1. Clostridium difficile infections

2. Objectives Microbiology and epidemiology of Clostridium difficile
Risk factors for transmission
Diagnosis
Treament

3. Microbiology Gram positive spore forming bacillus (rods)
Part of the gastrointestinal flora in
- 1-3% of healthy adult
- much higher percentage in children < 12 months
Most strains of C. difficile produces two toxins; - an enterotoxin (A) attracting neutrophils stimulating the release of cytokines. - a cytotoxin (B) that increases permeability of the intestinal wall -> diarrhea

4. Virulence
Resistance to anitbiotics such as clindamycin, cephalosporins, and fluoroquinolones allow C.diff. to overgrow the normal intestinal flora in patients exposed to these antibiotics and produces disease.
Spore formation makes it resistant to decontamination and can therefore persist in hospital environment.

5. Transmission Fecal-oral
Person to person in outpatient clinic and hospitals.
Reservoir: - human: colonized or infected pts contaminate environment
Spores can survive for up to 5 months on surfaces, particularly around hospital beds and in bathrooms.

6. Patients at risk Taking antibiotics
Staying in the hospital or a nursing home
Increasing age, especially over 65 years
Having a weakened immune system
Having a colon disease, such as inflammatory bowel disease or colorectal cancer
Undergoing intestinal surgery
Receiving chemotherapy treatment for cancer

7. Pathogenesis
Step 1- Ingestion
of spores transmitted
from other patients
Step 2- Germination into growing (vegetative) form
Step 4 . Toxin B & A production leads to colon damage +/- pseudomembranous colitis
Step 3 - Altered lower intestine flora (due to antimicrobial use) allows proliferation of C. difficile in colon
C diff spores resist the stomach acidity, then germinate into vegetative state in the small intestine,
Exotoxin is ptn produced to destroy the host cells

8. Clinical Manifestations
Ranges from
Asymptomatic carriers = Colonized
Mild or moderate diarrhea
Pseudo membranous colitis that can be fatal
A median time between exposure to onset of symptoms is of 2–3 days
Symptoms: Watery diarrhea, fever, nausea, loss of appetite, abdominal pain & cramping.

9. Pseudomembranous Colitis
The inflammation in pseudomembranous colitis is almost always associated with an overgrowth of the bacterium Clostridium difficile.
Severe pseudomembranous colitis can be life-threatening. However, treatment is usually successful.
Symptoms the same as C.diff infection but with: Bloody stool (not always) and pus or mucus in stools.

10. Complications of PMC
Abnormally low levels of potassium in your blood (hypokalemia), due to the loss of potassium during excessive diarrhea
Dehydration leading to hypotension, related to significant loss of fluids and electrolytes due to diarrhea
Recurrence of pseudomembranous colitis, days or even weeks after initial treatment
Kidney failure, due to severe dehydration resulting from diarrhea
Perforated colon which can lead to an infection of your abdominal cavity
Toxic megacolon, a rare but serious swelling of the colon, leaving it incapable of expelling gas and stool, which could cause your colon to rupture
If left untreated it can be fatal…

12. Diagnosis
C. Difficile diagnosis is confirmed by detecting cytotoxin, enterotoxin or toxin genes in patient’s feces.
It is possible to use commercial immunoassays, but these are insensitive and not recommended.
The recommended test is detection of toxin genes directly in specimen by nucleic acid amplification techniques.

13. Treatment, prevention and control
The implicated antibiotic should be discontinued.
Treatment with metronidazole or vancomycin should be used in severe diarrhea, or pseudomembranous colitis.
Relapse common, and multiple courses may be necessary due spore survival.
Hospital room should be carefully cleaned with appropriate sanitizer.

14. Sources Medical microbiology, 7th edition, Murray, Rosenthal, Pfaller
Harrison’s internal medicine, 18th ed