Overcoming Antifungal Resistance: The Case for Selenium Sulfide

To address this growing threat, the development of effective antifungal treatments is essential. However, the emergence of antifungal resistance is often driven by improper medication use, particularly when patients fail to complete the full course of treatment. Incomplete treatment or insufficient dosing can leave the infection partially treated, allowing more resistant fungal strains to survive and proliferate. Consequently, the prevalence of difficult-to-treat fungal infections has increased, underscoring the need for both proper antifungal usage and the ongoing development of new therapeutic strategies.[2]

Rise of antifungal resistance:

Historically, fungal infections, including severe cases, were relatively rare before the advent of advanced interventional medical practices. However, as medical interventions have progressed, the incidence of both invasive and cutaneous fungal infections has increased significantly.[4]

Fungal resistance can be categorized as either microbiological or clinical. Microbiological resistance arises from genetic alterations within fungal cells, while clinical resistance is influenced by factors related to the host or the antifungal drugs themselves. These factors may contribute to resistance independently or synergistically.[5]

The recent increase in fungal infections has been accompanied by a corresponding rise in the frequency of cases that are resistant to standard antifungal therapy. This trend has intensified the need for the development of next-generation antifungal agents, as many existing drugs are associated with undesirable adverse effects, lack efficacy against newly emerging or reemerging fungal species, and contribute to the rapid development of resistance.[6]

Antifungal drug resistance is not uniformly distributed among fungal cells within a population. The likelihood of resistance increases with the number of fungal cells present in an infection, as a larger population raises the probability of mutations that confer resistance.[6]

Several mechanisms contribute to the drug-resistant phenotype in eukaryotic cells. Common mechanisms include reduced drug import into the cell, modification or degradation of the drug within the cell, altered interactions between the drug and its target enzyme, changes in related enzymatic pathways, and increased drug efflux from the cell. These mechanisms collectively contribute to the growing challenge of antifungal resistance.[6]

Failure of antifungal resistance seen in other therapies: The treatment of SD and dandruff primarily focuses on symptom relief and maintaining long-term remission, targeting fungal colonization and inflammation. Common treatments involve synthetic topical antifungal and anti-inflammatory agents, as recommended by clinical guidelines in various countries. While these treatments are effective, their regular use can disrupt the scalp's microflora, potentially increasing the risk of antimicrobial resistance.[7]

Fungal resistance typically develops after prolonged exposure to antifungal drugs, evolving gradually due to continuous selective pressure, resulting in multiple alterations that contribute to a resistant phenotype.[6] It is crucial for healthcare providers to avoid over-prescribing combination antifungal-corticosteroids for unspecified rashes to prevent escalating resistance levels. Patients should also be educated to avoid the overuse or misuse of over-the-counter antifungal products, as many rashes are self-treated without proper diagnosis.[4]

Notably, Malassezia strains involved in SD pathogenesis have shown resistance to topical antifungal treatments, rendering these treatments ineffective in up to one-third of diagnosed SD patients. Although azoles are the first-choice antifungal treatment for Malassezia-associated conditions like dandruff and SD, their efficacy has diminished due to reduced sensitivity in Malassezia species.[7] Moreover, Malassezia furfur isolates have become less sensitive to treatments like terbinafine, clotrimazole, ketoconazole, amphotericin B, and miconazole, leading to increased minimum inhibitory concentrations (MICs) of these drugs.[7]

Recent studies have also identified Malassezia species with resistance to azole antifungals, likely due to increased prophylactic use, prolonged treatment regimens, or long-term low-dose azole use. The growing number of ketoconazole-resistant M. restricta strains in dandruff patients poses significant clinical challenges, especially in treating more severe fungal infections.[8]

Selenium Sulfide is the best choice and its antifungal resistance

Selenium sulfide was first approved for medical use in 1951. Since then, it has been widely used for the treatment of seborrheic dermatitis. As reported by Clark et al., selenium sulfide can control the symptoms associated with dandruff and seborrheic dermatitis at a fraction of the cost of other treatments.[8]

Selenium sulfide is a potent keratolytic agent used in dermatologic shampoos in the treatment of dandruff and seborrheic dermatitis. Reports suggest that selenium sulfide exhibits a cytostatic effect by reducing the turnover of corneocytes and keratinocytes involved in the formation of dandruff.

Agents that induce apoptosis in keratinocytes can be used for the treatment of dandruff. Anti-dandruff shampoo formulations apart from their antifungal ability should exhibit anti-proliferative ability against keratinocytes or keratolytic potential. However, while exhibiting the keratolytic activity, the growth of the normal cells should not be negatively affected. Cytotoxic agents kill all cells, whereas cytostatic agents inhibit the growth of abnormally differentiated cells without affecting the growth of normal cells. Thus, cytostatic compounds are presumably less toxic and more target-specific in nature. [9]

Selenium sulfide shampoo is usually a safe and efficient preparation for long-term control of seborrheic dermatitis. [10] It has antifungal properties and an inhibitory effect on the production of keratin in the stratum corneum. Selenium sulfide is well tolerated in most patients and rarely causes adverse events.[11]

Conclusion

In conclusion, the rising incidence of fungal infections and increasing antifungal resistance highlight the urgent need for effective and reliable treatment options. Selenium sulfide, with its long history of use and proven efficacy, stands out as a valuable addition to the therapeutic regimen for managing seborrheic dermatitis and dandruff. Its multifaceted action coupled with its low risk of resistance development, makes it a preferred choice for patients and healthcare providers alike. Despite the general challenges associated with antifungal resistance, selenium sulfide remains a reliable and effective treatment, offering significant benefits in managing and controlling seborrheic dermatitis and dandruff.

IND2363531 04 AUG 2025

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

References

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[2] Martinez-Rossi NM, Peres NTA, Rossi A. Antifungal resistance mechanisms in dermatophytes. Mycopathologia 2008;166:369–83. https://doi.org/10.1007/S11046-008-9110-7.

[3] Jafarlou M. Unveiling the menace: a thorough review of potential pandemic fungal disease. Frontiers in Fungal Biology 2024;5:1338726. https://doi.org/10.3389/FFUNB.2024.1338726/BIBTEX.

[4] McCormick TS, Ghannoum M. Time to Think Antifungal Resistance Increased Antifungal Resistance Exacerbates the Burden of Fungal Infections Including Resistant Dermatomycoses. Pathog Immun 2023;8:158. https://doi.org/10.20411/PAI.V8I2.656.

[5] Pai V, Ganavalli A, Kikkeri NN. Antifungal Resistance in Dermatology. Indian J Dermatol 2018;63:361. https://doi.org/10.4103/IJD.IJD_131_17.

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[7] Filatov VA, Kulyak OY, Kalenikova EI. Chemical Composition and Antimicrobial Potential of a Plant-Based Substance for the Treatment of Seborrheic Dermatitis. Pharmaceuticals 2023, Vol 16, Page 328 2023;16:328. https://doi.org/10.3390/PH16030328.

[8] Godse G, Godse K. Safety, Efficacy and Attributes of 2.5% Selenium Sulfide Shampoo in the Treatment of Dandruff: A Single-Center Study. Cureus 2024;16. https://doi.org/10.7759/CUREUS.57148.

[9] Barve SS, Deshpande S, Dhawal PP. Cytotoxic, cytostatic, and keratolytic activity of anti-dandruff shampoo formulations. International Journal of Research in Dermatology Barve SS et al Int J Res Dermatol 2023;9:61–6. https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20230036.

[10] Eisenberg BC. CONTACT DERMATITIS FROM SELENIUM SULFIDE SHAMPOO. AMA Arch Derm 1955;72:71–2. https://doi.org/10.1001/ARCHDERM.1955.03730310073016.

[11] Alkeswani A, Cantrell W, Elewski B. Treatment of Tinea Capitis. Skin Appendage Disord 2019;5:201. https://doi.org/10.1159/000495909.