Fungal infections Flashcards

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1
Q

Name 3 yeast fungi

A

Candida

Cryptococcus

Histoplasma

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2
Q

Name 3 mould fungi

A

Aspergillus

Dermatophytes

Agents of mucormycosis

Note: some fungi can go from being yeasts to moulds and therefore dimorphic e.g. histoplasma

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3
Q

What does this image show?

A
  • Candida gram stain
  • Much bigger than bacteria
  • Multiply by budding - most commonly candida
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4
Q
  1. What is candidiasis?
  2. Who is most at risk?
A
  1. Candidiasis is a primary or secondary mycotic infection caused by members of the genus Candida e.g. candida albicans.

Can cause mouth and thrush

  1. Candida is a commensal bacteria, and overgrowth can be seen in the immunocompetent especially after antibiotics as well as:
  • low birth weights
  • immunosuppressed
  • people on ITU
  • People with TPN

Candida is good at forming a biofilm and colonizing fake attachments/tubes

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5
Q

What is candida endopthalmitis associated with?

A

Candida endopthalmitis is associated with candidemia on indwelling catheters or drug abuse. Lesions are often localized near the macula and patients complain of cloudy vision

Rare

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6
Q

How is candidiasis diagnosed?

A
  • Blood cultures for candidaemia, other samples for short term fungal culture.
  • B D Glucan assay (serology)
  • Imaging e.g. for hepatosplenic candidaisis
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7
Q

How is candidiasis managed?

A
  • At least 2 weeks of antifungals from first negative blood cultures.
  • ECHO and fundoscopy
  • Echinicandin empirically and for non-albicans Candida
  • Fluconazole for Candida albicans
  • Ambisome (e.g. CNS), Fluconazole (e.g. urine) or Voriconazole (e.g. CNS) for organ-based disease.
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8
Q
  1. What is cryptococcosis?
  2. What is the aetiological agent?
  3. Who is at risk?
  4. What would the treatment be?
A
  1. Cryptococcosis is a chronic, subacute to acute pulmonary, systemic or meningitic disease, initated by the inhalation of the fungus. Has a predilection for the CNS
  2. Cryptococcus neoformans
  3. HIV people and transplant patients
  4. Treatment would be ambisome
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9
Q

Who is susceptible to cryptococcosis?

A
  • Greatly increased in patients with impaired T-cell immunity
  • Particularly AIDS patients, who have reduced CD4 helper T-cell numbers (typically less than 200/ml)
  • Second most common cause of death in AIDS
  • Patients taking T-cell immunosuppressants for solid organ transplant also have a 6% lifetime risk
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10
Q

What can cryptococcus neoformans var. gattii cause?

A

Causes a meningitis in apparently immunocompetent individuals in tropical latitudes esp. SE Asia and Australia

High incidence of space-occupying lesions

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11
Q

How is cryptococcosis diagnosed?

A

Diagnosis almost entirely around detection of Cryptococcal antigen in blood or CSF

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12
Q

How is cryptococcocosis managed?

A
  • 3/52 Amphotericin B +/- flucytosine
  • Repeat LP for pressure management
  • Secondary suppression with fluconazole
  • Some evidence that high dose fluconazole effective
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13
Q
  1. What is aspergillosis?
  2. How do you get it?
A
  1. Aspergillosis is a spectrum of diseases of humans and animals caused by members of the genus aspergillus.

  1. These include (1) mycotoxicosis due to ingestion of contaminated foods; (2) allergy and sequelae to the presence of conidia or transient growth of the organism in body orifices; (3) colonization without extension in preformed cavities and debilitated tissues; (4) invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs; and rarely (5) systemic and fatal disseminated disease. The type of disease and severity depends upon the physiologic state of the host and the species of Aspergillus involved.
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14
Q

How does aspergillus spread?

A

Grows filaments and then sheds spores

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15
Q

How is aspergillosis diagnosed?

A
  • Blood test and serology for IgE - to look for allergic response
  • Antigen - galactamanin - looked for in serology for aspergillus
  • Aspergillus PCR
  • Histology samples - look for invasion of aspergillus into tissue - chronic and brain lesions
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16
Q

What is the treatment for aspergillosis?

A
  • Voriconazole
  • Ambisome
  • Caspofungin/Itraconazole less good
  • At least 6 weeks of therapy
  • Duration based on host/radiological/mycological factors
17
Q

What is Ambisome?

A

Amphotericin B - treatment for aspergillus

18
Q

What are different dermatophyte infections?

A

Dermatophyte infections refers to fungal species that infect keratinized tissue

E.g. most commonly tinea/ring worm

19
Q

What is tinea pedis? What causes it?

A

Tinea pedis is athlete’s foot, commonlt caused by Trichophyton rubrum or T. interdigitale

20
Q

What is tinea cruris? What causes it?

A

Tinea cruris is the name used for infection of the groin with a dermatophyte fungus.

Caused by Tinea rubrum and E.floccosum

21
Q

what does this image show?

A

Tinea corporis or ring worm

22
Q

What causes tinea capitis?

A

T. rubrum and T.tonsurans

23
Q
  1. What is onchomycosis?
  2. What causes it?
A
  1. Also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed.
  2. Caused by Trichophyton spp, epidermophyton spp, microsporum spp.
24
Q
  1. What is pityriasis versicolor?
  2. What causes it?
A
  1. Fungal infection that causes scaling and discolouration of patches of skin
  2. M.sympodialis, m.globosa etc.
25
Q
  1. What is Murcormycosis?
  2. Who does it occur in?
  3. What can it cause?
A
  1. Mucormycosis is a serious yet infrequent fungal infection caused by Rhizopus spp. Rhizomucor spp or Mucor spp.
  2. occurs in immunocompromised patients - especially those with poorly controlled diabetes mellitus
  3. Can cause cellulitus of the orbit and face with black pus discharge, and can spread to the other areas including retro-orbital produing proptosis, chemosis and blindness. If the brain is involved it can cause reduced levels of consciousness. Facial swelling, painful eyes and headaches
  4. If found, debridement is needed to remove the infection. As well as antifungals e.g. high dose amphotericin (ambisome) and posacanazole
26
Q

What are the targets for antifungal therapy?

A
27
Q

Which antifungals target the cell membrane?

A
  • Polyene antibiotics e.g. Amphortericin B and Nystatin (topical)
  • Azole antifungals e.g. ketoconazole, itraconazole, fluconazole etc.

The azole family are far less toxic that amphotericin B

28
Q

What antifungals targets DNA/RNA synthesis?

A

Pyrimidine analogues such as Flucytosine, which is an anti-metabolite type of anti-fungal drug - can be given IV or PO

Mainly used now in combination therapy for cryptococcus infections

29
Q

Which antifungals target the cell wall?

A
  • Echinocandins
  • Caspofungin acetate
30
Q

What is the MOA of azoles?

A
  • In fungi, the cytochrome P450-enzyme lanosterol 14-a demethylase is responsible for the conversion of lanosterol to ergosterol. Therefore inhibit the erogsterol pathway. Causes sterols to be produced and build up, these are tpxic and get to high levels and kills the fungus
  • Azoles bind to lanosterol 14a-demethylas
31
Q

Which Azole has increased activity against Aspergillus?

A

Voriconazole is a water-soluble azole with a similar structure to fluconazole, but with increased activity against aspergillus species

32
Q
  1. What is the pharmocology of Echinocandins e.g. Capsofungin and Micafungin?
  2. What are they useful against?
A
  1. •Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase a key enzyme needed for the synthesis of B glucans. B glucans are specific structural components of the fungal cel wall. Depletion leads to cell wall disruption

Loss of cell wall glucan results in osmotic fragility

  1. spectrum:

–Candida species including non-albicans isolates resistant to fluconazole

–Aspergillus spp. but not activity against other moulds (Fusarium, Zygomycosis)

–No coverage of Cryptococcus neoformans

33
Q

Describe the action of Amphotericin B and what it is active against

A
  • Polyene antibiotic
  • Fermentation product of Streptomyces nodusus
  • Binds sterols in fungal cell membrane
  • Creates transmembrane channel and electrolyte leakage.
  • Active against most fungi except Aspergillus terreus, Scedosporium spp
34
Q

What is one of the main problems with Amphotericin B?

A
  • Classic amphotericin B deoxycholate (Fungizone™) formulation: serious toxic side effects.
  • Less toxic preparations:

1) Liposomal amphotericin B
2) Amphotericin B colloidal dispersion
3) Amphotericin B lipid complex

35
Q

What is the MOA of Polyenes like Amphotericin B?

A

Polyenes (amphotericin B deoxycholate and its lipid-associated formulations) act by inserting into the fungal membrane in close association with ergosterol. The subsequent formation of porin channels leads to loss of transmembrane potential and impaired cellular function.

36
Q
  1. What is the most common serious side effect of Amphotericin B?
  2. Why does this occur?
  3. Who is most susceptible?
A
  1. The commonest and most serious side effect of amphotericin B is renal toxicity. Most significant delayed toxicity
  2. Renovascular and tubular mechanisms:

–Vascular-decrease in renal blood flow leading to drop in GFR, azotemia

–Tubular-distal tubular ischemia, wasting of potassium, sodium, and magnesium

  1. The effect is enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents
37
Q
  1. What is the MOA of Flucytosine?
  2. What is it effective against?
  3. Side effects
A
  1. 5FC itself has no intrinsic antifungal activity; its anti-mycotic activity results from the rapid conversion of 5-FC into 5-FU within susceptible fungal cells.
  • First mechanism: 5FU is converted by UMP pyrophosphorylase into 5-fluorouridylic acid (FUMP), which is phosphorylated further to FUTP. This is incorporated into RNA, resulting in disruption of protein synthesis.
  • Second mechanism: 5FU is also converted to 5-fluorodeoxyuridine monophosphate (fdUMP), a potent inhibitor of thymidylate synthase, which is a key enzyme in the biosynthesis of DNA, since this enzyme is a crucial source of thymidine . Thus, 5FC acts by interfering with pyrimidine metabolism, as well as RNA, DNA, and protein synthesis in the fungal cell.
  1. Monotherapy is limited, but can be used in combination with amphotericin B or fluconazole to treat candidiasis or cryptococcosis
  2. Infrequent - include D&V, and alterations in LFTs. Blood levels need monitoring when used in conjunction with Amphotericin B