Morphological and ultrastructural changes in fungal agents after LASER application.

BACKGROUND: Onychomycosis is a fungal nail infection of difficult treatment due to the fungal survival capacity and reduced number of effective therapies. The present study aimed to isolate fungal agents that cause onychomycosis in immunocompetent patients and evaluate how LASER treatments affect the growth and ultrastructure of isolates. METHODS: In total, 21 patients with positive direct microscopic examination (DME) for onychomycosis had nail samples collected for cultivation and phenotypic identification of microorganisms. From these patients, 12 underwent LASER treatment, divided in Group 1 (n = 5) treated with Nd: YAG 1,064 nm, and Group 2 (n = 7) treated with Nd: YAG 1,064 nm + Er: YAG 2,940 nm + topical isoconazole. Transmission Electron Microscopy (TEM) was performed to evaluate ultrastructural changes after treatment. RESULTS: DME, cultivation, and phenotypic identification showed that the most identified fungus was Trichophyton rubrum spp. After LASER therapy, sample cultivation showed alterations in the fungal morphology with reduction of hyphae, conidia, and reproductive structures. Alterations in fungal cell wall structure, cytoplasm density, and organelles were observed by TEM. CONCLUSION: LASER irradiation causes changes in the fungal cells, especially in the number of hyphae and the presence of conidia. In addition, it affects fungal growth and reproduction capacity, which interferes with their infection ability and virulence.

Pathophysiology and Management of Onychomycosis and Novel Approaches for Effective Transdermal Applications.

Onychomycosis is the most common fungal nail infection accounting for 50% of nail disorders. This infection is most common in the toenails than in the nails of the fingers. It is caused by various fungal species like Trichophyton rubrum, Trichophyton mentagrophytes, Scopulariopsis brevicaulis, Aspergillus spp, Fusarium spp, Acremonium spp, Alternaria spp, and Neoscytalidium. Among them, dermatophyte fungus is involved in 70% to 80% of infections. Clinically, there are five types of onychomycosis classified based on causative organism and location of infection origin. Diagnosis of this infection uses a mycological study of nail samples using multiple staining techniques like periodic acid-Schiff, calcofluor, Grocott methenamine silver, fluorescence, and microscopy. The major risk factors of this infection include diabetes mellitus, psoriasis, peripheral vascular diseases, obesity, metabolic syndrome, nail trauma, human immunodeficiency virus and/or acquired immunodeficiency syndrome, immune-compromised individuals, chronic kidney failure, athletic activity, smoking, and hyperlipidemia. The treatment options for onychomycosis include topical and systemic antifungal agents, nanoparticles, laser therapy, photodynamic therapy, and nail avulsion. This article describes several types of onychomycosis, symptoms, diagnosis, currently available therapy and its drawback, current research to rectify the issues, and future medicinal approaches to improve patient health.

How Effective Are Devices in the Management of Onychomycosis?: A Systematic Review.

Onychomycosis is the most common nail disorder, with a global prevalence of approximately 5.5%. It is difficult to cure on both short-term and long-term bases. The most common treatments include the use of oral or topical antifungals. Recurrent infections are common, and the use of systemic oral antifungals raises concerns of hepatotoxicity and drug-drug interactions, particularly in patients with polypharmacy. A number of device-based treatments have been developed for onychomycosis treatment, to either directly treat fungal infection or act as adjuvants to increase the efficacy of topical and oral agents. These device-based treatments have been increasing in popularity over the past several years, and include photodynamic therapy, iontophoresis, plasma, microwaves, ultrasound, nail drilling, and lasers. Some, such as photodynamic therapy, provide more direct treatment, whereas others, such as ultrasound and nail drilling, aid the uptake of traditional antifungals. We conducted a systematic literature search investigating the efficacy of these device-based treatment methods. From an initial result of 841 studies, 26 were deemed relevant to the use of device-based treatments of onychomycosis. This review examines these methods and provides insight into the state of clinical research for each. Many device-based treatments show promising results, but require more research to assess their true impact on onychomycosis.

Photodynamic therapy-mediated extirpation of cutaneous-resistant dermatophytosis with Ag@ZnO nanoparticles: an efficient therapeutic approach for onychomycosis.

Aim: The aim of this study was to determine whether photodynamic therapy of resistant onychomycosis with Ag@ZnO nanoparticles can promote the treatment procedure and extirpates the recurrence of fungal infection. Methods: Ag@ZnO nanoparticles (NPs) under UVB-radiation were applied to treat T. rubrum and T. mentagrophytes in vitro through photodynamic therapy. In vivo therapeutic efficacy, biocompatibility and biodistribution of Ag@ZnO NPs were studied. Results: 40 µg/ml of UVB-activated Ag@ZnO NPs showed 100% antifungal activity against dermatophytosis in vitro and in vivo followed by complete growth prevention by degeneration of spores and mycelium after 180 days, while posed biocompatibility. Conclusion: This study showed the superiority of photodynamic therapy with Ag@ZnO NPs followed by proper regeneration of the skin with Zinc ion of the shell.

Hand-foot syndrome and nail disorders secondary to treatment with paclitaxel: Is there a relationship with the presence of fungi?

INTRODUCTION: This study aimed to evaluate the frequency of nail disorders and the presence of fungi on the nails of the hands and feet of patients with hand-foot syndrome secondary to treatment with paclitaxel. METHODS: Prospective study, carried out from October 2018 to December 2019, which included 81 patients undergoing treatment for breast cancer using paclitaxel and had signs and or symptoms of hand-foot syndrome with or without nail disorders. The data were collected through interviews guided by a structured questionnaire, information from medical records and reports of mycological exams. RESULTS: The average age of women was 54.7 ± 7.4 years. Nail disorders occurred in 69 patients (85.2%), and of these, 43 (62.3%) were positive for fungi. The fungi were yeasts (n = 38; 69%), dermatophytes (n = 15; 27.2%) and non-dermatophyte filamentous fungi (n = 8; 14.5%). CONCLUSIONS: Nail disorders were the most frequent manifestations in patients with hand-foot syndrome treated with paclitaxel and occurred in 85.2% of them. It was evidenced that fungi are present on the nails of these patients and can occur in up to 65.28%. The most prevalent fungi were Candida and Trichophyton. The nail lesion was associated with the type of treatment protocol used by the patient. The results of the study point to the need to select safe management alternatives for patients, so they can prevent nail lesions and prevent the proliferation of fungi, consequently reducing negative life impact during treatment.

Epidemiología de la Onicomicosis Pedis en adultos hospitalizados en un servicio de medicina en un hospital de tercer nivel en Chile / Epidemiology of Onychomycosis pedisinhospitalized adults at the internal medicine ward of a high complexity hospital in Chile

La prevalencia global de la onicomicosis pedis es de 4,3%, y en hospitalizados puede llegar hasta 8,9%. Aun así, se propone que está ampliamente subdiagnosticada. Personas añosas con comorbilidades presentan mayor riesgo de onicomicosis pedis y de sus complicaciones. Se examinaron aleatoriamente a 64 pacientes hospitalizados en el Servicio de Medicina del Hospital San José. A aquellos con signos clínicos de onicomicosis pedis se les realizó un examen micológico directo (MD) y estudio histopatológico de un corte de uña teñido con PAS (Bp/PAS). Muestra de 64 pacientes, un 78,1% presentó onicomicosis pedis clínica y en un 70,3% se confirmó el diagnóstico con MD y/o Bp/PAS positivo. De los pacientes con onicomicosis confirmada, el promedio de edad fue de 67,8 +/- 12,3 años. Un 44% correspondió al sexo femenino y un 56% al sexo masculino. La onicomicosis pedis en el servicio de medicina interna del Hospital San José es una condición frecuente. El conjunto de MD y Bp/PAS podría ser considerado como una buena alternativa diagnóstica. (AU)

Onychomycosis of the toenails has a global prevalence of 4,3% and can reach up to 8,9% in hospitalized patients. It has been hypothesized that it is widely under diagnosed. Aged patients with multiple diseases have an increased risk of Onychomycosis and its complications. 64 patients of the internal medicine ward were randomly selected. Those who had clinical signs of onychomycosis of the toenails were tested with direct microscopy and histological study of the nail plate with PAS staining. Of the 64 patients, 78,1% (50) had clinical signs of onychomycosis of the toenails and in 70,3% (45) the diagnosis was confirmed either by direct microscopy and/or by histological study of the nail plate with PAS staining. The mean age for the group with onychomycosis was 67,8 +/- 12,3 ages. 44% were female and 56% were male. Onychomycosis of the toenails is a frequent condition at the internal medicine ward of the San José Hospital. The direct microscopy together with the histological study of the nail plate with PAS staining seem to be a good diagnosis alternative. (AU)

Effect of Different Nail Penetration Enhancers in Solid Lipid Nanoparticles Containing Terbinafine Hydrochloride for Treatment of Onychomycosis.

Onychomycosis is considered a stubborn nail fungal infection that does not respond to conventional topical antifungal treatments. This study aimed to develop and characterize novel solid lipid nanoparticles (SLNs) formulae containing terbinafine HCl (TFH) and loaded with different nail penetration enhancers (nPEs). Three (nPEs) N-acetyl-L-cysteine, thioglycolic acid, and thiourea were used. Characterization of the prepared formulae was done regarding particle size, zeta potential, polydispersity index (PDI), entrapment efficiency (EE%), physical stability, in vitro release study, infrared (FT-IR), and their morphological structures. The selected formulae and the marketed cream Lamifen® were compared in terms of their antifungal activity against Trichophyton rubrum as well as their nail hydration and their drug uptake by the nail clippers. Thiourea was the nPE of choice; formulae (N2 and N8), with thiourea, were considered the optimum TFH SLNs containing nPEs. They were selected for their optimum particle size of 426.3 ± 10.18 and 450.8 ± 11.45 nm as well as their highest EE% of 89.76 ± 1.25 and 90.35 ± 1.33, respectively. The in vitro microbiological screening of the antifungal activity of these two formulae showed significantly larger zones of inhibition in comparison with the marketed product. The ex vivo screening of the drug uptake of the two selected formulae was significantly higher than that of the marketed product. The nPE formulae present a very promising option as they showed optimum physicochemical characterization with high antifungal activity and high drug uptake as well as good nail hydration effect.

Treatment and management strategies of onychomycosis.

Onychomycosis is one of the most prevalent and severe nail fungal infections, which is affecting a wide population across the globe. It leads to variations like nail thickening, disintegration and hardening. Oral and topical drug delivery systems are the most desirable in treating onychomycosis, but the efficacy of the results is low, resulting in a relapse rate of 25-30%. Due to systemic toxicity and various other disadvantages associated with oral therapy like gastrointestinal, hepatotoxicity, topical therapy is commonly used. Topical therapy improves patient compliance and reduces the cost of treatment. However, due to poor penetration of topical therapy across the nail plate, research is focused on different chemical, mechanical and physical methods to improve drug delivery. Penetration enhancers like Thioglycolic acid, Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), Sodium lauryl sulfate (SLS), carbocysteine, N-acetylcysteine etc. have shown results enhancing the drug penetration across the nail plate. Results with physical techniques such as iontophoresis, laser and Photodynamic therapy are quite promising, but the long-term suitability of these devices is in need to be determined. In this article, a brief analysis of the treatment procedures, factors affecting drug permeation across nail plate, chemical, mechanical and physical devices used to increase the drug delivery through nails for the onychomycosis management has been achieved.

Onicomicosis en pediatría: actualización y tratamiento / Pediatric onychomycosis: update and management

Resumen: La onicomicosis (OM) es una infección fúngica de las uñas, cuyo principal agente causal es el Tricophytum rubrum. Si bien es una patología infrecuente en niños, se ha observado un aumento en la prevalencia en el último tiempo. Hasta la fecha, existen diversos estudios y guías clínicas de OM en adultos. Sin embargo, la literatura en edad pediátrica es escasa, lo que dificulta el tratamiento en pediatría. En el presente articulo se revisa la literatura actual, los métodos diagnosticos de OM, datos epidemiológicos locales y globales, y se presentan las opciones de tratamiento disponibles conside rando su eficacia y perfil de seguridad en población pediátrica.

Abstract: Onychomycosis (OM) is a fungal infection of the nails, whose main etiologic agent is Trichophytum rubrum. Although, it is an unusual pathology in children, in the last years an increase in its preva lence has been observed. To date, there are several studies and clinical guidelines for OM in adults. However, literature in children is scarce, which makes pediatric treatment difficult. The objective of this publication was to review the current literature in order to establish diagnostic methods for OM, national and international epidemiological data, and to provide treatment options taking into account their efficiency and safety profile in the pediatric population.

Culture-Proven Candida Albicans Endogenous Endophthalmitis in a Patient with Onychomycosis.

Purpose: To report a case of Candida albicans endogenous endophthalmitis in an immunocompetent patient with onychomycosis.Methods: Retrospective case report.Results: A 40-year-old man with onychomycosis presented with C. albicans subretinal abscess in the left eye. Systemic and intravitreal injections did not prevent further progression of the infection. The patient underwent pars plana vitrectomy. One month after surgery, the intraocular inflammation gradually subsided. However, his visual acuity stayed at counting fingers as a result of macular scarring.Conclusion: The aim of this case presentation is to emphasize that endogenous fungal endophthalmitis can be seen in an immunocompetent patient. The use of systemic steroids in the past was the main reason for the progression of the disease in this case. In these situations, when the clinical findings suggest a fungal etiology, it should keep in mind that endogenous candida endophthalmitis can be a result of fungal infections from distant sites such as the toenails and systemic steroids should not be started before definite diagnosis.

Relationship between antifungal susceptibility profile and virulence factors in Candida albicans isolated from nail specimens

Abstract INTRODUCTION: The aim of this study was to evaluate some virulence factors in Candida albicans isolates from patients with onychomycosis and determine the correlation between these factors and the antifungal resistance profile. METHODS: Seventy species of C. albicans were confirmed using polymerase chain reaction amplification of the HWP1 gene. According to the Clinical & Laboratory Standards Institute guidelines, the susceptibility profile of four antifungal agents was investigated, and the production of aspartyl protease, phospholipase, haemolysin, and biofilm was determined. The correlation between these profiles was also investigated. RESULTS: The isolates indicated different levels of resistance and production of virulence factors. Significant correlations were observed between the minimum inhibitory concentration (MIC) of fluconazole/itraconazole and biofilm production, between phospholipase production and fluconazole/itraconazole MIC, and between fluconazole MIC and hemolytic activity in C. albicans isolates. The results also showed significant correlations between phospholipase activity and biofilm production. CONCLUSIONS: Our findings will contribute to a better understanding of the pathogenesis of C. albicans and characterize the relationship between virulence factors and antifungal resistance, which may suggest new therapeutic strategies considering the possible involvement of the virulence mechanism in the effectiveness of treatment.

Significativo aumento de onicomicosis por hongos filamentosos no dermatofitos en red de salud privada en Santiago de Chile entre los períodos 2008-2009 y 2016-2017 / Significant increase in onychomycosis due to Filamentous Fungi Non Dermatophytes in Network of Private Health in Santiago de Chile among the periods 2008-2009 and 2016-2017

INTRODUCCION: La onicomicosis corresponde a una patología prevalente causada por hongos dermatofitos, levaduras y en menor proporción, hongos filamentosos no dermatofitos (HFND). Se ha reportado un aumento a nivel mundial en la incidencia de onicomicosis por HFND1 , sin embargo, en Chile no hay registros de ello. OBJETIVO: Comparar la epidemiología local de onicomicosis por HFND en una red privada de Santiago de Chile entre dos períodos de tiempo. Material y métodos: Se realizó un estudio transversal de análisis de los registros de laboratorio de la Red de Salud UC-Christus entre los períodos 2008- 2009 y 2016-2017. RESULTADOS: Se obtuvieron un total de 9.579 muestras en ambos períodos, 4.985 entre 2008-2009 y 4.594 entre 2016-2017, con 3.442 (36%) cultivos positivos para hongos, 1.831 (36,7%) en el primer período y 1.611 (35%) en el segundo. Del total 40 muestras (1,2%) fueron de HFND, destacando que la prevalencia aumentó significativamente entre ambos períodos: 8 (0,4%) y 32 (2,0%) cultivos, respectivamente (p<0,0001). Del total, las especies de HFND más prevalentes fueron: 23 Fusarium sp (57,5%), 8 Scopulariopsis sp (20%) y 7 Acremonium sp (17,5%). En pacientes con cultivo positivo para HFND, se buscaron asociaciones probables en los antecedentes a través de la ficha clínica, sin encontrar resultados significativos. CONCLUCION: Los HFND son la tercera causa de onicomicosis y su prevalencia fue 1,2%. Las especies más frecuentes fueron Fusarium sp, Scopulariopsis sp, Acremonium sp. La prevalencia de HFND aumentó significativamente en un período de 6 años.

INTRODUCTION: Onychomycosis is a frequent nail disease caused mainly by dermatophytes, in less proportion yeast and last non-dermatophyte molds (NDM). NDM onychomycosis is an increasing problem worldwide, though in Chile there is no epidemiological registry about it. OBJETIVE: The aim of the study was to determine the local epidemiology of NDM onychomycosis. MATERIAL Y METHODS: We did a transversal cohort study in the Red de Salud UC-Christus between 2008-2009 and 2016-2017. RESULTS: Of the 9,579 clinically suspected cases of onychomycosis, 4,985 in 2008-2009 and 4,594 in 2016-2017, 3,448 (36%) cultures were positive in total, 1,831 (36.7%) in the first period and 1,611 (35%) in the second. Only 40 cultures (1.2%) were NDM in total, but the prevalence significantly increased between both periods with 8 (0.45%) and 32 (2.0%) cultures, respectively (p y (p<0.0001). Among the total of NDM, the most prevalent species were: 23 Fusarium sp (57.5%), 8 Scopulariopsis sp (20%) and 7 Acremonium sp (17.5%). We searched for possible associations of patients with NDM onychomycosis and morbid history, but found no significant result. COMCLUSION: NDM are the third cause of onychomycosis and its prevalence of 1.2% was predominantly from toe nails. The most frequent species were Fusarium sp, Scopulariopsis sp. and Acremonium sp. The prevalence of NDM increased significantly in a period of 6 years.

Tuberculosis, onychomycosis and immune deficiency in complicated Crohn's disease.

The immune system is composed of innate humoral defence and adaptive immunity. One of the key mechanisms of the innate humoral defence is through complement activation. Mutations of certain enzyme may affect the complement activation and result in decreased defence against microorganisms. Mannan-binding lectin serine protease 2 (MASP-2) mutation was associated with recurrent infections and autoimmune diseases. Tuberculosis (TB) has been linked with mannose-binding lectin and MASP-2 gene polymorphism. We report a case of a paediatric patient with MASP-2 deficiency with classical and atypical features associated with Crohn's, onychomycosis and severe cutaneous infections including TB. We also report the presence of a new mutation variant in MASP-2 reported in whole exome sequencing of our patient.

A Randomized, Double-Blind, Controlled Trial Evaluating the Efficacy of Nd:YAG 1064 nm Short-Pulse Laser Compared With Placebo in the Treatment of Toenail Onychomycosis.

INTRODUCTION: Laser and light-based therapies have emerged as interesting treatment options with minimal side effects or contraindications to treat onychomycosis. Although increasing reports of successful treatment exist, few randomized, controlled, prospective studies have evaluated their true efficacy. We conducted a prospective, randomized, double-blind, controlled trial to evaluate the cure rate of onychomycosis treated by laser. METHODS: Fifty-one patients were randomized to receive 3 treatments (0, 12, 24 weeks) of 1064 Nd:YAG short-pulse (Cutera GenesisPlus) laser or placebo sham laser. The primary efficacy end point is the proportion of patients with a complete cure rate of the target great toenail at week 52. The secondary efficacy end points, at week 52, were treatment success defined as almost clear nail (≤ 10%) and negative mycology, completely or almost clear nail of the great toenail, negative mycology, improvement from one OSI severity class to another of the target toenail, and the difference in proximal nail plate clearance between baseline and week 52. RESULTS: No patient (0%) in the laser group and 2 patients (7.7%) in the placebo group reached the primary outcome. One patient (4.8%) in the laser group reached treatment success vs 2 (7.7%) in the placebo group. Only 6 patients (33%) had negative cultures in the laser group vs 11 (50%) in the placebo group. None of the secondary end points were met. CONCLUSIONS: This study demonstrated that 3 treatments of Nd:YAG 1064 nm laser at 3-month intervals were not effective to treat onychomycosis.

[Evaluation of the usefulness of nail biopsy in the diagnosis of onychomycosis]. / Evaluación de la utilidad diagnóstica de la biopsia ungueal en las onicomicosis.

BACKGROUND: Onychomycosis affects between 2% to 30% of the world population. Nail biopsy may help in making a diagnosis and can distinguish between invasion and colonisation. AIMS: To evaluate the diagnostic usefulness of nail biopsy with Periodic acid-Schiff (PAS) staining for onychomycosis, compared to direct KOH examination, culture and its combination in a reference laboratory in Colombia. METHODS: The study included 66 patients in whom a blind and independent reading of the three tests was performed. The usefulness was defined based on the validity (sensitivity, specificity, Youden's index, likelihood ratios), performance (predictive values) efficiency (proportion of correctly diagnosed patients), and reproducibility (kappa coefficient). RESULTS: The mean age of the patients was 55±16 years, and included 76% women. The direct tests with KOH were positive in 66.7% (n=44), 62.1% (n=41) were positive with culture, and 56.1% (n=37) with the biopsy. The main causal agents were non-dermatophytes moulds in 36.4% (n=24). The most frequent species were Neoscytalidium dimidiatum (n=11), Trichophyton rubrum (n=11), and Candida parapsilosis (n=13). The sensitivity of nail biopsy, when compared to the standard (KOH and/or culture), was 71%, specificity 83%, Youden's index 0.54, positive likelihood ratio 4.25, negative likelihood ratio 0.35, positive predictive value 92%, negative predictive value 52%, efficiency 74% and kappa coefficient 0.45. When biopsy was evaluated only in patients with onycholysis of the nail plate greater than 50%, all the parameters of diagnostic usefulness increased. CONCLUSIONS: The overall usefulness of the biopsy was moderate for patients with more severe symptomatology, which makes its use advisable in cases of extensive onycholysis, and when discriminating colonisation from invasion is required.

Virulence properties and sensitivity profile of Candida parapsilosis complex species and Kodamaea ohmeri isolates from onychomycosis of HIV/AIDS patients.

Cutaneous fungal infections include onychomycosis, an infection of the nail that affects both healthy and immunocompromised patients. This study investigated the in vitro hydrolytic enzymes production, adhesion and biofilm formation capacity of Candida parapsilosis complex species and Kodamaea ohmeri isolates from onychomycoses of HIV/AIDS patients and also established the antifungal sensitivity profiles of these isolates. Onychomycosis in HIV/AIDS patients showed a high prevalence of emerging yeasts, among which C. parapsilosis complex species and K. ohmeri were the most frequent. Three C. parapsilosis sensu stricto and two C. orthopsilosis isolates were resistant to amphotericin B and 83% of isolates were resistant to terbinafine. All three different species evaluated were proteinase and hemolysin producers. All isolates adhered to stainless steel and siliconized latex surfaces, and carbohydrates intensified adhesion of all isolates. Isolates adhered to keratinous nail and 50% formed biofilms with strong intensity. In multispecies or polymicrobial biofilms, C. albicans and Staphylococcus aureus regulated the biofilm formation of the analyzed species, decreasing the number of their cells in biofilms. The isolation of emerging yeast species from onychomycosis which are great producers of hydrolytic enzymes and with high adhesion and biofilm formation capacity is a result that should be considered relevant in clinical practice. In addition, half of the isolates was resistant to at least one of the tested antifungals. Taken together these data corroborate the infectious capacity and viability of these isolates under favorable conditions.

Nail clipping in onychomycosis and comparison with normal nails and ungual psoriasis

Abstract: Background: Of all nail disorders seen in dermatology offices, half of them are due to onychomycosis. The main differential diagnosis is nail psoriasis. The objective of this study was to compare the microscopic findings, other than the presence of fungi, in the clipping of onychomycosis versus normal nails and nail psoriasis. Methods: Cross-sectional study of onychomycosis cases, analyzed by clipping and compared with data on normal nails and those with nail psoriasis. Results: Sixty-two onychomycosis samples were compared with 30 normal nails and 50 nails with psoriasis. In onychomycosis, measurement of subungual region, serous lakes, neutrophils and number of layers of parakeratosis are more intense than in psoriasis. Onychocariosis is less common in psoriasis, while bacteria are more frequent. The nail transition zone is more commonly blurred and irregular in onychomycosis. Conclusion: Clipping helps in the differential diagnosis of onychomycosis and nail psoriasis and may be useful even when fungi are not found.

Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-Aspergillus fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of >1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.

Formulation evaluation of ketoconazole microemulsion-loaded hydrogel with nigella oil as a penetration enhancer.

BACKGROUND: Onychomycosis is an opportunistic fungal infection often infecting people with compromised immune system. Currently available treatment interventions such as physical, surgical, and chemical-based approaches are successful in treating the condition, however, are painful and nonpatient complaint. Moreover, dermal creams with antifungal agents do not penetrate nail plate as required; hence, there is a necessity of developing a novel formulation with enhanced penetration. AIMS: The aim of the present research work was to develop ketoconazole microemulsion-loaded hydrogel formulation containing nigella oil as permeation enhancer for the treatment of onychomycosis. METHODS: Screening of oils, surfactants, and cosurfactants were done based on solubility studies followed by the construction of pseudo-ternary phase diagrams with 2% ketoconazole. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex-vivo studies were carried out using Franz diffusion cells using porcine skin membrane. The antifungal activity of microemulsion-loaded hydrogel was evaluated using cup plate method using Candida albicans and Aspergillus niger. RESULTS: The optimized microemulsion had a composition of 54.97% Capryol:Nigella (2:1), 36.07% Transcutol:Propylene glycol (2:1), and 7.13% water and was later incorporated into polymeric gel base. The microemulsion-loaded hydrogel exhibited a 10 hours sustained release profile as compared to the marketed cream and an enhanced activity against marketed ketoconazole cream and compared with marketed ketoconazole formulation. CONCLUSION: The thermodynamic stability, sustained drug release with greater permeation, and enhanced activity due to the presence of nigella oil in microemulsion-loaded hydrogel warrant its application as an excellent vehicle for treating fungal infections.

Factors associated with onychomycosis in nail psoriasis: a multicenter study in Pakistan.

BACKGROUND: Treatment of psoriatic nail disease is challenging, and dystrophic psoriatic nails can get secondarily infected with fungi. METHODS: This 2-year, matched case-control study was conducted at three tertiary care centers of Karachi, Pakistan. Data were collected from patients with nail psoriasis as cases with age- and gender-matched controls. A detailed questionnaire was filled for all study participants. Nail Psoriasis Severity Index (NAPSI) scoring tool was used to assess dystrophy. Fungal infection was inferred by nail clippings for fungal hyphae and culture. RESULTS: Among 477 participants, 159 cases and 318 controls completed the study. Their mean age was 44 years, and one-third were female. Fungal culture positivity was statistically significant in cases as compared to the control group (P < 0.001). The most frequent species identified was Candida parapsilosis in both cases and controls. Body mass index, NAPSI scoring, socioeconomic status, elevated diastolic blood pressure, smoking status psoriasis among first-degree relatives, and longstanding disease of more than 10 years were significant factors in univariable analysis. Multivariable logistic regression identified independent factors like low to middle socioeconomic status, history of psoriasis in first-degree relative, current smoker, and obesity. CONCLUSION: We found nearly one-third of the psoriatic patients with nail involvement having concomitant fungal infection. We emphasize that nail clipping for fungal smear and culture should be advised to those patients with coexisting factors found significant in our study results. This opinion can be incorporated in psoriasis management guidelines for improving treatment of psoriatic nails.