Comparison of Effectiveness of Topical Amphotericin B in 30% Dimethylsulphoxide and 30% Dimethylsulphoxide in Treating of Non-dermatophytes Onychomycosis: Randomized Double Blind Controlled Trial Pilot Study

Introduction Onychomycosis caused by non-dermatophyte molds (NDMs) have become more common in clinical practice, particularly in tropical and subtropical area. With worldwide prevalence as high as 10-24% for nail infection, more recent studies have focused on the treatment regimens for NDMs onychomycosis, especially of Neoscytalidium spp and Fusarium spp. etiology. However, there has been no consensus to-date regarding standard treatment of choice for NDMs onychomycosis.

NDMs onychomycosis was considered to be recalcitrant infection. Previous in vitro study in Malaysia reported high susceptibility of Neoscytalidium dimidiatum in amphotericin B, voriconazole, and miconazole treatment.Different therapeutic approaches such as oral antifungal agents, keratolytic agents, combined oral antifungal agents with keratolytic agents, or surgical nail avulsion, have been implemented but none has been considered a gold standard protocol in NDMs onychomycosis.

Amphotericin B is the polyene class of antimicrobial compounds. Its properties are fungicidal and have a broad spectrum with a low rate of resistance. In in vitro study, amphotericin B was reported to have better efficacy of treating N. dimidiatum infection followed by terbinafine and voricanazole. The mechanism of action is the interaction with ergosterol of fungi membrane resulting in forming permeable channels in cellular membrane of targeted fungi. This causes impairing membrane barrier function. In addition, it also causes growth inhibition. Amphotericin B is often used in treating disseminated fungal infection and visceral leishmaniasis. However, Amphotericin B can cause several side effects including nephrotocixicity, fever, chills, nausea, vomiting, headache, anemia, electrolytes imbalance (hypokalemia and hypomagnesaemia). Oral amphotercin B has poor bioavailability. Topical forms are not commonly used due to its highly lipophilic property. As a consequence, topical amphotericin B is not well absorbed through mucosa or skin resulting in low efficacy. High dose of topical amphotericin B had been developed but the results didn't work well because it caused severe adverse events such as blistering, itching, redness, peeling or severe irritation of the skin and did not even achieve the goal of treatment.

Dimethylsulphoxide (DMSO) is a promising vehicle to enhance the penetration of the drugs to animal or human skin. In addition, DMSO also has fungicidal activity. In vitro release study of amphotericin B from amphotericin B in 30% DMSO solution conducted in Siriraj Hospital revealed adequate amphotericin B concentration in the nails.

Since skin and nail infections caused by NDMs especially N. dimidiatum has been diagnosed in many countries with the majority cases being reported from Thailand, it could be implied that N. dimidiatum was endemic pathogens in this area. Published data on treatment regimens of NDMs nail infection using amphotericin B are still limited. According to the high antifungal property and low rate of drug resistance of amphotericin B, this randomized control trial study aimed to evaluate effectiveness and safety of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution.