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Antifungal TherapiesWe discussed the diagnosis and treatment of a patient with cryptococcal disease, KS, and PCP pneumonia. Fungal infections can be categorized as Yeasts or Molds. Some Fungi can exist as both Yeast and Mold depending on temperature and they are called Dimorphic Fungi. Here is a framework for thinking about treating fungal infections: ClassesNameMechanism/NotesMain UsesBinds ErgosterolAmphotericin B IVDisrupts Ergosterol in fungal cell membranes allowing K+ to leak out causing cell deathSevere BlastomycosisSevere HistoplasmosisCocci PNACocci Meningitis (can use intrathecal amphotericin for severe cases)Nystatin Same as aboveSuperficial infectionsOral CandidiasisAZOLES – Blocks Ergosterol SynthesisFluconazoleReaches CNSGreat bioavailability POCryptococcal InfectionCandidal infectionsOral Fluconazole used for Cocci MeningitisVoriconazoleBest Azole for AspergillusInvasive AspergillosisCandidaItraconazoleDoes NOT get into CNSOnly POBetter than Fluconazole for endemic fungiMild Pulm blasto, histo, cocci, sporothrixCandidaPosaconazoleDoes NOT get into CNSSuperficial infectionsCandidaMiconazoleTopical anti-fungalClotrimazoleCandida and topical anti-fungalsKetoconazoleSuperficial infectionsAnti-metabolite5-Flucytosine (PO)Inhibits DNA synthesis by blocking cytosine deaminase which is in fungal cells but not human cellsAlways used with an Azole or Ambisome5-Flucytosine + Amphotericin used for induction Cryptococcal treatmentCandidaEchinocandinsMicafunginCaspofunginInhibit Cell wall synthesis by irreversibly inhibiting B 13D Glucan needed for fungal cell wallBoth have similar spectrum of activityTOC for invasive CandidiasisAspergillus infection Yeast (think single celled organisms): Include Candida and CryptococcusMolds (think filaments/hyphae): Aspergillus, MucorDimorphic (can be yeast or Molds): Blasto, histo, cocci ................
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