0521 - Skin Microflora and Fungal Infections Flashcards
List the common skin commensals
Fungi - Candida, malassezia
Gram + Rods - corynebacterium, propionibacterium
Gram + Cocci - Coag negative Staph, Coag Positive Staph Aureus; Other Coag negs (e.g. Strep sp).
Others - Pseudomonas aeruginosa, micrococcus, acinetobacter, brevibacterium (not important).
What are the general characteristics of normal skin flora?
Withstand wide temperature, and pH range in a high-salt environment.
Fermentative metabolism that produces acids, further contributing to acidic/antimicrobial environment of skin.
Many can utilise free fatty acids as nutrients.
Produce extracellular enzymes (lipases, proteases, keratinases etc) that hydrolise host macromolecules into transportable nutrients.
Discuss how commensals become pathogenic
Disruption to normal skin barrier (surgery, catheter, IVDU, trauma, ulcers)
Disruption to normal skin flora (antibiotics leading to overgrowth of candida)
Obstruction of skin glands (Folliculitis)
Review basic structure of yeasts and moulds
Both are eukaryotes, capable of sexual and asexual reproduction.
Yeasts are unicellular, dividing by fission, budding, or pseudohyphae.
Moulds are multicellular, differentiated, and have true hyphae.
What is a common presentation of a superficial fungal infection?
Most common, and happen in normal host. Particularly in moist areas.
Can involve skin, mucosal membranes, nails/hair etc.
Cheesy, white, or red infection. Grows on agar - Gram + big cocci (?)
Often candidiasis, dermatophytes, or malassezia furfur
What is a common presentation for mucocutaneous candidiasis?
Commonly in warm, moist site - mouth, oesophagus, ‘the folds’, or vulvovaginal.
Typically in diabetic, post-antibiotic, obese, or immunodeficient patients.
Diagnosed by swab and incubation - appear as Gram+ very large cocci.
Describe a common presentation of Dermatophyte infection.
Cause of tinea. Nails and hair particularly difficult to treat. No invasion, but bauses inflammatory response.
Use keratin for nutrients, so difficult to grow - need to provide samples of the tissue.
ID’d based on microscopic appearance.
Has an advancing edge of raised, scaly, dermatophyte on skin, cf. candida infection.
Describe a common presentation of malassezia furfur.
Superficial infection of hairless skin on trunk, neck, face and arm. Pigments pale skin, but hypopigments dark skin. Accompanied by a fine scale but otherwise asymptomatic.
Microscopy - classic ‘spaghetti and meatballs appearance - rods and cocci.
What are the risk factors and disease mechanism for Subcutaneous fungal infections?
Comes from a traumatic innoculation. Tropical areas, developing countries, less footwear. Rarely from surgical wounds/cannulas in immunosuppressed patients.
What are the risk factors and disease mechanism for Dimorphic/Endemic fungal infections?
More invasive. Yeast at body temperature, mould in environment.
Localised to certain areas (in the Americas generally), spread by inhalation of spores from soil, compost, air, etc, followed by systemic dissemination (particularly to CNS - brain lesions and meningits).
What are the risk factors and disease mechanism for invasive/disseminated/opportunistic fungal infections?
Occurs in immunocompromised patients (so issue for hospitals). Invasive candidiasis, or aspergillus.
Candidaisis can become candidaemia, retinopathy, endocarditis, hepatosplenic infection a big problem.
Risk factors, immunosuppression, hospitalisation, central line, IVDU etc.
Neutropenia plays a key role.
What are the broad mechanisms of action for antifungal agents?
Most common aim to hit the cell membrane Ergosterol synthesis, as humans don’t have that pathway. (-azoles)
Also aim for cell wall synthesis (echinocandins), direct damage to cell membrane (Polyenes).
Some disrupt microtubules and thereby inhibit mitosis (Griseofulvin)
What are Azoles and Allylamines?
Antifungals that work on cell membrane, on ergosterol synthesis.
Allylamines work on squalene epoxidase to disrupt ergosterol pathway.
Azoles have 2 groups - early (keto) and late (tri). They work by targeting 14-alpha demethylase to dysrupt the ergosterol synthesis pathway.
Briefly outline Ketoconazole
Early azole. Not used orally due to side effects and interactions. Includes Miconazole, commonly used for topical treatments.
Briefly outline Triazoles
Mainly used for prevention/treatment of serious invasive haematological infections.
Fluconazole - only hits yeasts.
Itraconzole - broader spectrum hitting some moulds too.
