Nystatin

Overview

Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.[1] WP

Common side effects when applied to the skin include burning, itching, and a rash. Common side effects when taken by mouth include vomiting and diarrhea. During pregnancy use in the vagina is safe while other formulations have not been studied in this group. It works by disrupting the cell membrane of the fungal cells.[1] WP

Nystatin was discovered in 1950 by Rachel Fuller Brown and Elizabeth Lee Hazen. It was the first polyene macrolide antifungal. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. It is made from the bacterium Streptomyces noursei. In 2023, it was the 233rd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[1–6] WP

Uses, dosage and effects

Medical uses

Skin, vaginal, mouth, and esophageal Candida infections usually respond well to treatment with nystatin. Infections of nails or hyperkeratinized skin do not respond well.[7] WP

When given parenterally (that is, other routes besides oral/topical/vaginal), its activity is reduced due to presence of plasma.[8] WP

Oral nystatin is often used as a preventive treatment in people who are at risk for fungal infections, such as AIDS patients with a low CD4⁺ count and people receiving chemotherapy. It has been investigated for use in patients after liver transplantation, but fluconazole was found to be much more effective for preventing colonization, invasive infection, and death. It is effective in treating oral candidiasis in elderly people who wear dentures.[9][10] WP

It is also used in very low birth-weight (less than 1500 g or 3 lb 5oz o) infants to prevent invasive fungal infections, although fluconazole is the preferred treatment. It has been found to reduce the rate of invasive fungal infections and also reduce deaths when used in these babies.[11] WP

Liposomal nystatin is not commercially available, but investigational use has shown greater in vitro activity than colloidal formulations of amphotericin B, and demonstrated effectiveness against some amphotericin B-resistant forms of fungi. It offers an intriguing possibility for difficult-to-treat systemic infections, such as invasive aspergillosis, or infections that demonstrate resistance to amphotericin B. Cryptococcus is also sensitive to nystatin. Additionally, liposomal nystatin appears to cause fewer cases of and less severe nephrotoxicity than observed with amphotericin B.[12] WP

Risks and side effects

Adverse effects

Bitter taste and nausea are more common than most other adverse effects.[7] WP

The oral suspension form produces a number of adverse effects including but not limited to:[13] WP

• Diarrhea[13] WP
• Abdominal pain[13] WP
• Rarely, tachycardia, bronchospasm, facial swelling, muscle aches[13] WP

Both the oral suspension and the topical form can cause: WP

• Hypersensitivity reactions, including Stevens–Johnson syndrome in some cases[14] WP
• Rash, itching, burning and acute generalized exanthematous pustulosis[15] WP

Too high of a dosage can potentially lead to additional side effects such as:[16] WP

• Nephrotoxicity[16] WP
• Hypokalemia[16] WP
• Chills and skin rash[16] WP

Pharmacology

Mechanism of action

Like amphotericin B and natamycin, nystatin is an ionophore. It binds to ergosterol, a major component of the fungal cell membrane. When present in sufficient concentrations, it forms pores in the membrane that lead to K⁺ leakage, acidification, and death of the fungus. Ergosterol is a sterol unique to fungi, so the drug does not have such catastrophic effects on animals or plants. However, many of the systemic/toxic effects of nystatin in humans are attributable to its binding to mammalian sterols, namely cholesterol. This is the effect that accounts for the nephrotoxicity observed when high serum levels of nystatin are achieved. Despite the molecular similarities and differences of ergosterol and cholesterol, there is currently no consensus as to why nystatin has a higher binding affinity for ergosterol because it remains unclear how the nystatin pores are formed. Researchers have concluded thus far that nystatin pores are formed from 4-12 nystatin molecules, with an unknown number of the necessary sterol interactions.[16–19] WP

Nystatin also impacts cell membrane potential and transport by lipid peroxidation. Conjugated double bonds in nystatin's structure steal electron density from ergosterol in fungal cell membranes. Lipid peroxidation alters the hydrophilicity of the interior of channels in the membrane, which is necessary to transport ions and polar molecules. Disruption of membrane transport from nystatin results in rapid cell death. Lipid peroxidation by nystatin also contributes significantly to K⁺ leakage due to structural modifications of the membrane.[20][21] WP

History

History

Like many other antifungals and antibiotics, nystatin has bacterial origin. It was isolated from Streptomyces noursei in 1950 by Elizabeth Lee Hazen and Rachel Fuller Brown, who were doing research for the Division of Laboratories and Research of the New York State Department of Health. Hazen found a promising micro-organism in the soil of a friend's dairy farm. She named it Streptomyces noursei, after Jessie Nourse, the wife of the farm's owner. Hazen and Brown named nystatin after the New York State Health Department in 1954. The two discoverers patented the drug, and then donated the $13 million in profits to a foundation to fund similar research.[22][23][24] WP

Chemistry

Formula

C47H75NO17 PC

CAS number

1400-61-9 PC

Molar mass (g/mol)

926.1 PC

IUPAC name (computed by PubChem)

(1S,15S,16R,17R,18S)-33-[(2S,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,25,27,29,31-hexaene-36-carboxylic acid PC

SMILES

C[C@H]1C=CC=CCCC=CC=CC=CC=CC(CC2C(C(C[C@](O2)(CC(C(CCC(CC(CC(CC(=O)O[C@H]([C@@H]([C@@H]1O)C)C)O)O)O)O)O)O)O)C(=O)O)O[C@@H]3[C@H]([C@H]([C@@H]([C@H](O3)C)O)N)O PC

InChIKey

VQOXZBDYSJBXMA-DZCKSEKHSA-N PC

PubChem CID

14960

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

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Pop culture

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Sources

1. Other Nystatin
2. Other Espinel-Ingroff AV. Medical Mycology in the United States a Historical Analysis (1894-1996). 2013
3. Journal / agency Gupte M, Kulkarni P, Ganguli BN. Antifungal antibiotics. Applied Microbiology and Biotechnology. January 2002. doi:10.1007/s002530100822 · PMID 11831475
4. Other The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
5. Other The Top 300 of 2023
6. Other Nystatin Drug Usage Statistics, United States, 2014 - 2023
7. Other Hilal-Dandan R, Knollmann B, Brunton L. Goodman & Gilman's the Pharmacological Basis of Therapeutics. 5 December 2017
8. Other Satoskar RS, Rege N, Bhandarkar SD. Pharmacology and Pharmacotherapeutics. 2015
9. Journal / agency Gøtzsche PC, Johansen HK. Nystatin prophylaxis and treatment in severely immunodepressed patients. The Cochrane Database of Systematic Reviews. September 2014. doi:10.1002/14651858.CD002033.pub2 · PMID 25188770 · PMC6457783
10. Journal / agency Lyu X, Zhao C, Yan ZM, Hua H. Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis. Drug Design, Development and Therapy. 2016. doi:10.2147/DDDT.S100795 · PMID 27042008 · PMC4801147
11. Journal / agency Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. March 2009. doi:10.1086/596757 · PMID 19191635 · PMC7294538
12. Other Hamill RJ. Clinical Mycology. 2003
13. Journal / agency Nystatin (Oral route)
14. Journal / agency FDA approved package insert
15. Journal / agency Rosenberger A, Tebbe B, Treudler R, Orfanos CE. Acute generalized exanthematous pustulosis, induced by nystatin. Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete. June 1998. doi:10.1007/s001050050776 · PMID 9675578
16. Journal / agency Groll AH, Piscitelli SC, Walsh TJ. Clinical Pharmacology of Systemic Antifungal Agents: A Comprehensive Review of Agents in Clinical Use, Current Investigational Compounds, and Putative Targets for Antifungal Drug Development. 1 January 1998. doi:10.1016/S1054-3589(08)60129-5 · PMID 9547888
17. Other Rang HP, Dale MM, Flower RJ, Henderson G. Rang and Dale's pharmacology. 21 January 2015
18. Journal / agency Hammond SM. Biological activity of polyene antibiotics. 1977. doi:10.1016/S0079-6468(08)70148-6 · PMID 345355
19. Journal / agency Helrich CS, Schmucker JA, Woodbury DJ. Evidence that nystatin channels form at the boundaries, not the interiors of lipid domains. Biophysical Journal. August 2006. doi:10.1529/biophysj.105.076281 · PMID 16679364 · PMC1563755
20. Journal / agency Welman E, Peters TJ. Properties of lysosomes in guinea pig heart: subcellular distribution and in vitro stability. Journal of Molecular and Cellular Cardiology. June 1976. doi:10.1016/S0006-3495(93)81343-2 · PMID 7679 · PMC1262305
21. Journal / agency Stark G. The effect of ionizing radiation on lipid membranes. Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes. July 1991. doi:10.1016/0304-4157(91)90020-w · PMID 1854791
22. Other Espinel-Ingroff A. Medical mycology in the United States: a historical analysis (1894-1996). 2003
23. Other Kelly K. Medicine Becomes a Science: 1840-1999. 2010
24. Other Sicherman B, Green CH. Notable American Women: The Modern Period: a Biographical Dictionary. 1980

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