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CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA       Pseudomembranous Colitis              Dr.T.V.Rao MD                 Dr.T.V...
Clostridium difficile• Clostridium difficle (Greek cluster  spindle, and Latin difficle difficult), is  a species of Gram-...
Introduction• Clostridium difficle is a Gram-positive,  spore-forming anaerobic bacillus.• Most common cause of nosocomial...
History• 1893 – first case of pseudomembranous  colitis reported as diphtheritic colitis.• 1935 – “Bacillus difficle” isol...
Recent Developments• C difficle first described 1935 gram-positive anaerobic  bacillus• “difficult clostridium”-difficult ...
Introduction• Clostridium difficile is a Gram-  positive, spore-forming anaerobic  bacillus.• Most common cause of nosocom...
C.difficile• Clostridium difficile, often  called C. difficile or "C. diff,"  is a bacterium that can  cause symptoms rang...
Epidemiology• Present in environment.• Hospital is major reservoir. Spores can be  recovered from surfaces for months.• Sp...
Epidemiology• Colonizes the colon of up to 3% of healthy  adults.• 15 – 25% of debilitated and antibiotic-treated  hospita...
The antibiotics most likely to          cause diarrhea• Cephalosporins, such as cefixime (Suprax) and  cefpodoxime (Vantin...
Other predisposing factors• Previously experienced antibiotic-associated  diarrhea while taking an antibiotic medication• ...
Source of Infection• C. difficle bacteria can be found throughout  the environment — in soil, air, water, and  human and a...
Pathogenesis• Disruption of normal  colonic flora• Colonisation with C.  difficle• Production of toxin A  +/- B• Mucosal i...
Pathogenesis• Microflora of gut:   – 1012 bacteria/gram   – 400-500 species   – colonisation resistance• Transmission -  f...
Disruption of protectivecolonic flora (AB or AN)      Colonization with toxigenic C. difficle      by fecal-oral transmiss...
Clinical features• Mild disease – mild abdominal cramping pain.               - endoscopic findings of diffuse or  patchy,...
Clinical Manifestations• Fulminant colitis:  –   Rare, 2-3% of patients, esp elderly  –   Serious: ileus, perforation, meg...
Dr.T.V.Rao MD   18
Severe disease• Severe disease – usually profuse diarrhea, may  be little              or no diarrhea.                    ...
Complications of CDAD• Pseudomembranous  colitis• Toxic mega colon• Perforation of the  colon• Sepsis• Death              ...
Patients at increased risk for disease•   ANTIBIOTIC EXPOSURE•   Gastrointestinal surgery or manipulation•   Long length o...
Predictors of Severe Disease• Leukocytosis  > 20,000• Increased  creatinine  above the  baseline                 Dr.T.V.Ra...
Traditional list of Antibiotics associated with                       CDAD       MORE FREQUENT                            ...
DIAGNOSIS• Endoscopy (pseudomembranous  colitis)• Culture• Cell culture cytotoxins test• ELISA toxin test• PCR toxin gene ...
Laboratory Diagnosis• Stool culture• Latex agglutination to  detect antigen in stools• Tissue culture assay for  cytotoxic...
A new strain of C. difficle (NAP-1)• Toxin type III• Unsuppressed production of toxins A and  B• Associated with presence ...
Management• Enhanced infection  control measures.• Targeted antibiotic  restriction• Appropriate antibiotic  therapy• Adju...
Important supporting approaches• Surgery• Avoid ant peristaltic and opiate  drugs.• Experimental therapy – rifaximin,  tol...
Antibiotic Therapy• Oral therapy –  Vancomycin, metronidazole• Unable to tolerate oral therapy – IV  metronidazole, Vancom...
Indications for Vancomycin therapy• No response to  metronidazole• Metronidazole  intolerance• Pregnancy and child  < 10 y...
CDAD continues to be a Important Topic in                Clinical Practice• Increasing numbers and severity of  CDAD.• Act...
• Programme created by Dr.T.V.Rao MD       for Medical and Health Care  Professionals in the Developing World             ...
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Clostridium difficile associated diarrhea

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Clostridium difficile associated diarrhea

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Transcript of "Clostridium difficile associated diarrhea"

  1. 1. CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA Pseudomembranous Colitis Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Clostridium difficile• Clostridium difficle (Greek cluster spindle, and Latin difficle difficult), is a species of Gram-positive bacteria of the genus Clostridium that causes diarrhea and other intestinal disease when competing bacteria are wiped out by antibiotics. Dr.T.V.Rao MD 2
  3. 3. Introduction• Clostridium difficle is a Gram-positive, spore-forming anaerobic bacillus.• Most common cause of nosocomial diarrhea.• Rate and severity of C. difficle-associated diarrhea (CDAD) increasing.• New strain of C.difficile with increased resistance and virulence identified. Dr.T.V.Rao MD 3
  4. 4. History• 1893 – first case of pseudomembranous colitis reported as diphtheritic colitis.• 1935 – “Bacillus difficle” isolated.• 1970s – antibiotic-asociated colitis identified.• 1978 – C. difficle toxins identified in humans.• 1979 – therapy with Vancomycin or metronidazole• 2000 – increased incidence and virulence Dr.T.V.Rao MD 4
  5. 5. Recent Developments• C difficle first described 1935 gram-positive anaerobic bacillus• “difficult clostridium”-difficult to grow in culture• Found in stool specimens from healthy neonates leading to misclassification as a commensal organism• 1970s: “clindamycin colitis” pseudomembranous colitis in hospitalized patients• 1978: C diffficle recognized as causative organism Dr.T.V.Rao MD 5
  6. 6. 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. Dr.T.V.Rao MD 6
  7. 7. C.difficile• Clostridium difficile, often called C. difficile or "C. diff," is a bacterium that can cause symptoms ranging from diarrhea to life- threatening inflammation of the colon. Illness from C. difficile most commonly affects older adults in hospitals or in long term care facilities and typically occurs after use of antibiotic medication Dr.T.V.Rao MD 7
  8. 8. 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. Dr.T.V.Rao MD 8
  9. 9. 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 Dr.T.V.Rao MD 9
  10. 10. The antibiotics most likely to cause diarrhea• Cephalosporins, such as cefixime (Suprax) and cefpodoxime (Vantin)• Clindamycin (Cleocin)• Erythromycin (Erythrocin, E.E.S., others)• Penicillins, such as amoxicillin (Larotid, Moxatag, others) and ampicillin• Quinolones, such as ciprofloxacin (Cipro) and levofloxacin (Levaquin)• Tetracyclines, such as doxycycline (Vibramycin, Periostat, others) and minocycline (Minocin, Solodyn, others) Dr.T.V.Rao MD 10
  11. 11. Other predisposing factors• Previously experienced antibiotic-associated diarrhea while taking an antibiotic medication• Are age 65 or older• Have had surgery on your intestinal tract• Have recently stayed in a hospital or nursing home• Have a serious underlying illness affecting your intestines, such as colon cancer or inflammatory bowel disease Dr.T.V.Rao MD 11
  12. 12. Source of Infection• C. difficle bacteria can be found throughout the environment — in soil, air, water, and human and animal feces. A small number of healthy people naturally carry the bacteria in their large intestine. But C. difficle is most common in hospitals and other health care facilities, where a much higher percentage of people carry the bacteria. Dr.T.V.Rao MD 12
  13. 13. Pathogenesis• Disruption of normal colonic flora• Colonisation with C. difficle• Production of toxin A +/- B• Mucosal injury and inflammation Dr.T.V.Rao MD 13
  14. 14. Pathogenesis• Microflora of gut: – 1012 bacteria/gram – 400-500 species – colonisation resistance• Transmission - faecal/oral – spores• Late log / early stationary phase – toxin production Dr.T.V.Rao MD 14
  15. 15. Disruption of protectivecolonic flora (AB or AN) Colonization with toxigenic C. difficle by fecal-oral transmission Toxin A and B production A/B: Cytoskeletal damage, loss of tight junctions. A: Mucosal injury, inflammation, fluid secretion. Colitis and Diarrhea Dr.T.V.Rao MD 15
  16. 16. 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 Dr.T.V.Rao MD 16
  17. 17. Clinical Manifestations• Fulminant colitis: – Rare, 2-3% of patients, esp elderly – Serious: ileus, perforation, mega colon, death – High fever, chills, marked leukocytosis (>40K) – May not have diarrhea if ileus or mega colon – Risk of perforation w/ sigmoid/colonoscopy – Treatment surgical• Unusual presentations: – Long latency period (1-2months) – Absence of antibiotic exposure Dr.T.V.Rao MD 17
  18. 18. Dr.T.V.Rao MD 18
  19. 19. Severe disease• 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 Dr.T.V.Rao MD 19
  20. 20. Complications of CDAD• Pseudomembranous colitis• Toxic mega colon• Perforation of the colon• Sepsis• Death Dr.T.V.Rao MD 20
  21. 21. 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? Dr.T.V.Rao MD 21
  22. 22. Predictors of Severe Disease• Leukocytosis > 20,000• Increased creatinine above the baseline Dr.T.V.Rao MD 22
  23. 23. Traditional list of Antibiotics associated with CDAD MORE FREQUENT LESS FREQUENTCephalosporins (3rd and 4th generation) Ticarcillin-clavulanateAmpicillin/Amoxicillin MetronidazoleClindamycin FluoroquinolonesOther penicillins RifampinMacrolides 5-FluorouracilTetracyclines MethotrexateTrimethoprim-Sulphmethoxazole Cyclophosphamide Dr.T.V.Rao MD 23
  24. 24. DIAGNOSIS• Endoscopy (pseudomembranous colitis)• Culture• Cell culture cytotoxins test• ELISA toxin test• PCR toxin gene detection Dr.T.V.Rao MD 24
  25. 25. Laboratory Diagnosis• Stool culture• Latex agglutination to detect antigen in stools• Tissue culture assay for cytotoxicity of toxin B• Enzyme-linked Immuno- Sorbant assay (ELISA) for toxins A and B Dr.T.V.Rao MD 25
  26. 26. A new strain of C. difficle (NAP-1)• Toxin type 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. Dr.T.V.Rao MD 26
  27. 27. Management• Enhanced infection control measures.• Targeted antibiotic restriction• Appropriate antibiotic therapy• Adjunctive therapy – probiotics, IVIG, toxin binders Dr.T.V.Rao MD 27
  28. 28. Important supporting approaches• Surgery• Avoid ant peristaltic and opiate drugs.• Experimental therapy – rifaximin, tolevamar, corticosteroids, vaccine, monoclonal antibodies to toxins A and B, non-toxigenic C,difficile Dr.T.V.Rao MD 28
  29. 29. 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, fluidic acid Dr.T.V.Rao MD 29
  30. 30. Indications for Vancomycin therapy• No response to metronidazole• Metronidazole intolerance• Pregnancy and child < 10 yrs.• Severe/fulminant CDAD Dr.T.V.Rao MD 31
  31. 31. CDAD continues to be a Important Topic in Clinical Practice• 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. Dr.T.V.Rao MD 32
  32. 32. • Programme created by Dr.T.V.Rao MD for Medical and Health Care Professionals in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 33
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