Study and Development of an Anthroposophical Formula Based on Phosphorus and Formica rufa for Onychomycosis´s Treatment.

Onychomycosis is a fungal infection of the nail plate or nail bed that leads to the gradual destruction of the nail. The main difficulties in the treatment of onychomycosis refer to the duration of treatments and their side effects. Thus, it becomes relevant to look for new therapeutic alternatives in the treatment of such common diseases that are efficient without causing the undesirable side effects on the patient's body. In this way, the objective of this study was to develop an anthroposophical formula for the treatment of onychomycosis, based on Phosphorus and Formica rufa, from an extensive bibliographic survey on the functions of these components, evaluating within the principles of Anthroposophy. Considering the set of knowledge and practices on the use of these components, it was possible to arrive at a proposal therapy that can be effective for the treatment of onychomycosis. After an extensive review of several existing patents, it was observed that formulations containing Phosphorus and Formica rufa together have not been described in other studies. Subsequently, our research group published a patent of the anthroposophical formula using these two components, with the number BR1020180750755, which will be efficient to help the recovery of nails, and facilitate normal growth.

Microbial Growth on the Nails of Direct Patient Care Nurses Wearing Nail Polish.

OBJECTIVES: To determine whether nurses wearing nail polish pose a greater infection risk to patients than nurses who are not wearing nail polish. SAMPLE & SETTING: 89 direct patient care oncology nurses at a large midwestern National Cancer Institute-designated comprehensive cancer center. METHODS & VARIABLES: The investigators assigned participants' three middle fingers of their dominant hand to three groups. RESULTS: Comparison of colony-forming units revealed that one-day-old polish exhibited fewer gram-positive microorganisms than the unpolished nail (p = 0.04). The four-day-old polish showed significantly more microorganisms than the one-day-old polish (p = 0.03). The same trend was demonstrated for gram-negative microorganisms, but the difference was not statistically significant (p = 0.3 and p = 0.17, respectively). IMPLICATIONS FOR NURSING: The results should be interpreted and applied to expert nursing practice in the care of vulnerable patient populations. Each institution and practitioner should make their own decisions and interpretation of evidence into practice.

Conventional and natural compounds for the treatment of dermatophytosis.

Dermatophytes are a group of pathogenic fungi that exclusively infect the stratum corneum of the skin, nails, and hair, causing dermatophytosis. Superficial skin infections caused by dermatophytes have increased in the last decades. There are conventional antifungals that treat these infections, such as terbinafine, fluconazole, and others. However, the limitations of these treatments (resistance, side effects and toxicity) along with the increasing over-prescription, the misuse of these antifungals and the high treatment costs led to the search for new, alternative, natural-based antifungal drugs. These have multiple mechanisms of action, which works to their advantage, making it difficult for a fungus to create resistance mechanisms against all of them at the same time. The main objective of this work is to provide a state-of-the-art review on dermatophytes, dermatophytosis, and the existing treatments, both conventional and natural, such as chitosan and essential oils.

Allium sativum Extract Chemical Composition, Antioxidant Activity and Antifungal Effect against Meyerozyma guilliermondii and Rhodotorula mucilaginosa Causing Onychomycosis.

Onychomycosis is a major health problem due to its chronicity and resistance to therapy. Because some cases associate paronychia, any therapy must target the fungus and the inflammation. Medicinal plants represent an alternative for onychomycosis control. In the present work the antifungal and antioxidant activities of Alium sativum extract against Meyerozyma guilliermondii (Wick.) Kurtzman & M. Suzuki and Rhodotorula mucilaginosa (A. Jörg.) F.C. Harrison, isolated for the first time from a toenail onychomycosis case, were investigated. The fungal species were confirmed by DNA molecular analysis. A. sativum minimum inhibitory concentration (MIC) and ultrastructural effects were examined. At the MIC concentration (120 mg/mL) the micrographs indicated severe structural alterations with cell death. The antioxidant properties of the A. sativum extract were evaluated is a rat turpentine oil induced inflammation, and compared to an anti-inflammatory drug, diclofenac, and the main compound from the extract, allicin. A. sativum reduced serum total oxidative status, malondialdehyde and nitric oxide production, and increased total thiols. The effects were comparable to those of allicin and diclofenac. In conclusion, the garlic extract had antifungal effects against M. guilliermondii and R. mucilaginosa, and antioxidant effect in turpentine-induced inflammation. Together, the antifungal and antioxidant activities support that A. sativum is a potential alternative treatment in onychomycosis.

Occurrence of dermatophytoses in patients from the Sistema Único de Saúde.

BACKGROUND: Dermatophytosis is a cutaneous disease caused by filamentous keratinophilic fungi belonging to the genera Trichophyton, Microsporum and Epidermophyton, which present a high prevalence in the general population, being among the most common mycoses affecting about 20% of the world's population. OBJECTIVE: To carry out the epidemiological survey of cases of dermatophytosis in patients from the Sistema Único de Saúde in a regional Laboratory in the period of 5 years (2009 to 2013). METHODS: A retrospective study (January 2009 to December 2013) was carried out with a qualitative and quantitative design, through the registry book of the laboratory, Mycology Sector, where cases of patients with suspected dermatomycosis were analyzed. RESULTS: In a 5-year period, a total of 4467 cases were suspected of having a fungal infection. Of these, 68.74% (3071) cases were of dermatomycosis. In relation to cultures with fungal growth, 12.54% (385 cases) were dermatophyte fungi and 7.97% (245 cases) non-dermatophyte fungi were isolated. Among the species identified, there was a higher prevalence of T. rubrum complex (75%), T. mentagrophytes complex (11.68%) and M. canis (7.01%). Regarding the sites analyzed, nail involvement was the most frequent in 75% of the cases. STUDY LIMITATIONS: This work is representative in the studied region. CONCLUSIONS: Dermatomycosis samples are the most frequent among all samples of fungal infections from these patients, with the nail being the most affected area and the fungi T. rubrum complex and T. mentagrophytes complex the most frequent.

Occurrence of dermatophytoses in patients from the Sistema Único de Saúde

Abstract: Background: Dermatophytosis is a cutaneous disease caused by filamentous keratinophilic fungi belonging to the genera Trichophyton, Microsporum and Epidermophyton, which present a high prevalence in the general population, being among the most common mycoses affecting about 20% of the world's population. Objective: To carry out the epidemiological survey of cases of dermatophytosis in patients from the Sistema Único de Saúde in a regional Laboratory in the period of 5 years (2009 to 2013). Methods: A retrospective study (January 2009 to December 2013) was carried out with a qualitative and quantitative design, through the registry book of the laboratory, Mycology Sector, where cases of patients with suspected dermatomycosis were analyzed. Results: In a 5-year period, a total of 4467 cases were suspected of having a fungal infection. Of these, 68.74% (3071) cases were of dermatomycosis. In relation to cultures with fungal growth, 12.54% (385 cases) were dermatophyte fungi and 7.97% (245 cases) non-dermatophyte fungi were isolated. Among the species identified, there was a higher prevalence of T. rubrum complex (75%), T. mentagrophytes complex (11.68%) and M. canis (7.01%). Regarding the sites analyzed, nail involvement was the most frequent in 75% of the cases. Study Limitations: This work is representative in the studied region. Conclusions: Dermatomycosis samples are the most frequent among all samples of fungal infections from these patients, with the nail being the most affected area and the fungi T. rubrum complex and T. mentagrophytes complex the most frequent.

Improved Methods for Assessing Therapeutic Potential of Antifungal Agents against Dermatophytes and Their Application in the Development of NP213, a Novel Onychomycosis Therapy Candidate.

Onychomycosis is a common, difficult-to-treat nail infection that is mainly caused by dermatophytes. Current therapies are not wholly effective and are associated with manifold side effects. The development of treatments for onychomycosis is challenging because standard in vitro tests are not predictive of antifungal efficacy within the nail. We have developed a new antifungal agent, NP213, for the treatment of onychomycosis. NP213 is based on endogenous host defense peptides produced within the nail. We compared the in vitro activity of NP213 and existing antifungal agents using conventional antimicrobial susceptibility test (AST) systems and more physiologically relevant models based on the human nail. We observed that the standard in vitro AST methodologies failed to predict the efficacy of antifungal agents within the nail. To address that, we present a more physiologically relevant modified AST method. This method, alongside other standard in vitro assessments of activity (including mechanism-of-action and time-of-kill studies), better reflected the activity of NP213 and other antifungal agents within the nail than standard in vitro AST methods. NP213 is a rapidly acting, fungicidal peptide that is superior to existing antifungal agents in vitro It penetrated the nail more effectively than other antifungals, as confirmed by using an optimized in vitro nail infection model. The data presented here support the current clinical development status of NP213 as a novel agent for treating onychomycosis. We propose that the modified tests developed and applied for NP213 characterization are the most relevant to use for screening any potential therapeutic candidates for onychomycosis.

Onychomycosis of the Middle Finger of a Japanese Judo Athlete due to Trichophyton tonsurans

We present a 17-year-old Japanese male high school student, who had applied steroid ointment for atopic dermatitis, with fingernail onychomycosis due to Trichophyton tonsurans. He was found positive for T. tonsurans infection based on hairbrush culture performed due to an epidemic of T. tonsurans infection in his judo club. The hairbrush culture method is very important in screening for this infection, and dermatologists should examine the entire body of athletes who are found positive using this method. For the diagnosis of T. tonsurans infection, other than the skin and hair, the nails should also be checked by dermoscopy because the fingernail may be the origin of this fungus.

Examining the Benefits of the Boron-Based Mechanism of Action and Physicochemical Properties of Tavaborole in the Treatment of Onychomycosis.

Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed. The efficacy of tavaborole is associated with its novel mechanism of action, whereby it inhibits the fungal leucyl-tRNA synthetase (LeuRS) enzyme. Because LeuRS is an essential component in fungal protein synthesis, inhibition of LeuRS ultimately leads to fungal cell death. Tavaborole is the first boron-based antifungal medication approved for the treatment of mild-to-moderate onychomycosis and presents patients with a new topical option. Previously, ciclopirox and efinaconazole were the only approved topical treatments for onychomycosis. This article details the properties that are at the core of the clinical benefits associated with tavaborole.

Light treatments of nail fungal infections.

Nail fungal infections are notoriously persistent and difficult to treat which can lead to severe health impacts, particularly in the immunocompromized. Current antifungal treatments, including systemic and topical drugs, are prolonged and do not effectively provide a complete cure. Severe side effects are also associated with systemic antifungals, such as hepatotoxicity. Light treatments of onychomycosis are an emerging therapy that has localized photodynamic, photothermal or photoablative action. These treatments have shown to be an effective alternative to traditional antifungal remedies with comparable or better cure rates achieved in shorter times and without systemic side effects. This report reviews significant clinical and experimental studies in the field, highlighting mechanisms of action and major effects related to light therapy; in particular, the impact of light on fungal genetics.

Complete cure of Fusarium solani sp. complex onychomycosis with Qs NdYAG treatment.

The incidence of non dermatophytic mould (NDM) onychomycosis (OM) has been steadily increasing Fusarium spp is the most common cause of NDM OM in most geographical locations. Fusarium spp and other NDMs are largely resistant to commonly used anti-fungals. The successful use of laser and light based devices has been demonstrated in dermatophytic OM, but there is no previous report of their successful use in any NDM OM. We describe a patient with OM caused by Fusarium solani spp, who was clinically (with a normal appearing nail) and mycologically (with negative microscopy and culture on repeated samples) cured of her infection following treatment with 2 sessions of Qs NdYAG (532nm and 1064nm) given 1 month apart.

Clinical laser treatment of toenail onychomycoses.

Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.

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

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.

Onychomycosis in diabetic patients in Fako Division of Cameroon: prevalence, causative agents, associated factors and antifungal sensitivity patterns.

BACKGROUND: Onychomycosis is an infection of the nail unit by a fungus. This is a very common infection amongst diabetics. Its occurrence among diabetics in Fako division is unknown. In this study we provide information on the characteristics of onychomycosis in diabetics in Fako division, Cameroon. METHODS: A cross-sectional descriptive and analytical hospital-based study was conducted in two diabetic clinics in the Buea and Limbe regional hospitals. We recruited 152 consenting diabetics into the study. Demographic, behavioural, and clinical data of patients were obtained through the use of structured questionnaires. Toenail, finger nail, skin scrapings and nail clippings were collected from participants, KOH mounts were prepared and observed under the microscope and cultured on Sabouraud Dextrose Agar supplemented with chloramphenicol to isolate causative fungi. Identification of isolates was done to species level using the cello tape flag method and slide culture. The presence of a dermatophyte by either microscopy or culture or both methods was considered positive for onychomycosis. Antifungal susceptibility testing was carried out using selected antifungals by the Kirby-Bauer disk diffusion method on Sabouraud Dextrose Agar. RESULTS: Clinical onychomycosis was found in 77 of the 152 diabetics tested giving a prevalence of 50.7% (95% CI 42.4-58.9) in diabetics in Fako. No socio-demographic or clinical factor studied was significantly associated with onychomycosis. Trichophyton rubrum was the most common isolate (62%). Other isolates included Trichophyton metagraphyte (22%) and Trichophyton tonsurans (16%). Dermatophytes were sensitive to miconazole (66%), amphotericin B (19%) and ketoconazole (14%). CONCLUSION: Onychomycosis is common in diabetics in Fako signifying the need for regular screening by either microscopy or culture. Infected nails could be treated with miconazole.

Synergistic antimicrobial activity of Boswellia serrata Roxb. ex Colebr. (Burseraceae) essential oil with various azoles against pathogens associated with skin, scalp and nail infections.

Antimicrobials from natural sources have gained immense importance in recent times to combat the global challenge of antibiotic resistance. Essential oils are implicated in antimicrobial action against several species. Here, we have screened nine commercially available essential oils for their antimicrobial activity against organisms associated with skin, scalp and nail infections mainly Propionibacterium acnes, Malassezia spp., Candida albicans and Trichophyton spp. Among nine essential oils, Boswellia serrata essential oil demonstrated superior antimicrobial activity against all the micro-organisms and surprisingly it showed maximum activity against Trichophyton spp. The gas chromatography-mass spectrometry analysis of B. serrata oil indicates a major composition of α thujene, ρ cymene and sabinene. Additionally, B. serrata oil was found to inhibit Staphylococcus epidermidis biofilm, and its combination with azoles has shown synergistic activity against azole-resistant strain of C. albicans. These broad-spectrum antimicrobial activities of B. serrata oil will make it an ideal candidate for topical use. SIGNIFICANCE AND IMPACT OF THE STUDY: Eradication of skin and nail infections still remain a challenge and there are serious concerns regarding the recurrence of the diseases associated with these infections. Antimicrobials from plant sources are gaining importance in therapeutics because they encounter minimal challenges of emergence of resistance. We have demonstrated the antimicrobial activity of Boswellia serrata essential oil against micro-organisms involved in skin, scalp and nail infections, especially if it has shown favourable synergistic antifungal activity in combination with azoles against the azole-resistant Candida albicans strain. Thus, B. serrata oil can be one of the plausible therapeutic agents for management of skin, scalp and nail infections.

Efficacy Coefficients Determined Using Nail Permeability and Antifungal Activity in Keratin-Containing Media Are Useful for Predicting Clinical Efficacies of Topical Drugs for Onychomycosis.

Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1-3.9%). Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0-20%) in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients.

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

Fungal 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 the in vitro antifungal 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 against Trichophyton rubrum and Trichophyton 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 MIC50 and MIC90 of 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 of Trichophyton 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.

Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections.

Although topical antifungal therapies for treating onychomycosis are available, the cure rate is unsatisfactorily low with a simultaneously high risk of recurrence. One reason might be the formation of dormant fungal cells by the pathogen, known as spores, which can survive in the affected nail keratin, thereby evading the effect of antifungal drugs. In this in vitro study, the ability of amorolfine and four other antimycotics (ciclopirox, bifonazole, terbinafine and fluconazole) to kill microconidia of the dermatophyte Trichophyton rubrum, chlamydospores of the dermatophyte Epidermophyton floccosum and blastospores of the yeast Candida albicans was extensively studied as these fungi occur predominantly in onychomycosis. The effectiveness of all five antimycotics depended on the drug concentration and the incubation time: a concentration of 10-1000 times the minimum inhibitory concentration against growing hyphae cells is needed to exert a sporicidal action. Amorolfine and ciclopirox showed the same sporicidal efficacy and kinetics for all three varieties of spores. Both were more effective than fluconazole and bifonazole against microconidia and chlamydospores as well as slightly more potent against chlamydospores and blastospores than terbinafine after 4 days of incubation and at concentrations of ≥10 µg ml(-1). Finally, sporicidal activity on the tested strains was demonstrated for all five different antimycotics used for onychomycosis treatment.

Toenail Onychomycosis-A Canadian Approach With a New Transungual Treatment: Development of a Clinical Pathway.

BACKGROUND: Onychomycosis is a difficult-to-treat infection whose current treatment paradigm relies primarily on oral antifungals. The emergence of new topical drugs broadens the therapeutic options and prompts a re-evaluation of the current Canadian treatment strategy. OBJECTIVE: To define a patient-centred Canadian treatment strategy for onychomycosis. METHODS: An expert panel of doctors who treat onychomycosis was convened. A systematic review of the literature on treatments for onychomycosis was conducted. Based on the results, a survey was designed to determine a consensus treatment system. RESULTS: First-line therapy should be selected based on nail plate involvement, with terbinafine for severe onychomycosis (>60% involvement), terbinafine or efinaconazole for moderate onychomycosis (20%-60% involvement), and efinaconazole for mild onychomycosis (<20% involvement). Comorbidities, patient preference and adherence, or nail thickness may result in the use of alternative oral or topical antifungals. CONCLUSION: These guidelines allow healthcare providers and patients to make informed choices about preventing and treating onychomycosis.

Chloronychia: green nail syndrome caused by Pseudomonas aeruginosa in elderly persons.

Green nails, also known as chloronychia or green nail syndrome, are characterized by green discoloration of the nail plate (greenish-yellow, greenish-brown, greenish-black), proximal chronic non-tender paronychia, and distolateral onycholysis. The cause is Pseudomonas aeruginosa infection of the nail plate in persons whose hands are constantly exposed to water, soaps, and detergents or are subject to mechanical trauma, especially in the elderly. Green or black coloration of the nails should raise suspicion for Pseudomonas infection and be treated with an oral quinolone (ciprofloxacin), particularly in aged patients. We present three cases of green nails in elderly persons.