Antimicrobials: antifungals
Antifungals kill or inhibit fungi by disrupting ergosterol, the fungal cell wall, or fungal nucleic acid synthesis, and are used from superficial dermatophyte infection through life-threatening invasive mycoses. Polyenes, triazoles, echinocandins, flucytosine, and allylamines each cover a different organism spectrum; an echinocandin is first-line empiric therapy for candidemia, and voriconazole is first-line for invasive aspergillosis.
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What this article covers
- Overview
Antifungals kill or inhibit fungi by targeting structures absent from human cells: the membrane sterol ergosterol, the fungal cell wall glucan, or fungal nucleic acid synthesis.
- Epidemiology
Scale of use: Fluconazole and the echinocandins are among the most prescribed systemic antifungals, driven chiefly by candidemia in hospitalized and immunocompromised patients, including those with a…
- Risk factors
Renal impairment: Amphotericin B deoxycholate, and to a lesser degree flucytosine, requires dose adjustment as clearance falls.
- Pathophysiology
Polyenes bind ergosterol directly: Amphotericin B and nystatin bind fungal membrane ergosterol, forming pores that leak electrolytes and kill the cell; human membranes contain the related sterol cholesterol, explaining the toxicity.
- Clinical features
Amphotericin B reactions: Fever, rigors, and hypotension during infusion, plus dose-dependent nephrotoxicity, hypokalemia, and hypomagnesemia; liposomal formulations lower but do not eliminate this toxicity.
- Differential diagnosis
The relevant differential for a drug class is the competing agent actually chosen for the same infection, each with the discriminator that decides it.
- Diagnosis
Antifungal selection is established by identifying the pathogen category (yeast versus mold), the infected site, and host immune status, then confirming the organism by culture, histopathology, or a…
- Management
First-line, unstable or critically ill patient with suspected invasive candidiasis: start empiric echinocandin therapy immediately, before speciation returns, and remove any infected intravascular catheter promptly.
- Complications
Nephrotoxicity: Amphotericin B deoxycholate causes clinically significant renal impairment in up to 80% of prolonged courses; liposomal formulations lower but do not eliminate this risk.
- Prognosis
Candidemia mortality: Remains substantial because only 40% to 60% of infected patients have a positive blood culture at any single draw, delaying diagnosis.
- Prevention
Antifungal prophylaxis in neutropenia or transplantation: Fluconazole 400 mg PO or IV daily for lower-risk patients; posaconazole or voriconazole instead for higher-risk patients, such as acute…
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Candida species cause a spectrum from mucocutaneous disease (thrush, esophagitis, vulvovaginal candidiasis, intertrigo) to candidemia and invasive candidiasis, the fourth most common cause of bloodstream infection with 30-40% mortality. Diagnosis of invasive disease requires recognizing risk factors because only 40-60% of infected patients have positive blood cultures, and initial therapy is an echinocandin with prompt catheter removal.
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