinal microflora
  • Excluding aminoglycosides(e.g. Amikacin,
    Gentamicin, Tobramycin) nearly all antimicrobial
    agents have been implicated in CDAD

Risk Factors for Clostridium difficile Associated
Disease (CDAD)Antibiotics
  • Additional studies found that flouroquinolones
    (e.g. Levaquin, Cipro) to be strongly linked to
    CDAD more than any other antimicrobial
  • Multiple antimicrobials and longer therapy
    courses also increases risk
  • Broad-spectrum antimicrobials have more of an
    effect on normal intestinal flora and are more
    likely to lead to CDAD

Risk Factors for Clostridium difficile Associated
Disease (CDAD)
  • Most cases and outbreaks of CDAD occur in health
    care settings
  • Some studies have shown that medical patients are
    at more risk than surgical patients
  • CDAD most common cause of acute diarrheal illness
    in long term care facilities
  • C. difficile colonization in LTCs range from
    4-20 compared to 3 in healthy adults

Risk Factors for Clostridium difficile Associated
Disease (CDAD)Other Risk Factors
  • Age greater than 65 years
  • Severe underlying illness
  • Nasogastric intubation
  • Extended hospital stay
  • Anti-ulcer medications although there is
    conflicting evidence on this point

Mechanism of Action CDAD
  • In order for C. difficile to get a foothold and
    cause illness
  • The intestinal normal flora must be disturbed
    (as with antimicrobial therapy)
  • C. difficile must be ingested
  • Once both of the above occur a person can become
    colonized or develop CDAD
  • It is not well understood why some individuals
    develop disease and others do not

Toxins in Action
  • As C. difficile reproduces in intestinal crypts
    releasing toxins which cause inflammation
  • Toxin A attracts neutrophils and monocytes
  • Toxin B destroys colonic epithelial cells
  • As mucous and cellular debris are expelled into
    the lumen of the large intestine psuedomebranous
    lesions form
  • NAP1 strain of C. difficle produces 16 more times
    Toxin A and 23 more times Toxin B than other
    strains, possibly due to a deletion of a
    regulatory gene
  • The significance of the binary toxin is unknown

Fecal-Oral RouteThe C. difficile organism is
ingested either as the vegetative form or as a
hardy spore. Spores survive a long time in the
environment and can also survive the acidic
stomach.Cleveland Clinic Journal of
Medicine February 2006Medical Illustrator David
Pseudomembrane FormationC.difficile reproduces
in the intestinal crypts, releasing toxins A and
B leading to inflammation. Mucous and cellular
debris are expelled causing pseudomembrane
formation.Cleveland Clinic Journal of Medicine
February 2006Medical Illustrator David Schumick
C. difficile
Photomicrograph of Colonic MucosaIntact Mucosa
on left Damaged Mucosa on rightFrom J. Guarner
MD US Centers for Disease Control and Prevention
Clinical Presentations
  • Toxin production does not necessarily progress to
    disease symptoms
  • Colonization with C. difficile may protect
    against symptomatic disease because immunity
  • No clear cut incubation period from ingestion of
    C. difficile to clinical manifestation of
  • Immediately after beginning antimicrobial therapy
  • Or often there is delayed onset
  • Several weeks after antimicrobial therapy is
  • Clinical presentation is a continuum from
    asymptomatic carriage, diarrhea, colitis,
    pseudomembranous colitis, and toxic megacolon.

Clinical Presentations
  • Mild to Moderate CDAD
  • Non-bloody diarrhea
  • Possible lower abdominal cramping and mild
    abdominal tenderness
  • Leukocytosis
  • Possible fever
  • Systemic symptoms absent
  • BUT
  • Can progress quickly to.

Clinical Presentations
  • Severe CDAD
  • Colitis with more severe symptoms
  • Profuse watery diarrhea
  • Abdominal pain, distention
  • Fever
  • Nausea
  • Dehydration
  • Possible occult blood in stool
  • Pseudomembrane formation, usually distal colon
    occasionally proximal
  • Risk increases for development of paralytic
    ileus, toxic megacolon, sepsis, peritonitis,
    electrolyte imbalance, hypotension, and volume

Reinfection vs. Relapse
  • Often C. difficile associated disease recurs
  • Challenging complication
  • No set view on how to decide whether a second
    episode of CDAD is a relapse or a reinfection.
  • 12 to 24 of patients develop a second episode
    of CDAD within in two months of initial
  • One view defines a reinfection as a return of
    symptoms after 2 months
  • While a relapse is defined as recurrence of
    symptoms within 2 months of initial diagnosis
  • Ad hoc Clostridium difficile Surveillance Working
    Group put forth suggested definitions for
    Community Onset, Healthcare Onset, Community
    Onset, but still indeterminate areas.

Diagnosis of CDAD
  • Suspect in any adult with anti-microbial
    associated diarrhea
  • Test watery or loose stools
  • High rate of colonization in normal stool
    positive result in normal stool proves
    colonization, but not necessarily infection

  • Multiple types of Diagnostic Tests
  • Anaerobic Culture
  • Tissue Cytotoxic Assay
  • Common Antigen
  • Enzyme-linked immunosorbent assay-ELISA-toxin A
  • ELISA-toxin AB
  • Polymerase chain reaction (PCR)
  • Endoscopy

  • Enzyme immunoassays
  • Available in most clinical laboratories, fast
    turn around
  • Usually one negative result enough to rule out
    CDAD, however if there is a strong clinical
    suspicion repeat testing may be warranted
  • However once positive, C. difficile testing
    should not be repeated unless there is a relapse
    after clinically successful therapy

  • Anaerobic Bacterial Culture
  • Least employed method by hospitals
  • More expensive and 72 hour turn around time
  • Detects toxigenic and nontoxigenic strains
  • Culture methods and media not standardized
    variable accuracy
  • Allows for molecular typing of strains, useful in
    an outbreak

  • Endoscopy
  • Used to diagnosis pseudomembranous colitis
  • PCR
  • Highly specific and sensitive
  • Time-consuming, expensive

  • Supportive Care
  • Withdrawal of the implicated antibiotic
  • Avoidance of unnecessary drugs with
    antiperistaltic activity
  • If continued antibiotic treatment is necessary
    agents with a low probability of causing CDAD
    should be used

  • Mild cases may not require treatment other than
    stopping inciting antibiotic
  • For moderate to severe cases the usual first line
    treatments are oral vancomycin or oral
    metronidazole (Flagyl)
  • Oral vancomycin is the only FDA approved drug for
    C. difficile enteric infection
  • Ideal pharmacologic properties for treating an
    organism such as C. difficile
  • The drug is not absorbed which results in high
    levels available to fight the C. difficile

  • CDAD can progress rapidly despite appropriate
  • Patients need to be monitored closely for signs
    of improvement within 1 to 2 days of starting
  • Fever should resolve by the second day and
    diarrhea should resolve within two-five days
  • If disease progresses additional or alternative
    therapies should be considered

Alternative treatments
  • Intracolonic Vancomycin when oral therapy can not
    be given
  • Pulsed or tapered dosing of oral Vancomycin for
    recurrent cases
  • Probiotics such as Saccharomyces boulardii or
    Lactobacillus in conjunction with Vancomycin or
  • NG stool infusion
  • Fecal enemas or stool transplants to replace

Stool Transplant
  • Refractory Clostridium difficile diarrhea C.
    difficile diarrhea that is not responding to oral
    Vancomycin and/or Flagyl therapy, with worsening
    patient status, that could be potentially life
  • Colon Bacteriotherapy The instillation of donor
    stool and saline into the bowel via enema or
    fecal management system. Also, referred to as a
    stool transplant.
  • This is for refractory Clostridium difficile
    only. Cases of Clostridium difficile that are
    responding to antibiotic therapy do not qualify.
  • Assess patient for refractory nature of
    Clostridium difficile disease
  • Has patient had recurrent bouts of Clostridium
  • Is the patient non-responsive to traditional
    antibiotic therapy?
  • How many episodes of diarrhea is patient having
    per day?
  • Has the patient become dehydrated or malnourished
    from recurrent diarrhea?

Stool Transplant
  • Physician Role
  • Discuss risks, benefits, alternatives, and
    likelihood of success of Colon Bacteriotherapy
    with patient and or surrogate. Document
    discussion in Progress Notes. There must be a
    physician order for this therapy.
  • Determine stool donor. Document the name of the
    stool donor in Progress Notes.
  • Preferred stool donors
  • Individuals who had intimate contact with patient
    (spouse or significant partner)
  • Family household member
  • Any other healthy donor

Stool Transplant
  • Donor characteristics
  • Appears clinically well
  • Is without fever
  • Stool is formed and grossly non-bloody
  • Has not been on antibiotics for last month
  • Consider donor screening
  • Blood HIV rapid screen, hepatitis A, B and C
  • Stool O P, Crypto Giardia, hemoccult
  • Consider recipient screening for HIV, Hepatitis
    A, B, and C
  • Proceed with transplant without waiting for
    Hepatitis test results.
  • Consider discontinuing Flagyl and Vancomycin, to
    avoid killing the transplanted normal flora.
    Consider discontinuing other antibiotics, if not
    absolutely indicated.
  • Order stool for Clostridium difficile toxin assay
    24 hours after the transplant is performed. If
    this follow-up toxin assay is still positive,
    consider repeating the stool transplant that day.

  • Stool Transplant Procedure continued
  • Make arrangements for the donor to come in to
    unit at pre-arranged time, prepared to provide
    stool specimen.
  • Instruct donor to defecate into the container,
    apply the lid and present immediately to the
  • Prepare stool specimen in soiled utility.
  • If donor testing is ordered, send a small portion
    of stool for donor testing.
  • Remove wing holder from specimen container and
    add approximately 250 ml of the normal saline.
  • Use the flat end of the syringe plunger to mash
    the stool to mix it into a solution
  • Pour the mixture through the strainer and into
    the graduate/bucket.
  • Repeat steps e. through g. in order to get into
    solution as much bacteria as possible from the
  • For use with enema bag, pinch rim of bucket,
    carefully pour contents of bucket into enema bag,
    and add remainder of 1000 ml bottle of normal
    saline irrigant. Prime tubing.

Stool Transplant Procedure continued
  • For use with fecal management system, introduce
    the liquid via the irrigation port by the
    syringeful until the bucket is empty.
  • Place protective pads under the patient and
    position patient in left lateral decubitus
  • Lubricate enema tip and insert into rectum just
    proximal to internal sphincter.
  • Hold the enema bag slightly above the level of
    the buttocks to prevent the column of liquid from
    running into the rectum too quickly. If the bag
    is below the patient, the liquid will run back in
    to the bag.
  • Slowly deliver the enema into the patients
    rectum and allow to remain in the colon for as
    long as possible for a minimum of 20 minutes.
  • Properly discard used equipment.
  • Wash hands with soap and water. Alcohol-based
    hand foams and gels do not kill the Clostridium
    difficile spores.
  • Document.

Infection Control
  • Patient Isolation in a single room, preferably
    with a bathroom
  • Contact Precautions
  • Dedicated Equipment
  • Vigilant Hand Hygiene consisting of hand washing
    with friction for at least 15 seconds to remove
    Clostridia spores
  • May follow with alcohol based hand gel
  • Chlorhexidine soap in outbreaks
  • Do not treat colonization as can lead to
    increased rate of carriage
  • Formulary Control

Environmental Cleaning
  • Commonly used hospital approved disinfectants
    i.e. quaternary ammonium compounds are not
    sporicidal, but does kill vegetative C. difficile
  • FDA labeling change
  • Friction cleaning-elbow grease
  • Use of bleach (sodium hypochlorite) has had
    inconsistent results
  • Has been used in outbreaks
  • No EPA approved disinfectant for environmental
    surfaces that kills spores shortest exposure
    time for an EPA-registered sporocide (6,000 ppm
    of available chlorine) is six hours (immersion)
  • Has to be used correctly

How clean is that toilet seat????
Appearance to the naked eye-regular light Heavy
residual visualized with UV light
Gotcha! Ultra Violet Light -Residual
Moderate Residual Post Clean (Left) Light
Residual Post Clean (Right)
Hospital vs. Community Associated
  • Timeline

Point Prevalence Study
  • Point Prevalence Study
  • Nationwide study to evaluate the incidence and
    prevalence of C. difficile
  • Results should be published by the end of the year

  • Leading cause of antibiotic associated diarrhea
  • Incidence and severity of CDAD has increased
  • Epidemiology is changing
  • Transmission occurs primarily in healthcare
    facilities via the fecal-oral route
  • One should avoid unnecessary and inappropriate
    antimicrobial therapy
  • Important principles in treating CDAD include
    stopping the offending antimicrobial agent and
    following the patient closely
  • Environmental control/cleaning remains
  • Potential to move into the community

  • Sunenshine,R, McDonald LC. Clostridium
    difficile-associated disease New challenges from
    an established pathogen. Cleveland Clinic Journal
    of Medicine. February 2006 73187-197.
  • Miller, A, Smith, K, et al. Clostridium
    difficile-Associated Diarrhea A Review and
    Update on Changes in Disease Virulence and
    Treatment Response. PT. September 2006 31
  • Bartlett, J. Narrative Review The New Epidemic
    of Clostridium difficile-Associated Enteric
    Disease. Annals of Internal Medicine. November
    2006 145758-764.
  • Is New Toxic C. Diff Strain Emerging in the Food
    Supply? Hospital Infection Control Weekly Alert.
    January 17, 2007.
  • Dial, S, Delaney, A, et al. Use of Gastric
    Acid-Suppressive Agents and the Risk of
    Community-Acquired Clostridium difficile-Associate
    d Disease. JAMA. December 2005 294 2989-2995.

  • Gerding, D. New Definitions Will Help, but
    Cultures are Critical for Resolving Unanswered
    Questions About Clostridium difficile. Infection
    Control and Hospital Epidemiology. February 2007
  • Provincial Infectious Diseases Advisory Committee
    (PIDAC). Best Practices for the Management of
    Clostridium difficile in all health care
    settings. December 2004 1-24. (Canadian)
  • National Clostridium difficile Standards Group.
    Report to the Department of Health. February
    2003 1-91. (United Kingdom)
  • McDonald, LC, Coignard, B, et al. Recommendations
    for Surveillance of Clostridium
    difficile-Associated Disease. Infection Control
    and Hospital Epidemiology. February 2007. 28

  • Eckstein, B. et al Reduction of Clostridium
    Difficile and vancomycin
  • resistant Enterococcus contamination of
    environmental surfaces after an intervention to
    improve cleaning methods. BMC Infectious
    Diseases. 761. June 2007.
  • Alfa, M. et al UV-visible marker confirms that
    environmental persistence of Clostridium
    difficile spores in toilets of patients with C.
    difficile associated diarrhea is associated with
    lack of compliance with cleaning protocol. BMC
    Infectious Diseases. 864. May 2008.
  • McMullen, K. et al Use of Hypochlorite Solution
    to Decrease Rates of Clostridium
    difficile-Associated Diarrhea. Infection Control
    and Hospital Epidemiology. 282. February 2007.

  • McMullen, K, Zack, J, et al. Use of Hypochlorite
    Solution to Decrease Rates of Clostridium
    difficile-Associated Diarrhea. Infection Control
    and Hospital Epidemiology. February 2007
  • McFarland, L. Alternative treatments for
    Clostridium difficile disease what really works?
    Journal of Medical Microbiology. 2005 54
  • Sehulster, L, Chinn RY. Guidelines for
    Environmental Infection Control in Health-Care
    Facilities. Recommendations of CDC and the
    Healthcare Infection Control Practices Advisory
    Committee (HICPAC). MMWR Recomm Rep 2003
    52(RR-10) 1-42.
  • Gerding, D. New Insights in the Pathogenesis
    and Risks of Clostridium difficile. Hines VA
    Hospital. Loyola University Chicago Stritch
    School of Medicine. Powerpoint. Available online.
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