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YEAR 5: MICRO > MI: Fungal Infections > Flashcards

MI: Fungal Infections Flashcards

1
Q

List three examples of:

  • Yeast
  • Moulds

What’s the difference between them

A

Yeasts:

  • Candida
  • Cryptococcus
  • Histoplasma (dimorphic)

Moulds:

  • Aspergillus
  • Dermatophytes
  • Agents of mucormycosis

Eukaryotes

chitinous cell wall, plasma membrane with ergosterol, 80S RNA

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2
Q

What does ‘dimorphic’ mean with regards to fungi?

A

It can change between being a yeast and a mould

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3
Q

Describe the appearance of Candida under the microscope.

A
  • Single-celled organisms that replicated by budding
  • They are much bigger than bacteria
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4
Q

Which systemic infections can be caused by Candida?

A

Septicaemia, endocarditis, meningitis

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5
Q

List some patient groups that are at risk of invasive Candida infection.

A
  • VLBW infants
  • Immunocompromised - esp haem malignancy
  • Patients on ITU (especially if they have lines in)
  • Patients receiving TPN
  • Immunocompotent patients who have had antibiotic treatment
  • Burns
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6
Q

List some agents that can cause candidiasis.

A
  • Candida albicans (MOST COMMON)
  • Candida glabrata
  • Candida krusei
  • Candida tropicalis

cultured on chromogenic agair

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7
Q

Superifical candida infections

A

oral thrush

candia oesophagitis

vulvovaginitis

cutaneous

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8
Q

Describe a screening test for candidiasis.

A
  • Candida albicans forms a germ tube
  • Can be identified by microscopy
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9
Q

How can Candida affect the eyes?

A

Causes endophthalmitis

very serious

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10
Q

What does generalised candidiasis in babies usually occur secondary to?

A

Seborrheic dermatitis

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11
Q

What is the term used to describe candidiasis of babies that the skin folds?

A

Intertrigo

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12
Q

How can candidiasis lead to mediastinitis?

A

If oesophageal candidiasis invades the tissue leading to perforation

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13
Q

Outline the diagnostic tests used for candidiasis.

A
  • Swabs
  • Blood cultures
  • Beta-D glucan assay (serology)
  • Imaging

often clinical

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14
Q

What type of agar is needed for culturing Candida?

A

Sabouraud agar - impregnated with antibiotics to prevent bacteria from outcompeteing the fungi

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15
Q

Outline the management of superficial/localized candidiasis.

A

Topical:
* clotrimazole - vulvovaginitis, cutaenous
* nystatin - oral thrush

Oral:
* Fluconazole - vulvovaginitis, oesophagitis
(empirical for Candida albicans)

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16
Q

Managment of systemic candida infections

A
  • At least 2 weeks of antifungals after the last negative culture
  • Echo and fundoscopy to look for endocarditis/endophthalmitis
  • Echinocandins - empirical for non-albicans infections

Blood cultures every 48hrs
Remove any lines + prosthetic material

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17
Q

What type of disease does Cryptococcus tend to cause?

A

Pulmonary, systemic and meningitic disease

its an encapsulated yeast

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18
Q

Which group of antifungals is Cryptococcus inherently resistant to?

A

Echinocandins

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19
Q

What is the treatment of choice for Cryptococcus infection?

A

Ambisome (amphotericin B)

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20
Q

What animal is cryptococcus assoicated with

A

pigeons

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21
Q

What is the main aetiological agent in cryptococcosis.

A

Cryptococcus neoformans

affects immunocompromised

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22
Q

Which patients are particularly at risk of cryptococcosis?

A

Impaired T cell immunity (AIDS)

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23
Q

What is Cryptococcus gatii?

A
  • Crytopoccous gatti causes meningitis in apparently immunocompetent individuals in tropical countries
  • High incidence of space-occupying lesions in the lung and brain
  • Increasing resistance to amphotericin B
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24
Q

Describe the appearance of Cryptococcus under the microscope.

A
  • Distinc capsule around the yeast
  • India ink can be used to stain

NOTE: the capsule is not always present

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25
Which diagnostic test is important in the diagnosis of cryptococcosis?
Enzyme immunoassay (EIA) looking for components of the capsule
26
Why might a lumbar puncture be negative in cryptococcal meningitis?
Cryptococcal meningitis can cause hydrocephalus which prevents the circulation of CSF meaning that the sample taken at LP may not have been exposed to CSF within other parts of the ventricular system
27
Outline the treatment options for *Cryptococcus* infection.
* 3 weeks amphotericin B (ambisome) +/- flucytosine * Repeat LP for pressure measurement * Secondary suppression - fluconazole | often need at least 1 year maintenance with fluconzaole
28
List the diseases that can be caused by *Aspergillus*.
* Mycotoxicosis * Allergic bronchopulmonary aspergillosis * Aspergilloma * Invasive/disseminated aspergillosis
29
List the aetiological agents that can cause *Aspergillus* infection.
* *Aspergillus fumigatus* * *Aspergillus flavus* * *Aspergillus niger* * *Aspergillus niduland* * *Aspergillus terreus*
30
What is the mainstay of diagnosis of *Aspergillus* infection?
Microscopy - looking at fungal spores
31
List some investigations used in the diagnosis of *Aspergillus* infection.
* Blood test * Serology (check IgE for allergic response (e.g. ABPA)) * Antigen detection **(galactomannan)** * Also detected in BAL * PCR * Histology * Culture | ongoing fevers despite ABx
32
What is the mainstay of treatment for aspergillosis?
* Amphotericin for at least 6 weeks * Other options: voriconazole, caspofungin, itraconazole
33
What is main treatment for PCP Why might it antifungals in targeting cell membrane not work PCP
hihg dose co-trimoxazole steroids if hypoxia PCP cell membrane does not have ergosterol
34
List some examples of dermatophyte infections.
* Ringworm * Tinea * Nail infections
35
What is tinea pedis caused by?
* *Tricophyton rubrum* * *Tricophyton interdigitale* * *Epidermophyton floccosum*
36
What is tinea cruris caused by?
* *Tricophyton rubrum* * *Epidermophyton floccosum* | in groin
37
What is tinea corporis caused by?
* *Tricophyton rubrum* * *Tricophyton tonsurans*
38
What is onychomycosis caused by?
* *Tricophyton spp.* * *Epidermophyton spp.* * *Microsporum spp.*
39
How is onychomycosis treated?
* Nail lacquers * If unsuccessful, systemic treatment with terbinafine * Itraconazole is also an option
40
How are dermatophyte infections diagnosed?
Skin scarpings and microscopy
41
What is pityriasis versicolor caused by?
*Malassezia furfur*
42
What is mucormycosis?
Group of moulds that cause very severe and invasive disease
43
Which groups of patients are affected by mucormycosis?
* Immunocompromised patients * Patients with poorly controlled **diabetes**
44
What is the characteristic clinical manifestation of mucormycosis?
Cellulitis of the orbit and face which progresses with discharge and black pus from the palate and nose NOTE: black eschars may be seen as the fungus destroys the tissues
45
What can retro-orbital extension of mucormycosis lead to?
Proptosis, ophthalmoplegia and blindness
46
What is the term used to describe the invasion of the brain by mucormycosis?
Rhinocerebral mucormycosis
47
List three aetiological agents that can cause mucormyocosis.
* *Rhizopum spp.* * *Rhizomucor spp.* * *Mucor spp.*
48
How is mucormycosis managed?
* SURGICAL EMERGENCY * Refer to ENT for debridement * May need high-dose amphotericin
49
What are the three targets of antifungals?
* Cell membrane * DNA/RNA synthesis * Cell wall
50
List antifungals that target: * Cell membrane * DNA/RNA synthesis * Cell wall
**Cell membrane:** * Polyene - amphotericin B, nystatin * Azole - ketoconazole, itraconazole, fluconazole, clotrimazole **DNA/RNA synthesis:** * Flucytosine (pyrimidine analogue) **Cell wall:** * Echinocandins - caspofungin acetate
51
What is the mechanism of action of azoles?
* Inhibit ergosterol production by inhibiting CYP450 enzyme lanosterol 14a-demethylase * This inhibition leads to the accumulation of toxic steroids in the cell membrane which cause cell death
52
azoles most common side effect
abnormla LFTS
53
polyenes most common side effect
nephrotoxic
54
pyrimidine analogues most common side effects
blood disorders
55
What are the consequences of cross-reaction of azoles ith other CYP450 enzymes?
* Drug interactions * Impairment of steroidoneogenesis
56
List examples of the following types of azoles along with their usual indications: * Water-soluble triazoles * Lipophilic triazoles
**Water-soluble triazoles:** * Fluconazole - active against *Candida* and *Cryptococcus* * Voriconazole - similar to fluconazole but better activity against *Aspergillus* **Lipophilic triazoles:** * Itraconazole - useful against dermatophytes * Posaconazole - activity against mucor
57
List some examples of echinocandins.
* Caspofungin * Micafungin * Anidulafungin
58
What is the mechanism of action of echinocandins?
* Cyclic lipopeptide antibiotic that inhibits beta-(1,3) D-glucan synthase * This enzyme is responsible for the production of beta D-glucan which is a component of the fungal cell wall * This inhibition results in osmotic fragility of the cell
59
Which fungi are echinocandins active against?
* Candida* species * Aspergillus* species (NOT other moulds) NOTE: it has NO coverage for *Cryptococcus*
60
What is the main polyene antifungal?
Amphotericin B
61
How is amphotericin packaged in most formulations?
Put in liposomes to try and reduce toxicity and improve penetration
62
What is ambisome?
Amphotericin within a phospholipid bilayer
63
How is amphotericin B produced?
Fermentation product of *Streptomyces nodusus*
64
Describe the mechanism of action of amphotericin B.
* Binds to ergosterol in the fungal cell membrane and creates transmembrane channels leading to electroyte leakage * This leads to fungal cell death
65
Amphotericin B is active against must fungi except...
* *Aspergillus terreus* * *Scedosporium spp.*
66
What is the main side-effect of amphotericin B? Describe the mechanism of this toxicity.
* **Nephrotoxicity** * **Renovascular** - decrease in renal blood flow leads to reduced GFR (azotaemia) * **Tubular** - distal tubular ischaemia, wasting of sodium, potassium and magnesium
67
Describe the mechanism of action of flucytosine.
Inhibits DNA synthesis (pyrimidine analogue)
68
What are some mechanisms of resistance to flucytosine?
* Decreased uptake (permease activity) * Altered 5-FC metabolism
69
Which fungi are flucytosine active against?
Candidiasis Cryptococcus
70
List some side-effects of flucytosine.
* D&V * LFT changes * Blood disorders NOTE: blood concentrations should be monitored if used with amphotericin B

YEAR 5: MICRO (24 decks)

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