Antifungal Agents
Overview of Antifungal Agents
George R.Thompson III, MD, FACPa,b,*, Jose Cadena, MDa,b, Thomas F. Patterson, MDa,b
KEYWORDS
Fungal infection Invasive mycoses Triazoles Echinocandins Amphotericin Flucytosine
The number of agents available to treat fungal infections has increased by 30% since the year 2000, yet still only 15 agents are currently approved for clinical use. The greater number of medications now available allows for therapeutic choices; however, differences in antifungal spectrum of activity, bioavailability, formulation, drug interactions, and side effects necessitates a detailed knowledge of each drug class.
POLYENES
Amphotericin B (AMB) and nystatin are the currently available polyenes, although differing safety profiles have limited nystatin to topical use.1 The polyenes bind to ergosterol present within the fungal cell wall membrane. This process disrupts cell wall permeability by forming oligodendromes functioning as pores with the subsequent efflux of potassium and intracellular molecules causing fungal death.2 There is also evidence that AMB acts as a proinflammatory agent and further serves to stimulate innate host immunity. This process involves the interaction of AMB with toll-like receptor 2 (TLR-2), the CD14 receptor, and by stimulating the release of cytokines, chemokines, and other immunologic mediators. It has been suggested that AMB may interact with host humoral immunity after the observation of synergistic activity of AMB and antibodies directed at heat shock protein 90 (hsp90), although further confirmatory data are needed.2
When AMB resistance occurs, it is generally attributed to reductions in ergosterol biosynthesis or the synthesis of alternative sterols with a reduced affinity for AMB. Resistance to AMB is common in Aspergillus terreus, Scedosporium apiospermum, Scedosporium prolificans, Trichosporon spp, and Candida lusitaniae (Table 1). Resistance has been reported with several other species, however.3
George R.Thompson III, MD, FACPa,b,*, Jose Cadena, MDa,b, Thomas F. Patterson, MDa,b
KEYWORDS
Fungal infection Invasive mycoses Triazoles Echinocandins Amphotericin Flucytosine
The number of agents available to treat fungal infections has increased by 30% since the year 2000, yet still only 15 agents are currently approved for clinical use. The greater number of medications now available allows for therapeutic choices; however, differences in antifungal spectrum of activity, bioavailability, formulation, drug interactions, and side effects necessitates a detailed knowledge of each drug class.
POLYENES
Amphotericin B (AMB) and nystatin are the currently available polyenes, although differing safety profiles have limited nystatin to topical use.1 The polyenes bind to ergosterol present within the fungal cell wall membrane. This process disrupts cell wall permeability by forming oligodendromes functioning as pores with the subsequent efflux of potassium and intracellular molecules causing fungal death.2 There is also evidence that AMB acts as a proinflammatory agent and further serves to stimulate innate host immunity. This process involves the interaction of AMB with toll-like receptor 2 (TLR-2), the CD14 receptor, and by stimulating the release of cytokines, chemokines, and other immunologic mediators. It has been suggested that AMB may interact with host humoral immunity after the observation of synergistic activity of AMB and antibodies directed at heat shock protein 90 (hsp90), although further confirmatory data are needed.2
When AMB resistance occurs, it is generally attributed to reductions in ergosterol biosynthesis or the synthesis of alternative sterols with a reduced affinity for AMB. Resistance to AMB is common in Aspergillus terreus, Scedosporium apiospermum, Scedosporium prolificans, Trichosporon spp, and Candida lusitaniae (Table 1). Resistance has been reported with several other species, however.3