Pharmaceutical Microbiology


Written by MicroDok

The cytoplasmic membrane of fungal cell is vital to the sustenance and development of the fungal organism because this part of the cell helps to maintain a constant internal environment and it also help to regulate the inflow and outflow of materials from the cell. Antifungal agents that interfere with the synthesis of fungal cytoplasmic membrane include amphoteracin B and nystatin. Drugs that perform this vital function are generally known as polyenes. Amphotericin B (Figure 1) is a widely used polyene that is naturally produced by Streptomyces species; and with nystatin (an analogous polyene), both of these antifungal agents disrupt the structural integrity of fungal cytoplasmic membrane. Nystatin is also synthesized naturally by Streptomyces species. 

Figure 1: Chemical structure of amphoteracin B, a polyene.


Amphotericin B is an intravenous antifungal agent which is clinically used to treat systemic mycosis. It has a broad spectrum of activity and it is clinically used to treat infections caused by Coccidioides species, Histoplasma species and Blastomycosis species amongst other fungal agents that causes endemic or deep mycoses. Nystatin is a topical antifungal agent used topically to treat some yeast infections especially those caused by Candida species. Nystatin is also applied at the vaginal area and on the skin surfaces to control the multiplication of yeast cells (e.g. Candida) in those regions. Amphotericin B is also used in combination with 5-FC to treat some systemic mycoses; and such antimicrobial combinations achieves a synergistic antifungal effect.      


The polyenes (inclusive of amphoteracin B and nystatin) are antifungal agents with strong affinity for fungal sterol (i.e. ergosterol), and they generally disrupt the cell membrane of fungi. While amphoteracin B is administered intravenously (IV), nystatin is mainly available as creams or solutions and is used for topical treatment of fungal infections because of their toxicity which limits their usage for systemic administration. The binding of the cell membrane of fungi by the polyenes (i.e. amphoteracin B and nystatin) leads to the formation of channels or holes on the cytoplasmic membranes through which important cell molecules exit the fungal cell. Amphotericin and nystatin are fungicidal in action since their antimicrobial effect can lead to the death of the fungal organism.


Polyenes (inclusive of nystatin and amphotericin B) have untoward effects on human host cells upon usage. Nystatin is the most toxic and this limits its use to topical applications in the form of antifungal creams or solutions. Fever, chills, headache and dyspnea are some of the untoward effects of amphotericin administration. Their toxicity is also extended to the renal system causing nephrotoxicty, but this can be controlled when amphotericin B is co-administered with a lipid carrier such as liposomes. The development of resistance to the polyenes by pathogenic fungi is rare.


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