scholarly journals In VitroAntifungal Activity of ME1111, a New Topical Agent for Onychomycosis, against Clinical Isolates of Dermatophytes

2015 ◽  
Vol 59 (9) ◽  
pp. 5154-5158 ◽  
Author(s):  
M. Ghannoum ◽  
N. Isham ◽  
L. Long
Keyword(s):  
Antifungal Activity ◽  
Liver Toxicity ◽  
Nail Plate ◽  
Trichophyton Mentagrophytes ◽  
Small Molecular Weight ◽  
Content Type ◽  
Minimum Fungicidal Concentration ◽  
Development Of Resistance ◽  
Oral Agents ◽  
Induce Resistance

ABSTRACTThe 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 MIC90of ME1111 against dermatophyte strains was 0.25 μg/ml, which was equivalent to that of the comparators amorolfine and ciclopirox (0.25 and 0.5 μg/ml, respectively). ME1111 was fungicidal at clinically achievable concentrations against dermatophytes, and its MFC90s againstTrichophyton rubrumandTrichophyton mentagrophyteswere 8 μg/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.

scholarly journals Ciclopirox and Efinaconazole Transungual Permeation, Antifungal Activity, and Proficiency To Induce Resistance in Trichophyton rubrum

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Daniela Monti ◽  
Diletta Mazzantini ◽  
Silvia Tampucci ◽  
Alessandra Vecchione ◽  
Francesco Celandroni ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Nail Plate ◽  
Content Type ◽  
Nail Bed ◽  
Antimycotic Activity ◽  
Frequent Relapses ◽  
Induce Resistance ◽  
Over Time

ABSTRACT Onychomycosis is a nail fungal infection, mostly caused by dermatophytes. The treatment efficacy is impaired by difficulties of reaching effective drug levels at the site of infection; frequent relapses occur after cessation of antifungal therapy. The aim of the study was to compare two commercial products containing ciclopirox or efinaconazole for antimycotic activity and antifungal drug resistance. A study of permeation and penetration through bovine hoof membranes, as a nail model, was performed to evaluate the antimycotic activity of permeates against clinical isolates of selected fungi, and the frequency of spontaneous in vitro Trichophyton rubrum-resistant strains was assessed by broth microdilution assays. The results suggest that ciclopirox creates a depot in the nail, leading to a gradual release of the drug over time with action on both the nail plate and bed. Conversely, efinaconazole, mildly interacting with nail keratin, mainly exerts its antifungal activity in the nail bed. However, in the case of T. rubrum, the antifungal activities of the drugs in the nail plate seem comparable. Finally, efinaconazole showed a potential for induction of resistance in T. rubrum, which may limit its efficacy over time. Ciclopirox did not show any potential to induce resistance in T. rubrum and appears endowed with a more complete activity than efinaconazole in the management of onychomycosis as the nail keratin is a substrate for the growth of fungal cells, and the availability of drug in large concentration just in the nail bed may not be sufficient to guarantee the complete eradication of pathogens.

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

2015 ◽  
Vol 60 (2) ◽  
pp. 1035-1039 ◽  
Author(s):  
Yuji Tabata ◽  
Naomi Takei-Masuda ◽  
Natsuki Kubota ◽  
Sho Takahata ◽  
Makoto Ohyama ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agent ◽  
Fungal Growth ◽  
Trichophyton Mentagrophytes ◽  
Dependent Manner ◽  
Content Type ◽  
Etiologic Agents ◽  
Prevalent Disease ◽  
Penetration Ability

ABSTRACTFungal 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 thein vitroantifungal 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 againstTrichophyton rubrumandTrichophyton 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 MIC50and MIC90of 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 ofTrichophyton 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.

scholarly journals Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model

2016 ◽  
Vol 60 (4) ◽  
pp. 2343-2345 ◽  
Author(s):  
L. Long ◽  
C. Hager ◽  
M. Ghannoum
Keyword(s):  
Guinea Pig ◽  
Topical Treatment ◽  
Liver Toxicity ◽  
Trichophyton Mentagrophytes ◽  
Pig Model ◽  
Once Daily ◽  
Content Type ◽  
The Past ◽  
Guinea Pig Model

ABSTRACTThe treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, thein vivoefficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused byTrichophyton mentagrophytesusing a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with aPvalue of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding.

scholarly journals Evaluation of the Antifungal Activity of Mentha x piperita (Lamiaceae) of Pancalieri (Turin, Italy) Essential Oil and Its Synergistic Interaction with Azoles

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3148 ◽  
Author(s):  
Vivian Tullio ◽  
Janira Roana ◽  
Daniela Scalas ◽  
Narcisa Mandras
Keyword(s):  
Antifungal Activity ◽  
Fungicidal Activity ◽  
Inhibitory Concentration ◽  
Trichophyton Mentagrophytes ◽  
Candida Spp ◽  
Antimicrobial Drugs ◽  
Minimum Fungicidal Concentration ◽  
Fungistatic Activity ◽  
Mentha X Piperita ◽  
Infection Treatment

The promising antimicrobial activity of essential oils (EOs) has led researchers to use them in combination with antimicrobial drugs in order to reduce drug toxicity, side effects, and resistance to single agents. Mentha x piperita, known worldwide as “Mentha of Pancalieri”, is produced locally at Pancalieri (Turin, Italy). The EO from this Mentha species is considered as one of the best mint EOs in the world. In our research, we assessed the antifungal activity of “Mentha of Pancalieri” EO, either alone or in combination with azole drugs (fluconazole, itraconazole, ketoconazole) against a wide panel of yeast and dermatophyte clinical isolates. The EO was analyzed by GC-MS, and its antifungal properties were evaluated by minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) parameters, in accordance with the CLSI guidelines, with some modifications. The interaction of EO with azoles was evaluated through the chequerboard and isobologram methods. The results suggest that this EO exerts a fungicidal activity against yeasts and a fungistatic activity against dermatophytes. Interaction studies with azoles indicated mainly synergistic profiles between itraconazole and EO vs. Candida spp., Cryptococcus neoformans, and Trichophyton mentagrophytes. Thus, the “Mentha of Pancalieri” EO may act as a potential antifungal agent and could serve as a natural adjuvant for fungal infection treatment.

scholarly journals The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

2014 ◽  
Vol 58 (7) ◽  
pp. 3837-3842 ◽  
Author(s):  
Keita Sugiura ◽  
Noriaki Sugimoto ◽  
Shinya Hosaka ◽  
Maria Katafuchi-Nagashima ◽  
Yoshio Arakawa ◽  
...  
Keyword(s):  
Fungicidal Activity ◽  
Nail Plate ◽  
Trichophyton Mentagrophytes ◽  
Content Type ◽  
Topical Drugs ◽  
Human Nails ◽  
Deep Location ◽  
Nail Disease ◽  
Receptor Phase

ABSTRACTOnychomycosis is a common fungal nail disease that is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. Keratin affinity of topical drugs is an important physicochemical property impacting therapeutic efficacy. To be effective, topical drugs must penetrate the nail bed and retain their antifungal activity within the nail matrix, both of which are adversely affected by keratin binding. We investigated these properties for efinaconazole, a new topical antifungal for onychomycosis, compared with those of the existing topical drugs ciclopirox and amorolfine. The efinaconazole free-drug concentration in keratin suspensions was 14.3%, significantly higher than the concentrations of ciclopirox and amorolfine, which were 0.7% and 1.9%, respectively (P< 0.001). Efinaconazole was released from keratin at a higher proportion than in the reference drugs, with about half of the remaining keratin-bound efinaconazole removed after washing. In single-dosein vitrostudies, efinaconazole penetrated full-thickness human nails into the receptor phase and also inhibited the growth ofTrichophyton rubrumunder the nail. In the presence of keratin, efinaconazole exhibited fungicidal activity againstTrichophyton mentagrophytescomparable to that of amorolfine and superior to that of ciclopirox. In a guinea pig onychomycosis model withT. mentagrophytesinfection, an efinaconazole solution significantly decreased nail fungal burden compared to that of ciclopirox and amorolfine lacquers (P< 0.01). These results suggest that the high nail permeability of efinaconazole and its potent fungicidal activity in the presence of keratin are related to its low keratin affinity, which may contribute to its efficacy in onychomycosis.

scholarly journals THE STUDY OF ANTIFUNGAL ACTIVITY FROM INDIGENOUS PLANTS FROM INDONESIA: AN IN VITRO STUDY

2016 ◽  
Vol 10 (1) ◽  
pp. 196
Author(s):  
Dewi Safitri ◽  
Elin Yulinah Sukandar ◽  
Irda Fidrianny ◽  
Eriwan Susanto
Keyword(s):  
Antifungal Activity ◽  
In Vitro Study ◽  
Ethanolic Extract ◽  
Trichophyton Mentagrophytes ◽  
Rosmarinus Officinalis ◽  
Microsporum Gypseum ◽  
Indigenous Plants ◽  
Reference Drug ◽  
Minimum Fungicidal Concentration

Objective: This study aimed to look for new agents from extracted Indonesia herbs which have antifungal activity with better safety profile against Candida albicans, Microsporum gypseum, and Trichophyton mentagrophytes. Methods: Screening of eleven herbs was perform to determine the highest antifungal activity. Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of selected extracts, rosemary (Rosmarinus officinalis) leaves, Java turmeric (Curcuma xanthorriza) rhizome, and ginger (Zingiber officinalis) rhizome; were determined by using microdilution and agar diffusion methods. Extracts were then combined to evaluate further activities. Selected extracts were fractionated by using liquid-liquid extraction, analyzed by TLC bioautography.Results: ethanolic extract of rosemary (Rosmarinus officinalis) leaves, Java turmeric (Curcuma xanthorriza) rhizome, and ginger (Zingiber officinalis) rhizome in combination showed the highest activity and synergistic interaction against Trichophyton mentagrophytes. There were several components from fractions were actively inhibiting corresponding fungi according to TLC bioautography method. Conclusion: ethanolic extracts of rosemary, Java turmeric, and ginger had the highest antifungal potency, both as extract and in combination comparable to ketoconazole as reference drug. These selected extracts are potential to be used as new antifungal agents.

scholarly journals Nanoencapsulated Essential Oils with Enhanced Antifungal Activity for Potential Application on Agri-Food, Material and Environmental Fields

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
Magdaléna Kapustová ◽  
Giuseppe Granata ◽  
Edoardo Napoli ◽  
Andrea Puškárová ◽  
Mária Bučková ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Essential Oil ◽  
Essential Oils ◽  
Winning Strategy ◽  
Colloidal Suspensions ◽  
Fungal Species ◽  
Natural Environments ◽  
Food Material ◽  
Minimum Fungicidal Concentration ◽  
Fungal Strains

Nanotechnology is a new frontier of this century that finds applications in various fields of science with important effects on our life and on the environment. Nanoencapsulation of bioactive compounds is a promising topic of nanotechnology. The excessive use of synthetic compounds with antifungal activity has led to the selection of resistant fungal species. In this context, the use of plant essential oils (EOs) with antifungal activity encapsulated in ecofriendly nanosystems could be a new and winning strategy to overcome the problem. We prepared nanoencapsules containing the essential oils of Origanum vulgare (OV) and Thymus capitatus (TC) by the nanoprecipitation method. The colloidal suspensions were characterized for size, polydispersity index (PDI), zeta potential, efficiency of encapsulation (EE) and loading capacity (LC). Finally, the essential oil nanosuspensions were assayed against a panel of fourteen fungal strains belonging to the Ascomycota and Basidiomycota phyla. Our results show that the nanosystems containing thyme and oregano essential oils were active against various fungal strains from natural environments and materials. In particular, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were two to four times lower than the pure essential oils. The aqueous, ecofriendly essential oil nanosuspensions with broad-spectrum antifungal activity could be a valid alternative to synthetic products, finding interesting applications in the agri-food and environmental fields.

Fungitoxicity of 1,4-naphthoquinones to Candida albicans and Trichophyton mentagrophytes

1975 ◽  
Vol 21 (9) ◽  
pp. 1317-1321 ◽  
Author(s):  
Herman Gershon ◽  
Larry Shanks
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Trichophyton Mentagrophytes ◽  
Weak Electron

Twenty-one substituted 1,4-naphthoquinones and five 8-quinolinols and copper(II) chelates were tested for antifungal activity against Candida albicans and Trichophyton mentagrophytes. Compounds containing electron-releasing or weak electron-withdrawing groups in the 2 and 3 positions of the 1,4-naphthoquinone ring were the most active against C. albicans at pH 7.0 in the presence of beef serum in the following order: 2-CH3O = 2,3-(CH3O)2 > 2-CH3 > 2-CH3S > 2-NH2 > 2,6-(CH3)2. For T. mentagrophytes under the same conditions the inhibitory 1,4-naphthoquinones contained the substituents 2-CH3O > 2,3-(CH3O)2 > 2-CH3S > 2-CH3 > 2-CH3(NaHSO3) > 2-NH2 > 2-C2H5S, 3-CH3 > 2,6-(CH3)2 > 2,3-Cl2 > 5,8-(OH)2.

scholarly journals Expression of Ubiquitin Gene in Microsporum canis and Trichophyton mentagrophytes Cultured with Fluconazole

2001 ◽  
Vol 45 (9) ◽  
pp. 2559-2562 ◽  
Author(s):  
Rui Kano ◽  
Ken Okabayashi ◽  
Yuka Nakamura ◽  
Shinichi Watanabe ◽  
Atsuhiko Hasegawa
Keyword(s):  
Amino Acid ◽  
Antifungal Activity ◽  
Proteasome Inhibitor ◽  
Trichophyton Mentagrophytes ◽  
Nucleotide Sequences ◽  
Amino Acid Sequences ◽  
Antifungal Drug ◽  
Microsporum Canis

ABSTRACT The expression of the ubiquitin (Ub) gene in dermatophytes was examined for its relation to resistance against the antifungal drug fluconazole. The nucleotide sequences and the deduced amino acid sequences of the Ub gene in Microsporum canis were proven to be 99% similar to those of the Ub gene in Trichophyton mentagrophytes. Expression of mRNA of Ub in M. canisand T. mentagrophytes was enhanced when the fungi were cultured with fluconazole. The antifungal activity of fluconazole against these dermatophytes was increased in the presence of Ub proteasome inhibitor.

scholarly journals Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an In Vitro Hollow-Fiber Model

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
Debora Rubio-Aparicio ◽  
Thomas G. Nolan ◽  
Jonathan Parkinson ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Hollow Fiber ◽  
Phase 1 ◽  
Phase 3 ◽  
Fiber Model ◽  
Content Type ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Dosage Regimens

ABSTRACT The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains when tested at an inoculum of 108 CFU/ml. Thirteen K. pneumoniae isolates, three Enterobacter cloacae isolates, and one Escherichia coli isolate were examined in an in vitro hollow-fiber model over 32 h. Simulated dosage regimens of 1 to 2 g of meropenem with 1 to 2 g of vaborbactam, with meropenem administered every 8 h by a 3-h infusion based on phase 1 or phase 3 patient pharmacokinetic data, were studied in the model. A dosage of 2 g of meropenem in combination with 2 g of vaborbactam was bactericidal against K. pneumoniae, E. cloacae, and E. coli strains, with meropenem-vaborbactam MICs of up to 8 mg/liter. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in phase 3 trials (24-h free AUC, ∼550 mg · h/liter, versus 320 mg · h/liter in the phase 1 studies), 2 g of meropenem with 2 g of vaborbactam was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/liter. In addition, this level of vaborbactam also suppressed the development of resistance observed using phase 1 exposures. In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2 g of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of Enterobacteriaceae.

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