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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.

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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
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.

c difficile
C. difficile
  • 1935 - discovered
    • Obligate anaerobe
    • Motile
    • Gram positive bacillus
    • Oval, sub-terminal spores
  • Occasional case reports - infected wounds (1960s)
c difficile8
C. difficile
  • 1977 - C. difficile identified as cause
    • Birmingham General Hospital
  • AAD - 20-30%
  • AAC - 50-75%
  • >90% - pseudomembranous colitis
c difficile toxins
C. difficile Toxins
  • Toxigenic strains produce 2 major toxins:
    • toxin A (enterotoxin)
    • toxin B (cytotoxin)
  • Neutralised by C. sordellii antitoxin
toxin a
Toxin A
  • Binds to specific CHO receptors on intestinal epithelium
  • Toxin induced inflammatory process:
    • neutrophils
    • inflammatory mediators
    • fluid secretion
    • altered membrane permeability
    • haemorrhagic necrosis
toxin b
Toxin B
  • Binding site not yet identified
  • Depolymerization of filamentous actin
    • destruction of cell cytoskeleton
    • rounding of cells
clinical manifestations
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
clinical manifestations13
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
pathogenesis
Pathogenesis
  • Disruption of normal colonic flora
  • Colonisation with C. difficile
  • Production of toxin A +/- B
  • Mucosal injury and inflammation
pathogenesis18
Pathogenesis
  • Microflora of gut:
    • 1012 bacteria/gram
    • 400-500 species
    • colonisation resistance
  • Transmission - faecal/oral
    • spores
  • Late log / early stationary phase
    • toxin production
pathology
Pathology
  • Colonic mucosa - raised yellow / white plaques
    • initially small
    • enlarge and coalesce
  • Inflamed mucosa
mortality
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)
what changed
What Changed?
  • Hand hygiene?
  • Environmental cleanliness?
  • Antimicrobial prescribing?
  • Other factors?
what changed25
What Changed?
  • ?Different organism
pcr ribotype 027
PCR Ribotype 027
  • In North America – PFGE Type NAP1
  • International = NAP1/027
  • Major problems in Montreal and several states in the US
pcr ribotype 02728
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)
pcr ribotype 02729
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!!!
pcr ribotype 02730
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”
rwht response
RWHT Response

Also major problems with MRSA bacteraemias

rwht response36
RWHT Response

DoH MRSA HCAI Improvement Programme

Disband ICC

Form IPB:

chaired by Chief Executive

performance management for Divisions and Wards

rwht response to c difficile
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
rwht response to c difficile39
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
rwht response to c difficile40
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
c difficile antibiotic risk
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
c difficile antibiotic risk44
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

slide46

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

slide47

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

slide48

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 )

slide49

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)

recurrence
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.

third line drug regimes for recurrent disease
Third Line Drug Regimes for Recurrent Disease:-

6 weeks Tapering Vancomycin:

125mg every 6 hours for 1 week

125mg every 12 hrs for 1 week

125mg once daily for 1 week

125mg every other day for 1 week

125 mg every 3rd day for 2 weeks

IV Immunoglobulin

400mg/kg single dose with a repeat at 21 days if necessary

Yeast

Yeast preparations are contraindicated.

Prebiotic and Probiotics (live yoghurt)

No proven benefit of prebiotics or probiotics.

Cannot be prescribed and should not be advocated - no quality control over the agents that the patient will receive

slide55

Commode Audit

Commode replacement

Mattress replacement

Grand Round presentation

RCA for all c diff cases introduced

High Impact Intervention No 6 introduced

Bed space checklists introduced

Commode re-Audit &feedback

Matrons lead Ward Declutter programme

Medical division training

Antibiotic review commenced

Domestics training delivered by IPT

mortality58
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%
mortality59
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%
  • 1.12.06 – 31.3.07 23/85 27.1%
  • RR 0.70 (CI 0.47 – 1.03)
conclusions
Conclusions
  • New strain(s) of C. difficile cause more severe disease
    • ??sub-strains
  • Appear to spread more readily
  • More difficult to control
  • Multi-factorial approach to control needed
  • Requires involvement of entire Trust
    • not just a medical / nursing solution
  • Not just antibiotics!