Greenblatt Flashcards
(23 cards)
What is the target of antifungals?
Fungi have neither 70S ribosomes nor peptidoglycan; antifungals instead target beta-glucan and ergosterol
*Antifungals often have some toxicity in humans, and there are many fewer molecular targets available (many of their molecules are too similar to ours)
In what environment can fungi grow?
Fungi can grow in drier, higher-osmotic-pressure, and colder environments than bacteria: more cutaneous infections and food spoilage
What are the main two types of fungi and their characteristics?
Yeast:
- single-celled
- reproduce by budding
- closed mitosis
Molds:
- grow in hyphae/mycelia and have complex reproduction
- makes new cells by fungal mitosis
How many types of asexual spores (conidia) do fungi have?
Five types
*have distinctive microscopic appearances that may be used for diagnosis
What is thermal dimorphism?
Several important fungal pathogens grow as mold at 24C and as yeast at 37C
- yeast form has more immune-evasive properties
- dual cultures can be useful for diagnosis
What is the immune response to fungal infection?
Granulomatous, sometimes also suppurative
What characterizes most fungal pathogens?
Most fungal pathogens are environmental: little contagion or drug resistance, no eradication
*Exception: C. albicans yeast is normal flora/opportunistic pathogen
What causes mycotoxicosis?
Eating fungal toxins (wrong mushroom or spoiled food); not fungal infection
What can be said about fungal allergies?
Can also be dangerous (asthmatic reaction)
How is a fungal infection diagnosed?
- PPD
- KOH-mount microscopy with fungal stains
- culture on Sabouraud’s agar
- PCR available for dangerous systemics
- serology for epidemiology
Major classes of antifungal agents are polyenes (disrupt fungal cell membranes at ergosterol insertion sites), azoles (inhibit ergosterol synthesis), echinocandins (inhibit beta-glucan synthesis)
What are the treatments against fungi?
Major classes of anti fungal agents:
- polyenes
- disrupt fungal cell membranes at ergosterol insertion sites
- highly effective and broad-spectrum but toxic (Amphotericin B is the only systemic and is nephrotoxic)
- azoles
- inhibit ergosterol synthesis
- less toxic than polyenes
- different ones optimally active against different fungi (Fluconazole/Diflucan major one, treats candidiasis and cryptococcosis)
- echinocandins
- inhibit beta-glucan synthesis
- low-toxicity (highly effective against candida and aspergillus)
Describe superficial mycoses
- caused by fungal growth on the superficial skin layer
- does not require thermal dimorphism
- very common, but symptoms are minor: itch or discoloration
- treated with topical azoles, alt oral griseofulvin
What is dermatophytosis?
- very common
- caused by three different genera of fungi
- infect only superficial keratinized structures
- produce keratinases
- symptoms are called Tinea (jock itch, athlete’s foot, ringworm)
- transmitted by fomites or autoinnoculation
- diagnose by KOH mount, culture
- treat all affected body sites simultaneously w/ topical antifungal cream, alt oral griseofulvin
Describe subcutaneous mycoses
- introduced by trauma exposing subcutaneous tissue to soil or vegetation
- slow spread from trauma site toward trunk by lymphatics
- thermal dimorphism
- history of ineffective antibiotic treatment
- treated with oral azoles
- in serious cases, amphotericin B and local surgery
What is sporotrichosis?
- caused by Sporothrix spp
- thermally dimorphic fungi of vegetation that enters skin through small injuries (thorns, splinters)
- painless ulcer at site spreads up lymphatic over years
- if COPD, may be pulmonary
- if immunosuppressed, may be disseminated meningitis
- diagnosed by biopsy and culture at room temp from pus
- treat normal type with oral azoles, more serious forms with Amphotericin B
Describe systemic mycoses
- environmental: spores/fungi in soil
- inhaled into lungs
- thermal dimorphism
- range of severity: asymptomatic clearance to death
- NOT person-to-person transmissible
- may mimic TB, but source is American dirt, not foreign crowds
What is coccidioides?
- thermally dimorphic (mold/spherule)
- endemic to US Southwest
- mold grows in wet weather; releases infectious arthrospores in dry; spores inhaled; change form
- 60% mild: asymptomatic or flulike clearance by innate or containment by CMI
- moderate: valley fever/ desert rheumatism: pulmonary+EN
- severe: major pneumonia or dissemination (either bare or in macrophages)
- risk factors: age, race, pregnancy, immunocompromise, occupational high exposure
- diagnosed by exam, history, PPD, biopsy for spherules, culture, serology for dissemination
- treat if predisposed to complications (oral azoles), meningitis (fluconazole), pregnant or disseminated (Amphotericin B)
Describe opportunistic mycoses
- diseases and severity are widely varied, depending on the patients’ pre-existing conditions
- optimal treatment addresses both the infection and the underlying problem
What is cryptococcosis?
- environmental
- enabled by reduced CMI, suppresses host inflammatory response
- presents late in disease with meningitis and skin nodules or pulmonary symptoms
- diagnose by biopsy, CSF, crag
- treat with combinations of azoles and Amphotericin B
What is characteristic of the hepatitis viruses as a group?
- the hepatitis viruses are NOT closely evolutionarily related to each other, but symptoms are similar because they all infect hepatocytes
- all can cause acute hepatitis, treated with supportive care
What are some of the differences among Hep A, B & C?
- A is fecal-oral
- B&C are sex/birth/blood transmitted
- A&B controlled by vaccination
How do you diagnose Hep A, B & C by serology?
- HepA: IgM=acute, IgG=recovered/vaccinated
- HepB: viral surface antigen=acute, IgG against viral surface antigen=recovered/vaccinated
- HepC: EIA=real or false positive, RIBA=confirmation
What are the complications regarding Hep B & C?
- B and C can cause chronic hepatitis leading to cirrhosis and/or cancer
- treatment with polymerase inhibitors + IFN has many side effects, often ineffective
- first-generation protease inhibitors are improving treatment of serotype 1 but have their own side effects
- second-generation antivirals released last winter are producing exciting early results
- grueling treatment and uncertain prognosis for chronic HepB&C invites competition from alternative medicine -respectfully but thoroughly determine what the patient is doing or consuming along with or instead of your prescribed treatment
