1 / 56

Clostridium difficile Separating key facts from fiction

Clostridium difficile Separating key facts from fiction . S P Borriello 16.5.08. 1. Pathogenesis - colonisation resistance - virulence factors of C.difficile 2. Laboratory diagnosis 3. Treatment and Management. Why should we be interested?.

ilandere
Télécharger la présentation

Clostridium difficile Separating key facts from fiction

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Clostridium difficile Separating key facts from fiction S P Borriello 16.5.08

  2. 1. Pathogenesis • - colonisation resistance • - virulence factors of C.difficile • 2. Laboratory diagnosis • 3. Treatment and Management

  3. Why should we be interested? • 1. It is the most common identifiable cause of nosocomial gut infection • 2. It kills • 3. It is preventable

  4. PATHOGENESIS • A risk of infection with C. difficile follows antibiotic treatment and exposure to C. difficile

  5. This risk increases with age. The majority of cases are older than 60 years.

  6. Disease follows infection with toxigenic strains of C. difficile and production of toxin in vivo.

  7. Why is it that you need antibiotic treatment to make you susceptible to infection. It is due to the barrier effect of the normal gut bacteria (colonisation resistance).

  8. What antibiotics cause this disease? • All of them other than parenteral aminoglycosides. • Even chemotherapeutic agents eg 5-fluorouracil can have this effect.

  9. Some antibiotics do seem to pre-dispose to infection more than others eg: • Clindamycin • Cephalosporins, especially 3rd generation

  10. Antibiotic Weighted odds ratio • (95% CL) • Erythromycin 3.5 (2.1 – 5.8) • Clindamycin 7.8 (3.8 – 16.1) • Ceftazidine 28.8 (12.7 – 65.1) • Cefotaxime 36.2 (19 - 68.9)

  11. C. Difficile is due to overgrowth of strains resistant to the inciting antibiotic NO

  12. In the animal model the biggest difference between antibiotics seems to be the length of time susceptibility is induced.

  13. Comparison of antibiotics in hamsters • Antibiotic Number of deaths on day • (3mg) 1 3 4 • Ampicilllin 4/4 1/4 - • Cefuroxime 4/4 0/4 - • Flucloxacillin 6/6 7/8 2/8

  14. C. difficile can cause a range of disease from mild diarrhoea

  15. A number of factors could contribute to outcome of infection eg • Host factors • Degree of disruption of colonisation resistance • Virulence of the C. difficile strain

  16. COMPARATIVE VIRULENCE OF C. DIFFICLE No. of strains Source Virulence Serogroup Ribotype 5 1 1 3 PMC AAD Animal Infant High Medium Weak Weak/none A(x3) S3 I C G, ?(x2) 5 9 12 1, 20, 26

  17. Virulence factors of C. difficile • 1. Toxins • 2. Adhesion • 3. Fimbriae • 4. Enzymes • 5. Capsule

  18. Both toxins A and B are the largest bacterial protein toxins known. • Toxin A 300 kDa • Toxin B 270 kDA

  19. Effects of toxins A and B • A B • Cytotoxicity + + • Haemagglutination + - • Increase vascular permeability + + • Haemorrhage + + • Fluid accumulation + -

  20. Virulence factors of C. difficile • 1. Toxins • 2. Adhesion • 3. Fimbriae • 4. Enzymes • 5. Capsule

  21. Virulence factors of C. difficile • 1. Toxins • 2. Adhesion • 3. Fimbriae • 4. Enzymes • 5. Capsule

  22. Virulence factors of C. difficile • 1. Toxins • 2. Adhesion • 3. Fimbriae • 4. Enzymes • 5. Capsule

  23. Virulence factors of C. difficile • 1. Toxins • 2. Adhesion • 3. Fimbriae • 4. Enzymes • 5. Capsule

  24. LABORATORY DIAGNOSIS • 1. Do not investigate formed stools • 2. Do not investigate infants under six months

  25. Faecal cytotoxin is the gold standard. • Vero cells are the best choice cell line.

  26. Kits are available for toxin A or toxin A and B. • Those that detect both are most sensitive.

  27. There also exist toxin A-ve B+ve strains which cause diseases. • Toxin A kits miss these.

  28. Culture is best achieved by growth on a selective medium incorporating cyloserine (250mg/l) and cefoxatin (8mg/l). • Colonies fluoresce under long wave UV light.

More Related