Clostridium difficile: An overview

1
Clostridium difficile An overview

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

2
Objectives

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

3
Clostridium difficile

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

4
Transmission

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

5
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

6
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

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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

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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

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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

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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

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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
Schumick
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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
Pseudomembrane
Toxins
Monocyte
Neutrophil
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Photomicrograph of Colonic MucosaIntact Mucosa
on left Damaged Mucosa on rightFrom J. Guarner
MD US Centers for Disease Control and Prevention
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Clinical Presentations

• Toxin production does not necessarily progress to
  disease symptoms
• Colonization with C. difficile may protect
  against symptomatic disease because immunity
  develops
• No clear cut incubation period from ingestion of
  C. difficile to clinical manifestation of
  symptoms
• Immediately after beginning antimicrobial therapy
• Or often there is delayed onset
• Several weeks after antimicrobial therapy is
  completed
• Clinical presentation is a continuum from
  asymptomatic carriage, diarrhea, colitis,
  pseudomembranous colitis, and toxic megacolon.

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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.

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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
  depletion

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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
  diagnosis.
• 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.

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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

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Diagnosis

• 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

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Diagnosis

• 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

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Diagnosis

• 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

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Diagnosis

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

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Treatment

• 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

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Treatment

• 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
  infection

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Treatment

• CDAD can progress rapidly despite appropriate
  therapy
• Patients need to be monitored closely for signs
  of improvement within 1 to 2 days of starting
  therapy
• 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

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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
  Flagyl
• NG stool infusion
• Fecal enemas or stool transplants to replace
  microflora

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Stool Transplant

• DEFINITIONS
• 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
  threatening.
• 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.
• EXCEPTIONS
• This is for refractory Clostridium difficile
  only. Cases of Clostridium difficile that are
  responding to antibiotic therapy do not qualify.
• ASSESSMENT
• Assess patient for refractory nature of
  Clostridium difficile disease
• Has patient had recurrent bouts of Clostridium
  difficile?
• 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?

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Stool Transplant

• INTERVENTIONS
• 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

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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.

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• 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
  nurse
• 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
  particulates.
• 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.

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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
  position.
• 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.

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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

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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

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How clean is that toilet seat????
Appearance to the naked eye-regular light Heavy
residual visualized with UV light
35
Gotcha! Ultra Violet Light -Residual
Moderate Residual Post Clean (Left) Light
Residual Post Clean (Right)
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Hospital vs. Community Associated

• Timeline

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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

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Summary

• 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
  problematic
• Potential to move into the community

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Questions?
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