![]() ![]() Additionally, L-AMB is an empiric antifungal therapy in febrile neutropenic patients and HIV-infected patients with cryptococcal meningitis. Liposomal amphotericin B (L-AMB) has FDA approval to treat systemic aspergillosis, candidiasis, and cryptococcosis in patients with renal function impairment and patients refractory to AMB-d therapy. AMB-d has an off-label use for esophageal candidiasis (both HIV infected and non-HIV infected adults and adolescents HIV-exposed and or infected infants and children), fluconazole-refractory oropharyngeal candidiasis, candidal endophthalmitis, candidal urinary tract infections, visceral leishmaniasis, and ophthalmic aspergillosis. AMB-d is also approved for treating the parasitic disease American mucocutaneous leishmaniasis. Ĭommon, medically relevant fungal infections include, but are not limited to, the following ( Fungal Infection - Typical causative organisms) :Īmphotericin B deoxycholate (AMB-d) is FDA indicated for treating life-threatening or potentially life-threatening fungal infections: aspergillosis, cryptococcosis, blastomycosis, systemic candidiasis, coccidioidomycosis, histoplasmosis, and mucormycosis. This discussion will focus on the currently available antifungal agents. Mechanistically, antifungal agents are diverse, yet due to the alarming and rapid increase in drug-resistant systemic fungal infections, new agents are necessary more than ever. While the echinocandins demonstrate less renal toxicity than amphotericin B, they cause significant hepatotoxicity and are more expensive than azoles this effectively relegates this class to second or third-line agents. Following lipid formulations of azoles, a new class of antifungal agents that are highly effective in treating some systemic mycoses, are the recently developed echinocandins class. ![]() The next breakthrough in systemic therapy would have a basis in amphotericin B lipid formulations, which have more favorable side effect profiles. Terbinafine, an allylamine antifungal, was FDA approved in 1996 but has indications for the treatment of local, non-systemic fungal infections. Azoles first became available in 1973 with the arrival of clotrimazole with additional azoles that have the pharmaceutical industry has rolled out over the past five decades: miconazole (1979), ketoconazole (1981), fluconazole (1990), itraconazole (1992), voriconazole (2002), posaconazole (2006), and most recently isavuconazonium (2015). The next significant introduction would not take place until 1971, when the antimetabolite drug flucytosine entered the market. ![]() Griseofulvin was introduced in 1959, representing the second class of antifungals. While this drug is an effective agent, the demand for other efficacious topical, oral, and intravenous was apparent. Amphotericin B deoxycholate, a polyene antibiotic, was the first antimycotic agent introduced in 1958 to treat systemic mycoses. While antimycotic pharmacology has advanced significantly, particularly in the last three decades, common invasive fungal infections still carry a high mortality rate: Candida albicans (approximately 20 to 40% mortality), Aspergillus fumigatus (approximately 50 to 90%), Cryptococcus neoformans (approximately 20 to 70%). Īntifungal drugs represent a pharmacologically diverse group of drugs that are crucial components in the modern medical management of mycoses. The virulence of the organism is classified as either a primary infection (disease arising in a healthy host) or opportunistic infection (disease arising in human hosts that have a compromised immune system or other defenses). The acquisition of the fungal infection is either an exogenous (airborne/inhalation, cutaneous exposure, percutaneous inoculation) or an endogenous process (normal flora or reactivated infection). These classifications are essential when determining the most effective treatment regimen for a particular mycosis. Mycoses classify as local (superficial, cutaneous, subcutaneous) or systemic (deep, bloodborne). The term 'antifungals' encompasses all chemical compounds, pharmacologic agents, and natural products used to treat mycoses.Ĭlinically, fungal infections are best categorized first according to the site and extent of the infection, then the route of acquisition, and finally, the virulence of the causative organism. Fungal infections (mycoses) range from common benign infections like 'jock itch' to serious, life-threatening infections such as cryptococcal meningitis. While most fungi do not play a significant role in human disease, there are several hundred fungi that do, resulting in fungal infection or disease. From fungi visible to the naked eye, such as mushrooms, to microscopic yeasts and molds, they exist in many forms. Fungi are unicellular or multi-cellular eukaryotic organisms that exist in all environments worldwide.
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