A Cautionary Tale of Treatment Resistance at Annual Meeting

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“Onychomycosis should only be treated if there is a confirmatory diagnosis [via] fungal culture or PCR [polymerase chain reaction] positive of a dermatophyte confirmatory culture, and identification of pathogen is ideal,” Boni E. Elewski, MD, told attendees at the 2023 Annual Meeting of the American Academy of Dermatology.¹

Elewski, the James Elder Professor and chair of dermatology at the University of Alabama, said there has been a tendency to treat before diagnosing, which is one of the reasons onychomycosis is becoming treatment resistant. She added PCR, PAS/KOH are preferred ways to confirm the diagnosis.

Next, choosing appropriate treatment strategies is crucial. Although there are topical options (ie, 10% efinaconazole solution, 5% tavaborole solution, 8% ciclopirox lacquer, and 5% Amorolfine lacquer), Elewski focused on the 3 oral medications. Terbinafine 250mg/day should be prescribed for daily treatment over 3 months for toenails and 6 weeks for fingernails. Unfortunately, according to available data, the cure rate was only 38% at 3 months, and often treatment is cut short, she added. Itraconazole can be given in pulse method (ie, 1 week on, next 3 weeks off) at 400 mg/day for 4 months or 200 mg/day for 3 months; she noted pulse dosage is not recommended for toenails. Although fluconazole is not approved by the US Food and Drug Administration for this indication, it has been used with some positive results. It should be used until the nail is normal, she said. According to study data,at 4 months, there was 48% complete cure with 450 mg/week, 46% complete cure with 300 mg/week, and 37% complete cure with 150 mg/week.

Unfortunately, Elewski noted treatment is stopped at a certain period of time, not as a result of the nail being fungus free, and the duration is often chosen for economic reasons. As a result, not all nails are cured of infection, which can lead to recurrent disease. “You may get rid of it in one nail, but it may not totally eradicate the fungus,” she explained. This, coupled with patient adherence, leads increased treatment resistance.

“Treatment resistance is not new,” Elewski added, “it’s been described for the past 10 years.” However, the problem may be getting more widespread. In India, she said colleagues are seeing more than 100 individuals a day with treatment resistant onychomycosis. Furthermore, the resistance is not just in India. Elewski shared data indicating Europe is also impacted.² After sending standardized questionnaires to dermatologists in 20 countries in Europe, researchers found clinicians observed clinical and/or mycological confirmed antifungal resistance in 85% of those countries, she explained. Although 1 country had no known cases of resistance, 2 countries reported published cases of antifungal resistance. “Antifungal resistance is endemic and will be coming to your office soon,” she warned attendees.

"Antifungal resistance is endemic and will be coming to your office soon."

Elewski used a published case example to explain the need to treat until clear.³ The patient was a 45 year old man who had a 20 year history of onychomycosis. Dermatophytosis spread to his feet, thighs, groin, and buttocks. He had hereditary spherocytosis and was on apixaban anticoagulation therapy. After fungal culture grew T. rubrum, and he was given 250 mg oral terbinafine 250 for 3 months; itraconazole or fluconazole were not prescribed initial due to potential drug-drug interactions on cytochrome P450 3A4. At 3 month follow-up, the patient reported minimal improvement, and clinical examination concluded status was largely unchanged. After consulting with his hematologist, the patient’s medication was changed. Itraconazole was initiated at 200 mg daily for 3 months, which resulted in treatment success.

“So, my message to you all is that we all need to lead the way as antifungal stewards,” Elewski told attendees. She endorsed aggressive treatment to eliminate uncertainty in resolution and reminded colleagues that intermittent dosing could lead to resistance. “Treat with a full course of antifungal agent or until infection is resolved.”

Stay tuned to Dermatology Times for continued conference coverage, news, and updates.

References

1. Elewski BE. Update: onychomycosis management. Presented at the 2023 Annual Meeting of the American Academy of Dermatology. March 17 – 21, 2023; New Orleans, Louisiana.

2. Saunte DML, Ferrieros M, Rodríguez-Cerdeira C, et al. Emerging antifungal treatment failure of dermatophytosis in Europe: take care or it may become endemic. J Euro Acad Dermatol Venereol. 2021;35(7):1582-1586. doi:10.1111/jdv.17241

3. Gu D, Hatch M, Grannum M, Elewski BE. Treatment-resistant dermatophytosis: A representative case highlighting an emerging public health threat. JAAD Case Rep. 2020;6(11):1153-1155. Published 2020 Jun 3. doi:10.1016/j.jdcr.2020.05.025