c difficile Flashcards
what is c difficile
anaerobic gram positive bacterium which affects individiuals who are taking antibiotics where the commensal bacteria is lost and virus disrupts epithelial barrier using toxins to allow leakage of immune cells, red blood cells and bacteria across the lining
transmission
features of the bacterium
f-O route
highly resistance to acid, heat, anti-biotics
how does it occur?
the production of toxin A and B which disrupt the epithelial barrier through the apical and basolateral membrane respectively.
-cytoskeletondamage , inactivation of GTPase
possibly a third toxin binary toxin
what can cdifficle cause
colitis
diarrhoea
how is it diagnosed?
glutamate dehydrogenase antigen
toxin A and EIA
PCR
treatments at present
vancoymcin
metronidazole
IV immunoglobulins
colectomy
problems with drug therap
hypervirulent strans
non responsiveness to antibiotics
recurrence and treatment failure with metronidazole
more recently there has been evidence for treatment failure from before and after 2000 from 2% approx. to 18%
and recurrence from 6.7 to 28.6%
new three ways in approaches
Padua 2016
barrier support
antibacterials
and immune support
how many new approaches :
[1] fidaxomicin [2]antibacterials rifaxamin and tigylcine [3] toxin binder [4] Actoxumab and Bezlotoxumab: [5] faecal transplant [6] pribiotics [7] non toxigenic cdi [8] probiotics [9] ribamaxamase [10] immunisation
discuss fidaxomicin
poorly absorbed macrolide
limited to afew anaerobic gram positive bcteriums
inhibits RNA polymerase
very exensive 1300k vs 2.53 and 188 for met and vanco
no effect on recurrence against 027
ribaxmase
beta lactamase
breaks down beta lactam iv antibiotic in gut
toxin binders
attempted but no benefit of cholestyramine
immunisation
phase 3 study trial
worry about elderly patients due to reduced seroconverison
microbiota
loss of biodiversity with antibiotic increase in CDI risk
stopping antibiotic and increase antibiotic reduce CDI risk
probiota
reviews/metanalyasis not available conflicting data fugemia in immunocompromised found to improve symptoms but not treat CDI
actoxumab and bezlotoxumab
anti-toxin A antibody and B antibody prevent infection in rodents neutralises toxins expensive diarrhoea main sde effect
non toxgenic agent
M3 strain with no virulence -lack of gene for toxin
RCT given to patients and found to improve CDI
where it may outcompete with CDI
11 vs 30% in treatment and placebo for recurrence
in hamsters
faecal microbiota transplant
Chinese medicine 4th century
post www2 America
conintradication: pregnancy, nutallergies and immunosuppression drug patients
use : severe 2 episodes of Cdifficile
colitis with no improvement after 48 hr with no improvement
capsule- many tables would be need
filtered stool shown promising result
mechanism of Faeceal transplant?
-bile acid pathway
immune mediation
completed with gut micriobita for nutrients in the colon
production antibmicrobial peptides
