In Vitro Antifungal Activity of ME1111, a New Topical Agent for Onychomycosis, against Clinical Isolates of Dermatophytes
Authors: M. Ghannoum, N. Isham, and L. Long
Publication Year: 2015
Among superficial fungal infections, by far the most difficult to cure is toenail onychomycosis, which is responsible for 50% of all nail disease (1). Onychomycosis, a fungal nail infection affecting up to 13% of the general population (2,–8) and 25% of the geriatric and diabetic population (7, 9, 10), is more than just a cosmetic problem. More importantly, onychomycosis has been reported to cause chronic pain associated with prolonged standing or walking and acute pain from footwear and cutting of the nails (11,–13).
The greatest predisposing risk factor for developing onychomycosis is advanced age, as the risk is reported to be 18.2% in patients 60 to 79 years of age compared to 0.7% in patients younger than 19 years of age. Further, men are up to 3 times more likely to have onychomycosis than women, though the reasons for this gender difference are not clear (5, 14). Other risk factors include diabetes and conditions contributing to poor peripheral circulation (15). In fact, onychomycosis may represent an important predictor for the development of diabetic foot syndrome and foot ulcers (16). Patients who are immunosuppressed, such as those with HIV infection and those undergoing cancer therapy, are also predisposed to fungal nail infection (17).
Several nonclinical risk factors also affect a person’s chance of developing fungal nail infections. For example, toenail onychomycosis is not prevalent in tropical climates, presumably because people in those areas are not in the habit of wearing occlusive footwear that creates a warm, moist environment for the proliferation of fungi. Further, the spread of foot infections, including tinea pedis (athlete’s foot), may occur in places such as shower stalls, bathrooms, or locker rooms, where floor surfaces often are wet and people are barefoot (18). Nail trauma will also increase the risk of fungal infection of the affected nail, especially in the geriatric population (5, 17).
The treatment of onychomycosis has improved considerably over the past several decades following the introduction of the oral antifungals terbinafine and itraconazole. However, these drugs may have side effects such as liver damage or drug interactions, which are particularly relevant in the elderly population (19). Unfortunately, currently available topical agents such as ciclopirox 8% and amorolfine 5% have low efficacy (approximately 5 to 12%) (20, 21). This low efficacy can be attributed mainly to the inability of the drug to penetrate through the nail plate to the nail bed, where the infection resides (22). Additionally, thickened nails, extensive involvement of the entire nail, lateral disease, and yellow spikes (hyperkeratotic bands extending to the nail matrix) contribute to a poor response to topical treatment (17). Thus, there remains a need for new topical agents that are effective against onychomycosis. ME1111 is a novel antifungal discovered by Meiji Seika Pharma Co., Ltd. (Tokyo, Japan), and its small molecular mass (202.25 g/mol) enhances its ability to penetrate the nail plate (Fig. 1). The investigational drug is currently undergoing clinical evaluation. In this study, we determined the antifungal activity of ME1111 against dermatophyte species known to cause onychomycosis, as measured by MIC and minimum fungicidal concentration (MFC). Additionally, we examined the potential for resistance development in dermatophytes following repeated exposure to ME1111.
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