Fungal Nail Infections (Onychomycosis): A Never-Ending Story?

Ghannoum, Mahmoud A.; Isham, N.

doi:10.1371/journal.ppat.1004105

Cited by 104 publications

(88 citation statements)

References 28 publications

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“…It mainly occurs in older adults, and in Europe its prevalence has been estimated to be as high as 23% [1,2] . Onychomycosis is not dangerous as such, but it does not resolve without treatment, can be transmitted from nail to nail and even between individuals [3] , and negatively affects quality of life in long-term sufferers [4] .…”

Section: Introductionmentioning

confidence: 99%

Early Visible Improvements during K101-03 Treatment: An Open-Label Multicenter Clinical Investigation in Patients with Onychomycosis and/or Nail Psoriasis

Piraccini

Starace²,

Toft³

2017

Dermatology

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Introduction: Onychomycosis and nail psoriasis can be embarrassing to patients, so improving the appearance of affected nails should be one of the key short-term goals of treatment. Methods: An 8-week open-label multicenter study was conducted to assess whether K101-03, a marketed topical treatment containing propylene glycol, glycerol, urea, and lactic acid, could produce rapid cosmetic improvements in affected nails. Adult patients with a big toenail or thumbnail (the “target” nail) affected by onychomycosis (n = 72) or psoriasis (n = 34) or both (n = 1) applied K101-03 to their affected nails once a day for 8 weeks. During and after treatment, patients rated the overall appearance of their target nail on a 4-point scale. They also assessed whether thickening, discoloration, brittleness, and softness of the target nail had improved since baseline. Adverse events (AEs) that occurred between the first application of K101-03 and the end of treatment were recorded and categorized according to severity and relationship to K101-03. Results: After 8 weeks of K101-03 treatment, 92.2% of patients (95% confidence interval [CI] 87.06-97.40) reported at least some improvement in the target nail. After 1 week of treatment, 78.3% of patients with onychomycosis (95% CI 68.53-87.99) reported at least some improvement in the target nail, and 55.1% of them reported that discoloration of their target nail had improved. Three patients reported a total of 5 AEs, none of which were judged to be related to K101-03. Conclusions: In summary, K101-03 was well tolerated in patients with onychomycosis or nail psoriasis and rapidly improved their nails.

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Section: Introductionmentioning

confidence: 99%

Early Visible Improvements during K101-03 Treatment: An Open-Label Multicenter Clinical Investigation in Patients with Onychomycosis and/or Nail Psoriasis

Piraccini

Starace²,

Toft³

2017

Dermatology

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“…The disease affects up to 23% of adults worldwide (1)(2)(3)(4). The prevalence of the disease increases in the elderly, affecting approximately 28% of people over the age of 60 (5).…”

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confidence: 99%

Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

Tabata

Takei-Masuda

Kubota

et al. 2016

Antimicrob Agents Chemother

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Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC 50 and MIC 90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation.

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“…A mong 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)(3)(4)(5)(6)(7)(8) and 25% of the geriatric and diabetic population (7,9,10), is more than just a cosmetic problem.…”

mentioning

confidence: 99%

In Vitro Antifungal Activity of ME1111, a New Topical Agent for Onychomycosis, against Clinical Isolates of Dermatophytes

Ghannoum

Isham

Long

2015

Antimicrob Agents Chemother

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The treatment of onychomycosis has improved considerably over the past several decades following the introduction of the oral antifungals terbinafine and itraconazole. However, these oral agents suffer from certain disadvantages, including drug interactions and potential liver toxicity. Thus, there is a need for new topical agents that are effective against onychomycosis. ME1111 is a novel selective inhibitor of succinate dehydrogenase (complex II) of dermatophyte species, whose small molecular weight enhances its ability to penetrate the nail plate. In this study, we determined the antifungal activity of ME1111 against dermatophyte strains, most of which are known to cause nail infections, as measured by the MIC (n ‫؍‬ 400) and the minimum fungicidal concentration (MFC) (n ‫؍‬ 300). Additionally, we examined the potential for resistance development in dermatophytes (n ‫؍‬ 4) following repeated exposure to ME1111. Our data show that the MIC 90 of ME1111 against dermatophyte strains was 0.25 g/ml, which was equivalent to that of the comparators amorolfine and ciclopirox (0.25 and 0.5 g/ml, respectively). ME1111 was fungicidal at clinically achievable concentrations against dermatophytes, and its MFC 90 s against Trichophyton rubrum and Trichophyton mentagrophytes were 8 g/ml, comparable to those of ciclopirox. Furthermore, ME1111, as well as ciclopirox, did not induce resistance in 4 dermatophytes tested. Our studies show that ME1111 possesses potent antifungal activity and suggest that it has low potential for the development of resistance in dermatophytes.A mong 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...

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Fungal Nail Infections (Onychomycosis): A Never-Ending Story?

Cited by 104 publications

References 28 publications

Early Visible Improvements during K101-03 Treatment: An Open-Label Multicenter Clinical Investigation in Patients with Onychomycosis and/or Nail Psoriasis

Early Visible Improvements during K101-03 Treatment: An Open-Label Multicenter Clinical Investigation in Patients with Onychomycosis and/or Nail Psoriasis

Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

In Vitro Antifungal Activity of ME1111, a New Topical Agent for Onychomycosis, against Clinical Isolates of Dermatophytes

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