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BDS3 BAMS Microbiology and Oral Pathology > Biofilm III - candida > Flashcards

Biofilm III - candida Flashcards

1
Q

usual fungi presence on body

A

many

depending on immunosuppression and predisposition to disease impact their effect

inter-kingdom : candida doesnt exist in isolation - bacteria present as well

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2
Q

candida interactions with bacteria in oral cavity

A

Interact with many bacteria becomes different scenario especially in management, diagnosis and treatment

  • Periodontal disease
  • caries
  • angular cheilitis
  • denture related
  • endodontic PA infection
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3
Q

issue with swab and trying to demonstrate interkingdom interaction

A

Unclear in clinical swab – hard to differentiate in sample where organisms came from (i.e. site)

so hard to tell role in certain pathologies

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4
Q

biovolume comparison

A

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
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5
Q

risk factors for developing candidiasis

A
  • 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
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6
Q

spectrum of canididal disease

A
  • 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

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7
Q

classifications of oral candidosis (2 inital categories)

A

confined to mouth and commissure

generalised candidosis with oral manifestations

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8
Q

confined to mouth and commisures

4

classes or oral candidosis

A

pseudomembranous

  • thrush

erythematous

  • atrophic (e.g. HIV related)
  • denture related

hyperplastic

  • candidal leukoplakia - premalignancy

angular cheilitis

  • causes great discomfort in elderly pts, stroke pt
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9
Q

example generalised candidosis with oral manifestations

A

chronic mucocutaneous

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10
Q

pseudomembranous oral candidosis

A

thrush

  • white plaques pronounced on surface of mucosa
  • easily brushed away
    • may bleed

yeast and hyphe attached

more common pre retroviral therapy for HIV

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11
Q

chronic hyperplastic oral candidosis

A

Hyphe Grow into tissue

  • cannot be scraped off

need to do a biopsy to ensure not pre-malignant lesion

long course of antifungal agents

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12
Q

angular cheilitis

A

Angles of mouth

  • Candida with interaction with gram +ve bacteria (staph)

Miconazole is key antifungal - topical

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13
Q

miconazole

A

key antifungal for angular cheilitis

topical

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14
Q

3 types of denture induced stomatitis (erythematous)

A

newton’s type I

  • localised inflammation

newton’s type II

  • diffuse inflammation

newton’s type III

  • granular inflammation
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15
Q

how does denture stomatitis develop

A

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

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16
Q

5 signs and symptoms of denture stomatitis

A
  • Inflamed mucosa – particularly under upper denture
  • Burning sensation
  • Discomfort
  • Bad taste
  • In most cases patients are unaware of the problem
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17
Q

dangerous risk of denture stomatitis

A

remove denture at night

aspirate biofilm in sleep -> pneumonia

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18
Q

candida species is

A

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
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19
Q

candida albicans sensitive to

A

fluconazole and miconazole

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20
Q

candida glabrata sensitive to

A

no known used antifungals (e.g. fluconazole, miconazole)

more frequent

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21
Q

why is there a limited arsenal of antifungal drugs that work

A

sensitvity variation of canidida species

  • Overuse of fluconazole and miconazole is driving epidemiological changes*
  • less albicans and more glabrata - issue
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22
Q

candida albicans

site, presence

A
  • 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
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23
Q

morphogensis of candida albicans

A

when stressed from hyphe

allow to move from adhering to tissue to invading the tissue

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24
Q

difference between candida glabrata and albicans

A

candida albican - forms hype, sensitvie to antfungals

candida glabrata - doesn’t form hyphe but is intolerant to antifungals

differing pathogenicity

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25
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
26
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
27
hydrolytic enzymes
made within the biofilm by candida an enzyme that catalyzes the hydrolysis of a substrate through the addition of water
28
3 hydrolytic enzymes
phopholipase haemolysin proteinase
29
phopholipase substrate and contribution to infection
lipid host cell penetration
30
haemolysin substrate and contribution to infection
red blood cells facilitates hyphal invasion
31
proteinase substrate and contribution to infection
proteins adhesion to epithelial cells
32
uses of fungi
e.g. yeast turns sugar (glucose) into alcohol and CO2 make beer and bread
33
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*
34
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) Oral rinse - standard Candida leukoplakia – biopsy
35
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*
36
antifungal therapy options (3)
azoles (FUNGISTATIC) polyenes (FUNGICIDAL) echinocandins
37
fungi structure than impacts therapy
thick beta glucans chitin is present which strengthens cell wall
38
azoles
fungistatic * work indirectly on ergosterol * inhibiting molecules across the pathway prevent ergosterol being synthesised
39
polyenes
fungicidal * better, can be very toxic * act directly on ergosterol * cause pores * leakage of cytomplasm contents = cell death and lysis
40
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
41
5 antifungal drugs
nystatin amphotericin B miconazole fluconazole itraconazole chlorohexidine
42
nystatin amphotericin B preparations activity
topical - suspension, pastilles, lozenges, ointment all Candida sensitive resistance rare and no antibac activity pt compliance often poor
43
miconazole preparations activity
topical - oral gel or cream candida variable sensitivtiy possess anti-staphylococcal activity
44
fluconazole preparations activity
systemic - capsules ## Footnote **c albicans sensitive generally** **c glabrata and krusei naturally resistant**
45
itraconazole preparations activity
systemic -capsules systemic and topical - cyclodextrin solution candida generall sensitive little sign of resistance developing to date
46
chlorohexidine preparation activity
topical - solution antibacterial and anticandidal
47
first line candida tx
Chlorhexidine useful antiseptic as antibacterial and anticandidal * Then move onto somehting else if pt doesn’t response Flucanzole- can be pointless if glabrata or krusei
48
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
49
inappropriate tx of pts leads to
* evolution and action - resistance to drugs (CDR and MDR pumps increase)* * Changes in genetics in organism as a result of how it is treated*
50
antifungal penetrations of biofilm challenge
many things prevent * ECM * persisters * stress * density * efflux * over expressed targets * physiology
51
pro and con of biofilm
help prevent fungal penetrations initially (biofilm resistance) but then has features which prevent antifungal penetration
52
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
53
4 anti-fungal agents use in dentistry
Azoles ineffective against biofilms * need liposomal formulation to kill and penetrate through biofilm (as biofilm grows become intrinsic resistant to azole) Polyenes and echinocandins active **Chlorhexidine effective** * **First go to** Novel antifungal compounds - Tea tree oil
54
intrinsic resistance
innate ability of a bacterial species to resist activity of a particular antimicrobial agent through its inherent structural or functional characteristics, which allow tolerance of a particular drug or antimicrobial class.
55
candida tx algorithm
think about pt and what is best for them in whole picture
56
difference between candidosis and cadidiasis
no real difference interchangeable
57
is candidosis a problem
yes managable but if left unchecked can become problematic - sore discomfort for pt
58
what causes candidosis
Candida albicans and many more * Need to be able to differentiate them to know what treatment effective
59
should we specifically diagnose and tx candidosis
Yes – disease of a disease * Underlying condition needs diagnosed and managed effectively
60
how to dx and tx candidosis
Take an appropriate clinical specimen (swab, rinse, biopsy) Treat with good OH, chlorohexidine then itraconazole, fluconazole then nystatin * If not responding then newer antifungals - echinocandins
61
problems associated with dx and tx of candidosis (3)
Remember it is a biofilm – need to mechanical remove to be effective More than one organism – deal with like that If pt not responding to tx - reevaluate

BDS3 BAMS Microbiology and Oral Pathology (6 decks)

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