Features of infection
- gram +ve
- spore forming
- anaerobic bacillus
Route of transmission
faecal-oral
Where does CDI colonise
LI
*when normal flora is reduced by Abs
Where is CDI most commonly acquired
nosocomical
i.e. hospital acquired
Risk factors associted with CDI
- x8-10 higher after antimicrobial therapy e.g clindamycin
- patients over 65 yrs have x5-10 risk
What part of body is affected
Any part of colon
*mostly the distal segment
Main protective barrier against CDI
normal intestinal microflora
Associated conditions
- Pseudomembranous colitis (PMC)
- antibiotic associated diarrhea (AAD)
Pathogenesis
- in intestine, bile acids play important role in induction of C.diff spore germination
Primary bile and secondary bile conc. in healthy vs C.diff patients
primary bile (cholic acid)
- higher in feaces of CDI patients
secondary bile (deoxycholic acid)
- higher in faeces of healthy patients
What causes virulence of C.diff
- not invasive
- virulence caused by enzymes (collagenase, hyaluronidase)
- leads to damage of epi cell cytoskeleton, disruption of tight junctions, fluid secretion, NF adhesion, local inflammation
- breakdown of gut barrier integrity and loss of functionality
Toxins
A (enterotoxin)
B (cytotoxin)
- transported to cytoplams -> activate Rho family of GTPases
- inactivates G protein
- impaires actin polymerisation
- loss of function and shape in mucousal cells
Strains of c.diff
Toxin A negative
Toxin B positive
Binary toxin (6% strains)
Binary toxin
- one ligand to a receptor
- one enzymatically active toxic component inside host cell
- displays actin specific activity that leads to cytoskeletal disorganisation
New strain
C.diff 027
- framshift stop codon in tdcC negative regulator
- hyperexpresses A and B toxins
- all isolates are +ve for binary toxin
- increased sporulation rate
- resistant to floroquinolones
Diagnosis
- ELISA assays
Gold standard
- detection of toxicity of stool filtrates for cell cultured cells (often fibroblats)
- cytopathic effect blocked by Abs to toxin A or B
Culturing C.diff
- cycloserine-cefoxitin fructose agar (CCFA)
Treatment
- cessation of antibiotics
- witch to vancomycin or fidaxomicin
Control of C.diff
- restrict specific Abs (cephalosporins & clindamycin) in elderly
- prevent transmission of spores (hygiene)
- isolate cases
- surveillance
Potential new therapies
- probiotics
- FMT
mAb
Bezlotoxumab
- against c.diff toxin B
- reduce risk of recurrent c.diff
- binds toxin B with equilibrium dissociation constant (Kd) of <1x10-9M
- inhibits binding of toxin B -> prevents effects on mammalian cells
