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Resistance to Antifungal Medications

Updated: Apr 18, 2022

Have you had a hard time getting rid of your toenail fungus? One reason may be the emerging resistance of fungi to antifungal medications. Read on to learn more about why fungal infections can persist despite the use of medication, how antifungal medications usually work, and some suggestions on how you can help clear a toenail infection for good.

Resistance to Antifungal Medication Athlete's foot is a fungal infection of the skin. Onychomycosis is a fungal infection of the nails and nail beds. The strains of fungi that cause these infections are typically susceptible to a myriad of available antifungals. Medciations like Lamisil (Terbinafine), Tolnaftate, Ketoconazole, Clotrimazole, Undecylenic acid, ciclopirox, and efinaconazole are examples of commonly used medications to treat fungal infections of the skin and nails. While these medicines have traditionally been very effective, new cases of fungal resistance have been emerging.

The first report of fugal resistance to medication was published in 2003.* One of the most common strains of fungus that causes skin and nail infections, Trichophyton Rubrum, was found to resist the effects of Terbinafine, our most powerful antifungal medication. Since then, reports of fungal infections not responding to medication have been on the rise.**

How Antifungal Medications Work Antifungal medications fall in to categories labeled azoles, triazoles, and allylamines. Although they all have different mechanisms, they all stop th efungal cell from building an dmaintaing it's cell wall and or plasma membrane. Much like a willow bark, a fungus grows by developing buds off if its main frame. In order for these buds to grow, their lining, or cell wall needs to be intact. Our antifungal medications inactivate several enzymes and pathways that the fungus uses to build that cell wall.

How do the fungi resist the effects of medication? One way that the fungi have found to thrive despite exposure to effective medicines is through mutation. Researchers have shown that amino acid substitution as a result of mutation leads to increased Terbinafine resistance.*** Biofilm is another fungal protection that creates resistance to mecidine. Biofilm describes "extracellular matrix" that is secreted by the fungi cells. This biofilm is structural, and made up of proteins, lipids, and polysaccharides. This material acts as a physical barrier, protecting the fungus against drugs and our immune response.

How To Get Rid Of a Fungal Infection A fungal infection fo the toenails can be difficult to clear. The best way to avoid problem is early detection. There are several treatments available, including oral medication, topical medication, surgical removal of the nail, laser, and microwave therapy. When medicines are not effective, physical removal of the fungus through laser, microwave or surgical care may be appropriate.

At Ace Feet, we offer toenails consultations, where your feet and toenails will be evaluated, and your best treatment options discussed. Feel free to book an appointment here or send Dr. Thompson an email if you have questions.

*Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine.Mukherjee PK, Leidich SD, Isham N, Leitner I, Ryder NS, Ghannoum MA Antimicrob Agents Chemother. 2003 Jan; 47(1):82-6. **Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study.Ebert A, Monod M, Salamin K, Burmester A, Uhrlaß S, Wiegand C, Hipler UC, Krüger C, Koch D, Wittig F, Verma SB, Singal A, Gupta S, Vasani R, Saraswat A, Madhu R, Panda S, Das A, Kura MM, Kumar A, Poojary S, Schirm S, Gräser Y, Paasch U, Nenoff P Mycoses. 2020 Jul; 63(7):717-728. ***Yamada, T., Maeda, M., Alshahni, M. M., Tanaka, R., Yaguchi, T., Bontems, O., et al. (2017). Terbinafine resistance of Trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob. Agents Chemother. 61:e00115-17. doi: 10.1128/AAC.00115-17

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