Search Results (4)

Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine’s in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063–0.5 µg/mL and 0.125–0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC₅₀ and MIC₉₀ were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy. Full article

Widespread resistance to QoIs, DMI and SDHIs fungicides has been reported for Brazilian populations of the wheat blast pathogen Pyricularia oryzae Triticum lineage (PoTl). A pre-existing resistance mechanism not associated with target site mutations has been indicated for resistance to DMIs and SDHIs, with strong indication that PoTl has multidrugresistance (MDR). Therefore, the main objective of this study was to test the hypothesis that resistance to DMI and SDHI fungicides detected in PoTl was due to efflux pump mediated MDR mechanism(s) by characterizing the sensitivity to antifungal efflux pump substrates. Four antifungal substrates were tested: tolnaftate (TOL), cycloheximide (CHX), rhodamine 6G (RH6G) and triphenyltin chloride (TPCL). TPCL and RH6G were considered the most relevant indicators for enhanced MDR activity. Among the 16 PoTl isolates tested, 9 were insensitive to TPCL, 1 to TOL, 16 to RH6G and 1 to CHX. The PoTl isolates were grouped into four distinct multidrug resistance phenotypes (MDRPs) based on resistance to combinations of fungicides and antifungal efflux pump substrates. Insensitivity to TPCL, RH6G and or TOL correlated well with DMI insensitivity, but MDR was not associated with SDHI resistance. The identification of multiple MDRP phenotypes associated with DMI resistance in our study warrants further research aimed at revealing the exact mechanisms of multidrug resistance in the wheat blast pathogen, including efflux pumps overexpression via transcriptomic analyses of differentially expressed genes; identification and discovery of mutations associated with changes in promoter regions or transcription factors of efflux transporters associated with multidrug resistance. Full article

Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 3² factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 3¹.2¹ factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of −32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery. Full article

Dermatophytosis, topical fungal infection is the most common cause of skin bug in the world, generally underestimated and ignored. It is commonly caused by immensely mortifying and keratinophilic fungal eukaryotes which invade keratinized tissues and generate different tinea diseases in Mediterranean countries. We herein fabricated nanofibers/scaffolds embedded with thiocarbamate derivative topical antifungal tolnaftatefor the first time to target the complete elimination of dermatophyte at the site of infection. In this regard, variable combinations of biocompatible Eudragit grades (ERL100 and ERS100) were selected to provide better adhesion on the site of dermatophytosis, ample absorption of exudates during treatment, and customized controlled drug release. Surface topography analysis indicated that the fabricated nanofibers were regular and defect-free, comprising distinct pockets with nanoscaled diameters. Characterization and compatibility studies of tolnaftate, polymers, and their nanofibers were performed through ATR-FTIR, TGA, and PXRD. Remarkable hydrophilicity and an excellent swelling index were obtained from a 3:1 ratio of ERL100/ERS100 electrospun D3 nanofibers, which is an essential benchmark for the fabrication of nanofibrous scaffolds for alleviating dermatophytosis. In vitro drug release investigation revealed that a nonwoven nanomesh of nanofibers could control the rate of drug release for 8 h. A microdilution assay exhibited inhibition of more than 95% viable cells of Trichophyton rubrum for 96 h. However, Microsporum species rigidly restricted the effect of bioactive antifungal nanofibers and hence showed resistance. In vivo activity on Trichophyton rubrum infected Swiss albino mice revealed complete inhibition of fungal pathogens on successive applications of D3 nanofibers for 7 days. This investigation suggests potential uses of tolnaftate loaded polyacrylate nanofibers as dressing materials/scaffolds for effective management of dermatophytosis. Full article