Topical Azole Research Articles

Successful Treatment of Seborrheic Dermatitis with Topical Roflumilast: A Case Series

Background: Seborrheic dermatitis (SD) is a common skin disease that presents with pink scaly patches in areas with higher sebaceous gland density, such as the scalp, glabella, retroauricular folds, nasolabial folds, chest, and groin. Case Reports: This is a case series of two patients with longstanding SD that did not respond adequately to topical corticosteroids or azoles, and were successfully treated monotherapy with roflumilast cream 0.3%. Both patients responded within two months and continue to respond to treatment with topical roflumilast monotherapy. Discussion: SD is commonly considered to be caused by Malassezia yeast proliferation and activity, however recent research has revealed that the inflammatory skin disease results from immune dysregulation and skin barrier disruption with Malassezia contributing as an exacerbating factor secondary to the primary pathogenesis. Thus treatment with topical roflumilast, a highly potent phosphodiesterase-4 inhibitor, has been studied and demonstrated to be effective in treating the signs and symptoms of SD. Topical roflumilast 0.3% is formulated as a cream and a foam, with the foam approved for the treatment of SD. These cases demonstrate a successful treatment of patients with longstanding SD with roflumilast cream 0.3%. Conclusion: These cases demonstrate that SD, treated with either roflumilast cream 0.3% or roflumilast foam 0.3% may provide improvement in signs and symptoms of SD.

A cost-effectiveness analysis of the use of oral ibrexafungerp versus fluconazole for acute vulvovaginal candidiasis in the UK NHS primary care service.

Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women's quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care. To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS. A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication. An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio. This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability.

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.

Treatment of Vulvovaginal Candidiasis-An Overview of Guidelines and the Latest Treatment Methods.

Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse treatment regimens are developed; the newest ones include oteseconazole and ibrexafungerp. Here, we focus on the most up-to-date recommendations regarding VVC treatment, as well as novel treatment options. Topical and oral azoles are the drugs of choice in uncomplicated mycosis. The efficacy of probiotics and substances such as TOL-463 and chlorhexidine is indicated as satisfactory; however, there are no relevant guidelines. Although the majority of researchers agree that the treatment of non-albicans VVC should be long-lasting, the recommendations are inconsistent. Another clinical problem is the treatment of VVC with azole intolerance or resistance, for which literature proposes the use of several drugs including oteseconazole, ibrexafungerp, and voriconazole. The treatment schedules for recurrent VVC include mainly fluconazole; however, alternative options such as immunotherapeutic vaccine (NDV-3A) or designed antimicrobial peptides (dAMPs) were also described. We also focused on VVC affecting pregnant women, which is a substantial challenge in clinical practice, also due to the heterogeneous relevant guidelines. Thus far, few precise recommendations are available in the literature. Future studies should focus on atypical VVC forms to elucidate the inconsistent findings.

Modulatory effect of Origanum vulgare essential oil and carvacrol on Malassezia spp. virulence factors.

Malassezia sympodialis and Malassezia furfur are recognized as an important part of the human and animals healthy skin microbiota, but also as an opportunistic fungus due to their association with a broad spectrum of skin and systemic infections. Human skin infections associated with Malassezia spp. are often chronic, recurrent, and topical or oral azole treatments are challenging with not always successful outcomes. A wide inter and intraspecies antifungal susceptibility variability that may suggest a combination of wild-type strains and resistant mutants was reported. The essential oils are complex hydrophobic mixtures of different compounds extracted from plants by distillation and have demonstrated antimicrobial activity. In this study, toxicity in the larvae model and the ability of Origanum vulgare essential oil (OVEO) and carvacrol to inhibit virulence factors such as hydrophobicity, adherence, and biofilm formation of M. sympodialis and M. furfur was evaluated. We have demonstrated the antifungal activity of OVEO and carvacrol against both species. Carvacrol was more active and less toxic than OVEO at low concentrations (< 1mg/ml). Malassezia sympodialis showed a significant decrease in adherence and its ability to form biofilms when OVEO or carvacrol is present. Both Malassezia species showed reduced hydrophobicity in the presence of carvacrol. Further studies will have to be carried out to understand how these substances act, but the inhibition of some virulence factors could represent a new target to overcome the problem of drug resistance.

Ibrexafungerp for the Treatment of Vulvovaginal Candidiasis: Design, Development and Place in Therapy.

Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.

Vulvovaginal candidiasis (VVC): A review of the literature

Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis after bacterial vaginosis. VVC often occurs in women of reproductive age (20-40 years). Risk factors for VVC can be divided into two, such as host factors (pregnancy, hor-mone replacement, uncontrolled diabetes mellitus, immunosuppression, antibiotics, use of glucocorticoids, genetic influences) and behavioral factors (oral contracep-tives, sexual habits, hygiene, and clothes that are used). To diagnose VVC in a per-son, evaluation from anamnesis and clinical manifestation can be conducted. It can also be confirmed by laboratory examination. The management is based on the clas-sification. Uncomplicated VVC is most effectively treated with topical azoles, but a single dose of fluconazole can also be given orally. Treatment of VVC with compli-cations can be given fluconazole 150 mg for 3 days or topical azole for 7 days. However, when the VVC case that caused by non-albicans Candida not responding to conventional treatment such as antimycotics, the amphotericin B can be given to cure the disease. VVC caused by Candida glabrata can be given topical boric acid or flucytosine. This article consists of several theoretical references that have been viewed to have a better understanding of candidiasis vulvovaginitis.

Vulvovaginal candidiasis: Epidemiology, treatment and prevention strategies

Vulvovaginal candidiasis (VVC) is a commonly encountered clinical condition. At least three-fourth women experience one episode of VVC in their lifetime. In India, the prevalence of VVC is 10 to 35%. Laboratory methods often supplement clinical diagnosis. VVC should be confirmed with culture and other investigative techniques, especially in complicated and recurrent cases. Topical and intravaginal azoles remain the mainstay of therapy. In women who have predisposing risk factors or develop recurrent VVC, oral antifungal agents are used. Topical steroids may be used in women having vulvar symptoms along with pruritus. Pregnancy is a significant risk factor. Intravaginal azoles remain the standard of treatment and can be offered from the second trimester onwards. The emergence of non-albicans species has caused difficulties in the management of VVCs. Thus, all women with vaginal discharge should be correctly diagnosed to tailor the therapy.

Review on Antifungal Agents

The four main classes of antifungal drugs are the polyenes, Azoles, allylamines and echinocandins. Clinically useful “older” agents include topical azole Formulations (for superficial yeast and dermatophyte Infections), first-generation triazoles (fluconazole and Itraconazole, for a range of superficial and invasive fungal Infections), amphotericin B formulations (for a broad range of Invasive fungal infections) and terbinafine (for dermatophyte Infections). Clinically important “newer” agents include members of the Echinocandin class (eg, caspofungin) and second-generation Triazoles (eg, voriconazole and posaconazole). Voriconazole and posaconazole have broad-spectrum activity Against yeasts and moulds, including Aspergillus species. Posaconazole is the only azole drug with activity against Zygomycete fungi. Caspofungin and the other echinocandins are effective in Treating Candida and Aspergillus infections. The azoles are relatively safe, but clinicians should be aware Of drug–drug interactions and adverse effects, including Visual disturbances (with voriconazole), elevations in liver Transaminase levels, and skin rashes. Caspofungin has Minimal adverse effects. Combination antifungal therapy may be appropriate in Selected patients with invasive fungal infections, but is Empiric and driven by individual physician practice. Clinical needs for novel antifungal agents have altered.

Treatment Approach for Superficial Dermatophytosis Infections and Factors Contributing for Noncompliance to Antifungal Therapy in India

Background: The prevalence of superficial dermatophytosis has ascended in India over the past 6–7 years. Chronic, recurrent, and steroid-modified tinea with nonresponse to the conventional treatment regimens are being commonly reported. This can be attributed to a complex interplay of factors related to environment, host, and virulence of the organism and a rampant use of topical corticosteroid, antifungal, antibacterial, and irrational combination creams. Host factors such as living conditions, immunity, poor adherence to general measures, and non-compliance to treatment may affect the spread of infection and clinical presentation. Objective: The objective of this study was to understand the prevailing treatment approach for superficial dermatophytosis in India and the host factors contributing to noncompliance to antifungal therapy. Materials and Methods: This was a cross-sectional qualitative knowledge, attitude, and practice study conducted with 220 dermatologists who participated in DERMACON national conference held at Kochi in 2018. Results: Of the 220 dermatologists, 87.3% stated that there was a rise of tinea fungal infection clinical cases in India. About, 42.3% reported that recalcitrant tinea infection attributed to 10%–30% of increase in the number of clinical cases per week. The treatment of choice for superficial dermatophytosis, as per majority of the surveyed dermatologists is a combination of oral azole and topical azole. For recalcitrant fungal infections, 37.3% of the dermatologists stated that at least 4 weeks of antifungal therapy would be the optimal duration for new tinea cases. Overall, 30%–50% of the patients were noncompliant to the prescribed treatment as per 35.5% of the dermatologists. Almost all (97.7%) dermatologists agreed that there is a need for treatment consensus on treating superficial fungal infection. Conclusion: Majority of the dermatologists agreed that there is an increase in the prevalence of superficial dermatophytosis in India. Appropriate use of oral (optimal dosage) and topical antifungals are considered vital for the successful management of this infection. Appropriate use of topical and systemic antifungal agents for the right duration along with proper counseling is considered vital for the successful management of this infection.

Systematic Review and Meta-analysis on Synthetic Antifungal versus Keratolytic Agents for Topical Treatment of Pityriasis Versicolor

Background. Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malasseziafurfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking.Objectives. To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review.Methods. We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www.isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. Results. We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole,bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. Conclusion. It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance andoccurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.

Expert opinion on current and emerging treatments in dermatophytosis

&lt;p class="abstract"&gt;Dermatophytosis continues to be a worldwide public health problem, predominantly in developing countries like India. Early diagnosis and appropriate management are imperative to enhance patient outcomes and improve quality of life of individuals with dermatophytosis. Multiple focused group discussions involving 76 dermatologists across 36 cities in India were conducted to provide a consensus clinical viewpoint of expert dermatologists to gain insights toward effective diagnosis and management of Indian subjects with dermatophytosis. These discussions mainly aimed at reviewing current literature on prevalence, etiology, diagnosis and management of dermatophytosis and highlighting variations in diagnostic and treatment approaches in routine clinical practice. The current article summarizes the experts’ clinical viewpoint on overall management of dermatophytosis. Diagnosis of dermatophytosis involves clinical observation, microscopic examination and dermoscopy. Molecular techniques have certain advantages over conventional microscopy and culture methods but are associated with issues of cost and technique complexity. Oral itraconazole 200 mg–400 mg daily and terbinafine 500 mg/day could be considered for recalcitrant tinea infections. Topical azoles like luliconazole, sertaconazole, and terbinafine could be beneficial. A combination of oral and topical antifungal drugs is effective in patients with steroid-modified and difficult-to-treat tinea infections. Also, patient counselling and use of adjunctive therapies like antihistamines, retinoids, and moisturizers are essential for managing tinea infections. &lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Review on Antifungal Agents

There are so many type of daisies are founded because of ‘Fungal’ such daisies given in follow. also the treatment on this particular daisies with the help of ‘Anti-fungal’ drug or anti- fungal agent and anti-fungal medication as follows The four main classes of antifungal drugs are the polyenes, Azoles, allylamines and echinocandins. Clinically useful “older” agents include topical azole Formulations (for superficial yeast and dermatophyte Infections), first-generation triazoles (fluconazole and Itraconazole, for a range of superficial and invasive fungal Infections), amphotericin B formulations (for a broad range of Invasive fungal infections) and terbinafine (for dermatophyte Infections). Clinically important “newer” agents include members of the Echinocandin class (eg, caspofungin) and second-generation Triazoles (eg, voriconazole and posaconazole). Voriconazole and posaconazole have broad-spectrum activity Against yeasts and moulds, including Aspergillus species. Posaconazole is the only azole drug with activity against Zygomycete fungi. Caspofungin and the other echinocandins are effective in Treating Candida and Aspergillus infections. The azoles are relatively safe, but clinicians should be aware of drug–drug interactions and adverse effects, including Visual disturbances (with voriconazole), elevations in liver Transaminase levels, and skin rashes. Caspofungin has Minimal adverse effects. Combination antifungal therapy may be appropriate in Selected patients with invasive fungal infections, but is Empiric and driven by individual physician practice. Clinical needs for novel antifungal agents have altered

How does clotrimazole compare with other topical azole treatments for people with otomycosis?

How does clotrimazole compare with other topical azole treatments for people with otomycosis?

Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran

BackgroundBleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations. MethodsUsing nationwide Danish registers, we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban, or dabigatran from 2012-2018. We investigated associations between bleeding incidents and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). ResultsWe included 32,340 (36%), 32,409 (36%), and 24,940 (28%) patients initiated on apixaban, rivaroxaban, and dabigatran, respectively. Patients on apixaban were older (median age: 77 years; interquartile range [IQR] 70-84) compared with rivaroxaban users (median age: 75 years; IQR 68-82) and patients on dabigatran (median age: 73 years; IQR 66-80). Apixaban users had a significantly increased risk of bleeding following exposure to systemic fluconazole: odds ratio (OR) 3.5; 95% confidence interval (CI), 1.4-10.6. No increased risk was found among rivaroxaban and dabigatran users: ORs of 0.9 (95% CI, 0.2-3.0) and 1.7 (95% CI, 0.5-5.6), respectively. As to bleeding risk pertaining to topical azole exposure among apixaban, rivaroxaban, and dabigatran users, no association was found, with corresponding ORs of 0.8 (95% CI, 0.5-1.3); 1.3 (95% CI, 0.9-2.1); and 1.2 (95% CI 0.8-1.8), respectively. ConclusionIn patients with atrial fibrillation on either apixaban, rivaroxaban, or dabigatran, an association between an elevated bleeding risk and use of systemic fluconazole was found among patients on apixaban. We found no increased risk of bleeding following co-exposure to topical azoles.

Treatment of vulvovaginal candidiasis in preparation programs for in vitro fertilization

Vulvovaginal candidiasis (VVC) is considered as the second most common cause of vaginitis after bacterial vaginosis. About three quarters of women of reproductive age have a history of at least one episode of VVC, and about a half of women have two or more episodes. Candida albicans is responsible for85% to 90% of vulvovaginal candidiasis. There are uncomplicated and complicated forms of VVC. Uncomplicated forms are not severe cases caused by C. albicans. Complicated forms are cases caused by other Candida species, severe cases, cases that develop during pregnancy or associated with other diseases such as diabetes mellitus or immunosuppressive conditions. Reccurent cases are also complicated ones. Therapeutic schemes should depend on the form of the VVC. Short-term topical therapy or a single oral dose are effective in 90% of uncomplicated cases. Complicated forms of VVC require longer treatment. Oral fluconazole can be administered three times with a break of 72 hours. Topical azoles can be administered daily for at least 1 week. So, sertaconazole in the form of suppositories is used once intravaginally. The data on the use of probiotics in the treatment of VVC today are contradictory and heterogeneous. Treatment of VVC during pregnancy, especially in the first trimester, may be associated with adverse perinatal outcomes. On the other hand, during pregnancy, VVC can be more severe than in non-pregnant women, especially in the second half of pregnancy. In addition, the risk of transmission to a newborn is about 50%. Thus, the identification and treatment of VVC is one of the important tasks in pregnancy planning, including assisted reproduction.

Topical azole treatments for otomycosis.

Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. To evaluate the benefits and harms of topical azole treatments for otomycosis. The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.

A High Rate of Recurrent Vulvovaginal Candidiasis and Therapeutic Failure of Azole Derivatives Among Iranian Women.

Recurrent vulvovaginal candidiasis (RVVC) is one of the most prevalent fungal infections in humans, especially in developing countries; however, it is underestimated and regarded as an easy-to-treat condition. RVVC may be caused by dysbiosis of the microbiome and other host-, pathogen-, and antifungal drug-related factors. Although multiple studies on host-related factors affecting the outcome have been conducted, such studies on Candida-derived factors and their association with RVVC are lacking. Thus, fluconazole-tolerant (FLZT) isolates may cause fluconazole therapeutic failure (FTF), but this concept has not been assessed in the context of Candida-associated vaginitis. Iran is among the countries with the highest burden of RVVC; however, comprehensive studies detailing the clinical and microbiological features of this complication are scarce. Therefore, we conducted a 1-year prospective study with the aim to determine the RVVC burden among women referred to a gynecology hospital in Tehran, the association of the previous exposure to clotrimazole and fluconazole with the emergence of FLZT and fluconazole-resistant (FLZR) Candida isolates, and the relevance of these phenotypes to FTF. The results indicated that about 53% of the patients (43/81) experienced RVVC. Candida albicans and C. glabrata constituted approximately 90% of the yeast isolates (72 patients). Except for one FLZT C. tropicalis isolate, FLZR and FLZT phenotypes were detected exclusively in patients with RVVC; among them, 27.9% (12/43) harbored FLZR strains. C. albicans constituted 81.2% of FLZR (13/16) and 100% of the FLZT (13/13) isolates, respectively, and both phenotypes were likely responsible for FTF, which was also observed among patients with RVVC infected with fluconazole-susceptible isolates. Thus, FTF could be due to host-, drug-, and pathogen-related characteristics. Our study indicates that FLZT and FLZR isolates may arise following the exposure to over-the-counter (OTC) topical azole (clotrimazole) and that both phenotypes can cause FTF. Therefore, the widespread use of OTC azoles can influence fluconazole therapeutic success, highlighting the necessity of controlling the use of weak topical antifungals among Iranian women.

Detection and Control of Dermatophytosis in Wild European Hedgehogs (Erinaceus europaeus) Admitted to a French Wildlife Rehabilitation Centre.

The rising number of European hedgehogs (Erinaceus europaeus) admitted every year to wildlife rehabilitation centres might be a source of concern to animal and public health since transmissible diseases, such as dermatophytosis, can be easily disseminated. This study seeks to evaluate the frequency of dermatophyte detection in hedgehogs admitted to a wildlife rehabilitation centre located near Paris, France, and to assess the risk of contamination in the centre in order to adapt prevention measures. A longitudinal cohort study was performed on 412 hedgehogs hosted at the Wildlife Animal Hospital of the Veterinary College of Alfort from January to December 2016. Animals were sampled once a month for fungal culture. Dermatophyte colonies were obtained from 174 out of 686 skin samples (25.4%). Besides Trichophyton erinacei, Trichophyton mentagrophytes and Nannizzia gypsea were also found. Dermatophyte detection seemed to be associated with the presence of skin lesions, while more than one-third of T. erinacei-positive animals were asymptomatic carriers. Healing required several months of treatment with topical and systemic azoles, but dermatophytosis did not seem to reduce the probability of release. Daily disinfection procedures and early detection and treatment of infected and asymptomatic carriers succeeded in limiting dermatophyte transmission between hedgehogs and humans.

13937 Dupilumab for the treatment of dyshidrotic eczema: A multi-institution experience of 15 consecutive patients

Dupilumab is a human monoclonal antibody that is approved for the treatment of atopic dermatitis. Several case reports and small case series (≤3 patients) have reported using dupilumab in the treatment of dyshidrotic eczema; however, data supporting dupilumab’s use in this condition is still limited. To highlight the role of dupilumab in dyshidrotic eczema we present a series of 15 consecutive patients from three institutions treated with dupilumab for dyshidrosis. Patients with eczema only on hands and/or feet were included. All patients initially received atopic dermatitis dosing of dupilumab. Demographics are as follows: 10 males, 5 females, average age 56 (range 32-76). All patients had previously failed topical corticosteroids and 11/15 patients had previously failed at least one oral immunosuppressive and/or phototherapy. All patients demonstrated at least partial response to dupilumab with 6 patients clearing. 14/15 patients started on dupilumab for dyshidrotic eczema are still on dupilumab with an average treatment duration of 12.5 months. 7 patients have been on dupilumab for more than one year. The one patient in our cohort who stopped dupilumab was responding appropriately but decided to discontinue because she was concerned about possible side-effects. Dupilumab was well tolerated in our cohort with only 3 reported adverse events. One patient developed conjunctivitis that is being managed satisfactorily with artificial tears. Two patients developed dupilumab facial redness that was refractory to treatment with topical corticosteroids, topical azoles, and topical calcineurin inhibitors. Our series suggests that dupilumab is a generally well tolerated and frequently effective treatment for dyshidrotic eczema.