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Microbiology

Pathogens

Question 111 of 180

A patient is sent to ED by his GP with profuse watery diarrhoea. A stool sample taken by the GP has demonstrated C. difficile cytotoxin. First line treatment of Clostridium difficile colitis is typically with:

Answer:

  • First-line antibiotic for a first episode of mild, moderate or severe C. difficile infection: Vancomycin 125 mg orally four times a day for 10 days
  • Second-line antibiotic for a first episode of mild, moderate or severe C. difficile infection if vancomycin is ineffective: Fidaxomicin 200 mg orally twice a day for 10 days
  • Antibiotics for life-threatening C. difficile infection: Seek urgent specialist advice, which may include surgery. Antibiotics that specialists may initially offer are: Vancomycin 500 mg orally four times a day for 10 days with metronidazole 500 mg intravenously three times a day for 10 days

Clostridium Difficile

Microorganism Clostridium Difficile
Gram stain Gram positive
Shape Rod
Oxygen requirements Obligate anaerobe
Additional features Spore-forming, Produces Toxin A (enterotoxin) and Toxin B (cytotoxin)
Reservoir Intestinal flora & environment
Diseases Pseudomembranous colitis

Pathogenesis and Clinical Disease

C. difficile causes pseudomembranous colitis, an acute inflammatory diarrhoeal disease and an important cause of morbidity and mortality in hospitals.

C. difficile is normally found in the gut flora but its growth is normally suppressed by more dominant anaerobes. Broad-spectrum antibiotics disturb the normal gut flora and can result in C. difficile overgrowth. C. difficile spores can be transmitted via the faecal-oral route.

C. difficile produces exotoxins A (an enterotoxin) and B (a cytotoxin) which cause intestinal fluid secretion and tissue damage resulting in profuse watery diarrhoea, abdominal cramps, fever, rigors and sepsis.

Possible complications of pseudomembranous colitis include:

  • Toxic megacolon
  • Bowel perforation
  • Dehydration and AKI
  • Electrolyte disturbance
  • Systemic toxicity

Diagnosis

Diagnosis is with ELISA detection of toxins in stool.

Treatment and Prevention

  • Stopping the implicated antibiotic
    • Clindamycin, cephalosporins, fluoroquinolones and co-amoxiclav are particularly high risk
  • Appropriate antibiotic therapy
    • First-line antibiotic for a first episode of mild, moderate or severe C. difficile infection: Vancomycin 125 mg orally four times a day for 10 days
    • Second-line antibiotic for a first episode of mild, moderate or severe C. difficile infection if vancomycin is ineffective: Fidaxomicin 200 mg orally twice a day for 10 days
    • Antibiotics for life-threatening C. difficile infection: Seek urgent specialist advice, which may include surgery. Antibiotics that specialists may initially offer are: Vancomycin 500 mg orally four times a day for 10 days with metronidazole 500 mg intravenously three times a day for 10 days
  • Fluid and electrolyte management
  • Rapid and strict isolation with barrier nursing
  • Enhanced ward cleaning and attention to hand hygiene
    • C. difficile spores are resistant to alcohol hand gel, so strict handwashing with soap

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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