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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 3 rd generation
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Antibiotic Weighted odds ratio (95% CL) Erythromycin3.5 (2.1 – 5.8) Clindamycin7.8 (3.8 – 16.1) Ceftazidine28.8 (12.7 – 65.1) Cefotaxime36.2 (19 - 68.9)
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C. Difficile is due to overgrowth of strains resistant to the inciting antibiotic NO
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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)134 Ampicilllin4/41/4- Cefuroxime4/40/4- Flucloxacillin6/67/82/8
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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 strainsSourceVirulenceSerogroupRibotype 51135113 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 B270 kDA
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Effects of toxins A and B AB 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
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