Potential Inhibitory Effect of Miltefosine against Terbinafine-Resistant Trichophyton indotineae

Haghani, Iman; Akhtari, Javad; Yahyazadeh, Zahra; Espahbodi, Amirreza; Kermani, Firoozeh; Javidnia, Javad; Hedayati, Mohammad Taghi; Shokohi, Tahereh; Badali, Hamid; Rezaei‐Matehkolaei, Ali; Âghili, Seyed Reza; Al‐Rawahi, Ahmed; Al‐Harrasi, Ahmed; Abastabar, Mahdi; Al‐Hatmi, Abdullah M. S.

doi:10.3390/pathogens12040606

Cited by 9 publications

(2 citation statements)

References 52 publications

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“…[ 22 23 ] New agents such as voriconazole have also been effective,[ 29 ] as has miltefosine in an in vitro trial. [ 30 ]…”

Section: Managementmentioning

confidence: 99%

Trichophyton

Chatterjee,

Datta

2023

Indian Journal of Dermatology

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Trichophyton interdigitale had been regarded as anthropophilic, mainly causing non-inflammatory tinea unguium and tinea pedis. T. mentagrophytes, thought to be zoophilic, were regarded as responsible for more inflammatory dermatophytosis. Indian terbinafine-resistant strains, identified with ribosomal internal transcribed spacer as 'genotype VIII', have recently been termed Trichophyton indotineae based on clinical and mycological features. Some of these have shown selective azole resistance as well. Phenotypic studies have shown some similarities and some differences between Trichophyton indotineae, T. mentagrophytes, and T. interdigitale, which are optimally distinguished with HMG locus analyses as three main genotypic groups containing the type strains of T. indotineae (CBS 146623), T. interdigitale (CBS 428.63), and T.mentagrophytes (IHEM 4268) and having approximate differences in geographic distribution. Trichophyton interdigitale was prevalently isolated from superficial infections on exposed body sites such as the scalp and face, while also feet and nails. Trichophyton mentagrophytes has a similar predilection but are also often found on the trunk and genitals. Trichophyton indotineae is mostly restricted to the trunk and groin. T. indotineae lesions are generally highly inflammatory, strongly associated with tinea cruris, corporis, and faciei and less commonly with fingernail onychomycosis and tinea pedis. They cause papulosquamous, pustular, pseudo-imbricata (tinea faciei), lichenoid, and pityriasis rosea (tinea corporis of the neck) types of lesions and spread rapidly to multiple sites and cause painful lesions with itching or burning. Lipolytic abilities of T. mentagrophytes and T. interdigitale are very similar and are higher than those of T. indotineae, which is associated with a higher prevalence of T. mentagrophytes on the human scalp, which is relatively rich in lipids. Keratin degradation is significantly larger in T. interdigitale due to location (tinea pedis and tinea unguium). Identification of T. indotineae through culture alone may not be sufficient for effective treatment decision-making; genetic analysis for resistance profiles is needed for optimum treatment selection. In India, steroid-induced suppression of local cellular immunity as well as an altered cutaneous microbiome provided a window of opportunity for the unique, multidrug-resistant species Trichophyton indotineae.

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“…[ 22 23 ] New agents such as voriconazole have also been effective,[ 29 ] as has miltefosine in an in vitro trial. [ 30 ]…”

Section: Managementmentioning

confidence: 99%

Trichophyton

Chatterjee,

Datta

2023

Indian Journal of Dermatology

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“…It works by blocking the synthesis of ergosterol, a crucial component in fungal cell membranes, through inhibiting squalene epoxidase, an enzyme involved in the fungal membrane synthesis process. Additionally, it hinders the conversion of squalene into lanosterol, inhibiting ergosterol and ultimately causing fungal cell breakdown [5]. Terbinafine HCl cream and powder are employed to treat surface skin infections like jock itch (tinea crusis), athlete's foot (tinea pedis), and ringworm.…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of Terbinafine-Loaded Nanoemulgel for Effective Management of Dermatophytosis

Phagna,

Badhwar,

Singh

et al. 2023

Gels

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Dermatophytosis, the most prevalent fungal infection, is witnessing a rising incidence annually. To address this challenge, we developed a terbinafine-loaded oil-in-water nanoemulsion (TH-NE) through the aqueous microtitration method. The formulation comprised olive oil (oil phase), Span 80 (surfactant), and propylene glycol (co-surfactant). Pseudo-phase ternary diagrams and thermodynamic studies underscored the stability of TH-NE. Employing the Box–Behnken design (BBD), we optimized TH-NE, which resulted in a remarkable particle size of 28.07 nm ± 0.5, a low polydispersity index (PDI) of 0.1922 ± 0.1, and a substantial negative zeta potential of −41.87 mV ± 1. Subsequently, TH-NE was integrated into a 1.5% carbopol matrix, yielding a nanoemulgel (TH-NEG). Texture analysis of TH-NEG demonstrated a firmness of 168.00 g, a consistency of 229.81 g/s, negative cohesiveness (−83.36 g), and a work of cohesion at −107.02 g/s. In vitro drug release studies revealed an initial burst effect followed by sustained release, with TH-NEG achieving an impressive 88% release over 48 h, outperforming TH-NE (74%) and the marketed formulation (66%). Ex vivo release studies mirrored these results, with TH-NEG (86%) and TH-NE (71%) showcasing sustained drug release in comparison to the marketed formulation (67%). Confocal microscopy illustrated that TH-NEG and TH-NE penetrated to depths of 30 µm and 25 µm, respectively, into the epidermal layer. Furthermore, dermatokinetic studies highlighted the enhanced drug penetration of TH-NEG compared to TH-NE through mouse skin. In summary, our study establishes TH-NEG as a promising carrier for terbinafine in treating dermatophytosis, offering improved drug delivery and sustained release potential.

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