C. difficile Flashcards
(98 cards)
What is the prerequisite for C.diff infection
Dysbiosis
- disruption of the healthy normal microbiota
Often caused by antibiotics
Koch’s Postulates for microbiota studies
Identify all species in both healthy and diseased individuals
Isolate, purify and culture relevant bacterial species
Intervene and ameliorate
Detect and reisolate those species
What type of bacteria is C.difficile?
gram-positive (monoderm)
strict anaerobe
C.difficile niche
large intestine of mammals
particularly humans
Name for the spectrum of human diseases caused by C.difficile
C.diff associated diseases (CDAD)
CDADs
Diarrhoea
Pseudomembranous colitis
Toxic megacolon
Common symptom in C.difficile infection
Colitis
- inflammation of colon
Accumulation of neutrophils in tissue
Diarrhoea
simplest form of C.diff infection
majority of cases are self-limiting
recurring in small number of patients
Pseudomembranous colitis
neutrophils penetrate epithelium causing neutrophil filled blisters
on epithelium lining of colon
if untreated can lead to perforation of large bowel, causing sepsis
Treatment for pseudomembranous colitis
Treatment involves surgical removal of infected part of bowel
Toxic megacolon
Neutrophil accumulation in tissue releases more pro-inflammatory cytokines
- vicious cycle
More dangerous; less common
Inflammation of entire large bowel
What percentage of CDAD deaths are associated with inflammatory complications?
90%
What is the leading cause of hospital inquired infection?
C.difficile
MRSA affects only 1/5 of amount of patients that C.diff does
C.diff disease progression
Patient received antibiotics
Alteration in normal gut flora (dysbiosis)
Infection with C.diff spores
Spore germinate in gut forming vegetative cells
Cells multiply, produce toxins and sporulate
Spores excereted
Affect of antibiotics on microbiota
Changes species that make up biomass but not biomass itself
Kill susceptible bacteria
- their place in ecosystem will be replaced by other bacteria
- proliferate to fill same ecological niche
Left with more resistant species and strains
C.diff introduction to microbiome
Spores introduced via faecal-oral route
If introduced at the right time during dysbiosis it can proliferate and thrive
North American C.diff epidemic (2003)
Caused by two separate branches of 027 strain
Hypervirulent strain that is resistant to fluoroquinolone
Appeared in Philadelphia and Quebec
In 2004, epidemic strains appeared in UK
078 strain
In 2008, appeared in hospitals
Hypervirulent strain
Previously associated with animal infection
History of C.diff strains
(2001) 001 strain was dominant in UK
(2004/2005) outbreaks attributable to 027 strains
(2007) >50% infection in UK due to 027 strains
Measures put in place by NHS for control 027 outbreaks
Reintroduction of soap and water on wards in UK
- spores immune to killing by alcohol
Banned jewellery, watches and ties
Deep cleaning of beds, hospital wards
Isolation of rooms after cases for 24 hrs
- bleach every surface
What does the large diversity of C.diff ribotypes ciruclating suggest?
Source of infection if not transmission within hospitals
If C.diff transmission was primarily confined to hospitals you would expect to see a limited number of dominant ribotypes
Characteristics of Ribotype 027
Hypervirulent and fluoroquinolone resistant
Form complex, structured biofilms
Produce more spores
Produces more toxin in vitro
Produces third toxin (CDT)
- binary toxin
Contain 18bp deletion in tcdC (negative regulator of toxin expression)
Two branches of 027 strain in North America outbreak
Fluoroquinolone resistance had been acquired independently
Lineage FQR1 and FQR2
Lineage FQR1
Largely affecting hospitals in USA and in Korea
Didn’t appear anywhere else
- not as good penetrance as other lineage