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 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 In VitroandIn VivoAssessment of Dermatophyte Acquired Resistance to Efinaconazole, a Novel Triazole Antifungal

2014 ◽  
Vol 58 (8) ◽  
pp. 4920-4922 ◽  
Author(s):  
Atsushi Iwata ◽  
Yoko Watanabe ◽  
Naomichi Kumagai ◽  
Maria Katafuchi-Nagashima ◽  
Keita Sugiura ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Trichophyton Rubrum ◽  
Acquired Resistance ◽  
Continuous Exposure ◽  
Experimental Conditions ◽  
Resistance Development ◽  
Content Type ◽  
Induce Resistance ◽  
Nail Infection

ABSTRACTEfinaconazole is a novel triazole antifungal drug for the topical treatment of onychomycosis, a nail infection caused mainly by dermatophytes. We assessed the potential of efinaconazole to induce resistance in dermatophytes by continuous exposure ofTrichophyton rubrumstrains to efinaconazolein vitro(12 passages) and in a guinea pig onychomycosis model (8 weeks). There was no evidence of efinaconazole resistance development in the tested strains under the experimental conditions used.

scholarly journals In Vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Ali Rezaei-Matehkolaei ◽  
Sadegh Khodavaisy ◽  
Mohamad Mahdi Alshahni ◽  
Takashi Tamura ◽  
Kazuo Satoh ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Geometric Mean ◽  
Clinical Isolates ◽  
The Novel ◽  
Large Collection ◽  
Content Type ◽  
Trichophyton Interdigitale ◽  
In Vitro Antifungal Activity

ABSTRACT The objective of this study was to assess the in vitro activity of the novel triazole antifungal drug, efinaconazole, and five comparators (luliconazole, lanoconazole, terbinafine, itraconazole, and fluconazole) against a large collection of Trichophyton interdigitale and Trichophyton rubrum clinical isolates. The geometric mean MICs were the lowest for luliconazole (0.0005 μg/ml), followed by lanoconazole (0.002 μg/ml), efinaconazole (0.007 μg/ml), terbinafine (0.011 μg/ml), itraconazole (0.095 μg/ml), and fluconazole (12.77 μg/ml). It appears that efinaconazole, lanoconazole, and luliconazole are promising candidates for the treatment of dermatophytosis due to T. interdigitale and T. rubrum .

scholarly journals Complete Genome Sequence of Lanthionine-Producing Lactobacillus brevis Strain 100D8, Generated by PacBio Sequencing

2018 ◽  
Vol 7 (14) ◽  
Author(s):  
Min-Jung Kim ◽  
Hye Sun Kim ◽  
Sam Churl Kim ◽  
Youn-Sig Kwak
Keyword(s):  
Antifungal Activity ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Lactobacillus Brevis ◽  
Pacbio Sequencing ◽  
Circular Chromosome ◽  
Coding Sequences ◽  
Content Type

Lactobacillus brevis strain 100D8 was isolated from rye silage and showed rapid acidification ability in vitro and antifungal activity against mycotoxin-producing fungi. We report here the complete genome sequence of L. brevis strain 100D8, which has a circular chromosome (2,351,988 bp, 2,304 coding sequences [CDSs]) and three plasmids (45,061 bp, 57 CDSs; 40,740 bp, 40 CDSs; and 39,943 bp, 57 CDSs).

scholarly journals Low In Vitro Antifungal Activity of Tavaborole against Yeasts and Molds from Onychomycosis

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Mahdi Abastabar ◽  
Iman Haghani ◽  
Tahereh Shokohi ◽  
Mohammad Taghi Hedayati ◽  
Seyed Reza Aghili ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Antifungal Drug ◽  
Content Type ◽  
Fungal Isolates ◽  
Yeasts And Molds ◽  
Low Activity ◽  
In Vitro Antifungal Activity

ABSTRACT The in vitro activity of tavaborole, an FDA-approved antifungal drug, was compared to that of four antifungal agents against 170 clinical fungal isolates originating from patients with onychomycosis. Tavaborole had low activity against all isolates compared to itraconazole, terbinafine, and fluconazole, the principal choices for treatment of onychomycosis. Thus, it appears that tavaborole is not a candidate for the treatment of onychomycosis due to Candida species, Aspergillus species, and dermatophytes.

scholarly journals Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

2014 ◽  
Vol 58 (6) ◽  
pp. 3029-3034 ◽  
Author(s):  
Minh Lam ◽  
Matthew L. Dimaano ◽  
Patricia Oyetakin-White ◽  
Mauricio A. Retuerto ◽  
Jyotsna Chandra ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Trichophyton Rubrum ◽  
Therapeutic Option ◽  
Age Related Macular Degeneration ◽  
Noninvasive Treatment ◽  
Content Type ◽  
Age Related ◽  
Wide Range ◽  
Silicon Phthalocyanine

ABSTRACTTrichophyton rubrumis the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDTin vitrousing the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2(CH2)3N(CH3)2)(OH)] inT. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 μM Pc 4 followed by 670 to 675 nm light at 2.0 J/cm2reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis.

scholarly journals In Vitro Human Onychopharmacokinetic and Pharmacodynamic Analyses of ME1111, a New Topical Agent for Onychomycosis

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Natsuki Kubota-Ishida ◽  
Naomi Takei-Masuda ◽  
Kaori Kaneda ◽  
Yu Nagira ◽  
Tsubasa Chikada ◽  
...  
Keyword(s):  
Antifungal Agent ◽  
Antifungal Agents ◽  
Nail Plate ◽  
Free Drug ◽  
Content Type ◽  
Clinical Dose ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
Human Nails

ABSTRACT ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in the application of topical onychomycotics is penetration and dissemination of antifungal agent into the infected nail plate and bed. In this study, pharmacokinetic/pharmacodynamic parameters of ME1111 that potentially correlate with clinical efficacy were compared with those of marketed topical onychomycosis antifungal agents: efinaconazole, tavaborole, ciclopirox, and amorolfine. An ME1111 solution and other launched topical formulations were applied to an in vitro dose model for 14 days based on their clinical dose and administration. Drug concentrations in the deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-tandem mass spectrometry. Concentrations of ME1111 in the nail and cotton pads were much higher than those of efinaconazole, ciclopirox, and amorolfine. Free drug concentrations of ME1111 in deep nail layers and cotton pads were orders of magnitude higher than the MIC90 value against Trichophyton rubrum (n = 30). Unlike other drugs, the in vitro antifungal activity of ME1111 was not affected by 5% human keratin and under a mild acidic condition (pH 5.0). The in vitro antidermatophytic efficacy coefficients (ratio of free drug concentration to MIC90s against T. rubrum) of ME1111, as measured in deep nail layers, were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine (P < 0.05). This suggests that ME1111 has excellent permeation of human nails and, consequently, the potential to be an effective topical onychomycosis treatment.

scholarly journals In vitro evaluation of the antifungal activity of Marco (Ambrosia arborescens Mill.) and Matico (Aristeguietia glutinosa Lam.) on the pathogenic fungi that cause dermatomycosis (ringworm)

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 559
Author(s):  
Tatiana de los Ángeles Mosquera Tayupanta ◽  
Sandra Elizabeth Ayala Valarezo ◽  
Tatiana Alexandra Vasquez Villareal ◽  
María Belén Montaluisa Álvarez
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Therapeutic Potential ◽  
Pathogenic Fungi ◽  
Trichophyton Mentagrophytes ◽  
Microsporum Canis ◽  
The One ◽  
One Way Anova

Background: Currently, there is a trend towards using natural and ethnopharmacological species with therapeutic potential. This investigation evaluated the antifungal activity of two species in the Ecuadorian Andes, which are used in treating dermatomycosis: Ambrosia arborescens Mill. (Marco) and Aristeguietia glutinosa Lam. (Matico). Methods: We worked with seven concentrations (100 to 700ppm) of Ambrosia arborescens Mill. extract and ten concentrations (0.5 to 5%) of essential oil (EO) of Aristeguietia glutinosa Lam. on Trichophyton mentagrophytes ATCC 9533, Trichophyton rubrum ATCC 28188, Microsporum canis ATCC 36299 and Candida albicans ATCC 10231. The methodology used was a modified version of the Kirby-Bauer method, using diffusion in agar wells. Results: The Tukey test, after the one-way Anova, determined effective concentrations of EO: 5% for Trichophyton mentagrophytes, 4.5% for Trichophyton rubrum, 5% for Microsporum canis and 2% for Candida albicans. In the extracts, the concentration of 700ppm was used for Trichophyton mentagrophytes, Trichophyton rubrum, and 600ppm for Microsporum canis and Candida albicans. Conclusions: The evaluation of the antifungal activity of the Ambrosia arborescens extract showed inhibition in the studied dermatophytes in each one of the planted concentrations (100 to 700ppm). The evaluation of the antifungal activity of Aristeguietia glutinosa EO showed inhibition in the studied dermatophytes in each of the planted concentrations (0.5 to 5%).

scholarly journals A Mycological and Molecular Epidemiologic Study on Onychomycosis and Determination In Vitro Susceptibilities of Isolated Fungal Strains to Conventional and New Antifungals

2021 ◽  
Vol 11 ◽  
Author(s):  
Samaneh Halvaee ◽  
Roshanak Daie-Ghazvini ◽  
Seyed Jamal Hashemi ◽  
Sadegh Khodavaisy ◽  
Abbas Rahimi-Foroushani ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Susceptibility ◽  
Epidemiologic Study ◽  
Cross Sectional Study ◽  
Fungal Culture ◽  
Saprophytic Fungi ◽  
Cross Sectional ◽  
First Line Therapy ◽  
Antimycotic Activity

BackgroundOnychomycosis is one of the most common and recurrent dermatological diseases worldwide. The antimycotic activity of prescribed medications varies according to the causative agents, and treatment failure rates exceeding 30%. This study aimed to assess the epidemiological profile of onychomycosis in Iran. Also, the susceptibilities to conventional and new antifungals were investigated.MethodsIn this descriptive cross-sectional study, during the period of 18 months starting from September 2019 until March 2020, 594 nail specimens were obtained from patients who presented nail changes compatible with a clinical diagnosis of onychomycosis. The patients were referred from different cities, including Tehran, Kermanshah, Arak, Kashan, Rasht, Qom, Urmia, Zahedan, Hamadan, Zanjan, Borujerd, Bushehr, and Yazd. All the samples were subjected to microscopic examination and fungal culture. Fungi identified were confirmed through the PCR-sequencing method. The susceptibility to itraconazole, fluconazole, terbinafine, griseofulvin, posaconazole, ravuconazole, efinaconazole, luliconazole, and tavaborole was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A3 for yeasts.Results594 patients were included. Of these, in 179 cases (30.1%) (95% CI:0.3 ± 0.037) onychomycosis was confirmed. The majority of patients were ≥ 60 years of age (n=58, 32.6%) and female (n=113, 63.1%). Saprophytic fungi accounted for the vast majority of the nail isolates (n=92, 51.4%) (95% CI:0.051 ± 0.0.073), followed by dermatophytes (n=45, 25.1%) (95% CI:0.25 ± 0.063), and yeasts (n=42, 23.5%) (95% CI:0.23 ± 0.061). Diabetes mellitus (77.3%), hypothyroidism (18.2%), and solid tumors (4.5%) were documented as the most prevalent underlying conditions. Antifungal susceptibility testing was performed against 60 fungal isolates (20 each of Candida species, saprophytic fungi, and dermatophytes). Efinaconazole, ravuconazole, and luliconazole were the most active agents against Candida species. Also, luliconazole, posaconazole, and efinaconazole were most potent against dermatophytes. Luliconazole had the greatest antifungal activity against saprophytic fungi.ConclusionsThe prevalence of onychomycosis in Iranian patients was relatively high. LUL exhibited potent antifungal activity against the three groups of fungi tested, determining its broad-spectrum antimycotic activity and its probable use as the first-line therapy for onychomycosis.

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