Nondermatophyte Molds Research Articles

Potential of Ravuconazole and its Prodrugs as the New OralTherapeutics for Onychomycosis.

Onychomycosis is a fungal infection of the nail apparatus caused by dermatophytes, Candida and non-dermatophytic molds. It is highly prevalent in the general population worldwide and also responsible for significant morbidity and complications and does not usually cure itself. Thus, the condition needs to be treated in view of physical and psychological problems produced. Currently, oral medications using terbinafine are the most effective therapy, but it has relatively limited therapeutic success, particularly for long-term management. Such existing oral therapies are associated with high recurrence rates and treatment failure, as well as with potential adverse events and drug-drug interactions. In the light of these issues, development of more efficacious and safer alternatives for the treatment of onychomycosis is warranted.Ravuconazole and its prodrugs are promising new drug candidates for oral therapy of onychomycosis, among which a water-soluble prodrug, mono-lysine phosphoester derivative (E1224 or BFE1224) is in the most advanced stage of clinical development; a Phase II dose-finding study has been successfully completed and Phase III comparative studies are in progress in Japan.This review aims to summarize our current status of knowledge and information on ravuconazole and its prodrugs, particularly BFE1224, as the potential oral treatment option for onychomycosis. It also summarize the clinical features of onychomycosis with particular stress on its etiology, epidemiology, and current therapeutic options and their limitations. Given its clinical usefulness, BFE1224 may become a valuable addition to the current armamentarium for the treatment of onychomycosis.

Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis.

Species isolated as the cause of onychomycosis in patients with pemphigus vulgaris

BackgroundPemphigus vulgaris (PV) is an autoimmune disease that affects the skin and mucous membranes. It is caused by antibodies directed against desmoglein 3 which leads to the breakdown of the junctions between keratinocytes in the suprabasal epidermis, causing flaccid blisters. Nail involvement in PV has been associated with chronic PV and immunosuppressive therapy, which can increase the risk of bacterial, viral or fungal infection in the nail apparatus. ObjectivesTo determine which species cause onychomycosis in patients with PV treated with prednisone 1mg/kg/day. Materials and methodsAn observational, descriptive study was performed in 169 patients: 85 were diagnosed with PV and treated with prednisone at a dose of 1mg/kg/day (patients), and 84 without PV and not treated with steroids (controls). ResultsThe species most commonly isolated in the PV group was Trichophyton rubrum (29%), followed by Trichophyton mentagrophytes (6%), non-dermatophyte moulds (3%) and Candida albicans (3%). However, in 59% of cases, the causative agent was not identified. ConclusionsThe presence of onychomycosis in patients with PV was not associated with the use of glucocorticoids; no greater prevalence of onychomycosis was observed in patients without PV and without steroid therapy.

Laser Therapy for the Treatment of Onychomycosis: Best Evidence Based Practice or Not?

Onychomycosis is a very common condition that accounts for 50% of all nail pathologies. Currently 2–5% of the world population suffers from this disorder. It is primarily caused by dermatophytes, but the infection can also be caused by yeasts and non-dermatophyte moulds. Onychomycosis is a therapeutic challenge and recently there has been an increase in resistance to oral and topical antifungal agents, leading to 20-25% relapse and/or reinfection rate. During the past 5 years, the emergence of laser therapy has been the topic of discussion as a newer, safer modality of treatment. Nail clippings and scrapings are the most common methods of sampling for suspected onychomycosis. The simplest method for detecting fungi is by way of 20% potassium hydroxide (KOH) preparations, but lately show insufficient sensitivity in onychomycosis – as much as 40–68%. Fungi can also be grown in culture form; however a 70% sensitivity detection failure rate is seen. Recently, histological fungal detection – in the form of Periodic Acid- Schiff (PAS) stain – has shown high sensitivity at 92% in the detection of fungal elements. The exact mechanism of action of laser is unknown but it is believed that heat disintegrates fungal structures. One of the most appealing characteristics of laser therapy is its ability to deliver energy to the target tissue and avoid systemic side effects at the same time. In 2009 the United Kingdom (UK) Podiatry magazine Podiatry Now published a letter suggesting laser treatment was “possibly the most radical development in the treatment of onychomycosis our profession has ever seen”, although concerns were raised over the unproven efficacy and investment costs involved. Papers have been published investigating the efficacy of lasers for the treatment of onychomycosis. Even though laser therapy provides an alternative option with rapid procedure duration, conflicting evidence is shown in a variety of papers and studies with longer follow-up periods suggest onychomycosis relapse in those treated with laser, which warrants further investigation.

The Efficacy and Prognostic Factors for Long Pulse Neodymium: Yttrium-Aluminum-Garnet Laser Treatment on Onychomycosis: A Pilot Study.

The Efficacy and Prognostic Factors for Long Pulse Neodymium: Yttrium-Aluminum-Garnet Laser Treatment on Onychomycosis: A Pilot Study.

Nail Histomycology, Onychochromobiology, and Fungal Thigmatropism

Background: Thigmotropism is a biologic feature coping with the directional growth of cells following topographical guidance cues. This mechanism is involved in the invasive phase of pathogen and opportunistic fungi. It was shown experimentally with fungal hyphae of both dermatophytes and nondermatophyte molds, as well as with the mycelial phase of the dimorphic yeast Candida albicans. Objective: To revisit histomycology in onychomycoses of a diversity of fungal origins. Method: Histopathological section of nails plates were oriented parallel to the nail direction of growth. Result: Thigmotropism in part explains the patterns of orientations and shapes of fungi invading nail plates. It is probably influenced by onychochronobiology (speed of growth of the affected nails), and it governs various clinical presentations of onychomycoses.

Clinico-mycological study of onychomycosis in children from a tertiary care center

Introduction: Onychomycosis is rare in children as compared to adults and hence the presence of any nail changes in children needs careful examination and carrying out proper diagnostic tests to cure this treatable cause of dystrophic nails. Aim: The study was undertaken to study in detail the clinico-mycological aspects of onychomycosis in children. Materials and Methods: A prospective hospital-based cross-sectional study was done on ninety children with a strong clinical suspicion of onychomycosis during a period of 2 years. All the children were subjected to three diagnostic tests, namely direct microscopy, fungal culture, and histopathological examination using periodic acid Schiff staining (HPE-PAS). Results: Distal and lateral subungual onychomycosis is the most common type (82%), and toe nails (57.78%) are more commonly involved than fingernails. Direct microscopy yielded results in 62%, culture in 64%, and HPE-PAS in 71.1%. Dermatophytes were the most common group of organisms isolated (58%) with Trichophytonmentagrophytes as the most common isolate (31%). However, nondermatophytic molds and Candida species also accounted for 25% and 17% of the culture positive cases in children. Conclusion: As children <18 years constitute one-third of our population, we suggest the need for careful evaluation of onychomycosis in this subgroup.

Onychomycosis caused by Fusarium dimerum

Fusraium is a non-dermatophytic hyaline mould found as soil saprophytes and plant pathogens. Human infections are probably a result of various precipitating predisposing factors of impaired immune status. Immunocompetent individuals of older age group are also vulnerable to various unassuming saprophytic and plant pathogen. We report 5 cases with onychomycosis caused by a rare species of Fusarium , namely, Fusarium dimerum . Fusarium is known to cause a variety of infections like keratitis, eumycetoma, onychomycosis, skin lesions and sometimes disseminated infection in individuals with impaired immunity. Hence it is of utmost importance to identify this newly emerging fungal pathogen correctly and institute appropriate treatment to control human infections at the earliest so that disseminated infections can be avoided.

Randomized, double-blind, comparative study on efficacy and safety of itraconazole pulse therapy and terbinafine pulse therapy on nondermatophyte mold onychomycosis: A study with 90 patients

Background: Nondermatophyte mold (NDM) onychomycosis shows poor response to current topical, oral or device-related antifungal therapies. This study was aimed to determine the efficacy and safety of itraconazole and terbinafine pulse therapy on NDM onychomycosis. Methods: Mycologically proven subjects were treated with itraconazole 400 mg daily or terbinafine 500 mg daily for 7 days/month; two pulses for fingernails and three pulses for toenails(SLCTR/2013/013). Results: One-hundred seventy-eight patients underwent mycological studies and 148 had positive fungal isolates. NDM were the prevailing fungi, 68.2%, followed by candida species 21.6%, and dermatophytes made up only 10.1%. Out of NDM Aspergillus spp (75.1%) predominated followed by 8.9% Fusarium spp and 4.95% Penicillium spp. The clinical cure at completion of pulse therapy was statistically significant 9.2% versus 2.0% (p < 0.05) in itraconazole group. But no statistically significant difference was detected between the two regimens at the end of 12 months; 65.1% versus 54.64%. Recurrences observed in both groups (6.5% vs. 4.1%) were not statistically significant. With itraconazole pulse 68.22% Aspergillus spp, 50.0% Fusarium spp and 84.6% Penicillium spp showed clinical cure, while terbinafine pulse cured 55.0% Aspergillus spp and 50.0% Fusarium spp. Conclusions: NDM was the prevailing fungi in onychomycosis in Sri Lanka. Both itraconazole and terbinafine were partially effective on NDM onychomycosis showing a clinical cure of 54–65%. Future research should focus on searching more effective antifungal for NDM onychomycosis.

A Retrospective Review of Diagnostic Testing for Onychomycosis of the Foot.

Onychomycosis is a fungal infection of the nail that can be caused by dermatophytes, yeasts, or nondermatophyte molds. To diagnose onychomycosis, a clinician must use the patient's history, physical findings, and diagnostic testing, which can include calcofluor white/potassium hydroxide (KOH) mount, fungal culture (FC), and periodic acid-Schiff (PAS) stain. Some insurance companies require authorization for antifungal medication and request laboratory results to confirm infection. We sought to compare the reliability of KOH, PAS, and FC diagnostic results for confirmation of fungal disease, to determine the sensitivity and specificity of each test, and to investigate the cost of each test. In addition, we statistically observed the relationship between the test results and demographic variables. Toenail clippings were obtained from 108 patients clinically diagnosed as having onychomycosis. Diagnostic tests were then performed on each sample; the results were obtained from medical records. For PAS, KOH, and FC, 60.2%, 43.5%, and 39.8% of results, respectively, were positive. Agreement for each pair of tests was slightly higher for FC and KOH. Sensitivities for KOH and PAS were 0.64 and 0.79, respectively. Specificity was 0.79 for KOH and 0.54 for PAS. Both PAS and KOH had a higher percentage of positive test results for men than for women. Of the three tests evaluated, PAS gives the most consistent positive results and has the highest sensitivity. Therefore, PAS should be considered as the best test to verify clinically significant onychomycosis.

Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro.

Onychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml- 1 inhibited biofilm formation by 93%, whilst 256 μg ml- 1 reduced the metabolic activity of pre-formed nail biofilms by 93%. Treatment with miltefosine at 1000 μg ml- 1 inhibited biofilm formation by 89% and reduced the metabolic activity of pre-formed C. albicans biofilms by 99%. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment.

Management Strategies for Onychomycosis in Special Patient Populations.

Clinicians must be aware of characteristics unique to certain populations when diagnosing and treating onychomycosis. For example, although onychomycosis is uncommon in children, it should be considered in the differential diagnosis when young patients have nail changes, particularly if a family history of onychomycosis is present. In elderly patients, comorbid medical conditions may complicate systemic treatment, and physical impairments may interfere with topical therapy. Nondermatophyte molds and yeasts should be considered as possible pathogens in patients with diabetes and psoriasis. Patients who are immunosuppressed for any reason are at increased risk for nail infections. Semin Cutan Med Surg 34(supp3):S54-S55 © 2015 published by Frontline Medical Communications.

Efinaconazole in the treatment of onychomycosis.

Efinaconazole 10% topical solution is a new triazole recently approved for the treatment of onychomycosis. It inhibits fungal lanosterol 14α-demethylase in the ergosterol biosynthesis pathway, has potent antifungal activity against dermatophytes, as well as activity against Candida spp. and non-dermatophyte molds, and showed promising results in clinical trials. This review summarizes the mechanism of action, in vitro and in vivo data, clinical trials, safety, and quality-of-life data of efinaconazole as it applies to the treatment of onychomycosis.

Onychomycosis: A Rare Presentation of Fungal Urinary Tract Infection in an Extremely Preterm Neonate

Onychomycosis refers to nail infections, caused by fungi including yeasts and non-dermatophyte moulds. One or several toenails or fingernails (seldom all) may be involved in this condition. Many cases of fingernail onychomycosis are due to yeasts. Fungal infection has emerged as an important cause of neonatal infection, associated with significant morbidity and mortality, especially in very low birth weight (< 1500 g) and extremely low birth weight (< 1000 g) infants. Herein, we report a case of a 24-day-old male infant, who presented with onychomycosis on the left ring fingernail, associated with fungal urinary tract infection (UTI). The evaluation of nails helped us detect fungal UTI. To date, there have been no reports suggesting onychomycosis as a presentation of fungal UTI. We could not find the association between onychomycosis and neonatal fungal UTI. Hence, retrospectively, it can be said that onychomycosis was a presentation of fungal UTI. Further studies are required to evaluate the etiology and treatment of neonatal onychomycosis. Moreover, dermatologists should pay particular attention to this rare event.

Fusarium spp. is able to grow and invade healthy human nails as a single source of nutrients.

Onychomycosis caused by Fusarium spp. is emerging, but some factors associated with its development remain unclear, such as whether this genus is keratinolytic. The main aim of the present study was to evaluate the ability of Fusarium to use the human nail as a single source of nutrients. We also performed an epidemiological study and antifungal susceptibility testing of Fusarium spp. that were isolated from patients with onychomycosis. The epidemiological study showed that Fusarium species accounted for 12.4 % of onychomycosis cases, and it was the most common among nondermatophyte molds. The most frequent species identified were F. oxysporum (36.5 %), F. solani (31.8 %), and F. subglutinans (8.3 %). Fluconazole was not active against Fusarium spp., and the response to terbinafine varied according to species. Fusarium was able to grow in vitro without the addition of nutrients and invade healthy nails. Thus, we found that Fusarium uses keratin as a single source of nutrients, and the model proposed herein may be useful for future studies on the pathogenesis of onychomycosis.

A study of onychomycosis in patients attending a dermatology center in Tehran, Iran

To determine the incidence of onychomycosis based on age and sex, morphological pattern of the disease, predisposing factors and identification of fungus by direct microscopy and culture methods. A prospective study was conducted on 140 patients with nail disorders. A detailed history and thorough examination was done in all patients. The samples were taken from patients clinically suspected of fingernails and toenails infections attending a dermatology center in Tehran, Iran. The nails were subjected to potassium hydroxide (KOH) examination and fungal culture on Sabouraud's dextrose agar (SDA) medium. Specimens from 79 patients (56.4%) were positive for onychomycosis. The mycological observations showing positive fining with KOH were observed in 79 (56.4%) and culture positive in 35 (25%) cases. Females were more infected than males. The most common age group infected was 41-60 years (40.7%). Toenails were affected more frequently than fingernails and dystrophic onychomycosis was the most common clinical type seen in 39.2% patients. From the culture-positive samples, yeasts were the most common pathogens isolated from 25 (71.4%) patients, followed by non-dermatophytic moulds in 6 (17.1%) and dermatophytes in 4 (11.5%) patients. This study demonstrated that Candida species were the main agents causing onychomycosis in our region and accurate diagnosis of onychomycosis was based on direct microscopy and fungal culture.

Epidemiology of superficial mycoses in Northern Greece: a 4-year study.

Superficial mycoses are defined as the fungal infections of skin, hair or nails that are caused by dermatophytes, yeasts and non-dermatophytic moulds. Dermatophytes are the most frequently isolated fungi from specimens of patients with superficial mycoses. Studying the possible alteration of the epidemiology of superficial mycoses in Northern Greece during the last two to three decades. Data concerning the superficial mycoses from patients coming mainly from the region of Macedonia, Northern Greece, between January 2010 and January 2014 were recorded and analysed. They included specimens from 438 patients (146 M/292 F), within an age range of 2-85 years old. 503 samples were collected from skin (81, 16.1%), hair (18, 3.6%) and nails (fingernails 84, 16.7%, toenails 320, 63.6%) lesions. Of a total of 222 positive cultures, 50 were considered as yielding clinically non-significant isolates (saprophytes). Among the rest (172), dermatophytes were the most prevalent isolates (102, 59.3%), followed by yeasts (51, 29.7%) and non-dermatophytic moulds (19, 11%). Trichophyton rubrum (55, 53.9%), Trichophyton mentagrophytes (18, 17.6%) and Microsporum canis (23, 22.5%) were the most common isolates among dermatophytes (total = 102). Candida parapsilosis (26, 51%), and Candida albicans (10, 19.6%) among yeasts (total = 51) whereas Fusarium (6, 31.6%) and Acremonium species (3, 15.8%) among the non-dermatophytic moulds (total=19). Compared to previous studies from Northern Greece, the epidemiology of superficial mycoses in the specific geographic region seems not to have been altered the last two to three decades.

Onychomycosis: A Rare Presentation of Fungal Urinary Tract Infection (UTI) in Extremely Preterm Neonate

Onychomycosis refers to nail infections caused by any fungus, including yeasts and nondermatophyte molds. Fungal infection has emerged as an important cause of neonatal infections with significant morbidity and mortality, especially in extremely low and very low birth weight infants. We report a 24-days-old boy who presented with onychomycosis on left ring finger nail associated with fungal urine tract infection. Nail finding helped us in detecting fungal urinary tract infection (UTI). Further studies are needed to evaluate the etiologies and treatment of neonatal onychomycosis, and dermatologists should pay attention to this rare event. Hence we are reporting this rare case.

Management of Onychomycosis in Canada in 2014.

Onychomycosis has several clinical presentations and is caused by various infectious organisms. To provide guidance for selection of appropriate treatment. The literature on onychomycosis management was reviewed to generate an evidence-based decision tree. Several options are available: terbinafine, itraconazole, fluconazole, ciclopirox 8% nail lacquer, efinaconazole 10% nail solution, and laser therapy. Further studies on lasers are needed before use can be recommended. Nondermatophyte molds or mixed infection can be managed with terbinafine or itraconazole with or without topicals. Itraconazole, fluconazole, and efinaconazole can be used for Candida infection. For dermatophytes, topicals can be considered for mild to moderate onychomycosis. For moderate to severe cases, any oral monotherapy can be used; however, we suggest terbinafine if there is a possibility of a drug interaction. These recommendations can be applied for all ages, immune function, or metabolic status, but proper monitoring and contraindications should be taken into consideration.

Isolation of dermatophytes (and other fungi) from human nail and skin dust produced by podiatric medical treatments in Australia.

Podiatric physicians routinely use electric drills for the treatment of nail and skin conditions. The grinding process produces human nail and skin dust that is generally vacuumed into bags in the grinding unit. Many of the nails are thought to be mycotic, particularly because they are obtained from patients with symptoms of dermatophyte infections. Currently, there is limited information available on the detection of fungi from nail dust samples. Herein, we attempt to address this situation and outline some of the difficulties that pathology laboratories face in isolating and identifying dermatophytes from nail samples. Fifty nail dust bags from podiatric medical clinics across all of the states and territories of Australia were collected and analyzed. Samples from the bags were inoculated onto primary isolation media. Fungal colonies that grew were then inoculated onto potato dextrose agar for identification using standard morphological (macroscopic and microscopic) features. One hundred fifty-one colonies of dermatophytes were identified from 43 of the 50 samples. In addition 471 nondermatophyte molds were isolated, along with some yeasts and bacteria. The most common dermatophytes isolated were from the Trichophyton mentagrophytes/interdigitale complexes. Trichophyton rubrum, Trichophyton tonsurans, Trichophyton soudanense, and Epidermophyton floccosum were also isolated. An unidentified group of dermatophytes was also present. The three most common genera of nondermatophyte molds were Aspergillus, Penicillium, and Scopulariopsis, all of which have been implicated in onychomycosis and more general disease. The presence of viable fungal pathogens in the dust could potentially pose a health problem to podiatric physicians.