Number of Affected Nails Is the Primary Determinant of Efinaconazole 10% Solution Usage for Onychomycosis.

Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112.    doi:10.36849/JDD.7676.

Anti-bacterial effects of functional cosmetics containing silver ions (Ag+ ) on problematic toenails in Republic of Korea.

BACKGROUND: Problematic toenails caused by various diseases that are infected by various bacteria are discolored or deformed if left unattended for a long time are gradually increasing in modern society. Accordingly, the present study examines the anti-bacterial effects of LCN products, focused on Pseudomonas aeruginosa and Trichophyton rubrum, which can appear in problematic toenail symptoms. After the treatment, a significant anti-bacterial effect occurring on problematic toenails when a product containing silver ion (Ag+ ) will be analyzed. METHODS: The anti-bacterial activity of LCN functional gel products in anti-fungal and/or anti-bacterial potency was confirmed by the paper disk method against two strains (Pseudomonas aeruginosa and Trichophyton rubum). RESULTS: From July 2019 to October 2019, 30 men and women in their 20s and 50s who needed to manage problematic toenails in Wonju city, Gangwon-do, Republic of Korea, were asked to use LCN products once every two weeks. After 4 months, changes in the managed toenails were observed. Both products showed very good anti-microbial activity against, Trichophyton rubum but a very weak one against Pseudomonas aeruginosa. CONCLUSION: As a result of this study, although there was a difference between individuals, the feet treated with LCN products showed effective anti-bacterial activity against topical anti-bacterial effects.

Utility of polymerase chain reaction for assessment of onychomycosis during topical therapy.

BACKGROUND: Increased detection of fungi including non-dermatophyte molds (NDMs) using polymerase chain reaction (PCR) methods is well-established. However, the use of PCR to evaluate ongoing onychomycosis treatment outcome has not been investigated. METHODS: Nail samples from 28 patients receiving topical efinaconazole were evaluated by both KOH/culture and PCR methods across the study period. Detection of microorganisms by PCR was compared to the culture at baseline and end of study at month 24 (M24). Fungal detection by both methods was evaluated with respect to clinical cure observed as 100% visual clearance of the target toenail. RESULTS: By culture, all 28 subjects were dermatophyte-positive at pre-treatment; only 4/28 also exhibited an NDM microorganism. According to PCR, 24/28 subjects were dermatophyte-positive pre-treatment, with 25/28 also exhibiting NDMs. At M24, 18/28 (64.3%) participants had negative KOH/culture results, in contrast to 4/28 (14.3%) negative PCR results. PCR showed higher rates of NDM detection than the culture at baseline as well as M24. Calculations to compare the diagnostic utility of KOH/culture versus PCR found that positive tests with both methods reliably indicate the presence of onychomycosis, but negative PCR correlated better with onychomycosis cure than did KOH/culture. DISCUSSION: PCR confirmed a high presence of NDMs pre-treatment, and continued presence of NDMs to M24, with unknown significance requiring further investigation. Though both KOH/culture and PCR have diagnostic limitations, PCR showed better overall utility than culture in predicting onychomycosis topical treatment outcome and should be more strongly considered for evaluation of topical therapies.

Total Dystrophic Onychomycosis Successfully Treated with Efinaconazole Topical Solution in Times of Coronavirus Disease of 2019: A Case Study.

Toenail onychomycosis is a common condition that is equally challenging for podiatrists and patients. This case study documents a 26-year-old woman with bilateral total dystrophic onychomycosis of at least 5 years' duration. She had previously failed to respond to treatment with ciclopirox nail lacquer 8% and, despite hiding her condition with nail polish, was suffering from embarrassment, distress, and low self-esteem. At initial consultation, 100% of both great toenails was affected. After discussion of all treatment options, the patient opted for topical efinaconazole 10% solution, once daily for 48 weeks. Significant improvement was noted at the first (4-week) assessment period. This improvement was maintained through each subsequent virtual consultation, and complete cure was seen at a 30-week follow-up visit. To the author's knowledge, this is the first published report on the use of efinaconazole in total dystrophic onychomycosis. It suggests that the product may be effective in patients with even the most severe and treatment-recalcitrant disease, who are unwilling or unable to tolerate systemic antifungal therapy.

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)

Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment.

Introduction. Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. Trichophyton rubrum is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed.Hypothesis/Gap Statement. Ex vivo onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer.Aim. Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an ex vivo onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains.Methodology. The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an ex vivo onychomycosis model using porcine hooves was evaluated as well.Results. The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the ex vivo onychomycosis model was effective in the establishment of infection by T. rubrum.Conclusion. Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on T. rubrum strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.

Toe Web Infection: Epidemiology and Risk Factors in a Large Cohort Study.

INTRODUCTION: Toe web infection (TWI) is a bacterial infection of the interdigital space. In most cases, the infection is caused by gram-negative bacteria, secondary to a chronic fungal infection (dermatophytosis). The typical presentation includes macerations and erosions in the interdigital space. Predisposing factors include interdigital tinea, hyperhidrosis, and humidity. OBJECTIVE: The aim of this study was to characterize the TWI patient population and identify associated risk factors. METHODS: We conducted a retrospective study of patients diagnosed with TWI from 2006 to 2020 at Sheba Medical Center, Israel. Collected data included patients' demographics (age, sex, weight, and occupation), smoking pack-years, comorbidities, medications, and course of disease. RESULTS: A total of 200 patients were diagnosed with TWI. The median age at diagnosis was 51 years. The majority of the patients were men (72.5%). The most common comorbidities were dyslipidemia, hypertension, diabetes, and ischemic heart disease. We found that 71.2% of patients were smokers, and 46.4% of patients had occupations that required closed-toe shoes. TWI incidence did not increase seasonally. Bilateral TWI was found in 50% of the patients, 33% had recurrent infections, and 20% had secondary cellulitis. CONCLUSIONS: Smoking and diabetes were more prevalent among TWI patients than in the general population, and there was a correlation between smoking and TWI recurrences. We identified risk factors for TWI to identify at-risk populations.

Efficacy and safety of topical terbinafine 10% solution (MOB-015) in the treatment of mild to moderate distal subungual onychomycosis: A randomized, multicenter, double-blind, vehicle-controlled phase 3 study.

BACKGROUND: Onychomycosis is a recalcitrant fungal nail infection. Topical antifungal agents may be preferred over systemic agents due to lack of systemic adverse effects. OBJECTIVE: To investigate the efficacy and safety of topical terbinafine 10% solution (MOB-015) for the treatment of distal and lateral subungual onychomycosis. METHODS: In a multicenter, double-blind, phase III, North American study, patients with mild to moderate distal and lateral subungual onychomycosis involving 20% to 60% of at least 1 great toenail were randomized to once daily application of MOB-015 or matching vehicle for 48 weeks. The primary efficacy variable was complete cure, while the secondary efficacy variables were mycological cure and treatment success. Safety evaluations were also performed. RESULTS: At week 52, the mycological cure (negative culture and potassium hydroxide microscopy) rate in the MOB-015 and vehicle groups was 69.9% and 27.7%, respectively (P < .001), and complete cure (0% clinical disease involvement and mycological cure) was achieved in 4.5% and 0% of patients, respectively (P = .0195). At least 1 adverse event leading to discontinuation of treatment occurred in 2.8% of patients in the MOB-015 group and in 4.2% in the vehicle group. LIMITATION: The follow-up period after end of treatment may not be sufficient to accurately reflect cure in distal and lateral subungual onychomycosis. CONCLUSIONS: MOB-015 is a treatment option for onychomycosis with an adverse event profile similar to vehicle.

The Growing Problem of Antifungal Resistance in Onychomycosis and Other Superficial Mycoses.

Superficial mycoses are becoming increasingly resistant to current antifungal medications. As alternative therapeutic options are limited, the increasing frequency of reports of antifungal resistance is alarming. This epidemic parallels the rise of antibiotic resistance; however, the significance of this problem has yet to gain global attention. Here, we discuss the reports of antifungal resistance from around the world, present our own experience with treatment-resistant infections, and examine alternative treatment strategies. The majority of reports of recalcitrant infections indicate terbinafine resistance as the causative factor. Single-point mutations in the squalene oxidase gene is the most reported mechanism of resistance to terbinafine. Mixed infections of dermatophytes with non-dermatophyte molds and/or yeasts are becoming more prevalent and contributing to the resistant nature of these infections. The key to selecting an effective antifungal therapy for a recalcitrant infection is identification of the infectious organisms(s) and testing susceptibility of the organism(s) to antifungal drugs. Combination and sequential therapy regimens are options, but both require active monitoring for hepatic and renal function, drug interactions, and other adverse effects. Selected topical antifungals with a wide spectrum of activity may also be considerations in some clinical presentations. Innovative treatment regimens and novel therapeutics are needed to overcome the rising epidemic of antifungal resistance.

Onychomycosis: Current Understanding and Strategies for Enhancing Drug Delivery into Human Nail Tissue.

BACKGROUND: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life. OBJECTIVES: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement. CONCLUSION: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required.

Safety, Pharmacokinetics, and Efficacy of Efinaconazole 10% Topical Solution for Onychomycosis Treatment in Pediatric Patients.

BACKGROUND: Pediatric onychomycosis management is challenging as there are limited treatment options. The objective of this study was to evaluate efinaconazole 10% topical solution in children with onychomycosis. METHODS: This phase 4, multicenter, open-label study (NCT02812771) evaluated safety, pharmacokinetics (PK), and efficacy of efinaconazole 10% topical solution in pediatric participants (6-16 years). Efinaconazole was administered once daily for 48 weeks, with a 4-week posttreatment follow up. Participants had culture-positive, mild-to-severe distal lateral subungual onychomycosis affecting at least 20% of at least 1 great toenail. The PK subset included participants 12-16 years with moderate-to-severe onychomycosis affecting at least 50% of each great toenail and onychomycosis in at least 4 additional toenails. RESULTS: Of 62 enrolled participants, 60 were included in the safety population and 17 in the PK population. Efinaconazole 10% topical solution was well tolerated. The concentration-time profiles for efinaconazole and its major metabolite were relatively stable, with only minor fluctuations during the 24-hour dosing interval. Systemic exposure to efinaconazole was low. By week 52, 65.0% of participants achieved mycologic cure, with a 36.7% mycologic cure rate observed as early as week 12. A total of 40.0% of participants achieved complete cure, 50.0% achieved clinical efficacy, and 88.3% achieved fungal cure by week 52. CONCLUSION: Efinaconazole was safe and efficacious in pediatric participants with mild-to-severe onychomycosis, with improved mycologic cure and complete cure rates compared with adults from two 52-week studies. J Drugs Dermatol. 2020;19(9):867-872. doi:10.36849/JDD.2020.5401.

High prevalence of mixed infections in global onychomycosis.

Onychomycosis is estimated at a prevalence of 10% worldwide with the infecting organism most commonly Trichophyton rubrum (T. rubrum). Traditional culture identification of causative organisms has inherent risks of overestimating dermatophytes, like T. rubrum, by inhibiting the growth of possible nondermatophyte mould (NDM) environmental contaminants which could be causative agents. Recently, molecular methods have revealed that a proportion of onychomycosis cases in North America may be caused by mixed infections of T. rubrum as an agent co-infecting with one or more NDM. Determining the global burden of mixed infections is a necessary step to evaluating the best therapies for this difficult-to-treat disease. To determine the prevalence of mixed infections in a global population, nail samples from onychomycosis patients in Brazil, Canada, and Israel (n = 216) were analyzed by molecular methods for the presence of dermatophytes and five NDMs. If an NDM was detected, repeat sampling was performed to confirm the NDM. T. rubrum was detected in 98% (211/216) of infections with 39% mixed (84/216). The infection type was more likely to be mixed in samples from Brazil, but more likely to be a dermatophyte in samples from Canada and Israel (Χ2 = 16.92, df = 2, P<0.001). The most common cause of onychomycosis was T. rubrum. In all countries (Brazil, Canada and Israel combined) the prevalence of dermatophyte (Χ2 = 211.15, df = 3, P<0.001) and mixed (dermatophyte and NDM; Χ2 = 166.38, df = 3, P<0.001) infection increased with patient age. Our data suggest that mixed infection onychomycosis is more prevalent than previously reported with the aging population being at increased risk for mixed infections.

Prospective, comparative evaluation of a deep neural network and dermoscopy in the diagnosis of onychomycosis.

BACKGROUND: Onychomycosis is the most common nail disorder and is associated with diagnostic challenges. Emerging non-invasive, real-time techniques such as dermoscopy and deep convolutional neural networks have been proposed for the diagnosis of this condition. However, comparative studies of the two tools in the diagnosis of onychomycosis have not previously been conducted. OBJECTIVES: This study evaluated the diagnostic abilities of a deep neural network (http://nail.modelderm.com) and dermoscopic examination in patients with onychomycosis. METHODS: A prospective observational study was performed in patients presenting with dystrophic features in the toenails. Clinical photographs were taken by research assistants, and the ground truth was determined either by direct microscopy using the potassium hydroxide test or by fungal culture. Five board-certified dermatologists determined a diagnosis of onychomycosis using the clinical photographs. The diagnosis was also made using the algorithm and dermoscopic examination. RESULTS: A total of 90 patients (mean age, 55.3; male, 43.3%) assessed between September 2018 and July 2019 were included in the analysis. The detection of onychomycosis using the algorithm (AUC, 0.751; 95% CI, 0.646-0.856) and that by dermoscopy (AUC, 0.755; 95% CI, 0.654-0.855) were seen to be comparable (Delong's test; P = 0.952). The sensitivity and specificity of the algorithm at the operating point were 70.2% and 72.7%, respectively. The sensitivity and specificity of diagnosis by the five dermatologists were 73.0% and 49.7%, respectively. The Youden index of the algorithm (0.429) was also comparable to that of the dermatologists' diagnosis (0.230±0.176; Wilcoxon rank-sum test; P = 0.667). CONCLUSIONS: As a standalone method, the algorithm analyzed photographs taken by non-physician and showed comparable accuracy for the diagnosis of onychomycosis to that made by experienced dermatologists and by dermoscopic examination. Large sample size and world-wide, multicentered studies should be investigated to prove the performance of the algorithm.

Use of MALDI-TOF MS for fungal species distribution of interdigital intertrigo in seafarers, Dakar, Senegal.

To determine fungal species distribution of interdigital intertrigo among seafarers in Dakar, Senegal, a cross-sectional study was carried out from May to August 2017 among seafarers clinically diagnosed with interdigital intertrigo. A questionnaire was filled to each patient before sampling the affected folds and transporting to Aristide Le Dantec University Hospital where mycological analyses were realized. Species identification by MALDI-TOF MS was performed in Marseille, France. In total, 169 men (21-66 years) were included. Few of them (3%) had a high level of education and the duration of the mycosis exceed 10 years for 88% of patients. Direct microscopic examination (ME) was positive in 34.3%. Among samples with positive ME, 58.6% had positive culture. An overall incidence of 30.2% was found. Patients with confirmed cases aged between 28 and 66 years. Among them, those between 36-50 years were predominant (52.9%). Those with a high level of education were less representative (2%). For 52.1% of patients, the duration of the mycosis was superior to 10 years. Furthermore, 57% of cases were significantly associated with other types of tinea pedis and/or onychomycosis (P=0.03). Culture was positive in 23.7% isolating 43 strains successfully identified at the species level by MALDI-TOF MS for 31 isolates: 20 Candida and 11 dermatophytes. The rest was identified only at the genus level belonged to Fusarium. In definitive, MALDI-TOF MS could be a useful tool for routine and fast identification of dermatophytes, yeasts and NDFF in clinical mycology laboratories.

Case of cutaneous botryomycosis in an 8-year-old immunocompetent boy with a review of the published work.

Botryomycosis is a rare chronic suppurative granulomatous infection caused by several genera of non-filamentous bacteria. The clinical and histopathological findings are similar to those of mycetoma caused by true fungi or aerobic actinomycetes. Botryomycosis is divided into cutaneous and visceral disease, with the cutaneous form being more common. Histopathology shows granules of etiologic bacteria called "sulfur granules". Botryomycosis occurs more commonly among immunocompromised patients, although some cases have also been reported in immunocompetent patients. We report the case of an 8-year-old immunocompetent boy who visited our hospital with a 4-mm diameter subcutaneous tumor with mild tenderness on his right heel for several months. We surgically removed the tumor with an initial diagnosis of epidermal cyst. Histopathology showed sulfur granules surrounded by an eosinophilic matrix, indicating the Splendore-Hoeppli phenomenon. The granules consisted of Gram-positive cocci, leading to a diagnosis of botryomycosis. The patient was successfully treated by excision and oral trimethoprim/sulfamethoxazole (240 mg b.i.d.) for 2 weeks as adjuvant therapy. No recurrence was noted following treatment. The subcutaneous tumor in this case was smaller than the typical in botryomycosis infections. We reviewed the infection duration and tumor size in reported cases of botryomycosis in immunocompetent patients. Small tumor size may suggest that the case is in an early stage; therefore, it is important to remove and investigate these lesions proactively.

Onychomycosis, the Active Invasion of a Normal Nail Unit by a Dermatophytic Versus the Colonization of an Existing Abnormal Nail Unit by Environmental Fungus.

Onychomycosis was described by early investigators as the presence of an abnormal nail unit and a member of the order Mycota, producing the abnormality. This interpretation has caused more than 50 years of confusion in the dermatologic literature. Unquestionably, the clinician sees more abnormal toenails than fingernails, and investigators have described a multitude of fungi as the cause of the clinically abnormal toenail. In 2010, developmental scientists proved, what we have long recognized, that there is no bilateral symmetry in living organisms and, therefore, one sole is different from the other. This causes a gait asymmetry, coupled with the pressure the closed shoe exerts on toenails while walking. This produces a series of abnormalities, which are clinically identical to what has been described for dermatophytic onychomycosis. These are fungus free and result in toenail niches. These toenail abnormalities were recently described as the asymmetric gait nail unit syndrome (AGNUS). It is possible that environmental fungi can colonize these toenail niches and, therefore, were described by investigators as a new onychomycosis entity In the normal host, onychomycosis should be only used to describe the active invasion of the nail bed (NB) corneocytes by a dermatophyte, as seen in dermatophytic onychomycosis. Dermatophytes only affect those hosts who have inherited the dermatophytosis susceptibility gene, transmitted as an autosomal dominant trait. In studies encompassing 3,000 abnormal toenails, only 27%-30% were found as dermatophyte culture positive, 25% were negative and the rest environmental fungi were recovered.

The foot microbiome.

BACKGROUND: The human skin microbiome is represented by bacteria, fungi, viruses, and mites. AIMS: Every human being possess their own unique skin microbiome because intrinsic and environmental factors have a significant impact on the quality and quantity of microorganism. Every site of the body is a separate microbial niche. PATIENTS: The feet are one of the most unique and heterogeneous microbial niches of human body with areas that differ by skin thickness, anatomical features, distribution of sweat glands, pH, and the availability of oxygen. RESULTS: Healthy skin of the foot is inhabited by Corynebacteriaceae, Micrococcaceae, Propionibacteriaceae, Actinobacteria, Clostridiales, Lactobacillaceae, Streptococcaceae, Enterobacteriaceae, Moravellaceae, Neisseriaceae, Pastereullaceae, and Proteobacteria. The most common fungi present on the feet are Malassezzia, Cryptococcus, Aspergillus, Rhodotorula, Epicoccum, Saccharomyces, Candida, Epidermophyton Microsporum, and Trichophyton. CONCLUSIONS: The disturbance of the foot microbiome causes dysbiosis and may lead to pitted keratolysis, fungal, and viral infections or even to protothecosis.