Ss16

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Ss16

  1. 1. Clostridium difficile :An Emerging Threat and Update Diagnostic Aryati Infectious Disease ConsultantClinical Pathology Department School of MedicineAirlangga University - Surabaya 1
  2. 2. Clostridium difficile Anaerobic spore-forming bacillus (gram positive anaerobic bacteria) Ubiquitous in nature Prevalent in soil 1935 - First described by Hall and OToole Late 1970’s - Most commonly recognized cause of antimicrobial associated diarrhea  20% - 30% cases Hall I; OToole E (1935).. Am J Dis Child 49: 390 2
  3. 3. Clostridium difficile : Pathogenesis  Fecal oral transmission - Reservoirs: * Contaminated environment * Hands of healthcare personnel * Hospitals & long-term care  Survive gastric acidity  Small intestine – spores germinate into vegetative forms  Large intestine – normal flora disrupted by antibiotics 3 Diagram: Sunenshine et al Clev Clin J Med 2006 73(2) 187-197
  4. 4. Pathogenesis Disruption of normal colonic flora Colonisation with C. difficile Production of toxin A and or toxin B Mucosal injury and inflammation 4
  5. 5. C. difficle : Pathogenesis (cont) C. difficile produces two toxins  Toxin A – enterotoxin  Toxin B – cytotoxin 5Diagram: Sunenshine et al Clev Clin J Med 2006 73(2) 187-197
  6. 6. Toxin A Binds to specific receptors on intestinal epithelium Toxin induced inflammatory process :  neutrophils  inflammatory mediators  fluid secretion  altered membrane permeability  haemorrhagic necrosis 6
  7. 7. Toxin B Binding site not yet identified Depolymerization of filamentous actin  destruction of cell cytoskeleton  rounding of cells 7
  8. 8. Clinical Manifestations Asymptomatic carriage (neonates) Diarrhoea  5-10 days after starting antibiotics  maybe 1 day after starting  may be up to 10 weeks after stopping  may be after single dose  spectrum of disease:  brief, self limiting  cholera-like - 20X/day, watery stool 8
  9. 9. Clinical Manifestations Additional symptoms:  abdominal pain, fever, nausea, malaise, anorexia, hypoalbuminaemia, colonic bleeding, dehydration Acute toxic megacolon  acute dilatation of colon  systemic toxicity  signs of obstruction  high mortality (64%) Colonic perforation 9
  10. 10. C.difficile-Associated Disease (CDAD) Incubation period – not known Healthy colon Diarrhea – characteristic odor Pseudomembranous colitis - First described as a complication by Larson et al in 1978 - Hallmark of CDAD - Bloody diarrhea Pseudo- membranous - Raised whitish-yellow plaques colitis - Unexplained leukocytosis (>10,000/cubic mm ) Larson HE et al (1978). Lancet 1 (8073): 1063–1066. 10
  11. 11. Toxic megacolon Life-threatening acute dilation Characterized by - a dilated colon (megacolon) - Diameter : ≥ 5.5 cm - Fever, abdominal pain, abdominal distension - Radiograph: apparent edema of bowel wall Complications : - Perforation of colon - Sepsis, Shock - Death 11
  12. 12. 12
  13. 13. Endoscopy Endoscopic view of classic C diff–associated pseudomembranous colitis7 Juli 2011 Seminar Clostridium defficile 13
  14. 14. Response to C. difficile associated disease (CDAD) ‘Slide card’ for infection prevention for all staff C. difficile management / treatment guidelines New antimicrobial guidelines Antimicrobial prescribing policy Laboratory diagnostic properly 14
  15. 15. 15
  16. 16. C. difficile : Risk factors Increasing age (elderly people) Severe underlying gastrointestinal diseases Exposure to Antimicrobials Length of stay in hospital Infected patients (vulnerable patients)1.Brown E et al. Infect Control Hosp Epi 1990;11: 283-902. Johnson S, et al Lancet 1990;336:97-1003. M. Delmee Clin Microbiol Infect 2001; 7: 411-416 16
  17. 17. Risk factor : Antimicrobial exposure Major risk factor for disease  Acquisition and growth of C. difficile  Suppression of normal flora of the colon  The risk doubles with longer than three days of antibiotic therapy (risk ratio: 2.28) 1 Clindamycin, penicillins, cephalosporins Fluroquinolones21.Wistrom J et al. J Antimicrob Chemother 2001;47:43-502. Pepin J. Clin Infect Dis. 2005 Nov 1;41(9):1254-60 17
  18. 18. C. difficile – Antibiotic RiskHigh Risk Antibiotics: Medium Risk Antibiotics:Cefotaxime MeropenemCeftriaxone ErtapenemCefalexin Clindamycin (high dose)Cefuroxime Co-amoxiclavCeftazidime TazocinCiprofloxacin ErythromycinMoxifloxacin ClarithromycinClindamycin (low dose) 18
  19. 19. C. difficile – Antibiotic RiskLow Risk Antibiotics:Benzyl penicillin GentamicinAmoxicillin MetronidazoleFlucloxacillin VancomycinTetracyclines TeicoplaninTrimethoprim SynercidNitrofurantoin LinezolidFusidic acid TigecyclineRifampicin Daptomycin 19
  20. 20. Summary:Pathogenesis of C. difficile Antibiotic therapy Disturbed colonic microflora Exposed to C. difficile Toxin A & Toxin B Diarrhea & colitis 20
  21. 21. Effect of Antibiotics on Normal Flora Rupnik et al. Nat Rev Microbiol 2009;7:526-36.
  22. 22. C. difficile : Laboratory tests Stool culture: Most sensitive - Requiring 2-3 days for growth - Unable to distinguish between the presence of toxin positive strains or toxin negative strains Toxin detection (B) : faecal filtrate on culture cells-typical CPE neutralized specific antiserum - Requiring 6-48 hours incubation period Clostridium difficile PCR assay 22 C difficile colonies on agar plate: http://en.wikipedia.org/wiki/Clostridium_difficile
  23. 23. C. difficile : Laboratory tests (cont) Enzyme immunoassay : toxin A alone or toxin A/B  most frequent - Sensitivity : 33 – 86.3 % - Specificity : 84.2 – 96.7% GDH (Glutamat Dehydrogenase) 23 C difficile colonies on agar plate: http://en.wikipedia.org/wiki/Clostridium_difficile
  24. 24. Professor Mike Wren MBE Consultant Biomedical Scientist at University College Hospital, London (2008) : a two-step approach for the detection of Clostridium difficile as an initial screening test to detect the C. difficile antigen, glutamate dehydrogenase (GDH) Samples that are GDH-positive are tested for C. difficile toxins A/B and cultured for toxigenic strains 24
  25. 25. The evaluation has shown Rapid Simple Cost effective Negative predictive value (NPV) of 99.5% Demonstrates excellent concurrence with reference methods. 25
  26. 26. Swindells et al., J.Clin.Microbiol., 2010, 48(2) 26
  27. 27. New Updated GuidelinesInfectious Diseases Society of America (IDSA) and Society forHealthcare Epidemiology of America(SHEA) updated Clinicalpractice Guidelines for Clostridium difficile in May 2010.The main take aways from this document are; Recommends a two step algorithm using GDH as an initial screen. The guidelines recommend a GDH test with a reflex to either toxigenic culture or cell cytotoxicity. Does not recommend Enzyme Immunoassays to detect toxin as they are a suboptimal approach. Require more data on the utility of PCR testing before this methodology can be recommended. 27
  28. 28. Recommended Testing Algorithm GDH Screen Negative PositiveNo further testing required Toxin A/B Test Negative Positive Colonised/mild disease C. difficile Infection 28
  29. 29. THANK YOUFOR YOUR ATTENTION dr_aryati@yahoo.com 29

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