Clostridium difficile Separating key facts from fiction S P Borriello 16.5.08.
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Transcript of Clostridium difficile Separating key facts from fiction S P Borriello 16.5.08.
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Clostridium difficile
Separating key facts from fiction
S P Borriello
16.5.08
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1. Pathogenesis
- colonisation resistance
- virulence factors of C.difficile
2. Laboratory diagnosis
3. Treatment and Management
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Why should we be interested?
1.It is the most common identifiable cause of nosocomial gut infection
2.It kills
3.It is preventable
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PATHOGENESIS
A risk of infection with C. difficile follows antibiotic treatment and
exposure to C. difficile
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This risk increases with age. The majority of cases are older
than 60 years.
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Disease follows infection with toxigenic strains of C. difficile
and production of toxin in vivo.
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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).
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What antibiotics cause this disease?
All of them other than parenteral aminoglycosides.
Even chemotherapeutic agents eg 5-fluorouracil can have this effect.
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Some antibiotics do seem to pre-dispose to infection more than others eg:
Clindamycin
Cephalosporins, especially 3rd generation
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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)
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C. Difficile is due to overgrowth of strains resistant
to the inciting antibiotic
NONO
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In the animal model the biggest difference between antibiotics seems to be the length of time susceptibility
is induced.
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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
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C. difficile can cause a range of disease from mild diarrhoea
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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
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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
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Virulence factors of C. difficile
1. Toxins
2. Adhesion
3. Fimbriae
4. Enzymes
5. Capsule
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Both toxins A and B are the largest bacterial protein toxins known.
Toxin A 300 kDa
Toxin B 270 kDA
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Effects of toxins A and B
A B
Cytotoxicity + +
Haemagglutination + -
Increase vascular permeability + +
Haemorrhage + +
Fluid accumulation + -
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Virulence factors of C. difficile
1. Toxins
2. Adhesion
3. Fimbriae
4. Enzymes
5. Capsule
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Virulence factors of C. difficile
1. Toxins
2. Adhesion
3. Fimbriae
4. Enzymes
5. Capsule
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Virulence factors of C. difficile
1. Toxins
2. Adhesion
3. Fimbriae
4. Enzymes
5. Capsule
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Virulence factors of C. difficile
1. Toxins
2. Adhesion
3. Fimbriae
4. Enzymes
5. Capsule
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LABORATORY DIAGNOSIS
1. Do not investigate formed stools
2. Do not investigate infants under six months
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Faecal cytotoxin is the gold standard.
Vero cells are the best choice cell line.
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Kits are available for toxin A or toxin A and B.
Those that detect both are most sensitive.
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There also exist toxin A-ve B+ve strains which cause diseases.
Toxin A kits miss these.
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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.
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Alcohol (1 : 1 ratio) or heat (75˚c 20 mins) can be used to select for spores as an alternative isolation procedure.
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CONTROL / PREVENTION
1. Limit antimicrobial use
2. Good infection control
- Hand washing
- Enteric precautions
- Clean environment
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Decontamination must remove spores
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Decontamination
Hospital Surfaces: Routine cleaning
Equipment: 2% alkaline buffered glutaraldehyde
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TREATMENT OF CASES (Conventional)
Stop the precipitating antibiotics (15-25% success)
Vancomycin 125mg qds 7-10 days
OR
Metronidazole 400mg tds 7-10 days
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TREATMENT OF CASES (Unconventional)
1. Faecal enemas / faecal flora cocktails
2. Probiotics
- lactobacilli- Saccharomyces boulardii
3. Non-toxigenic C. difficile