Fungicidal Activity in the Presence of Keratin as an Important Factor Contributing to In Vivo Efficacy: A Comparison of Efinaconazole, Tavaborole, and Ciclopirox.

Naomichi Kumagai,Haruki Tachibana,Yoshiyuki Tatsumi

doi:10.3390/jof3040058

Naomichi Kumagai, Haruki Tachibana + Show 1 more

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https://doi.org/10.3390/jof3040058

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Abstract

Use of oral antifungals in the treatment of onychomycosis is commonplace; but their use can be limited by safety and patient concerns. Due to their broader safety margins, topical antifungals (efinaconazole, tavaborole, and ciclopirox) are a useful option in the treatment of mild-to-moderate onychomycosis in the USA, but their antifungal activity has yet to be directly compared. This study aims to identify important factors contributing to in vivo efficacies of the three topical antifungals. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth microdilution. The MIC90 values of efinaconazole, tavaborole, and ciclopirox for T. rubrum were 0.0078, 8.0, and 0.50 μg/mL, respectively. The MIC90 values for T. mentagrophytes were 0.016, 8.0, and 0.50 μg/mL, respectively. Efinaconazole showed potent fungicidal activity in keratin-containing medium, whereas tavaborole was fungistatic, and ciclopirox not active. In the guinea pig model of onychomycosis, the therapeutic efficacy of efinaconazole was superior to those of tavaborole and ciclopirox. This study suggests that not only fungistatic activity (MIC), but also fungicidal activity in the presence of keratin, is an important factor contributing to the in vivo efficacy of topical antifungal drugs against onychomycosis.

Highlights

Onychomycosis is a common fungal nail infection, mainly caused by Trichophyton rubrum (T. rubrum) and Trichophyton mentagrophytes (T. mentagrophytes) in the nail plate and nail bed
Minimum inhibitory concentrations (MICs) of efinaconazole, tavaborole, and ciclopirox for T. rubrum were in the ranges of
Since dermatophytes are mainly present under a densely keratinized nail plate in onychomycosis, the route of entry into the nail bed plays a vital role in determining the efficacy of a drug

Summary

Introduction

Onychomycosis is a common fungal nail infection, mainly caused by Trichophyton rubrum (T. rubrum) and Trichophyton mentagrophytes (T. mentagrophytes) in the nail plate and nail bed. Onychomycosis impacts the patient’s quality of life (QOL) due to walking difficulties and the poor appearance of the nail, and can be a source of secondary infection or spread to other family members. Several antifungals, such as oral itraconazole, oral terbinafine, topical amorolfine nail lacquer, and topical ciclopirox nail lacquer, have been used to treat onychomycosis. Oral treatment with itraconazole and terbinafine has been shown to be more effective with high complete cure rates of 26% and 55%, respectively [3], but they have the disadvantage of drug-drug interactions and systemic side effects (e.g., hepatotoxicity) [4]. Topical treatment with amorolfine or ciclopirox nail lacquer is not generally associated with systemic side effects due to their extremely low transition from the nail to the bloodstream, they appear to be less effective, with complete cure rates of 0.96%

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