Topical Amphotericin B in 30% Dimethylsulphoxide in Treating of Non-dermatophytes Onychomycosis
Topical Amphotericin B in 30% Dimethylsulphoxide in Treating of Non-dermatophytes Onychomycosis
The randomized control trial study aimed to evaluate effectiveness and safety of amphotericin
 B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment.
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.

 Objectives

 1. To evaluate effectiveness including mycological cure of amphotericin B in 30% DMSO
 solution comparing with 30% DMSO solution in NDMs onychomycosis treatment

 2. To evaluate safety of amphotericin B in 30% DMSO solution comparing with 30% DMSO
 solution in NDMs onychomycosis treatment

 Material and Methods Patients Since there was no previous study that compared amphotericin B
 in 30% DMSO with pure 30% DMSO in treating of NDMs onychomycosis, this study designated a
 total of 20 patients into two groups as 10 patients with NDMs onychomycosis treated with 30%
 DMSO (control group) and another 10 Patients with NDMs onychomycosis treated with
 amphotericin B in 30% DMSO. NDMs onychomycosis was diagnosed with diagnostic criteria for NDM
 onychomycosis proposed by Gupta et al. Patients with any systemic or topical antifungal
 agents at least 3 months prior to the study were excluded from this study.

 Design of medication Drugs were prepared in two solutions. First, amphotericin B (Alpharma,
 Denmark) was mixed with 30% DMSO (Sigma- Aldrich, Buchs, Switzerland) in 50:50 ratio. A final
 concentration of amphotericin B was 2 mg/ml. Later solution was pure 30% DMSO without
 amphotericin B. Those two final solutions had the same appearance, odor and texture. The
 solution will be kept in amber glass bottles with aluminum foil together with dropper. The
 drug regimen is to apply 1-3 drops of the solution once a day to each affected nail and
 briefly let the solution evaporate before continuing their usual activities.

 Treatment, Follow-up and measurement A randomized control trial study conducted in outpatient
 nail clinic, Siriraj Hospital. Patients will be divided into two groups by mixed block of
 randomization. First groups will be treated with amphotericin B in 30% DMSO solution. Another
 group will be given only 30% DMSO solution. Each patient is subjected to continuously apply
 his/ her own drugs followed instruction given for 12 weeks. They will be followed up at 12
 weeks, 24 weeks and 36 weeks for re-evaluation of clinical, mycological laboratories,
 adherence to the drug and adverse events. Effectiveness was evaluated by clinical improvement
 and mycological cure as well as median time to mycological cure. Clinical evaluation would be
 assessed by two treatment-blind dermatologists. Regarding mycological cure, it was defined as
 negative KOH and fungal culture. Data were analyzed using PASW Statistics version 18 (SPSS,
 Inc., Chicago, IL, USA).

 Duration of study: 1 year

 Study design: Randomized double blind control trial
Inclusion Criteria:

 1. Patients with non-dermatophyte onychomycosis.

 2. Patients aged more than 18 years.

 3. Patients has not been treated with any oral/ IV/ topical antifungal therapy within 36
 weeks before enrolled.

 Exclusion Criteria:

 1. Patients had concomitant nail diseases.

 2. Immunocompromised host.

 3. Patients with dermatophyte onychomycosis.