1 / 65

Clostridium difficile - a new Disease?

Clostridium difficile - a new Disease?. Dr Mike Cooper Consultant Microbiologist and DIPC New Cross Hospital Wolverhampton. Oxoid Infection Control Team of the Year Awards – 2006/2007 Winners Announced.

omer
Download Presentation

Clostridium difficile - a new Disease?

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 - a new Disease? Dr Mike Cooper Consultant Microbiologist and DIPC New Cross Hospital Wolverhampton

  2. Oxoid Infection Control Team of the Year Awards – 2006/2007 Winners Announced BASINGSTOKE, UK, 26 April 2007 - Oxoid, a world leader in microbiology, is pleased to announce the winners of the 2006/2007 Oxoid Infection Control Team of the Year Awards: 1st Prize:Royal Wolverhampton Hospitals NHS Trust, UK 2nd Prize:Cho Ray Hospital, Vietnam Joint 3rd Prize:Southampton University Hospitals NHS Trust, UK and Aminu Kano Teaching Hospital, Nigeria.

  3. C. difficile • 1935 - discovered • Obligate anaerobe • Motile • Gram positive bacillus • Oval, sub-terminal spores • Occasional case reports - infected wounds (1960s)

  4. C. difficile • 1977 - C. difficile identified as cause • Birmingham General Hospital • AAD - 20-30% • AAC - 50-75% • >90% - pseudomembranous colitis

  5. C. difficile Toxins • Toxigenic strains produce 2 major toxins: • toxin A (enterotoxin) • toxin B (cytotoxin) • Neutralised by C. sordellii antitoxin

  6. Toxin A • Binds to specific CHO receptors on intestinal epithelium • Toxin induced inflammatory process: • neutrophils • inflammatory mediators • fluid secretion • altered membrane permeability • haemorrhagic necrosis

  7. Toxin B • Binding site not yet identified • Depolymerization of filamentous actin • destruction of cell cytoskeleton • rounding of cells

  8. Clinical Manifestations • Asymptomatic carriage (neonates) • Diarrhoea • 5-10 days after starting antibiotics • maybe be 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

  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

  10. Pathogenesis • Disruption of normal colonic flora • Colonisation with C. difficile • Production of toxin A +/- B • Mucosal injury and inflammation

  11. Pathogenesis • Microflora of gut: • 1012 bacteria/gram • 400-500 species • colonisation resistance • Transmission - faecal/oral • spores • Late log / early stationary phase • toxin production

  12. Pathology • Colonic mucosa - raised yellow / white plaques • initially small • enlarge and coalesce • Inflamed mucosa

  13. Mortality • All cause 28/7 mortality for CDT positive: • 1.12.03 – 31.3.04 18/60 30.0% • 1.12.05 – 31.3.06 71/183 38.8% • RR 1.29 (CI 0.84 – 1.98)

  14. What Changed? • Hand hygiene? • Environmental cleanliness? • Antimicrobial prescribing? • Other factors?

  15. What Changed? • ?Different organism

  16. Independent 6-8th June 2005

  17. PCR Ribotype 027 • In North America – PFGE Type NAP1 • International = NAP1/027 • Major problems in Montreal and several states in the US

  18. PCR Ribotype 027 • Montreal – 30/7 mortality increased • 4.7% in 1991/2 • 8.6% in 2002 • 13.8% in 2003 • Incidence per 100,000 individuals aged >65 • 102 (1991-2) • 866 (2003)

  19. PCR Ribotype 027 • First UK isolate – Preston 1999 • Second UK isolate – Birmingham 2002 • Next seen – March 2004 – Stoke Mandeville • Wolverhampton – 8 isolates from Oct – Dec 2005 sent for typing • all 027!!!

  20. PCR Ribotype 027 • North American outbreak strain: • 8 to 16 X production of toxins A and B in-vitro • Hyper-toxin production: • 18bp deletion in the TcdC gene • regulates toxin production • Strong association with fluoroquinolone use • The Lancet 24th Sept 2005: • Warny, Pepin, Fang, Killgore, Thompson, Brazier, Frost and McDonald: “Toxin production by an emerging strain of C. difficile associated with outbreaks of severe disease in North America and Europe”

  21. RWHT Response Also major problems with MRSA bacteraemias

  22. RWHT Response DoH MRSA HCAI Improvement Programme Disband ICC Form IPB: chaired by Chief Executive performance management for Divisions and Wards

  23. RWHT Response to C. difficile • Regular commode auditing • Replacement of 100 old/damaged commodes • Replacement of 300 mattresses • Introduction of ‘Saving Lives’ HII Number 6 following every case of CDAD • Root cause analysis on every case • Introduction of hotel style bed space check lists following discharge of every patient

  24. RWHT Response to C. difficile • Matron led ward de-clutter programme • Introduction of monthly clutter collection • 200 domestics trained in CDAD and the role of the environment • Medical division nurse training on CDAD, spread and role of equipment • Grand Round presentation of case studies and action on CDAD. Mandatory attendance of at least one member of every clinical team. 250 attended

  25. RWHT Response to C. difficile • ‘Slide card’ for infection prevention for all staff • C. difficile management / treatment guidelines • New antimicrobial guidelines • Antimicrobial prescribing policy • Monitoring and antimicrobial prescribing performance management of Divisions • Ward refurbishment programme

  26. High Risk Antibiotics: Cefotaxime Ceftriaxone Cefalexin Cefuroxime Ceftazidime Ciprofloxacin Moxifloxacin Clindamycin (low dose) Medium Risk Antibiotics: Meropenem Ertapenem Clindamycin (high dose) Co-amoxiclav Tazocin Erythromycin Clarithromycin C. difficile – Antibiotic Risk

  27. C. difficile – Antibiotic Risk Low Risk Antibiotics: Benzyl penicillin Gentamicin Amoxicillin Metronidazole Flucloxacillin Vancomycin Tetracyclines Teicoplanin Trimethoprim Synercid Nitrofurantoin Linezolid Fusidic acid Tigecycline Rifampicin Daptomycin

  28. Treatment Algorithm For New Cases of C. difficile Diarrhoea Symptomatic Proven or Suspected C. diff infection Assess Patient: AXR, CRP, U& E’s, FBC Stool Chart Stool for C. diff & culture (if not done) Consider Flexi Sig if diagnosis in doubt Review Antibiotics

  29. Severe Disease Unwell WC > 20 * CRP >150 * Abnormal AXR * Distended Abdomen * (* = severe if any of these features) Moderate Disease Well WCC < 20 CRP <150 Normal AXR

  30. Moderate Severe Start treatment without delay -Metronidazole 400mg TDS for 5 days -Daily Review including stool chart - FBC, CRP, AXR if deteriorates Start treatment without delay -Vancomycin 500mg QDS PO -Metronidazole 500mg TDS IV or 400mg TDS PO - IVI -Consider HDU / ITU Colorectal Surgical Referral on day 1 Daily Surgical Review until improving : if fails to improve consider surgery ( If Deteriorates to Severe )

  31. Response Complete 14 day course of metronidazole No Response :- Add Vancomycin 500mg QDS PO for 5 days Complete 14 day course of metronidazole ( If Deteriorates to Severe ) Response Complete 14 day course of Vancomycin Complete course of metronidazole No Response :- Refer Gastroenterology for flexible sigmoidoscopy & advice. Continue Vanc & Met Treat as for severe if deteriorates Can be discharged on metronidazole and vancomycin (125mg QDS)

  32. Recurrence: ??re-infection Assess: if severe treat as above Moderate: metronidazole 400mg TDS and PO vancomycin 500mg QDS If responds by day 5: 14 days of metronidazole + 500mg QDS vancomycin, then 6 weeks tapering vancomycin If no response after 5 days of combined therapy refer to gastroenterology If remains symptomatic after 10 days and C. diff / PMC confirmed on flexible sigmoidoscopy then consider IV Immunoglobulin. If this is the third or more recurrence then consider immunoglobulin + 2 weeks metronidazole 400mg TDS PO / vancomycin 500mg QDS at the outset followed by 6 weeks of vancomycin.

More Related