CLINICAL USE AND APPLICATION OF FUNGAL CELL MEMBRANE INHIBITORS

The cytoplasmic membrane of fungal cell is vital to the sustenance and development of the fungal organism. This is because this part of the cell helps to maintain a constant internal environment. It also helps to regulate the inflow and outflow of materials from the cell. Antifungal agents that interfere with the synthesis of fungal cytoplasmic membrane include amphotericin 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.   

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Figure 1. Chemical structure of amphotericin B, a polyene. https://www.microbiologyclass.com

CLINICAL APPLICATION OF AMPHOTERICIN B

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 organisms 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.       

MECHANISM OF ACTION OF AMPHOTERICIN B

The polyenes (inclusive of amphotericin 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 amphotericin 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. amphotericin 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 B and nystatin are fungicidal in action since their antimicrobial effect can lead to the death of the fungal organism.     

SIDE EFFECTS AND FUNGAL RESISTANCE TO AMPHOTERICIN B

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.     

FURTHER READING

Ashutosh Kar (2008). Pharmaceutical Microbiology, 1st edition. New Age International Publishers: New Delhi, India. 

Block S.S (2001). Disinfection, sterilization and preservation. 5th edition. Lippincott Williams & Wilkins, Philadelphia and London.

Courvalin P, Leclercq R and Rice L.B (2010). Antibiogram. ESKA Publishing, ASM Press, Canada.

Denyer S.P., Hodges N.A and Gorman S.P (2004). Hugo & Russell’s Pharmaceutical Microbiology. 7th ed. Blackwell Publishing Company, USA. Pp.152-172.

Ejikeugwu Chika, Iroha Ifeanyichukwu, Adikwu Michael and Esimone Charles (2013). Susceptibility and Detection of Extended Spectrum β-Lactamase Enzymes from Otitis Media Pathogens. American Journal of Infectious Diseases. 9(1):24-29.

Finch R.G, Greenwood D, Norrby R and Whitley R (2002). Antibiotic and chemotherapy, 8th edition. Churchill Livingstone, London and Edinburg.

Russell A.D and Chopra I (1996). Understanding antibacterial action and resistance. 2nd edition. Ellis Horwood Publishers, New York, USA.

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