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Introduction
1. Anatomy
2. Microbiology
2.1 General bacteriology
2.2 Introduction to systemic bacteriology
2.3 Gram positive cocci
2.4 Gram negative cocci
2.5 Gram positive bacilli
2.5.1 Introduction
2.5.2 Bacillus anthracis
2.5.3 Bacillus cereus
2.5.4 Clostridium tetani
2.5.5 Clostridium botulinum
2.5.6 Clostridium perfringens
2.5.7 Clostridium difficile
2.5.8 Corynebacterium diphtheriae
2.5.9 Listeria monocytogenes
2.6 Gram negative bacilli
2.7 Other important bacteria
2.8 Virology
2.9 Parasitology
2.10 Mycology
3. Physiology
4. Pathology
5. Pharmacology
6. Immunology
7. Biochemistry
8. Cell and molecular biology
9. Biostatistics and epidemiology
10. Genetics
11. Behavioral science
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2.5.7 Clostridium difficile
Achievable USMLE/1
2. Microbiology
2.5. Gram positive bacilli

Clostridium difficile

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It is the causative agent of pseudomembranous colitis associated with the use of broad spectrum antibiotics. C.difficile is the leading cause of hospital-acquired diarrhea.

Morphology

It is a Gram positive bacillus with oval, terminal spores.

Classification

Not relevant.

Human pathology

It is normally present in 3% of the general population. Hospitalization increases the risk of colonization.

When antibiotics such as clindamycin, second and third generation cephalosporins, ampicillin, etc. are taken, they kill the normal colonic flora. This allows Cl.difficile to grow in large numbers and produce toxins. These exotoxins, TcdA and TcdB, cause the disease manifestations.

Once the toxin binds to its receptor on the cell surface, it is internalised by endocytosis. After release into the cytosol, the toxins glycosylate G proteins called Rho GTPases (Ras superfamily) and inactivate them. This disrupts intracellular signalling mechanisms and leads to both cytopathic and cytotoxic effects.

Cytopathic effects include:

  • Shrinking and rounding of cells
  • Disruption of the actin cytoskeleton
  • Disruption of tight and adherens junctions
  • Loss of cell-cell contacts
  • Increased epithelial permeability
  • Apoptosis
  • Diarrhea

Cytotoxic effects cause colitis and inflammation.

Clinically, it manifests as diarrhea with yellow white-looking pseudomembranes. Toxic megacolon and systemic complications can occur in severe cases.

Laboratory diagnosis of Cl.difficile infections

Detection of toxins in stool samples by ELISA is faster. Demonstration of toxin effects by its action on cell culture of Hep-2 or Human Diploid Cells, showing characteristic effects, is confirmatory.

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