Introduction to Mycology Flashcards
What are fungi?
Eukaryotic organisms with chitinous cell walls and ergosterol containing plasma membranes and 80S RNA.
What are yeasts?
Single celled, reproduce by budding
What are some examples of yeasts?
Candida
Cryptococcus
Histoplasma (dimorphic)
What are moulds?
Multicellular hyphae, grow by branching and extension
What are some examples of moulds?
Dermatophytes
Aspergillus
Agents of mucormycoses
Which is the commonest cause of fungal infections in human?
Candida spp
What is Candida Spp.?
> 150 Candida spp., but < 10 are human pathogens.
Clinical manifestations:
- Acute, subacute, chronic, episodic
- Superficial or systemic/invasive
What is this?
Oral candidiasis
What is this?
Candidal intertrigo
What are superficial Candida infections?
- Oral thrush
- Candida oesophagitis
- Vulvovaginitis
- Cutaneous – Localised or generalised
What is the topical management for Candida?
Oral thrush: Nystatin
Vulvovaginitis: Cotrimazole
Localised cutaneous: Cotrimazole
What is the oral management for Candida?
Vulvovaginitis: Fluconazole
Oesophagitis: Fluconazole
What are risk factors for Candidaemia?
Malignancies, esp haematological
Burns patients
Complicated post-op courses (e.g. Tx or GIT Sx)
Long lines
What is the general management for fungal infections?
Look for source and signs of dissemination:
- Imaging
- Serology for beta-D-glucan
- ECHO
- Fundoscopy
Antifungals for at least 2/52 (from date of first –ve blood culture): Echinocandin e.g. anidulafungin (whilst a/w identification and susceptibilities)
Blood culture every 48 hours
REMOVE ANY LINES/PROSTHETIC MATERIAL
What are some invasive Candida infections?
Candidaemia
CNS: Dissemination, trauma, Sx
Rx: Ambisome/voriconazole
Endocarditis: Abnormal valves/prosthetic valves, long lines, IVDU
Rx: Ambisome/voriconazole, Sx
Urinary tract: Vulvovaginits, catheters
Rx: Fluconazole
Bone and joint: Dissemination. Trauma
Rx: Ambisome/voriconazle, Sx
- *Intra-abdominal:** Peritoneal dialysis, Sx, perforation
- *Rx:** Echinocandin/Fluconazole
What is Cryptococcus spp and how is it transmitted?
Encapsulated yeast:
- Serotypes A&D = C neoformans (immunodeficient)
- Serotypes B&C = C gattii (immunocompetent)
Transmission by inhalation of aerosolised organisms.
Chronic, subacute to acute pulmonary, meningitic or systemic disease.
Which animal is cryptococcus associated with?
Pigeons
What are risk factors for cryptococcus?
Impaired T-cell immunity e.g patients with HIV, who have reduced CD4 helper T-cell numbers (typically less than 200/ml).
Patients taking T-cell immunosuppressants for solid organ transplant also have a 6% lifetime risk.
What is C. Gatti?
Causes a meningitis in apparently immunocompetent individuals in tropical latitudes, esp. SE Asia and Australia.
Outbreak in Vancouver Island 2004.
High incidence of space-occupying lesions in brain and lung. Increased resistance to amphotericin B clinically.
What type of ink is used for a cryptococcal stain?
India
What are appropriate investigations for cryptococcus?
Typical clinical history/features: Immunosuppressed host
Imaging
India ink staining of CSF
Serum/CSF cryptococcal Ag (CRAG)
Can culture from blood/body fluids
What is the management for cryptococcus?
Induction: Amphotericin B + flucytosine (at least 2/52)
Consolidation: High dose fluconazole (at least 8/52)
Maintenance: Low dose fluconazole (at least 1 year). Repeat LP for pressure management.
Pulmonary disease: If mild, fluconazole alone.
What is Aspergillosis?
A mould with worldwide distribution.
Causes a spectrum of disease in helath and immunocompromised patients:
- Mycotoxicosis: Ingestion of contaminated foods.
- Allergy and sequelae: Presence of conidia/transient growth of the organism in body orifices.
- Colonization: In preformed cavities and debilitated tissues.
- Invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs – systemic and fatal disseminated disease.
Type of disease and severity depends upon the physiologic state of the host and the species.
What is Aspergillosis associated with?
TB abscesses in the lung are most likely to be colonised by Aspergillosis.
What are appropriate investigations for Aspergillosis?
Imaging
Sputum/BAL – MC&S, Ag testing
Aspergillus Abs (precipitans)
Galactomannan
Bx – histology, MC&S
What is the management for Aspergillosis?
Voriconazole
Ambisome
Duration based on host/radiological/mycological factors – At least 6/52
What is Pneumocystis Jiroveci?
Ubiquitous in the environment and distributed worldwide.
Lacks ergosterol in its cell wall.
Acquisition by airborne route – Pneumonia.
Extrapulmonary disease is very rare.
What are risk factors for Pneumocystis Jiroveci?
Immunodeficiency
Immunosuppressive drugs
Debilitated infants
Severe protein malnutrition
What are appropriate investigations for Pneumocystis Jiroveci?
Microscopy
PCR
Beta-D-glucan
What is the management for Pneumocystis Jiroveci?
High dose cotrimoxazole 2-3/52
Alternatives: Atovaquone, clindamycin + primaquine
Steroids if hypoxia present
Why might antifungals targeting the cell membrane not work in pneumocystis pneumonia (PCP)?
It lacks ergosterol in its cell wall
What is mucomycoses?
Clinical syndrome caused by a number of fungal species belonging to the order Mucorales e.g. Rhizopus, Rhizomucor, Mucor.
Inoculation via inhalation of spores or primary cutaneous inoculation. Favours immunosuppressed/diabetic patients.
What are the clinical features of mucomycoses infection?
Rhinocerebral => CNS.
- Cellulitis of the orbit and face progress with discharge of black pus from the palate and nose.
- Retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness.
- As the brain is involved, there are decreasing levels of consciousness.
Pulmonary
Cutaneous
What are appropriate investigations for mucomycoses?
Isolation from tissue Bx
What is the management for mucomycoses?
Ambisome/Posaconazole
Symptomatic treatment guided by response
What are dermatophytes?
A group of fungi capable of ivading dead keratin of skin, hair and nails. Classified by site infected e.g. tinea capitis.
Spread via contact with desquamated skin scales.
What are risk factors for dermatophytes?
Moisture
Deficiencies in cell mediated immunity
Genetic predisposition
On which sites do different tinea infections occur?
Tinea pedis: Foot
Tinea capitis: Scalp
Tinea cruris: Groin
Tinea corporis: Abdomen
What are appropriate investigations for dermatophytes?
Skin scrapings, nail specimens and plucked hairs
MC&S
What is the management for dermatophytes?
Topical e.g. Clotrimazole, ketoconazole
Oral e.g. Griseofulvin, terbinafine, itraconazole
What are the side effects of azoles?
Abnormal LFTs
What are the side effects of polyenes?
Nephrotoxicity
What are the side effects of pyrimidine analogues?
Blood disorders
What are the side effects of echinocandins?
Relatively innocuous
What are the three common targets for antifungal therapy?
Cell membrane
DNA synthesis
Cell wall
Which antibiotics and antifungals target the cell membrane?
Polyene antibiotics:
- Amphotericin B, lipid formulations
- Nystatin (topical)
Azole antifungals:
- Ketoconazole
- Itraconazole
- Fluconazole
- Voriconazole
- Miconazole
- Clotrimazole (and other topicals)
How do 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 polyenes (e.g. Amphotericin B) work?
Amphotericin B is a fermentation product of Streptomyces nodusus.
It binds sterols in fungal cell membrane and creates transmembrane channel and electrolyte leakage. Active against most fungi except Aspergillus terreus, Scedosporium spp.
How do polyenes cause nephrotoxicity?
Most significant delayed toxicity.
Renovascular and tubular mechanisms:
- Vascular-decrease in renal blood flow leading to drop in GFR, azotemia (elevation of blood urea nitrogen (BUN) and serum creatinine levels).
- Tubular-distal tubular ischemia, wasting of potassium, sodium, and magnesium.
Enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents.
What can be done to mitigate the toxicity of Amphotericin B?
Classic amphotericin B deoxycholate (Fungizone™) formulation has serious toxic side effects.
Less toxic preparations:
- Liposomal amphotericin B
- Amphotericin B colloidal dispersion
- Amphotericin B lipid complex
Which antifungals target fungal cell walls?
Echinocandins
e.g. Caspofungin acetate (Cancidas)
How do echinocandins work?
Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase.
Loss of cell wall glucan results in osmotic fragility.
What is the spectrum of echinocandins?
Candida species including non-albicans isolates resistant to fluconazole.
Aspergillus spp. but not activity against other moulds (Fusarium, Zygomycosis).
No coverage of Cryptococcus neoformans.
Which antifungals target DNA/RNA synthesis?
Pyrimidine analogues e.g. Flucytosine
Why does flucytosine have a 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).
What are the uses and side effects of flucytosine?
Limited: Candida and cryptococcosis.
In combination with Ambisome/fluconazole.
Side effects: Infrequent – include D&V, alterations in liver function tests and blood disorders.
Blood concentrations need monitoring when used in conjunction with Amphotericin B.
