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30 Cards in this Set

  • Front
  • Back
Candida spp (ecology)

• Unusual in?

• Frequent colonizer and cause of disease in?

• Where in hospital?
• Unusual in soil, plants, atmosphere, and water
– restricted to sources where human or animal contamination are probable

• Frequent colonizer and cause of disease in many lower animals

• Frequent in hospital environment
– food
– air
– floors
– other surfaces in hospital wards
Candida spp (ecology)

Commonly found where?

Where else found in human body?
• Carriage in humans

– oropharynx
• 25-71%

– GI tract (GI commensal)
• ~ 50%

– vaginal secretions
• 4-27%

– skin (moist and damp skin)
• ~ 5-50%
Candida spp (ecology)

• Candida albicans is most frequently
acquired by _______ transmission of flora from the _________ ?.
Newborn gut is sterile.

• Candida albicans is most frequently
acquired by vertical transmission of flora from the maternal genital tract.
– 14-18% of full-term infants colonized in oropharynx on 1st day of life
– 80% by 3-4 weeks of age
Candidiasis:

Incidence? (increasing/decreasing?)

why?
Increasing
- patients are sicker now a days
- patients that would be in hospitals are now at home
- immunosuppresion also a factor
Candida blood stream infections - increasing/decreasing?
Blood stream candida infections are going down but not as fast as other blood stream infections so proportion is actually going up
Impact of Candidemia
(3)
• 4th most common isolates from blood cultures in U.S.
• Increases length of stay by 22 days
• Increases costs
Risk Factors for Candida BSI

Biggest risk factor?

Some others?
Candida Colonization biggest risk factor

Other:
- Broad-spectrum antimicrobials
- Mucosal surface disruption
(cytotoxins, hypotension, surgery)
- Neutropenia
- Central Venous Catheter
Candida almost NEVER causes _______
pneumonia
Spectrum of Systemic Candida Infections

From _________ to _______
From Candidemia to Organ involvement
Defining ‘invasive’ candidiasis

• Candida bloodstream infection (candidemia)
– How do we know we have candidemia?
– Does it precede or follow deep tissue organ infection?
– Critical diagnostic sign of ____ __________ ______________

• Disseminated disease (invasive candidiasis)
– Culture of histologic evidence of tissue invasion at ≥__ non-adjacent
normally sterile sites (all proven)
– Dissemination via?
• Candida bloodstream infection (candidemia)
– Isolation of a Candida sp. from one or more blood cultures (candida spp is a rare, so even if found in only 1 blood draw, is considered true infection)
– Can precede or follow deep-organ infection
– Critical diagnostic sign of acute disseminated candidiasis

• Disseminated disease (invasive candidiasis)
– Culture of histologic evidence of tissue invasion at ≥2 non-adjacent
normally sterile sites (all proven)
– Suggests haematogenous dissemination
• From GI tract to catheter/other organs
• From Catheters to other organs
Disseminated candidiasis
(clinical findings) (7 total)

• _________ in seriously ill patient

• _____ lesions (2 types)

•___________(esp. without catheter)

• _________ colonization

• ____________ despite antibiotics

• ____________ in seriously ill patient after initial improvement
• new fever or septic picture in seriously ill patient

• skin lesions

• retinal lesions

• candiduria (esp. without catheter)

• wound colonization

• persistent fever despite antibiotics

• gradual deterioration in seriously ill patient after initial improvement
Disseminated Candidiasis (diagnosis)

(7)
• Blood cultures (lysis centrifugation)

• Compatible retinal lesions

• Imaging (abdominal CT, MRI)

• Biopsy or smear of skin lesions

• Demonstration of candidal organisms in normally sterile site

• Candiduria in febrile, neutropenic patient with otherwise normal urinary tract

• Compatible patient with multiple sites of colonization
Candidemia and Acute Systemic
Candidiasis (treatment)

• Treat when?

• Treatment options?
• Treat as soon as positive culture, or
empirically in appropriate patients

• Remove catheter if possible

• Treatment options
– Candin (caspofungin, anidulofungin)
– Azole (fluconazole, voriconazole)
– Amphotericin B (DOC or lipid formulation)
What guides therapy?

Which 2 organisms are generally problematic?
Fungal species guides therapy
different species resistant/sensitive to different drugs

c. glabrata
c. krusei
Candida Treatment Strategies

What drug should you avoid using if the patient is hemodynamically unstable or neutropenic?

Which drug should you avoid if there is high likelihood that they are colonized by C. glabrata or C. krusei?
Avoid FLUCONAZOLE for both situations
Vulvovaginal candidiasis

STD?
Almost always due to which species?
Vaginal symptoms?

What kind of prep is used for diagnosis?

Therapy?
• Not an STD

• VVC almost always C. albicans

• May have vaginal pruritis/irritation without significant discharge

• Organisms may be seen on KOH prep

• Therapy
– Intravaginal azole therapy (OTC)
– Fluconazole 150 mg PO x 1
Thrush

Seen on which patients?

How do you treat?
HIV patients OR patients on antibiotics

Treat: topical nystatin or clomtrimazole; fluconazole
Diaper Rash

Tx:?
Topical anti-fungal therapy (nyastatin, fluconazole)
Classes of Antifungals

(4)
• Polyenes
• Azoles
• Echinocandins
• Other
Unlike mammalian cell walls, fungi use what on their cell walls?
Glucan and ergosterol
Polyenes

Name drugs
which one is topical?
which one is gold standard?
• Nystatin - topical
• Amphotericin B = gold standard
– deoxycholate
– lipid preparations
Amphotericin B

• Mechanism?
• Binds?
• Cost?
• Toxicity?
• Inserts into cell membrane
• Binds to sterols
• Increases membrane permeability
• “Gold standard”
• Inexpensive
• Fairly toxic (kidney)
Lipid preparations of
Amphotericin B

What is the advantage of lipid preparations?

Which one has the best toxicity profile?
Lipid preparations make it more soluble and minimize nephrotoxicity

Liposomal Amp B (AmBisome)
Lipid Preparations of AmB

More/less Toxicity than AmBdeoxycholate

Therapeutic index?

Acquisition costs?
• Less nephrotoxic than AmB deoxycholate

• Increased therapeutic index (can give higher doses)

• Acquisition costs significantly higher than AmB deoxycholate

• Substantial pharmacokinetic differences among them
– No prospective, randomized human trials comparing one to another
– No long-term studies demonstrating mortality benefit
Azoles

Oral? (4)

Topical? (3)
Oral
• fluconazole
• itraconazole
• voriconazole
• posaconazole

Topical
• ketoconazole (also oral)
• clotrimazole
• miconazole
Azoles

Mechanism of action?
Binds to Fe(cytochrome) of ergosterol synthesis enzyme

Increases cell membrane permeability (makes membrane more leaky)

Is fungostatic rather than fungocidal (amphotericin B)
Azoles - Key Points

• Many well absorbed ______?

• organisms covered?

• Problematic with decrease ______ function?

• Toxicities?
• Many well absorbed orally

• Significant variations in organisms covered

• IV forms of itraconazole and voriconazole have cyclodextran carrier; problematic with creatinine clearance < 50

• Toxicities minimal
– voriconazole with ocular side effects
Echinocandins

Mechanism?

_____: bacteria just as ______: fungi

Name 3
Inhibit synthesis of (1,3)-β-D-glucans in cell wall

Beta-lactam : bacteria just as Echinocandins : fungi

3 Echinocandins
•Caspofungin
• Micafungin
• Anidulofungin
Echinocandins - Key Points

• Mostly used against _______?
• Toxicities, drug-drug interactions?

Cost?
Administration?
• Mostly used against Candida
• Well tolerated
• Disadvantages
– expensive
– IV only
Other Antifungals (2)

1.___________
non-azole inhibitors of ________ synthesis?
– Use (topical/oral)?
– oral form used for?

2. _________
– inhibits DNA synthesis; also metabolized to _____ in fungi, incorporates into ____ and interferes with ____________
– Toxicity?
• Allylamines
– Terbinafine, naftifine
– non-azole inhibitors of sterol synthesis
– topical
– oral terbinafine used for onychomycosis

• Flucytosine (5-FC)
– inhibits DNA synthesis; also metabolized to 5-FU in fungi, incorporates into RNA and interferes with protein synthesis
– significant toxicity GI intolerance and bone marrow suppression