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Ss16 Presentation Transcript

  • 1. Clostridium difficile :An Emerging Threat and Update Diagnostic Aryati Infectious Disease ConsultantClinical Pathology Department School of MedicineAirlangga University - Surabaya 1
  • 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. 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. Pathogenesis Disruption of normal colonic flora Colonisation with C. difficile Production of toxin A and or toxin B Mucosal injury and inflammation 4
  • 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. 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. Toxin B Binding site not yet identified Depolymerization of filamentous actin  destruction of cell cytoskeleton  rounding of cells 7
  • 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. 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. 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. 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
  • 13. Endoscopy Endoscopic view of classic C diff–associated pseudomembranous colitis7 Juli 2011 Seminar Clostridium defficile 13
  • 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
  • 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. 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. 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. C. difficile – Antibiotic RiskLow Risk Antibiotics:Benzyl penicillin GentamicinAmoxicillin MetronidazoleFlucloxacillin VancomycinTetracyclines TeicoplaninTrimethoprim SynercidNitrofurantoin LinezolidFusidic acid TigecyclineRifampicin Daptomycin 19
  • 20. Summary:Pathogenesis of C. difficile Antibiotic therapy Disturbed colonic microflora Exposed to C. difficile Toxin A & Toxin B Diarrhea & colitis 20
  • 21. Effect of Antibiotics on Normal Flora Rupnik et al. Nat Rev Microbiol 2009;7:526-36.
  • 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. 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. 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. The evaluation has shown Rapid Simple Cost effective Negative predictive value (NPV) of 99.5% Demonstrates excellent concurrence with reference methods. 25
  • 26. Swindells et al., J.Clin.Microbiol., 2010, 48(2) 26
  • 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. Recommended Testing Algorithm GDH Screen Negative PositiveNo further testing required Toxin A/B Test Negative Positive Colonised/mild disease C. difficile Infection 28
  • 29. THANK YOUFOR YOUR ATTENTION dr_aryati@yahoo.com 29