Fungi Flashcards

1
Q

Describe the clinical presentation of a Sporothrix schenkii infection

A

Subcutaneous mycosis

  • Penetrates epethilial layers, but typically remains localized in the subcutaneous tissue
  • Granulomatous lesions may spread slowly through the lymphatics
  • Systemic infections possible in immunocompromised hosts
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2
Q

You see broad-based budding yeast in a patient sample.

Which organism is likely causing this?

A

Blastomycosis

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3
Q

What are fungal cell walls made from?

A

Glucans and chitin

(different from bacteria => beta-lactam abx won’t kill fungi)

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4
Q

Give an example of a cutaneous mycosis

Which organisms are most likely to cause this?

A

Tinea captis, Tinea pedis, Tinea cruris, Tinea manus

Most likely caused by Dermatophytes

(Ex: Trichopyton, microsporum, epidermophyton)

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5
Q

Which organisms can cause opportunistic mycoses?

What infections do they cause?

A
  • Candida spp -> Candidiasis
    • C. albicans, C. glabrata, C. parapsilosis, C. tropicalis
  • Cryptococcus neoformans -> Cryptococcosis
  • Aspergillus fumigatus -> Aspergillosis
  • Zygomycosis spp -> Murcormycosis
    • Z. rhizopus, Z. rhizomucor, Z. mucor
  • Pneumocystis jiroveci -> pneumocystosis
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6
Q

Which fungal infection would require close monitoring of intracerebral pressure during treatment? Why?

A

Cryptococcosis (Cryptococcus neoformans)

The fungus is assosiated with meningoencephalitis. The polysaccharide capsule fragments into bits during treatment and can cause stick together, causing an increase in intracerebral pressure.

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7
Q

What is likely causing this infection?

A

Sporothris schenkii

Subcutaneous mycoses - Sporotrichosis

Nodular lesions with lymphatic spread

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8
Q

Which fungal infections are most common in healthy people?

How are they spread?

A

Endemic mycoses; usually cause pulmonary infection in healthy individuals

  • Coccidioidomycosis
  • Histoplasmosis
  • Blastomycosis

Spread via spore inhalation (no person-person transmission)

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9
Q

Describe the clinical presentation of Candidiasis

How is it different from the other opportunistic mycoses?

A

Typically only find in its yeast form; look for white patches on mucosal surfaces

  • Colonizes the mucosal surface following trauma or unchecked proliferation (due to antibiotics)
  • 3 kinds
    • Superficial (mucosal + cutaneous)
      • Thrush
      • Vulvovaginitis
    • Chronic (mucocutaneous)
      • Results from childhood immunodeficiency
    • Systemic
      • Heart
      • Kidneys
      • Eyes
      • CNS

More likely to appear on only mucosal surfaces than other opportunistic mycoses; characterisitc white patches

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10
Q

What are the 3 major targets of antifungal drugs?

Give examples

A

All 3 classes basically target the cell wall or cell membrane

  • Membrane distruption
    • Polyenes: Bind to ergosterol to cause leaks
      • Amphotericin B, nystatin
  • Sterol synthesis inhibitors
    • Azoles (Inhibit cytochrome p450)
      • Ketoconazole, fluconazole, itraconazole, etc.
    • Allylamines (Inhibit squalene epoxidase)
      • Terbinafine
  • Glucan synthesis inhibition
    • Echinocandins (inhibit beta-1,3 glucan production)
      • Micafungin, caspofungin, anidulafungin)
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11
Q

Which organism is shown in this picture?

A

Blastomyces dermatidis

(look for broad-based budding yeast)

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12
Q

What similarities do all of the opportunistic mycoses share?

A

(Candidiasis, cryptococcosis, aspergillosis, murcormycosis, pneumocystosis)

  • Marginal pathogenicity
  • Usually co-exist with the host
  • Cause infection when…
    • The host is immunosuppressed
    • The bacterial niche is altered (ex: antibiotics)
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13
Q

Which organism exhibits this pattern of hypae grwoth?

A

Aspergillus spp.

Lookd for septate hyphae and acut angle branching

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14
Q

Which individuals are at an increased risk of mucosal fungal infections?

A

Anyone with impaired T-cell immunity

(Ex: HIV, SCID, corticosteroid use, transplant rejection medication, very old or very young)

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15
Q

A 57 year-old man presents with pneumonia worsens despite treatment with empiric antibacterial antibiotics (ceftriaxone plus azithromycin). Bronchoscopy shows broad-based budding yeast. What is the likely cause of his pneumonia?

A

Blastomyces dermatitidis

Blastomyces = broad based budding yeast

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16
Q

Describe the clinical presentation of murcormycosis

How is it different from the other opportunisitic mycoses?

A
  • Highly invasive local tissue infections
  • May spread to CNS
    • Thrombosis, infarction

More invasive tissue involvement than other opportunistic mycoses
High risk in Diabetes Melitus patients
Look for 90 degree angle growth of hyphae
Treatment may require surgery

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17
Q

A 37 year-old male presents with burning in his mouth; on exam he has white plaques over his palate. What is the likely cause of this condition?

A

Candida albicans

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18
Q

Which methods would you use to determine whether a lwoer respiratory tract infection is bacterial or fungal?

A
  • Growth pattern on culture
  • Gram stain
    • Fungus will not stain
  • KOH scrape (to confirm fungus)
  • History/exposure
  • Lung imaging
  • Measure cell wall products in the blood
    • Antigen assay
  • Lack of response to antibiotic therapy
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19
Q

Give an example of a subcutaneous mycosis

What organism might cause this?

A

Sporotrichosis

Caused by Sporothrix schenkii

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20
Q

Describe the clinical presentation of cryptococcosis

How is it different from the other opportunisitic mycoses?

A
  • Pulmonary infection
    • Asymptomatic or flu-like
  • May spread to CNS
    • Chronic meningoencephalitis
      • Polysaccharide capsule fragments and causes problems durign treatment; must monitor intracerebral pressure
  • History of interaction with pigeon guano

Only one found in pigeon guano; can cause seriosus CNS effects

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21
Q

What is the mechanism of fluconazole?

A

Disrupts the cell membrane by inhibiting ergosterol synthesis

(Same mechanism as all -azoles)

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22
Q

Which organism exhibits this characteristic pattern:

  • Enter the cell and remodel into spherical cells
  • Endospores divide
  • Rupture and release endospores into tissue
A

Coccidioidomycosis

23
Q

What is the only fungal infection that can be treated with an antibiotic?

Which antibiotic?

A

Pneumocystosis caused by pneumocystis jiroveci

Treat wiht trimethoprim-sulfamethoxazole

(Other anti-fungals will not work)

24
Q

What is likely causing this infection?

A

A dermatophyte (Trichophyton, microsporum, epidermophyton)

Cutaneous mycoses - tinea corporis

25
Q

What similarities do all of the endemic mycoses share?

A

(Coccidioidomycosis, histoplasmosis, blastomycosis)

  • Thermally dimorphic
  • Transmission via inhalation of spores
    • No person-person transmission
  • Can infect healthy people
    • But infections more severe in immunocompromised
26
Q

A 28-year-old white female presented with a recent-onset rash that involved the upper arms. She was otherwise healthy, with no known allergies and no history of medication or chemical exposure. Physical examination reveals multiple, discrete, 1- to 4-cm, salmon-colored, round, slightly scaly patches on both arms. There was no evidence of lymphadenopathy. What is the cause of her rash?

A

Malassezia furfur

27
Q

What are echinocandins?

What is their mechanism of action?

A

Echinocandins are anti-fungal drugs that inhibit glucan synthesis

They inhibit beta-1,3 glucan production, which impairs cell wall stress tolerance

28
Q

Describe the clinical presentation of blastomycosis

How is it different from the other endemic mycosis?

A
  • Pulmonary infection
    • Lower respiratory
  • May spread to CNS, gonadal tissues, bone

Look for broad-based budding yeast
More likely to involve CNS than coccidioidomycosis or histoplasmosis
Does not form granulomas like histoplasmosis

Endemic to North America, Canada, Africa, South America, Asia

29
Q

How are fungi different from bacteria?

A
  • Category
    • Fungi are eukaryotic
    • Bacteria are prokaryotic
  • Size
    • Fungi are larger (smallest spores = 2-3.5 uM)
    • Bacteria = ~1 uM
  • Mode of replication
    • Fungi = sexual or asexual
    • Bacteria = binary fission
  • Structure
    • Fungi = unicellular (yeast) or multicellular
      • Exhibit dimorphism (yeast form or mold form)
    • Bacteria = unicellular
  • Cell wall
    • Fungi = Chitin + mannan and glucan polysaccharide
    • Bacteria = Peptidoglycan, LPS
30
Q

How is Sporothrix schenkii spread?

A

Contaminated objectst that penetrate the skin

31
Q

Describe the clinical presentation of aspergillosis

How is it different from the other opportunisitic mycoses?

A
  • Hypersensitivity reaction
    • Allergic bronchopulonary aspergillosis
      • Recurrent asthma
      • Peripheral eosinophilia
  • Pulmonary invasion
    • Causes invasive hyphae
  • Macrophages control the infection
    • Except in immunosuppressed hosts
    • May form aspergillomas (similar to granulomas)

Always in mold (Hyphae) form
Look for acute angle growth (45 degrees)

32
Q

What are the three phyla of fungi that are pathogenic to humans?

Name a few organisms in each category

A
  • Ascomycetes
    • Candida
    • Coccidioides
    • Blastomyces
    • Histoplasma
  • Zygomycetes (cause murcormycosis)
    • Rhizopus
    • Rhizomucor
    • Mucor
  • Basidiomycetes
    • Cryptococcus
    • Malassezia
33
Q

What clinical scenarios promote fungal disease?

A
  • Environment
    • Warm, wet
    • Antibiotic use (disrupts natural flora)
    • Catheter or prosthetic device
  • Immune status
    • Immunosuppression
      • Transplant anti-rejection therapy
    • Chemotherapy
    • Corticosteroids
    • HIV/AIDS
    • Malnutrition
    • Very old or very young
  • Disease
    • HIV/AIDS
    • Neutropenia
    • Diabetes melitus (ketoacidosis)
34
Q

Which individuals are at an increased risk of invasive fungal infections?

A

Anyone with impaired neutrophils

(Ex: chemotherapy, corticosteroid use)

35
Q

Describe the clinical presentaiton of an infection by a dermatophyte such as epidermophyton

A

Invasion of superficial keratinized tissue (skin, hair, nails)

  • The tissue will likely be inflamed
  • Distant manifestations may be caused by a delayed hypersensitivity reaction
  • Systemic infections possile in immunocompomised hosts
36
Q

Which organism is this?

A

Coccidiodes

  • Enter the cell and remodel into spherical cells
  • Endospores divide
  • Rupture and release endospores into tissue
37
Q

What major comonent of the fungal cell membrane is different from the mammalian cell membrane?

A

The sterol

Fungi have ergosterol, mammals have cholesterol

38
Q

Describe the clinical presentation of a Malassezia furfur infection

A

Hypo or hyper pigmented regions only affecting the stratum corneum

39
Q

How is tinea captis spread?

A

Tinea captis and other cutaneous mycoses caused by dermatophytes are spred via direct contact

  • Group settings
  • Skin injury
  • Favorable growth conditions
  • Immunodeficiency
40
Q

Describe the clinical presentation of histoplasmosis

How is it different from the other endemic mycosis?

A
  • Pulmonary infection that replicates in macrophages
    • May cause acute pulmonary disease if exposure is high
  • May form caseating or non-caseating granulomas
    • May look like M**ycobacterium tuberculosis
  • May disseminate to RES organs
    • More likely in immunocompromised host

More likely to disseminate than coccidiodomycosis
Forms granulomas
Less likely to involve CNS than blastomycosis

Endemic to central and eastern USA

41
Q

Which fungi are thermally dimorphic?

A
  • Coccidioides immitis*
  • Histoplasma capsulatum*
  • Blastomyces dermatitidis*
42
Q

What is dimorphism, in the context of fungi?

A

Many fungi have multiple forms; Dimorphism = it can switch back and forth

  • Mold form = hyphae
  • Yeast form
  • Spore
    • Mode of replication and transmission
    • Created in the sexual phase
43
Q

Describe the clinical presentation of coccidioidomycosis

How is it different from the other endemic mycoses?

A
  • Mild pulmonary infection
    • May be subclinical
  • Severe pulmonary infection in an immunocompromised host

Less likely to disseminate than other endemic mycosis

Endemic to the Southern USA and Latin America

44
Q

Which organisms can cause endemic mycosis?

What infections do they cause?

A
  • Coccidioides immitis -> Coccidioidomycosis
  • Histoplasma capsulatum -> Histoplasmosis
  • Blastomyces dermatitidis -> Blastomycosis
45
Q

What kind of drug is itraconazole?

What is the mechanism of action of itraconazole?

A

Itraconazole is an Azole, one of the steroid-synthesis inhibiting anti-fungal drugs

Itraconazole (and the other azols) bind to fungal cytochrome p450 to inhibit sterol synthesis

This causes membrane substrates and toxic intermediates to accumulate

Note: potential drug-drug interactions and hepatic toxicity

46
Q

One of your patients had a liver transplant 1 year ago. He is adherent to his immunosuppression regimin and is tolerating the graft well.

He was recently diagnosed with a case of tinea capitis.

Which agents might be prescribed as treatment?

Which would not be prescribed?

A

Most of the antifungal agents will work

Allylamine such as terbinafine may be prescribed

Azoles would not be recommended due to risk of hepatic toxicity (Azoles inhibit cytochrome p405)

47
Q

Describe the clinical presentation of pneumocystosis

How is it different from the other opportunisitic mycoses?

A
  • Only causes infection in immunocompromised
    • Pneumocystis jiroveci is a commensal of the lung
    • Seen especially in premature or malnourished infants and HIV/AIDs patients
  • Grows on surfactant of alveolus
    • Increases barrer to gas exchange

The only fungal infection that is treated with trimethoprim-sulfamethoxazole (the antifungals don’t work)

48
Q

What is the mechanism of action of Allyamines?

A

Allyamines are anti-fungal drugs that work via sterol synthesis inhibition

Specifically, the inhibit squalene epoxidase (an earlier step in sterol synthesis)

49
Q

What are the 3 fungal virulence factor categories?

Give examples of each

A
  • Thermotolerance
    • Dimorphism may depend on temperature
      • Coccidioidomycosis, histoplasmosis, blastomycosis
    • Not easily killed by heat
  • Exoenzymes
    • Proteases, lipases, phospholipases
      • Damage barriers, liberate nutrients
    • Toxins
      • Ex: aflatoxins can be carcinogenic
  • Cell wall components
    • Polysaccharide components (mannan and glucan) are highly immunogenic
50
Q

What is likely causing this infection?

A

Malassezia furfur

This is a superficial mycoses infection (pityriasis versicolor)

51
Q

Give an example of a superficial mycosis

Which organism is likely to cause this?

A

Pityriasis versicolor

Malassezia furfur

52
Q

Assume that the white patches would scrape off of you tried

What organism is causing this?

A

One of the Candidia spp

This mucosal infection is associated with T-cell dysfunction (invasive is associated with neutrophils)

53
Q

What is kind of drug is amphotericin B?

What is the mechanism?

A

Amphotericin B is a polyene, used as an anti-fungal

It binds to ergosterol in the cell membrane causing leakage of electrolytes. This leads to loss of membrane potential