Chapter 20, 21: The Fungi & Antifungals
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- Why are fungal infections on the rise?
- More immunocompromised patients with weak cell-mediated immunities
- Do fungi require an aerobic environment?
- YES! They are eukaryotic cells
- What is a yeast?
- unicellular form of fungi; can appear spherical or ellipsoidal
- What are pseudohyphae?
- long chains of yeast cell that haven't separated after budding
- What are hyphae?
- threadlike, branching, cylindrical tubules made of fungal cells attached end to end
- What are molds or mycelia?
- multicellular colonies composed of clumps of intertwined branching hyphae; produce spores
- What are spores?
- reproducing bodies of spores; spores are rarely seen in skin scrapings
- What are dimorphic fungi?
- fungi that can grow as either yeast or mold, depending on environment and temperature
- What are saprophytes?
- fungi that live in and utilize organic matter as an energy source
- What is the essential sterol in fungal cell membranes?
- ergosterol
- How do amphotericin B and nystatin work?
- bind to ergosterol and punch holes in the fungal cell membrane
- How does ketoconazole work?
- Inhibits ergosterol synthesis
- How can fungal capsules be visualized in the lab?
- India ink stain
- How are the fungal infections organized?
- by skin layer affected: 1. superficial; 2. cutaneous; 3. subcutaneous; 4. systemic
- What are the 2 superficial fungal infections?
- 1. pityriasis versicolor; 2. tinea nigra
- Are the superficial fungal infections dangerous?
- No, they cause change in skin color and are not associated with other symptoms
- How are superficial skin infections diagnosed?
- skin scrapings mixed with KOH reveal hyphae and spherical yeast as the KOH digests non-fungal debris
- How do you treat superficial fungal infections?
- With dandruff shampoo or antifungal imidazoles.
- What is dermatophytosis?
- category of cutaneous fungal infections caused by more than 30 species of fungi; fungi live in skin, hair, nails
- What enzyme do the dermatophytotic fungi release?
- keratinase
- What are the 5 dermatophytoses?
- 1. tinea corporis; 2. tinea cruris; 3. tinea pedis; 4. tinea capitis; 5. tinea unguium (onychomycosis)
- What is ringworm?
- fungi spread into the horny layer of the skin to form a red, raised border in a ring shape
- What is tinea cruris?
- jock itch
- What is tinea pedis?
- athlete's foot
- What is tinea capitis?
- in kids, expanding ring of scaly red lesions with hair loss
- What is tinea unguium?
- thickened, discolored nails
- How do you diagnose a dermatophyte infection?
- 1. dissolve skin scrapings in KOH; 2. direct exam of hair and skin with Wood's light (some microsporum will fluoresce a brilliant green)
- What is the first line drug against the dermatophytes?
- topical imidazoles; keep skin dry and exposed to air; oral griseofulvin for tinea capitis and tinea unguium
- What are the 2 subcutaneous fungal infections?
- sporotrichosis and chromoblastomycosis
- How do subcutaneous fungal infections develop?
- trauma to skin, fungus remains localized to subcutaneous tissue or spreads along lymphatics to local nodes; these fungi have low virulence
- What is sporotrichosis and how is it treated?
- Caused by sporothrix schenckii, which is a hazard to gardeners; it is a dimorphic fungus which causes nodules along the lymphatics. Treated with potassium iodide or amphtericin B
- What is chromoblastomycosis?
- subcutaneous infection caused by copper-colored soil saprophytes found on rotting wood; forms violet wart-like lesions; treated with itraconazole and local excision
- What are the 3 fungi that cause systemic infections?
- 1. histoplasma capsulatum; 2. blastomyces dermatitidis; 3. coccidioides immitis; all 3 are dimorphic fungi
- Can the 3 systemic fungi be transmitted person to person?
- no
- What makes the 3 fungi dimorphic?
- grow as mycelial forms with spores at 25C on Sabouraud's agar, at 37C on blood agar they grow in yeast form. in their natural habitat (soil) they grow as mycelia and release spores into the air where humans inhale them and then they grow as yeast cells in the body
- Where are the histoplasma and blastomyces fungi endemic?
- Mississippi region
- Where is coccidioides endemic?
- southwest US
- What is the 2nd most common opportunistic infection in AIDS patients in Arizona?
- coccidioides
- How do the 3 systemic fungi present clinically?
- 1. asymptomatic or mild resp disease; 2.mild pneumonia with fever, cough, x-ray infiltrates, granulomas with calcifications after resolution - or chronic pneumonia like in TB; 3. disseminated: this occurs rarely and only in immunocomprimised host...can lead to meningitis, bone lytic granulomas, skin granulomas and other organ lesions
- How are blastomyces infections treated?
- aggressive amphotericin B or itraconazole treatment
- How is acute pulmonary histoplasmosis or coccidioidomycosis treated?
- no treatment unless it's chronic or disseminated - then itraconazole or amphotericin B
- Which of the 3 systemic fungal infection is most severe?
- blastomyces dermatitidis
- What does cryptococcus neoformans cause?
- meningoencephalitis
- Where is the cryptococcus neoformans found?
- this encapsulated fungus is found in pigeon droppings; 75% of cases are found in AIDS patients
- How do you diagnose cryptococcus infection?
- lumbar puncture to analyze CSF, an India ink stain to show yeast cells with the surrounding halo, the polysaccharide capsule
- What is the most sensitive test to diagnose cryptococcal funal infection?
- cryptococcal antigen test
- What is the treatment for cryptococcus?
- amphotericin B and flucytosine
- Is candida albicans ubiquitous?
- YES! given out like CANDY to humanity
- Who does candida albicans affect?
- women with vaginitis, babies with diaper rash, AIDS patients
- What does candida albicans cause in immunocomprimised patients?
- the same things as in normal hosts, but also...1. esophagitis: thrush extends into the esophagus; 2. disseminated disease: can invade the blood stream and virtually every organ
- How can candida albicans be diagnosed?
- examine retina to uncover white fluffy candidal patches, treat skin scrapings with KOH, culture biopsied tissue
- Is candida albicans part of the normal flora?
- YES! will often be cultured from urine, sputum, and stool samples
- What are mycotoxins?
- toxins that can cause liver damage and liver cancer that are released by fungi
- What is the mycotoxin released by aspergillus flavus?
- aflatoxin
- What parts of the world does aspergillus affect?
- south of the Sahara in Africa, half the cancers are liver cancers and 40% of screened foods contain aspergillus
- What are the two bacteria that ACT like fungi?
- ACTinomycetes and nocardia
- Why are actinomyces and nocardia discussed with fungi?
- they grow in the form of mycelia and are water and soil saprophytes
- What type of bacteria are actinomyces and nocardia?
- gram + rods
- What are the 4 important concepts to remember for actinomyces israelii?
- 1. gram + filamentous anaerobe that grows in the mouth and GI normally; 2. causes eroding abscesses following trauma to mucous membranes of mouth or GI; 3. abscess pus reveals "sulfur granule" that aren't really sulfur, but microcolonies of actinomyces; 4. treatment is with penicillin G and surgical drainage
- How do you identify nocardia asteroides?
- forms weakly gram +, partially acid fast beaded branching thin filaments
- How do you treat nocardia infections?
- trimethoprim and sulfamethoxazole
- Treatment of actinomyces and nocardia is a SNAP...
- Sulfa for Nocardia, Actinomyces give Penicillin
- What does nocardia cause?
- inhaled into lung, causing lung abscesses and cavitations
- What is the main binding target of antifungal antibiotics?
- ergosterol, the sterol unique to fungal cell membranes
- How are antifungal antibiotics grouped?
- 1. serious systemic infections: amphotericin B, itraconazole; 2. less serious systemic infections: the oral azole drugs (ketoconazole, fluconazole, itraconazole); 3. superficial fungal infections: griseofulvin, nystatin and 2 azole drugs (clotrimazole and miconazole)
- What are adverse effects of amphotericin?
- 1. reversible renal toxicity; 2. acute febrile reaction; 3. anemia; 4. inflammation of the vein at the IV site
- How do you manage the amphotericin side effects?
- give aspirin or acetominophen to prevent febrile reaction, monitor BUN and creatinine levels daily
- How do new preparations of amphotericin atenuate side effects?
- combined with lipids, they lower nephrotoxicity, but febrile rigors still occur
- When is flucytosine used?
- rarely because of widespread resistance; used in conjunction with amphotericin B to fight cryptococcal meningitis
- How does flucytosine work?
- inhibits DNA/RNA synthesis
- What are side effects of flucytosine?
- 1. bone marrow depression; 2. nausea, vomiting, diarrhea
- What causes the flucytosine side effects?
- drug damages DNA of rapidly dividing cells in the bone marrow and GI epithelium
- How does the azole family of drugs work?
- inhibits p-450 enzyme system which is involved in ergosterol synthesis; pretty broad spectrum coverage
- What are the 2 groups of azole drugs?
- 1. imidazoles (ketoconazole, miconazole, clotrimazole); 2. triazoles (fluconazole, itraconazole, voriconazole)
- How do you remember the triazoles?
- "TRY FIVe": fluconazole, itraconazole, voriconazole
- What is used primarily for topical fungal infections?
- clotrimazole and miconazole
- What is used for systemic infections?
- fluconazole and itraconazole
- What are side effects of the ketoconazole drugs?
- 1.GI (nausea, vomiting, anorexia); 2. hepatotoxicity (increased hepatic enzymes); 3: inhibition of testosterone synthesis; 4. adrenal suppression
- What is fluconazole used for?
- kills candida albicans very well, prevents relapse of cryptococcal meningitis in AIDS patients
- How is amphotericin B administered?
- IV
- What is the use of itraconazole?
- it's becoming the next amphotericin B without the side effects; used in first line treatment for chromoblastomycosis, histoplasmosis, coccidioidomycosis, blastomycosis
- What is special about voriconazole?
- has a "VORacious" appetite for fungi; it's a new triazole with more clinical trials necessary to prove efficacy
- How does nystatin work?
- binds to ergosterol, increasing permeability and leading to lysis
- What is nystatin used for?
- used topically on skin and mucous membranes; order "Nystatin, Swish and Swallow" for treatment of oral, esophageal and gastric candidiasis
- How does griseofulvin work?
- disrupts spindle formation, blocking mitosis; deposits in keratin precursor cells in skin, hair and nails
- What are adverse effects of griseofulvin?
- uncommon, headache, nausea, vomiting, photosensitivity, mental confusion, bone marrow suppression (again, rapidly dividing cells!)
- What is KI used for?
- to fight local sporotrichosis infections
- What is terbinafine?
- new fungicidal agent that blocks fungal cell wall synthesis; good for tinea unguium, tinea pedis, tinea capitis, and tinea corporis