Biofilm III - candida Flashcards
usual fungi presence on body
many
depending on immunosuppression and predisposition to disease impact their effect
inter-kingdom : candida doesnt exist in isolation - bacteria present as well
candida interactions with bacteria in oral cavity
Interact with many bacteria becomes different scenario especially in management, diagnosis and treatment
- Periodontal disease
- caries
- angular cheilitis
- denture related
- endodontic PA infection
issue with swab and trying to demonstrate interkingdom interaction
Unclear in clinical swab – hard to differentiate in sample where organisms came from (i.e. site)
so hard to tell role in certain pathologies
biovolume comparison
Yeast cells approx. 25-50x (likely 100) the biovolume of bacteria
- Fungi occupy high physical volume in colonisation and infection
Provide physical scaffold for bacteria
- ‘Mycofilms’
- Create protective environment
risk factors for developing candidiasis
- Immuno-compromised pts
- Immunosuppressive drugs
- Advanced HIV infection
- Intra-abdominal surgery
- Central venous catheter
- Parenteral nutrition
- Broad-spectrum antibiotics
- Dialysis
- Colonisation at a sterile site
- Diabetes
- Burn unit pt
- trauma pt
- long-term corticosteroid use
spectrum of canididal disease
- Periodontitis
- Dental implants
- Denture stomatitis
- CF lung infections
- Ventilator associated pneumonia
- Urinary tract infections
- Infectious kidney stones/biliary tract infections
- Chronic wounds
- Musculoskeletal infections/osteomyelitis
- Sutures
- Endocarditis
- Implant/medical device
- Catheters and stents
Candidaemia is associated with considerable morbidity in critically ill patients leading to an overall prolonged ICU stay, a longer duration of mechanical ventilation and
classifications of oral candidosis (2 inital categories)
confined to mouth and commissure
generalised candidosis with oral manifestations
confined to mouth and commisures
4
classes or oral candidosis
pseudomembranous
- thrush
erythematous
- atrophic (e.g. HIV related)
- denture related
hyperplastic
- candidal leukoplakia - premalignancy
angular cheilitis
- causes great discomfort in elderly pts, stroke pt
example generalised candidosis with oral manifestations
chronic mucocutaneous
pseudomembranous oral candidosis
thrush
- white plaques pronounced on surface of mucosa
- easily brushed away
- may bleed
yeast and hyphe attached
more common pre retroviral therapy for HIV
chronic hyperplastic oral candidosis
Hyphe Grow into tissue
- cannot be scraped off
need to do a biopsy to ensure not pre-malignant lesion
long course of antifungal agents
angular cheilitis
Angles of mouth
- Candida with interaction with gram +ve bacteria (staph)
Miconazole is key antifungal - topical
miconazole
key antifungal for angular cheilitis
topical
3 types of denture induced stomatitis (erythematous)
newton’s type I
- localised inflammation
newton’s type II
- diffuse inflammation
newton’s type III
- granular inflammation
how does denture stomatitis develop
candida Adhere and colonise acrylic surfaces
- Co-aggregation, biofilm formation, denture not cleaned effectively regularly
- infiltrate into nooks and crannies of PMMA
pt may not be aware they have
Down to denture and oral hygiene need mechanical removal of organisms regularly
5 signs and symptoms of denture stomatitis
- Inflamed mucosa – particularly under upper denture
- Burning sensation
- Discomfort
- Bad taste
- In most cases patients are unaware of the problem
dangerous risk of denture stomatitis
remove denture at night
aspirate biofilm in sleep -> pneumonia
candida species is
Opportunistic pathogenic yeasts
- Candida albicans
- Candida glabrata
- Candida parapsilosis
- Candida tropicalis
150 species of Candida described
- Different sensitivities to antifungals used to treat pt
4th leading cause of nosocomial bloodstream infections
Morbidity and mortality rates unacceptably high:
- Limited arsenal of antifungal drugs
- Toxicity of some antifungal agents
- Emergence of resistance
candida albicans sensitive to
fluconazole and miconazole
candida glabrata sensitive to
no known used antifungals (e.g. fluconazole, miconazole)
more frequent
why is there a limited arsenal of antifungal drugs that work
sensitvity variation of canidida species
- Overuse of fluconazole and miconazole is driving epidemiological changes*
- less albicans and more glabrata - issue
candida albicans
site, presence
- Present in 71% of healthy individuals
- Oral carriage varies (35-55%)
- Variable anatomical sites
- Oral cavity, vagina, gut (mucosal surfaces)
- Nutrient limitation/competition with bacteria
- Issue with broad spectrum AB – candida able to outcompete bacteria thrush
- 35% mortality rate (ICU candida blood stream infection 50% mortality)
- Various virulence attributes
morphogensis of candida albicans
when stressed from hyphe
allow to move from adhering to tissue to invading the tissue
difference between candida glabrata and albicans
candida albican - forms hype, sensitvie to antfungals
candida glabrata - doesn’t form hyphe but is intolerant to antifungals
differing pathogenicity
candidaemia
associated with considerable morbidity in critically ill patients leading to an overall prolonged ICU stay, a longer duration of mechanical ventilation and haemodialysis
candid adhere, make biofilm, invade into distal tissue causing severe systemic candidiasis infection
unlike pt will survive even when given antifungals and tx
events leading denture stomatitis
candida in oral cavity/biofiilm
attach to denture surface (not removed by mechanical cleaning)
stressed - form hyphe and penetrate PMMA
form ECM
ECM thickens on denture surface - making it even more difficult to remove organisms
phopholipase
substrate and contribution to infection
lipid
host cell penetration
uses of fungi
e.g. yeast
turns sugar (glucose) into alcohol and CO2
make beer and bread
candida and oral cancer
Alcohol not carcinogenic
Acetaldehyde is a carcinogen
- DNA damage
- ADH enzymes in human and yeast
- ADH genes key to biofilm formation
Can cause oral cancer processes
- Chronic candida in mouth is imp driver in head and neck cancer
- Autoimmune disease in bottlenecks of population – e.g. Finland*
- Often get oral cancer in 20s
how to diagnose pt with candidosis
Pseudomembranous
- smear onto slide
- hyphae? then candida albicans
- treat with azole (biofilm intolerant but pt will respond to some extent)
- hyphae? then candida albicans
Oral rinse - standard
Candida leukoplakia – biopsy
phenotypic, biochemic and genotypic diagnosis of candida
chromgenic agar better than sabouraud agar
- Different colours for colonies
- Determine specific organisms
- Often multiple mixed infections
- Help determine tx
antifungal therapy options (3)
azoles (FUNGISTATIC)
polyenes (FUNGICIDAL)
echinocandins
fungi structure than impacts therapy
thick beta glucans
chitin is present which strengthens cell wall
azoles
fungistatic
- work indirectly on ergosterol
- inhibiting molecules across the pathway prevent ergosterol being synthesised
echinocandins
- Act on beta 1, 3 glucans synthase
- Produce the beta glucans
- Inhibit enzyme - Destabilise cell wall = cell death
- Very good
- Not currently used in dentistry yet
azole resistance
work by inhibiting ergosterol indirectly
Changes across pathway or overexpression of certain elements
Leads to resistance and overexpression of CDR (candida drug resistance pumps) and MDR (multi drug resistance pumps)
- Azoles spat straight out
antifungal penetrations of biofilm challenge
many things prevent
- ECM
- persisters
- stress
- density
- efflux
- over expressed targets
- physiology
pro and con of biofilm
help prevent fungal penetrations initially (biofilm resistance)
but then has features which prevent antifungal penetration
dual resistance mechanisms
Staph aureus can coat is candida polymers
- Becomes resistant to vacomycin
So in mix species biofilms have vancomyocin resistance (s.aureus use candida to protect themselves) and candida become miconazole resistant
use each other to evade drugs
candida tx algorithm
think about pt and what is best for them in whole picture
