Fungal Infections

Superficial Fungal Infections Malassezia furfur – Malassezia’s Italian Restaurant  Disease includes pityriasis versicolor (hypo- and hyperpigmented patches on skin)  Treatment via topical selenium sulfide (or imidazoles)  Other comments o Spaghetti and meatball appearance with KOH prep o Thrives under heat and humid conditions, e.g. sunlight exposure o Fungus is localized to the stratum corneum o Neonates that receive total parenteral nutrition (lipid-based transfusion) are susceptible to sepsis and thrombocytopenia Exophiala werneckii  Disease includes dark to brown painless patches on the soles of hands and feet  Treatment via topical selenium sulfide (or imidazoles) Cutaneous Fungal Infections (on skin, hair, and nails) Dermatophytes (Trichophyton, Epidermophyton, and Microsporum) – Tinea Tin Man  Disease includes tinea infections o Tinea capitis o Tinea corporis – “ring worm” o Tinea cruris – “jock itch” o Tinea pedis – “athlete’s foot” o Tinea unguium – onychomycosis  Treatment via topical imidazole; more serious infections via griseofulvin (has lots of associated GI side effects)  Other comments o Hyphae present with KOH prep or direct examination of Microsporum via Wood’s Light o Thrives under hot and humid conditions; athletes are commonly affected, but transmission also occurs via pets o Fungi functions to secrete keratinase, which digests the keratin resulting in scaling of skin, hair loss, and crumbling of nails Subcutaneous Fungal Infections Sporothrix schenckii – Shanked by a Rose  Disease includes ulcerations, nodules, and ascending lymphadenitis – “Rose Gardener’s Disease”  Treatment via itraconazole or saturated potassium iodide (outdated)  Other comments o (Dimorphic fungi) Hyphae present with KOH prep in the cold or cigar-shaped budding yeast at 37ºC Chromoblastomycosis  Disease includes small violet wart-like lesions that cluster like cauliflowers  Treatment via itraconazole and local excision  Other comments o Copper-colored sclerotic bodies with KOH prep; saprophytes are commonly found in rotting wood Systemic Fungal Infections Histoplasma capsulatum – The Historian’s Cave  Disease includes pneumonia (cavitary lesions similar to TB), erythema nodosum (common to legs), and hepatosplenomegaly in immunocompromised patients  Transmission via respiratory droplets – common in bird and bat droppings (cave) and the Mississippi, Missouri, and Ohio River Valley  Treatment via -azole drugs; systemic infections via amphotericin B  Other comments o (Dimorphic fungi) Macrophages will small intracellular oval bodies on histological slide and is smaller than RBCs; serum and urine rapid antigen test Blastomyces dermatitis – The Blast of the Cannons  Disease includes pneumonia (patchy alveolar infiltrate on CXR or cavitary lesions) and osteomyelitis (skin and bone) in immunocompromised patients  Transmission via respiratory droplets – common to the Great Lakes and Ohio River Valley (more than Histoplasma capsulatum)  Treatment via -azoles; systemic infections via amphotericin B  Other comments o (Dimorphic fungi) Broad-based budding on histological slide and is the same size of RBCs; urine rapid antigen test Coccidiodes immitis – Presidio San Joaquin     Disease includes San Joaquin Valley Fever characterized by pneumonia (cavitary lesions), arthralgia, erythema nodosum, and meningitis in immunocompromised patients Transmission via respiratory droplets – common in dust and earthquakes, e.g. California and S.W. United States and N. Mexico Treatment via -azole drugs; systemic infections via amphotericin B Other comments o (Dimorphic fungi) “Mold in the cold, spherule endospore in the heat”, much larger than RBCs Cryptococcus neoformans & gatti – Crypt for Cryptococcus  Disease includes pulmonary symptoms, meningitis, fever, skin ulcers, and bone lesions  Transmission via respiratory droplets – common in pigeon droppings  Treatment via joint therapy of amphotericin B, flucytosine, and fluconazole for maintenance  Other comments o Fungi is heavy encapsulated (and urease positive) and therefore can be visualized with an India Ink stain, which shows wide encapsulated halo o Latex agglutination test can be used to detect the polysaccharide antigen, which induces agglutination o Bronchopulmonary washings of lung tissue resemble “soap bubble” lesions in the brain Candida albicans – Candid Canadians  Disease includes oral thrush (pseudomembranes with white exudate), vaginitis, diaper rash, esophagitis, and disseminated  Transmission via direct contact – common in immunocompromised patients, steroid users, diabetics, women on birth control, and patients using excessive antibiotics  Treatment via nystatin, fluconazole, and amphotericin B  Other comments o (Dimorphic fungi) “Yeast in the cold and mold in the heat”; catalase positive thus chronic granulomatous disease patients are highly susceptible to fungal infection o Present in normal GI tract and oral cavity, thus is common contaminant in sputum but NOT blood cultures o This is an AIDS defining illness when CD4+ count <100 Aspergillus – Asparagus Farm  Disease includes allergic bronchopulmonary aspergillus (ABPA, migratory pulmonary infiltrate), aspergillomas, and angioinvasive disease in patients with neutropenia  Transmission via respiratory droplets (specifically conidiophores)  Treatment via voriconazole; angioinvasive disease via amphotericin B  Other comments o Acute branching with septa on KOH prep; multiple nodular infiltrates on chest CT; ring enhancing lesions in the brain o Fungi is catalase positive; produces a mycotoxin or aflatoxin (common in peanuts) that is carcinogenic Mucormycosis (zygomycosis) (Rhizopus, Rhizomucor, and Mucor) – Mu Car Auto Shop  Disease includes invasion of sinus, cranial bones (cribriform plate), and blood vessels leading to necrosis of tissue, neurological deficits, and even death  Transmission via respiratory droplets – common in diabetics in DKA, immunocompromised patients, burn patients, and patients taking iron chelator (deferoxamine)  Treatment via debridement and amphotericin B  Other comments o Hyphae are non-septate and have 90º angle branching on microscope on KOH prep Fungi-like Bacteria Actinomyces israelii – Israeli Soldier  Disease includes eroding abscesses in the oral cavity and GI tract (mucous membranes; infection is named by the region affected)  Treatment via surgical drainage and penicillin G  Other comments o Gram positive bacillus (rod), obligate anaerobe that is common to oral cavity and GI tract o Pus draining abscess has yellow sulfur granules o Fungal-life infection is common in dentists due to frequent exposure to the oral cavity Nocardia asteroides – No Card Game for Old Men  Disease includes brain abscess formation, pneumonia-like symptoms (cavitary lesions), and cutaneous lesions – “mimics TB symptoms”  Treatment via trimethoprim and sulfamethoxazole (Bactrim)  Other comments o Gram positive bacillus (rod), obligate aerobe, catalase and urease positive; also contains mycolic acids therefore stains lightly acid fast o Fungal-like infection is more common in men than in women; most common in immunocompromised patients, esp. patients taking corticosteroids Anti-Fungal Agents Amphotericin B  Bactericidal  Mechanism of action – binds to ergosterol on cell membrane and alters cell membrane permeability.  Adverse effects – dose-dependent impaired renal function, renal hypokalemia, leukemia, and thrombocytopenia.  Treatment of systemic mycoses of severely ill patients and fungal meningitis, including… o Histoplasmosis o Blastomycosis o Coccidioidomycoses o Candida o Cryptococcus  Other comments o Amphotericin B is commonly co-administered with steroids, heparin, and anti-histamines to reduce adverse effects; synergistic with flucytosine. Griseofulvin  Bacteriostatic  Mechanism of action – binds to fungal microtubules and interferes with spindle formation and inhibits cell division.  Mechanism of resistance – decrease energy-dependent transport of drug.  Adverse effects – increased metabolism of warfarin, decreased absorption via interaction with phenobarbital, leukopenia, albuminuria, relapse of SLE, and teratogenicity.  Treatment of dermatomycoses, including… o Microsporum o Trichophyton o Epidermophyton  Other comments o Griseofulvin has been largely replaced by itraconazole. Flucytosine  Bacteriostatic  Mechanism of action – inhibits thymidylate synthetase and produces 5-fluoruracil.  Adverse effects – bone marrow depression and Steven-Johnson syndrome in immunocompromised patients.  Treatment of systemic mycoses (see amphotericin B) and Chromoblastomycosis (in combination with itraconazole). Ketoconazole, clotrimazole, miconazole, fluconazole, itraconazole, and voriconazole (and tolfnaftate)  Bacteriostatic  Mechanism of action – inhibits the synthesis of ergosterol, part of the cell membrane.  Treatment of uncomplicated/complicated vaginitis (Candida) and dermatomycoses, including… o Microsporum o Trichophyton o Epidermophyton  Other comments o Miconazole is an over-the-counter drug that is specifically used to treat tinea pedis but is rarely used due to the severe GI side effects. Therefore, tolnaftate is the DOC for both tinea pedis and tinea cruris. o Fluconazole, itraconazole, and voriconazole are used to treat systemic mycoses of non-seriously ill patients. o Fluconazole is used to treat uncomplicated vaginitis; clotrimazole is used to treat complicated vaginitis Echinocandins (-fungins)  Bacteriostatic  Mechanism of action – inhibition of cell wall synthesis, specifically inhibition of glucan formation  Treatment of systemic mycoses, specifically Candida and Aspergillus