Clostridium difficile
Separating key facts from
fiction
S P Borriello
16.5.08
1.
Pathogenesis
- colonisation resistance
- virulence factors of C.difficile
2.
Laboratory diagnosis
3.
Treatment and Management
Why should we be interested?
1.It is the most common identifiable cause of
nosocomial gut infection
2.It kills
3.It is preventable
PATHOGENESIS
A risk of infection with C. difficile
follows antibiotic treatment and
exposure to C. difficile
This risk increases with age.
The majority of cases are older
than 60 years.
Disease follows infection with
toxigenic strains of C. difficile
and production of toxin in vivo.
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).
What antibiotics cause
this disease?
All of them other than parenteral
aminoglycosides.
Even chemotherapeutic agents eg 5fluorouracil can have this effect.
Some antibiotics do seem to pre-dispose
to infection more than others eg:
Clindamycin
Cephalosporins, especially 3rd generation
Antibiotic
Erythromycin
Clindamycin
Ceftazidine
Cefotaxime
Weighted odds ratio
(95% CL)
3.5 (2.1 – 5.8)
7.8 (3.8 – 16.1)
28.8 (12.7 – 65.1)
36.2 (19 - 68.9)
C. Difficile is due to
overgrowth of strains resistant
to the inciting antibiotic
NO
In the animal model the biggest
difference between antibiotics seems
to be the length of time susceptibility
is induced.
Comparison of antibiotics
in hamsters
Antibiotic
(3mg)
Ampicilllin
Cefuroxime
Flucloxacillin
Number of deaths on day
1
3
4
4/4
4/4
6/6
1/4
0/4
7/8
2/8
C. difficile can cause a range of
disease from mild diarrhoea
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
COMPARATIVE VIRULENCE
OF C. DIFFICLE
No. of strains
Source
Virulence
Serogroup
Ribotype
5
PMC
High
A(x3) S3
5
1
AAD
Medium
I
9
1
Animal
Weak
C
12
3
Infant
Weak/none
G, ?(x2)
1, 20, 26
Virulence factors of C. difficile
1.
2.
3.
4.
5.
Toxins
Adhesion
Fimbriae
Enzymes
Capsule
Both toxins A and B are the largest
bacterial protein toxins known.
Toxin A
300 kDa
Toxin B
270 kDA
Effects of toxins A and B
Cytotoxicity
Haemagglutination
Increase vascular permeability
Haemorrhage
Fluid accumulation
A
+
+
+
+
+
B
+
+
+
-
Virulence factors of C. difficile
1.
2.
3.
4.
5.
Toxins
Adhesion
Fimbriae
Enzymes
Capsule
Virulence factors of C. difficile
1.
2.
3.
4.
5.
Toxins
Adhesion
Fimbriae
Enzymes
Capsule
Virulence factors of C. difficile
1.
2.
3.
4.
5.
Toxins
Adhesion
Fimbriae
Enzymes
Capsule
Virulence factors of C. difficile
1.
2.
3.
4.
5.
Toxins
Adhesion
Fimbriae
Enzymes
Capsule
LABORATORY DIAGNOSIS
1. Do not investigate formed stools
2. Do not investigate infants under six
months
Faecal cytotoxin is the
gold standard.
Vero cells are the best
choice cell line.
Kits are available for toxin
A or toxin A and B.
Those that detect both are
most sensitive.
There also exist toxin A-ve B+ve
strains which cause diseases.
Toxin A kits miss these.
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.
Alcohol (1 : 1 ratio) or heat (75˚c 20
mins) can be used to select for spores
as an alternative isolation procedure.
CONTROL / PREVENTION
1. Limit antimicrobial use
2. Good infection control
- Hand washing
- Enteric precautions
- Clean environment
Decontamination must remove spores
Decontamination
Hospital Surfaces: Routine cleaning
Equipment: 2% alkaline buffered
glutaraldehyde
TREATMENT OF CASES
(Conventional)
Stop the precipitating antibiotics (15-25%
success)
Vancomycin 125mg qds 7-10 days
OR
Metronidazole 400mg tds 7-10 days
TREATMENT OF CASES
(Unconventional)
1. Faecal enemas / faecal flora cocktails
2. Probiotics
- lactobacilli
- Saccharomyces boulardii
3. Non-toxigenic C. difficile