Microbiology
Pathogens
A 78 year old woman, recovering in hospital after a fractured neck of femur, develops profuse diarrhoea. She has been on broad spectrum antibiotics for a postoperative urinary tract infection. Which of the following pathogens is the most likely cause of her diarrhoea:
Answer:
Clostridium difficile is the most likely cause given the hospital stay and the prolonged course of a broad spectrum antibiotic. In this case the antibiotic prescribing for the UTI was inappropriate - a 3 day course of either trimethoprim or nitrofurantoin is usually adequate for an uncomplicated lower UTI in female patients.Clostridium Difficile
Microbiology / Pathogens / Clostridial Infection
Last Updated: 8th September 2021
| 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 |
