Infections Lecture 6: Fungal infections and anti fungal drugs Flashcards
What is a fungus
Single celled or multicellular organism
Give examples of single celled fungus organisms
Candida SPP, Cryptococcus
Give examples of filamentous, mould, multicellular organisms
Aspergillus SPP
Dermatophytes
What is the fungal cell wall normally made of
Beta 1,3 glucans
Beta 1,6 gluons
Chitin
Ergosterol
Beta 1,3 glucan synthase
State all the main anti fungal drugs PAAEFG or FAGPAE
POLEYENES (main one)
AZOLES (main one)
ALLYLAMINE (main one)
ECHINOCANDINS
FLUCYTOSINE
GRISEOFULVIN
Give an example of a Polyene, its route/indication, spectrum and side effects
Example: Amophotericin B, NYSTATIN
Route:
Oral, not toxic: Oral candida
IV, highly toxic: life threatening cryptococcal meningitis
Spectrum: Broad
What is the polyene mechanism of action
Binds to ergosterol to form pores in plasma membrane
Leaks out K+ and Mg2+
Lysis- cell death
Fungicidal
What are the two types of Azoles that are available
Imidazole
Triazole
Give examples of imidazole and the route
Miconazole (Daktarin)
Clotrimazole (canesten cream)
Ketoconazole (nizoral cream/shampoo)
Route: topical for superficial mycoses
Give examples of Triazoles and the route
Fluconazole (capsules, liquids, IV, systemic)
Itraconazole (sporanox, capsules, liquid, IV)
Posaconazole (tablet or suspension)
Route: oral or systemic
What is the mechanism of action of azole
Inhibition of lanosterol 14 alpha-demethylase (cytochrome P450) this interrupts ergosterol biosynthesis
Disrupts plasma membrane and acts as fungistatic
Give an example of Allylamines, its spectrum
Example: TERBINAFINE (lamisal)- fungal nail infection
Spectrum: mainly dermatophytes
Mechanism:
What is the mechanism of action of Allylamine
Inhibits squalene epoxidase which inhibits the production of lanosterol from squalene in ergosterol biosynthesis
Give an example of Echinocandins, its route and spectrum/indication
Lipopeptides (caspofungin)
Route: Intravenous (1 per day)
Spectrum: BROAD against candida, aspergillus
What is the mechanism of action of Echinocandins
Inhibition of production of Beta 1-3
Gluten (part of cell wall) 1-3
Beta glucan synthase- fungicidal
Give a type of flucytosine, a route, spectrum/indication
Type: Fluoropyrimidine
Route: oral or IV
spectrum: can be used with other drugs against severe cryptococcal or candida infections
What is the mechanism of action of flucytosine
Converted into 5-FU which disrupts RNA and DNA synthesis (fungistatic)
Give a type of Griseofulvin, route and spectrum
Type: Benzofuran
Route: Oral (tablets or suspensions)
Spectrum: normally dermatophytes like Tinea Capitis
What is the mechanism of action of Griseofulvin and side effects
Binds to polymerised microtubules to inhibit mitosis (half growth)
Side effects: Rash, urticaria, nausea, vomtiing, anorexia
In candidiasis, what is the common causative organism and common cause
C.albicans
Cause:
Broad spectrum antibiotics
Immunodeficiency
Localised thrush: due to balance upset
What are the symptoms of candidiasis and in immunocompromised patients
Usually localised: skin, mucosal, vaginal, oral thrush
Pain
Itching
Creamy curd like plaques on mucosa surface
Itching
Immunocompromised:
pharyngitis
oesophagi’s
dysphagia with weight loss and sepsis
How do you diagnose candidasis
clinical features
Laboratory culture
What is the cause of Aspergillosis (fungi) and the symptoms?
Aspergillus Spp
Affects the respiratory tract
Severe: affects heart, brain and skin
Symptoms: wheezing, breathlessness, fatigue, cough (mucus plugs), feeling unwell
How do you diagnose Aspergillosis?
Sputum Culture- limited value
Bronchoalveolar lavage
Antigen detection, NAAT detection
How do you treat Aspergillosis
Voriconazole
Itraconazole, caspofungin, posaconazole - alternatives: bronchodilators and steroids
Isolation for neuropathic pain
What are the three types of Dermatophytosis
Epidermophyton
Microsporum
Trichophyton
What are the symptoms of Dermatophytosis
Red scaly patch like lesions (skin)
Nail discolouration and thickening
Hair loss and scarring (scalp)
Itchy but painful
What is the clinical diagnosis of dermatophytosis on different locations of infection site called (3)
Tinea Capitis (head scalp)
Tinea Corporis (trunk and leisions)
Tinea Pedis (Athletes foot)
What is pityriasis versicolor caused by, its symptoms, diagnosis and treatment
Malassezi fur fur
Brown Patchy sections
Skin culture scraping
Topical anti fungal (Imidazole): ketoconazole
Oral itraconazole or fluconazole
What is histoplasmosis caused by, transmitted by, and symptoms, diagnosis, treatment
Histoplasma capsuatum
Spore inhalation
Lung infections: flu like symptoms
Chronic infections: TB resemblance
Diagnosis: blood samples and cultures
Treatment: oral intraconazole
Severe: IV amphotericin B
What normally causes cryptococcal infection
Cryptococcus Neoformans (inhalation)
Lung infection (pneumonia)
Cryptococcus meningitis in HIV and AIDS
What are the symptoms, diagnosis and treatment of cryptococcal infection
Symptoms:
Fever, fatigue, dry cough, headache, nausea, confusion, chest pain, skin rash, blurred vision
Diagnosis:
Blood test, sputum and urine screening
Treatment:
Amphotericin B and flu cytosine (2 weeks IV)
Oral fluconazole: 8 weeks
What are the four mechanisms of resistance in fungi same as bacteria
- Altered drug metabolism
- Efflux Pumps
- Change in protein target
- Prevention of drug entry
