CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA

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CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA

• VALERIE FLETCHER M.D.
• INFECTIOUS DISEASES
• SOUTHERN OHIO MEDICAL CENTER
• August 2006

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Introduction

• Clostridium difficile is a Gram-positive
  spore-forming anaerobic bacillus.
• Most common cause of nosocomial diarrhea.
• Rate and severity of C. difficile-associated
  diarrhea (CDAD) increasing.
• New strain of C.difficile with increased
  resistance and virulence identified.

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History

• 1893 first case of pseudomembraneous colitis
  reported as diphtheritic colitis.
• 1935 Bacillus difficile isolated.
• 1970s antibiotic-asociated colitis identified.
• 1978 C. difficile toxins identified in humans.
• 1979 therapy with vancomycin or metronidazole
• 2000 increased incidence and virulence

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Annual CDAD rates for hospitals with gt500 beds
(NNIS 1987 2001)
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(No Transcript)
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Epidemiology

• Present in environment.
• Hospital is major reservoir. Spores can be
  recovered from surfaces for months.
• Spread primarily on hands of HCW.
• Fecal-oral transmission.
• Transmission may occur from asymptomatic
  colonized persons.

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Epidemiology

• Colonizes the colon of up to 3 of healthy
  adults.
• 15 25 of debilitated and antibiotic-treated
  hospitalized adults colonized.
• Toxigenic strains may cause disease in colonized
  patients.
• Implicated in approx. 25 of cases of antibiotic-
  associated diarrhea

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Clinical features

• Mild disease mild abdominal cramping pain.
  - endoscopic findings of diffuse or patchy
  nonspecific colitis.
• Moderate disease fever dehydration nausea
  anorexia malaise profuse diarrhea
  abdominal distention and cramping
  pain. - moderate leukocytosis fecal
  leukocytes. - diffuse patchy colitis
  on endoscopy

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• Severe disease usually profuse diarrhea may be
  little or no diarrhea. -
  abdominal pain - fever
  - volume depletion - marked
  leukocytosis - peritoneal signs
  - radiologic signs include ileus dilated
  colon and edematous colonic mucosa -
  endoscopic findings of adherent yellow plaques

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Complications of CDAD

• Pseudomembraneous colitis
• Toxic megacolon
• Perforation of the colon
• Sepsis
• Death

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Patients at increased risk for disease

• ANTIBIOTIC EXPOSURE
• Gastrointestinal surgery or manipulation
• Long length of stay in healthcare setting
• Infected roommate
• Co-morbid illnesses
• Immunosuppression
• Advanced age
• Proton-pump inhibitors and H2-blockers

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Predictors of Severe Disease

• Leukocytosis gt 20000
• Increased creatinine above the baseline

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Traditional list of Antibiotics associated with
CDAD
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Laboratory Diagnosis

• Stool culture
• Latex agglutination to detect antigen in stools
• Tissue culture assay for cytotoxicity of toxin B
• Enzyme-linked immunosorbent assay (ELISA) for
  toxins A and B

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A new strain of C. difficile (NAP-1)

• Toxinotype III
• Unsuppressed production of toxins A and B
• Associated with presence of binary toxin.
• Increased resistance to clindamycin and
  fluoroquinolones.
• Potential for increased complications and adverse
  outcome.

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States with the North American Pulsed Field Type
1 strain of C. difficile confirmed by CDC as of
May 15 2006 (N17)
DC
HI
PR
AK
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Rate of antibiotic resistance in 91 C. difficile
isolates from a Pittsburg hospital that
experienced a large CDAD outbreak beginning
January 2000
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The risk of CDAD and antibiotic use in a study of
1703 patients from 12 Canadian hospitals
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Number of inpatients tested and percentage of
stools positive for Clostridium difficile
toxin at SOMC 2004 - 2006
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Number of positive Clostridium difficile toxin
tests SOMC laboratory 2003 -2006
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CDAD - SOMC 2006

• 114 patients had C. difficile toxin detected in
  stools between Jan 2006 June 2006.
• 46 charts were available for review.
• 31 (67) patients were female.
• 2 (4) patients had recurrent CDAD.
• 13 (28) patients did not receive a
  fluoroquinolone during or immediately before
  admission.

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Antibiotics associated with CDAD - SOMC 2006
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Ceftriaxone and Levofloxacin use SOMC Jan
Aug 2006
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Proton Pump Inhibitors H2-blockers and
C.difficile toxin detection SOMC 2006
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Management

• Enhanced infection control measures.
• Targeted antibiotic restriction
• Appropriate antibiotic therapy
• Adjunctive therapy probiotics IVIG toxin
  binders

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• Surgery
• Avoid antiperistaltic and opiate drugs.
• Experimental therapy rifaximin tolevamar
  corticosteroids vaccine monoclonal antibodies
  to toxins A and B non-toxigenic Cdifficile

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Antibiotic Therapy

• Oral therapy vancomycin metronidazole
• Unable to tolerate oral therapy IV
  metronidazole vancomycin via NG tube or enema.
• Vancomycin rifampin
• Less frequently used Bacitracin fusidic acid

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Antibiotic therapy for CDAD
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Indications for Vancomycin therapy

• No response to metronidazole
• Metronidazole intolerance
• Pregnancy and child lt 10 yrs
• Severe/fulminant CDAD

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Conclusion

• Increasing numbers and severity of CDAD.
• Active surveillance recommended.
• Early diagnosis and treatment are important for
  reducing severe outcome.
• Judicious use of antibiotics may reduce incidence
  of CDAD
• Strict infection control practices essential.