Safety and efficacy of new generation azole antifungals in the management of recalcitrant superficial fungal infections and onychomycosis.

INTRODUCTION: Terbinafine is considered the gold standard for treating skin fungal infections and onychomycosis. However, recent reports suggest that dermatophytes are developing resistance to terbinafine and the other traditional antifungal agents, itraconazole and fluconazole. When there is resistance to terbinafine, itraconazole or fluconazole, or when these agents cannot used, for example, due to potential drug interactions with the patient's current medications, clinicians may need to consider off-label use of new generation azoles, such as voriconazole, posaconazole, fosravuconazole, or oteseconazole. It is essential to emphasize that we do not advocate the use of newer generation azoles unless traditional agents such as terbinafine, itraconazole, or fluconazole have been thoroughly evaluated as first-line therapies. AREAS COVERED: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals. EXPERT OPINION: Antifungal stewardship should be the top priority when prescribing new-generation azoles. First-line antifungal therapy is terbinafine and itraconazole. Fluconazole is a consideration but is generally less effective and its use may be off-label in many countries. For difficult-to-treat skin fungal infections and onychomycosis, that have failed terbinafine, itraconazole and fluconazole, we propose consideration of off-label voriconazole or posaconazole.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Effect of the Intralesional Forms of Methylprednisolone Acetate and Methotrexate on Psoriatic Nails.

Individuals with psoriatic nails often have a lower quality of life relative to their counterparts with healthy nails. Methotrexate (MTX), an anti-neoplastic agent, is a longstanding treatment option for nail psoriasis. In the current study, we compared the effects of MTX to that of a corticosteroid, namely, methylprednisolone acetate (i.e., Depo-Medrol®) across individuals with nail psoriasis. We used a cohort study design, and both agents were administered intralesionally. Outcome variables were based on the Nail Psoriasis Severity Index (NAPSI). We quantified the effect in terms of change in NAPSI, complete cure at week 16, and cure between 32 and 36 weeks. Our regressions demonstrated that reduced NAPSI scores with Depo-Medrol were, on average, greater than that with MTX by 2.27 (n = 48, P = 0.000255) at week 16. Similarly, the odds of complete cure at week 16 was greater with Depo-Medrol® than with MTX (odds ratio = 18.6, P < 0.0001). In terms of both complete cure and change in NAPSI, Depo-Medrol® was significantly more effective than MTX at a follow-up period of 32-36 weeks. Our study established that intralesional Depo-Medrol® is more effective than intralesional methotrexate for treating nail psoriasis.

Efficacy and safety of low-dose oral minoxidil in the management of androgenetic alopecia.

INTRODUCTION: Treating alopecia can be challenging. The available treatments are topical minoxidil, low-dose oral minoxidil (LDOM), and 5-α reductase inhibitors like finasteride and dutasteride. Only topical minoxidil and finasteride 1 mg daily are FDA-approved, while the rest are used off-label. Recent research has suggested that oral minoxidil may be a safe and effective treatment for both female androgenetic alopecia (female AGA) and male androgenetic alopecia (male AGA). AREAS COVERED: In this review, we explore the pharmacokinetics, mechanism of action, safety, and efficacy of oral minoxidil. Additionally, we discuss its effectiveness compared to other treatments available for female AGA and male AGA. EXPERT OPINION: LDOM has demonstrated a favorable efficacy and safety profile in several trials. Subsequently, its use for the treatment of male AGA and female AGA is increasing. However, its use remains off-label, and through increased usage, we will get a better idea of the best dosage and monitoring guidelines. LDOM has also been used with some effectiveness in other forms of hair loss.

SNG100, a novel topical treatment for moderate atopic dermatitis, in patients aged 6 years or older: A randomised, double-blind, active-controlled trial.

Background: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. It is associated with significant itch and impaired quality of life. Systemic treatments are efficient but associated with side effects. Novel topical treatments with a favourable safety profile are needed. SNG100 is a novel composition of hydrocortisone 1% in a cream base comprising sulphated polysaccharide (SPS; extracted from in-house cultivated Porphyridium Cruentum unicellular algae), a well-known hydrating, moisturising and a skin barrier repairing agent. Objectives: To assess the safety, usability and efficacy of SNG100 cream in patients aged ≥6 years with moderate AD. Methods: In this proof of concept phase I, double-blind, randomised trial, participants received one of three treatments for 14 days: SNG100 twice daily (BID), hydrocortisone 1% BID or mometasone furoate once daily (QD). The primary endpoint was the safety and tolerability of SNG100 cream compared to hydrocortisone 1% and mometasone furoate. The secondary endpoint was the subject's usability of SNG100. Exploratory efficacy endpoints included percent change from baseline in SCOring AD (SCORAD), Eczema Area and Severity Index, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, pruritus Numerical Rating Score (NRS), peak pruritus-NRS and Investigator's Global Assessment. Subjects were also followed up without any treatment for additional 14 days. Results: Overall, 66 participants were screened, and 60 patients were randomised. SNG100 demonstrated a high safety profile, similar to marketed products hydrocortisone 1% and mometasone furoate 0.1%, with no unanticipated drug safety related events. SNG100 and mometasone furoate 0.1% cream achieved almost similar and statistically significant greater percentage reductions from baseline in SCORAD as compared to hydrocortisone 1% cream. SNG100 demonstrated significant improvement in NRS as compared to hydrocortisone 1% cream. Remarkably, SNG100 led to a lasting effect with only 29.4% of subjects returning to IGA3 during the follow-up period compared to 50% and 38.9% in the hydrocortisone 1% and in mometasone furoate treatment arms, respectively. Conclusions: Topical SNG100 is an effective, safe, and well-tolerated innovative treatment for moderate AD. Trial registration number: NCT04615962 (Topical Cream SNG100 for Treatment in Moderate AD Subjects).

Age of onset defines two distinct profiles of atopic dermatitis in adults.

BACKGROUND: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. METHODS: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. RESULTS: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects. CONCLUSION: Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.

The Role of Histological Examination of Nail Clipping in the Diagnosis of Onychomycosis.

BACKGROUND: Diagnosis of onychomycosis is based on potassium hydroxide (KOH), direct smear, culture, and polymerase chain reaction. Nail clippings are rarely used as a diagnostic tool. OBJECTIVES: To evaluate nail clippings for the diagnosis of onychomycosis and to compare it to KOH smears. METHODS: Nail clipping specimens of 39 patients were collected: 34 with onychomycosis proved by positive culture and 5 from normal nails. The specimens were submitted to histological processing and then stained with periodic acid-Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) stains. For each nail, KOH smear was also performed. Two pathologists who had no information on the KOH smear and the culture results evaluated the nail clipping histology for the presence of fungal element. Their assessment was compared to the KOH smear and culture results. RESULTS: Of the 34 specimens that had positive culture, 25 were dermatophytes, 5 were molds, and 4 were candida. Clipping specimens were positive in 30 cases (88%): 23/25 dermatophyte, 4/5 molds, and 3/4 candida. Pathologists were able to classify the pathogens into dermatophytes and non-dermatophytes based on the morphology. PAS stain results were the same as GMS in evaluation of the nail specimen. KOH smear was positive in 29 nails (85%): 20/25 dermatophytes, all 5 molds, and 4 candida. In all five nails where the culture was negative, both clipping and KOH smear did not show fungal elements. CONCLUSIONS: Nail clippings can serve as a rapid, inexpensive, and reliable method for evaluation of onychomycosis, comparable to KOH smear, with the advantage of pathogen group identification.

Tinea capitis caused by Trichophyton tonsurans among adults: Clinical characteristics and treatment response.

BACKGROUND: Trichophyton tonsurans tinea capitis has become a growing epidemiological concern. Yet, its clinical manifestations and treatment response, specifically among adults, have only been described among small sample size studies. OBJECTIVE: To assess clinical manifestations and treatment outcome of T. tonsurans tinea capitis among adults. PATIENTS AND METHODS: A retrospective cohort study was carried out among 111 adults with T. tonsurans tinea capitis. Diagnosis was confirmed by fungal culture or polymerase chain reaction. Examinees' demographics, disease characteristics and treatment response were measured. The risk factors for the treatment failure were evaluated. RESULTS: The mean age was 20.1 years (±3.1), with men (98.2%) outnumbering women. The follow-up lasted 12.2 months (±5.6). The majority of T. tonsurans tinea capitis was seen in the occipital area (87.6%). In 78.9% of the cases, the scalp manifestation was non-inflammatory (scaly plaques and papules:76.1% and seborrhoea-like: 2.8%). 21.1% of cases presented with inflammatory tinea capitis (21.1%; Kerion: 10.1% and pustular: 11%). Concomitant involvement of other than scalp areas was common: tinea corporis was seen in 38.7% of the cases; tinea faciei and barbae in 24.3%; nape and anterior neck in 76.6% and 2.7% of the cases, respectively. An adequate treatment course with oral terbinafine resulted in 83.2% clinical cure rate. Treatment failure was significantly associated with concomitant tinea corporis (odds ratio 3.9; 95% confidence interval 1.3-12.1, p-Value< .02). CONCLUSION: The most common clinical presentation of T. tonsurans tinea capitis included occipital scaly plaques and papules with concomitant non-scalp lesions. Oral terbinafine was found to be highly effective. Concomitant tinea corporis increased the risk for treatment failure.

Low-Dose Oral Minoxidil for Alopecia: A Comprehensive Review.

Low-dose oral minoxidil (LDOM) has demonstrated a promising safety and efficacy profile in the treatment of various hair disorders, including male androgenetic alopecia (AGA) and female-pattern hair loss (FPHL); however, it lacks FDA approval. The usual LDOM starting dose for male AGA is 1-5 mg/day, depending on physician preference and the patient's condition. For FPHL, it is 0.5-1 mg/day. The maximum dose is generally 5 mg/day. If patients respond well without major side effects, the dose may be gradually increased since the LDOM's efficacy appears to be dose-dependent. Patients may use LDOM long term if the treatment outcome is satisfactory. The common side effects of LDOM are hypertrichosis and cardiovascular symptoms. Females are more prone to hypertrichosis than males. The side effects of LDOM can be categorized as (a) dose-dependent type A side effects (hypertrichosis and cardiovascular symptoms) and (b) idiosyncratic type B side effects (pericardial effusion). Minoxidil acts via multiple pathways. Although minoxidil has a relatively short half-life of around 4 h, its hypotensive effect may last approximately 72 h. Effective treatments for alopecia are limited. Therefore, LDOM could be an important addition to the available therapies for managing some hair disorders, including AGA.

Diagnostic approach to tinea capitis with kerion: A retrospective study.

BACKGROUND: Kerion is an inflammatory type of tinea capitis manifesting as boggy crusted nodules. Diagnosis of kerion is often challenging due to high rates of false-negative mycological samples. METHODS: A retrospective study among children with kerion, prior to antifungal treatment, was conducted to assess rates of false-negative mycological samples. Specimens for direct microscopy and fungal culture were collected at baseline and after administration of an oral antibiotic course, with or without an oral steroid course. Kerion was categorized as highly inflammatory when a painful, moist scalp nodule with spontaneous purulent discharge or exuberant crust was present, or mildly inflammatory when an erythematous, dry scalp nodule was seen. RESULTS: Twenty-three children (mean age 7.9 ± 3.0 years) were included in the study. Trichophyton tonsurans was the most common species isolated (69.6%). Highly inflammatory kerions were significantly more likely to be culture negative before treatment than mildly inflammatory kerions (80% vs. 16.7%, p < .01). Non-inflammatory tinea capitis lesions (n = 13) were culture positive in all cases. Following a combined oral antibiotic and steroid course given to most highly inflammatory kerions (n = 11/13), higher rates of positive fungal cultures were found compared to baseline (90.9% vs. 18.2%, p < .01). CONCLUSION: High rates of negative fungal cultures were found only in highly inflammatory kerion. Sampling a highly inflammatory kerion after a combined oral antibiotic and steroid course improved rates of positive fungal cultures. In addition, sampling of non-inflammatory tinea capitis lesions (when present in addition to the kerion) had the highest culture sensitivity.

Efficacy of Fluocinonide\Bifonazole Cream for the Treatment of Trachyonychia: A Retrospective Case Series.

Background: Trachyonychia is a benign nail condition, most commonly seen in children. Trachyonychia manifests as excessive longitudinal ridging, nail roughness, and nail brittleness. Treatment is sought mainly for esthetic reasons as well as functional reasons. A number of therapeutic approaches exist, mainly based on case reports or small non-comparative case series. Aims: To report treatment outcome among patients with trachyonychia. Methods: A retrospective case-series study was conducted among patients who were treated trachyonychia between years 2017 and 2020. Patients were prescribed fluocinonide 0.05% with bifonazole 1% cream, applied with or without occlusion, and methylprednisolone 1-2 mg/nail, injected into the involved nail matrix, or oral cyclosporine 3 mg/kg. Complete response (over 90% improvement) and partial response (over 50% improvement) were assessed. Results: A total of 43 patients with trachyonychia were included [mean age 10.0 years (±5.7), 69.8% males, mean disease duration 4.7 years (±3.0)]. In 90.7% of the cases, topical fluocinonide\bifonazole cream was prescribed. Under-occlusion topical application was found to be highly effective, achieving complete response in 35.3% and partial response in an additional 52.9% of the patients. Occluded application was also found to be significantly more effective than non-occluded application. Treatment efficacy was not affected by the severity of nail roughness, trachyonychia morphology, or whether trachyonychia was idiopathic or coexisted with other dermatological conditions. Conclusion: Occluded application of fluocinonide plus bifonazole cream is efficient for the treatment of trachyonychia and should be considered a first line of treatment.

Management of tinea capitis in Israel: A comparative study.

BACKGROUND: Tinea capitis is a common fungal infection in Israel, most commonly caused by the dermatophyte Trichophyton tonsurans. OBJECTIVES: To investigate the effectiveness of oral antifungal monotherapy in producing clinical or complete cure. We also evaluated the impact of topical therapy (bifonazole 1% shampoo and/or betamethasone valerate 0.1% solution), prior to oral treatment, on patients' likelihood of clinical or complete cure. METHODS: A retrospective chart review was conducted. Patients with mycologically confirmed tinea capitis were treated with one of four regimens: (1) terbinafine (greater than 40 kg: 250 mg/day, 20 to 40 kg: 125 mg/day, less than 20 kg: 62.5 mg/day), (2) itraconazole 5 mg/kg daily, (3) fluconazole 6 mg/kg daily, or (4) griseofulvin 20 mg/kg daily. We used generalized linear models (GLM) to determine whether there was a significant association between the odds of cure and choice of treatment. RESULTS: The causative species was Trichophyton tonsurans in all but 6 cases that grew T violaceum. For pediatric patients, the odds of having complete or clinical cure within 6 weeks was greater if they used terbinafine compared to itraconazole, fluconazole, or griseofulvin (odds ratio [OR] = 9.06, P = .047). The likelihood of complete or clinical cure within 8 weeks of oral therapy was lower if topical steroids were previously used compared to if topical antifungals were used prior to systemic treatment (OR = 0.29, P = .046). CONCLUSIONS: Our findings substantiate prior literature demonstrating that terbinafine is non-inferior to griseofulvin, itraconazole, and fluconazole in the therapy of pediatric tinea capitis caused by T tonsurans.

Low-dose isotretinoin versus minocycline in the treatment of rosacea.

Rosacea is a common inflammatory facial skin condition affecting the adult population. Its papulopustular subtype is mainly treated pharmacologically by topical and oral antibiotics. For severe or antibiotics-recalcitrant disease, daily low-dose isotretinoin has also been reported to be effective. However, no previous study has assessed the efficacy of once-weekly administered isotretinoin for papulopustular rosacea. For this purpose, a retrospective comparative study was conducted. For severe rosacea, 40 mg/week isotretinoin (24 patients) was administered. For mild to moderate rosacea, once-weekly 20 mg/week isotretinoin (28 patients) was compared with 100 mg/day minocycline (24 patients). Treatment courses lasted 4 to 7 months. Forty milligrams per week isotretinoin was highly effective for severe rosacea, achieving complete response (over 90% improvement) in 62.5% of patients and partial response (50%-90% improvement) in additional 29.2% of patients. Twenty milligrams per week isotretinoin and hundred milligrams per day minocycline showed comparable efficacy for mild to moderate rosacea (complete response of 10.7% vs 8.3% and partial response of 28.6% vs 33.3%, respectively). This study demonstrates that that the use of a weekly low-dose isotretinoin is an effective treatment for papulopustular rosacea, including among patients with severe disease.

Continuous terbinafine and pulse itraconazole for the treatment of non-dermatophyte mold toenail onychomycosis.

INTRODUCTION: Although dermatophytes are considered the predominant causative organisms in onychomycosis, non-dermatophyte mold (NDM) infections may be more prevalent than originally thought and may be more difficult to treat. There are limited data of oral antifungal efficacy in treating NDM onychomycosis. METHOD: A retrospective chart review (2009-2016) was conducted in patients receiving continuous oral terbinafine or pulse itraconazole for toenail onychomycosis due to NDMs. Mycology results and percent nail affected were recorded with patient characteristics including demographics and concurrent diseases. Complete, clinical, and mycological cure were tabulated. RESULTS: Data from 176 patients were collected. Mycological and complete cure rates for terbinafine (69.8% and 17%) and itraconazole (67.5% and 22%) were not significantly different from each other. Regardless of oral treatment, age (p = .013), baseline severity (p = .016), and presence of atherosclerosis (p = .040) or hyperlipidemia (p = .033) decreased the likelihood of mycological cure, while age decreased the likelihood of complete cure (p = .001). CONCLUSION: Continuous terbinafine and pulse itraconazole were similar in efficacy for curing NDM onychomycosis. Age was the most consistent prognostic factor affecting likelihood of cure, with factors that may influence drug reaching the site of infection also decreasing likelihood of mycological cure.

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.

Once Weekly Application of Urea 40% and Bifonazole 1% Leads to Earlier Nail Removal in Onychomycosis.

INTRODUCTION: Onychomycosis is a chronic nail fungal infection resulting in nail damage and a decreased quality of life. Chemical avulsion of the nail with urea and bifonazole -removes fungally infected debris, increasing antifungal treatment efficacy and penetration. Previous clinical ob-servations describe patients who applied their urea and -bifonazole ointment less frequently, achieving earlier nail removal. In this study, we analyzed the relationship between duration of urea and bifonazole application and time to nail avulsion. METHODS: χ2 tests, multiple regression analysis, and ANOVA were performed to analyze the similarities between treatment regimens (daily, every 3 days, or once a week), association of regimens or patient characteristics to nail removal, and compare time to nail removal between each regimen, respectively. RESULTS: Daily application of ointment and sealing resulted in an average length of time (±SD) to nail removal of 18.7 days (±6.8 days); once every 3 days resulted in nail removal at 12.7 days (±6.2 days) and once per week at 11 days (±4.46 days) (p < 0.001). Age was the only patient factor that affected duration to nail removal. CONCLUSION: Once weekly application of ointment with sealing for a 1-week duration is associated with a decrease in time to complete chemical avulsion of the nail by approximately 1 week.

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.

Cold sub-atmospheric and atmospheric pressure plasma for the treatment of Trichophyton rubrum onychomycosis: An in-vitro study.

Previous studies have suggested the applicability of cold atmospheric pressure plasma for the treatment of onychomycosis. Whether delivering cold plasma in sub-atmospheric pressure would be beneficial for this purpose is yet to be established. The current study aimed to evaluate efficacy of cold sub-atmospheric and atmospheric pressure plasma in Trichophyton rubrum growth inhibition. Bovine nails infected with T. rubrum were treated by a cold air plasma device, which enables utilizing plasma in sub-atmospheric pressures (Low = 100 millibar; High = 300 millibar) or atmospheric pressure. The infected foci were exposed to the plasma source directly or indirectly. Treatment with high sub-atmospheric pressure setting achieved T. rubrum growth reduction of 94.0% and 73.0%, for direct and indirect exposure to the plasma source, respectively (P < .001). Low sub-atmospheric pressure setting achieved similar T. rubrum growth reduction of 86.2% for direct exposure to the plasma source (P < .001), but only marginally significant 58.8% reduction rate for indirect exposure to the plasma source (P = .056). None statistically significant fungal growth reduction was attained with the use of atmospheric pressure setting. Cold plasma was shown to effectively inhibit T. rubrum nail growth, with sub-atmospheric pressure setting achieving better outcome than atmospheric pressure.

Clinical significance of Candida isolation from dystrophic fingernails.

BACKGROUND: Candida onychomycosis mostly involves fingernails. Yet, in contrast to dermatophytes, Candida isolation from dystrophic fingernails does not prove casualty, as sample contamination and non-pathogenic Candida growth occur. Characterising treatment outcome of Candida-positive dystrophic nails is crucial to avoid unnecessary treatment. OBJECTIVE: To investigate predicators associated with treatment outcome among Candida-positive dystrophic fingernails. PATIENTS AND METHODS: A retrospective cohort study was carried out among 108 adults with Candida-positive dystrophic fingernails not cured with adequate systemic anti-fungal course. Diagnosis was based on a single mycological culture. Patients with treatment failure (n = 85; 78.7% of the cases) were compared to patients with partial response (mild to almost cure; n = 23; 21.3% of the cases) at 9 to 12 months following treatment initiation. RESULTS: Treatment failure was significantly associated with primary onycholysis (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.1-7.4) and prolonged dystrophy (12.8 vs. 3.7 years in average), compared to partial treatment response. Non-responders had lower odds to present with distal lateral subungual onychomycosis, compared to partial responders (OR 0.3; 95% CI 0.1-0.7). Demographic and mycological characteristics, as well as number of nails affected, co-presence of paronychia, and treatment regime were not found to be associated with treatment response. CONCLUSION: Candida-positive primary onycholysis was shown to be non-responsive to systemic anti-fungal treatment, suggesting that anti-fungal treatment is not indicated. For other clinical scenarios, high proportions of treatment non-response suggest that determining causality of Candida should not be based on a single positive mycological culture.