Fungal Infections Flashcards by Raunak Chandiramani

What are fungi?

Eukaryotic organism that possesses chitinous cell walls, plasma membrane containing ergosterol, 80S ribosomes

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What types of fungi exist?

2 types:

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What is the commonest cause of fungal infections in human?

Candida spp.

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What is candida? What is the clinical manifestations?

• A yeast and the commonest fungal infection
• > 150 Candida spp., but < 10 are human pathogens
• Clinical manifestations
– Acute, subacute, chronic, episodic
– Superficial or systemic/invasive

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How can we differentiate types of candida on plates?

We use chromogenic agar plates - different appearances.

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What’s wrong with Mr. X’s tongue?

Oral candidiasis.

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What are the types of superficial candida infections?

• Oral thrush
• Candida oesophagitis 
• Vulvovaginitis
• Cutaneous
– Localised or generalised

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What tx is available for superficial candidiasis

Send for plates.

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Which one is the yeast?

Left - larger, oval shaped.

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What are the risks of candidaemia?

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How do you manage candidaemia?

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What are the invasive candida infections? How does tx differ?

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What is cryptococcosis? How is it transmitted? How does it present?

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Describe the lifecycle of cryptococcosis.

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What are the RFs for cryptococcosis?

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What type of ink is used for a cryptococcal stain?

India ink.

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How is cryptococcosis treated?

Where is Aspergillosis found? What diseases does it cause?

What does this show?

An aspergilloma secondary to TB

How can you diagnose aspergillosis?

How is aspergillosis managed?

Where is pneumocystis jiroveci found? How is it different? What is the route of transmission? What are the risk factors?

How do you diagnose and manage pneumocystis pneumonia?

What is Mucornycoses? What is it caused by? How is it transmitted? What are the RFs?

Clinical syndrome caused by a number of fungal species belonging to the order Mucorales eg Rhizopus, Rhizomucor, Mucor
Inoculation via inhalation of spores or primary cutaneous inoculation
Favours immunosuppressed/diabetic patients

What are the clinical features of mucormycosis?

What is the diagnosis and management of mucormycosis?

What are dermatophytes? Where does it have effect?

What are the investigations and management of dermatophytes?

• Dx – Skin scrapings, nail specimens and plucked hairs • MC&S • Mx – Topical eg clotrimazole, ketoconazole – Oral eg griseofulvin, terbinafine, itraconazole

What are azoles associated with?

Abnormal LFTs.

What Polyenes associated with?

Nephrotoxicity

What are echinocandins associated with?

Relatively innocuous

What are pyrimidine analogues associated with?

Blood disorders

What are the targets of antifungal therapy?

What drugs target the cell membrane?

How to azoles work?

• In fungi, the cytochrome P450-enzyme lanosterol 14-a demethylase is responsible for the conversion of lanosterol to ergosterol • Azoles bind to lanosterol 14a-demethylase inhibiting the production of ergosterol – Some cross-reactivity is seen with mammalian cytochrome p450 enzymes • Drug Interactions • Impairment of steroidneogenesis (ketoconazole, itraconazole)

How do the polyenes work? What do we need to consider?

Amphotericin B * 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. • Most significant delayed toxicity • 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 • Enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents • Classic amphotericin B deoxycholate (FungizoneTM) formulation: serious toxic side effects • Less toxic preparations: 1) Liposomal amphotericin B 2) Amphotericin B colloidal dispersion 3) Amphotericin B lipid complex

What drugs target the cell wall?

How do the echinocandins work?

What drugs target DNA/RNA synthesis?

- DNA/RNA synthesis • Pyrimidine analogues | - Flucytosine

How does flucytosine work?

``` -• Restricted spectrum of activity • Acquired Resistance – result of monotherapy – rapid onset • Due to: – Decreased uptake (permease activity) – Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity) ``` • Limited – Candida and cryptococcosis • In combination with Ambisome/fluconazole • Ses – Infrequent – include D&V, alterations in liver function tests and blood disorders. • Blood concentrations need monitoring when used in conjunction with Amphotericin B