Step1: Micro Fungi

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Systemic Mycoses

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Histo, Blasto, Cocci, Paracocci
Dimorphic fungi (cold mold, heat yeast) that can cause pneumonia and can disseminate
**Cocci is a spherule not a yeast at body temp

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Treating systemic mycoses

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local: azole
systemic: amphotericin B

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Histoplasmosis

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Spores inhaled from bird/bad droppings from Mississippi/Ohio River valleys
-lemon-shaped budding yeast in tissue
-hides in macrophages

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Blastomycosis

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-East of Mississippi, Central America
-broad-base budding, same size as RBC
-Inflammatory lung dz, disseminates to skin/bone
-forms granulomatous nodules

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Cocci

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-found in Southwest US
-increased incidence after earthquake
-spherule >RBC filled w/ endospores
-causes pneumonia, meningitis, can disseminate to bone/skin
**spherule, not yeast in tissue

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Paracocci

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-latin america
-budding yeast w/ captain's wheel formation (larger than RBC)

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Tinea versicolor

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Cutaneous mycosis caused by Malessezia furfur
-Lipid degradation >> acids that damage melanocytes and cause hypo/hyperpigmented patches.
Occurs in hot/humid weather
-spaghetti and meatballs appearance

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cutaneous mycoses tx

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topical miconazole, selenium sulfide

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Candida Albicans

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Dimorphic yeast that forms germ tubes at 37 degrees. Normal flora of skin/mucus membranes that can cause superficial or systemic fungal infection

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Candida Albicans dz

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oral/esoph thrush - immunocompromised (oral CD4<400, esoph <100)
vaginitis - DM, AB use
diaper rash
disseminated dz in immunocompromised

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treating vaginal candida

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topical azole

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treating oral/esophageal candida

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fluconazole or caspofungin

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treating systemic dz

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fluconazole, amphotericin B, capsofungin

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Aspergillus

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Ubiquitous spores are inhaled, can cause a range of dz

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Aspergillus dz

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Allergic alspergillosis, Aspergilloma, invasive aspergillosis

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Allergic aspergillosis

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ABPA; type I hypersensitivity rxn mediated by IgE;
associated w/ asthma and cystic fibrosis;
may cause bronchiectasis and eosinophilia

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Aspergillomas

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fungal ball can grow in lung cavities formed by TB

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Invasive aspergillus

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occurs in immunocompromised, those w/ chronic granulomatous dz. pleuritic pain, hemoptysis, infiltrates.

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aflatoxins

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toxin produced by some species; associated w/ hepatocellular carcinoma

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A for Aspergillus

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Acute Angles in Aspergillus; not dimorphic

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Mucormycosis

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caused by mucor and rhizopus species

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Mucormycosis presentation

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Occurs mostly in ketoacidotic diabetic and leukemia pts. Rhinocerebral, frontal lobe abscesses, facial pain, headache, black necrotic eschar on face, cranial nerve involvement

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Mucormycosis mechanism

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Fungi proliferate in blood vessel walls in presence of excess ketone/glucose, can penetrate cribiform plate and enter brain.

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Mucormycosis tx

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amphotericin B

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Cryptococcus

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heavily encapsulated yeast (not dimorphic)
found in soil, esp pigeon droppings
inhaled and spreads to brain via bloodstream

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Cryptococcus dz

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pneumonia meningoencephalitis; soap bubble lesions in brain

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Crypto dx and tx

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LP and analyze CSF. India ink shows yeast w/ capsule
Tx is amphotericin B +/- flucytosine

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Pneumocystic jiroveci

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Yeast that is inhaled and causes diffuse interstitial pneumonia (PCP), most often asx.

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PCP in immunocompromised host

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diffuse, bilateral CXR appearance w/ ground-glass appearance

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Pneumocystis dx

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lung biopsy or lavage; disc-shaped yeast forms on silver stain of lung tissue

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treatment/prophylaxis of Pneumocystis

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TMP-SMZ, pentamidine, dapsome

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when to prophylax in HIV pts

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when CD4 count <200

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Sporothrix schenckii

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cigar-shaped budding yeast that lives on vegetation and causes rose gardener's disease when spores are traumatically introduced into skin.

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sporothrix presentation

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local pustule or ulcer with nodules along draining lymphatics. Little systemic illness

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treating rose gardener's dz

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itraconazole or potassium iodide
"plant a rose in the pot"

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Polyenes

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Amphotericin B, Nystatin
bind ergosterol (unique to fungal cell memb) and form pores

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Amphotericin uses

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Used for serious, systemic mucoses, intrathecally for fungal meningitis.

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Amphotericin toxicity

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Fever/chills (shake and bake), hypotension, nephrotoxicity, arrhythmia, anemia, IV phlebitis
-fluids can limit nephrotoxicity
-liposomal preparation can limit toxicity
Supplement K+, Mg++ due to altered renal tubule permeability

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Nystatin

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Topical form of amphotericin B, less toxic.
-swish and swallow for oral thrush; topical for diaper rash or yeast infection

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Azoles

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Inhibit ergosterol synthesis by inhibiting cytochrome P-450 enzyme that converts lanosterol >> ergosterol

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Azole uses

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local/less serious systemic mycoses
-Fluconazole to suppress crypto meningitis in AIDS, candida
-Itraconazole for dimorphics
-Clotrimazole, miconazole for topical infections

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Azole toxicity

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T synthesis inhibition (see gynecomastia, esp w/ ketoconazole), liver dysfunction (inhibits P450)

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Flucytosine

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Pyrimidine analog that inhibits DNA/RNA synthesis by converting 5-fluorouracil >> cytosine deaminase

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Flucytosine uses

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systemic fungal infections, esp crypto meningitis in combo w/ amphotericin B

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Flucytosine toxicity

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bone marrow suppression

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Echinocandins

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"fungins"
Inhibit cell wall synthesis by blocking beta glycan synthesis

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Echinocandin uses

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invasive aspergillosis, candida

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Echinocandin toxicity

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GI upset, flushing (due to histamine release)

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Terbafine

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inhibits fungal enzyme squalene epoxidase

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Terbafine uses

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dermatophytoses, especially nail onychomycosis

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Terbafine toxicity

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GI upset, headaches, hepatotoxicity, taste changes

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Griseofulvin

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interferes w/ microtubule function, disrupts mitosis. Deposits in keratin-containing nails.

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Griseofulvin uses

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oral tx of superficial infections; inhibits growth of dermatophytes

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Griseofulvin toxicity

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teratogenic, carcinogenic, confusion, headaches, increases P450 and warfarin metabolism

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why are antifungals more toxic than antimicrobials

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many targets in the fungal cell are shared by host cells.