The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis.

BACKGROUND: Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to each case. This study aimed to evaluate the therapeutic effects of topical application of miconazole and miconazole-loaded chitosan nanoparticles in treatment of diabetic patients with oral candidiasis. METHODS: In this randomized controlled clinical trial. A total of 80 diabetic patients presenting with symptomatic oral candidiasis were randomly assigned into two treatment groups: miconazole and miconazole-loaded chitosan nanoparticles. The patients were treated for 28 days, and clinical assessments were conducted at baseline, 7, 14, 21 and 28 days. Clinical parameters, including signs and symptoms of oral candidiasis were evaluated and microbiological analysis was performed to determine the Candida species and assess their susceptibility to the antifungal agents. Statistical analysis was done to the categorical and numerical data using chi-square test and Kruskal Wallis test. RESULTS: The antifungal efficacy between the miconazole and miconazole-loaded chitosan nanoparticles (CS-MCZ) groups insignificant difference (P >  0.05) was observed. Both treatment modalities exhibited comparable effectiveness in controlling oral candidiasis symptoms and reducing Candida colonization as miconazole-loaded chitosan nanoparticles group showed a significant difference in the clinical improvement in respect of both signs and symptoms from baseline (70%) until the end of study at 28 days (5%) (P <  0.05) Moreover, miconazole-loaded chitosan nanoparticles, there was a significant reduction in the number of colonies forming units of Candida albicans from baseline until the end of the study at 28-day with P value <  0.000. CONCLUSIONS: This randomized controlled clinical trial and microbiological analysis demonstrate that both miconazole and miconazole-loaded chitosan nanoparticles are effective in the treatment of oral candidiasis in diabetic patients with no adverse reactions. TRIAL REGISTRATION: NCT06072716 with first registration first registration in 10/10/2023.

Efficacy of photodynamic therapy in the treatment of oral candidiasis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of photodynamic therapy (PDT) as an adjunct or alternative to traditional antifungal drugs in the treatment of oral candidiasis, and to provide evidence-based medical evidence for its use in the treatment of oral candidiasis. METHODS: Computer combined with manual retrieval of China Academic Journals Full-text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Science and Technology Journal Database (VIP), Wanfang Database, PubMed, Web of Science, Cochrane Library, Embase, Scopus retrieval for articles published before January 2023, basic information and required data were extracted according to the inclusion and exclusion criteria, and the Revman V5.4 software was used to conduct Meta-analysis of the included literature. RESULTS: A total of 11 articles were included, 7 of which used nystatin as an antifungal drug, 2 of which were combined treatment of PDT and nystatin, 2 of the remaining 4 articles were treated with fluconazole, and 2 were treated with miconazole. Meta results showed that PDT was superior to nystatin in reducing the number of oral candida colonies in the palate of patients MD = -0.87, 95%CI = (-1.52,-0.23), P = 0.008, the difference was statistically significant, and the denture site MD = -1.03, 95%CI = (-2.21, -0.15), P = 0.09, the difference was not statistically significant; compared with the efficacy of fluconazole, RR = 1.01, 95%CI = (0.56,1.83), P = 0.96; compared with miconazole RR = 0.55, 95%CI = (0.38, 0.81), P = 0.002; PDT combined with nystatin RR = 1.27, 95%CI = (1.06, 1.52), P = 0.01; recurrence rate RR = 0.28, 95%CI = (0.09, 0.88), P = 0.03. CONCLUSIONS: PDT was effective in the treatment of oral candidiasis; PDT was more effective than nystatin for the treatment of denture stomatitis in the palate, while there was no significant difference between the two for the denture site; The efficacy of PDT for oral candidiasis was similar to that of fluconazole; PDT was less effective than miconazole for oral candidiasis; Compared with nystatin alone, the combination of PDT and nystatin is more effective in treating oral candidiasis with less risk of recurrence.

Chitosan-coated miconazole as an effective anti-inflammatory agent for the treatment of postoperative infections in obstetrics and vaginal yeast infection control on in vitro evaluations.

People with immune deficiency are at risk of developing infections caused by several bacterial and fungal species. In this work, chitosan-coated miconazole was developed by a simple sol-gel method. Miconazole is considered an effective drug to treat vaginal infection-causing bacteria and fungi. The coating of chitosan with miconazole nitrate showed the highest drug loading efficiency (62.43%) and mean particle size (2 µm). FTIR spectroscopic analysis confirmed the entrapment of miconazole nitrate into chitosan polymer. The antifungal result demonstrated that MN@CS microgel possessed notable anti-Aspergillus fumigatus and Candida albicans activity in lower doses. Antibacterial activity results revealed excellent bacterial growth inhibition of MN@CS microgel towards human skin infectious pathogens Escherichia coli and Staphylococcus aureus. The biocompatibility studies of In vitro cell viability and Artemia salina lethality assay suggested that MN@CS microgel is more biosafe and suitable for human external applications. In the future, it will be an efficient anti-inflammatory agent for the treatment of vaginal infections.

Efficacy and Safety of Naftifine Hydrochloride 2% Gel in Interdigital Tinea Pedis: A Phase III Randomised, Double-Blind, Parallel-Group, Active-Controlled Study in Indian Adult Patients.

BACKGROUND AND OBJECTIVE: Naftifine, an allylamine, is highly effective against tinea pedis and exhibits relatively greater affinity to skin and nail beds, possibly due to its high lipophilicity. To study the efficacy and safety of naftifine 2% gel in an Indian population, a phase III multicentre double-blind, comparative, parallel-group study was conducted in comparison with miconazole 2% gel in patients with interdigital tinea pedis, with mild to moderate symptoms. PATIENTS AND METHODS: Patients presenting with mild to moderate signs and symptoms of interdigital tinea pedis and mycologically confirmed tinea infection were randomised to either naftifine hydrochloride 2% gel (n = 112) or miconazole 2% gel (n = 112) in 1:1 ratio. All patients were treated for 2 weeks with a follow-up of up to 12 weeks. Study evaluations were done at the end of 2, 6, and 12 weeks. The primary efficacy endpoint was the proportion of patients achieving clinical cure at week 6 (± 4 days) and secondary endpoints were the mycological cure at week 6 and week 12 and complete cure at week 12. RESULTS: At the end of week 6, clinical cure was 54.55% and 50.00% in the naftifine and miconazole groups (p = 0.4960), respectively, and it was increased to 78.18% and 76.36% in the naftifine and miconazole group (p = 0.7455) at the end of week 12. Mycological and clinical cure were similar in the naftifine and miconazole groups at week 6 and week 12. The safety and tolerability profiles of both treatments were similar. CONCLUSIONS: Naftifine 2% gel was efficacious and safe for the treatment of mild to moderate interdigital tinea pedis. Its clinical effectiveness was comparable to that of miconazole 2% gel. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2021/01/030753.

Miconazole-loaded nanoparticles coated with hyaluronic acid to treat vulvovaginal candidiasis.

Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.

Efficacy of adjunct photodynamic therapy on Candida growth and oral health quality of life in denture stomatitis patients with type 2 diabetes mellitus wearing implant-retained overdentures: A randomized clinical study.

AIM: The aim of the present clinical trial was to study the efficacy of combined miconazole and PDT in the improvement of quality of life and levels of Candida species in chronic hyperglycemic patients with denture stomatitis (DS). METHODS: One hundred patients were randomly divided into five groups; 20 each in the miconazole, PDT, miconazole+ PDT, CHX and distilled water groups. Methylene blue mediated irradiation was conducted using 600 nm diode laser with power, energy density and radiance as 100 mW, 3527 mW/cm2 and 9 J, respectively. Patients were advised to apply 2.5 ml of 2% topical miconazole four times a day. The existence of Candida spp. was detected by means of microbiological culture technique. Candida colony counts from the palates and dentures surfaces, quantified as colony forming unit (CFU)/mL were evaluated at baseline, end of 14 days, 28 days and 60 days. Oral health related quality of life was assessed with the help of a questionnaire. RESULTS: The quality of life showed significant improvement in the group where combination treatment was executed. The overall CFU/mL values were greater in the dentures in comparison to those from the palates of the patients of all the five groups. During all time periods of the study, the CFU/mL values obtained from combination treatment group showed significant differences. Candida albicans was the most predominant yeast. CONCLUSION: This study showed the effectiveness of methylene blue- PDT in combination with miconazole in improving oral health related quality of life and significantly reducing Candida CFU counts to resolve palatal inflammation in diabetic individuals with implant-supported complete dentures.

Does protocol miconazole administration improve mortality and morbidity on surgical necrotizing enterocolitis?

PURPOSE: Our previous clinical pilot study reported that miconazole (MCZ) prevented morbidity from surgical necrotizing enterocolitis (NEC). The present study re-investigated this effect in a long-term cohort over 20 years. METHODS: We conducted a retrospective cohort study from April 1998 to March 2020. A total of 1169 extremely low-birth-weight infants (ELBWIs) admitted to our neonatal intensive care unit, including 45 with NEC (3.8%), underwent surgery. Since 2002, protocol MCZ administration for 3 weeks has been applied for neonates born before 26 weeks' gestation or weighing under 1000 g. We compared the background characteristics and clinical outcomes between patients with and without MCZ administration. RESULTS: The morbidity rate decreased after applying the MCZ protocol, but no improvement in mortality was seen. A propensity score-matched analysis indicated that treated patients by MCZ showed a delay in developing surgical NEC by 12 days. The MCZ protocol also helped increase body weight at surgery. Prophylactic MCZ administration did not improve the neurological development of the language-social and postural-motor domains in the surgical NEC patients. But cognitive-adaptive domain caught up by a chronological age of 3 years old. CONCLUSIONS: Revising the protocol to extend the dosing period may improve the outcomes of surgical NEC after the onset.

Stimuli-Responsive in situ Spray Gel of Miconazole Nitrate for Vaginal Candidiasis.

Vaginal candidiasis is a common form of infection in women caused by Candida species. Due to several drawbacks of conventional treatments, the current research is attempted to formulate and optimize a miconazole nitrate-loaded in situ spray gel for vaginal candidiasis. The stimuli-responsive (pH and thermo-responsive) polymers selected for the in situ gel were chitosan and poloxamer 407, respectively, whereas hydroxypropyl methylcellulose (HPMC) was introduced in the formulation to further improve the mucoadhesive property. The dispersion of each polymer was carried out using the cold method, whereas the optimization of the formulation was achieved using Box-Behnken statistical design considering viscosity and gelation temperature as dependent variables. Present design achieved the optimized outcome with HPMC, poloxamer and chitosan at 0.52% (w/v), 18.68% (w/v) and 0.41% (w/v), respectively. Evaluation of drug-excipients compatibility was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermogravimetric analysis where the results showed the absence of any chemical interaction between the polymers and drug component. The optimized formulation showed gelation temperature at 31°C allowing in situ phase transition in a vaginal environment; pH of 4.21 is suitable for use in the vaginal cavity, and appropriate viscosity (290 cP) at storage temperature (below 30°C) would allow spraying at ease, whereas strong mucoadhesive force (22.4±0.513 g) would prevent leaking of the formulation after application. The drug release profile showed sustained release up to 24 h with a cumulative drug release of 81.72%, which is significantly better than the marketed miconazole nitrate cream. In addition, an improved antifungal activity could be correlated to the sustained release of the drug from the formulation. Finally, the safety of the formulation was established while tested on HaCaT cell lines. Based on our findings, it could be concluded that the in situ hydrogel formulation using stimuli-responsive polymers could be a viable alternative to the conventional dosage form that can help to reduce the frequency of administration with ease of application to the site of infection, thus will provide better patient compliance.

[Analysis of resistance and sensitivity of 1 200 strains of vulvovaginal candidiasis in China to five common antifungal drugs].

Objective: To test the antibiotic susceptibility of vulvovaginal candidiasis pathogenic strains to 5 antifungal drugs commonly used in clinic. Methods: A total of 1 200 vulvovaginal candida patients from 23 gynecological and family planning outpatient departments in China were enrolled. Their vaginal secretions were collected for candida strain isolation and species identification. According to Clinical and Laboratory Standards Institute (CLSI) M27-S3, the sensitivity of 1 200 strains to clotrimazole, fluconazole, miconazole, itraconazole and nystatin was tested. Results: (1) The sensitivity and resistance of 1 200 vulvovaginal candidiasis pathogens to 5 antifungal drugs were statistically different (χ2=3 513.201, P<0.01). (2) All strains had higher sensitivity to nystatin [99.92% (1 199/1 200)], followed by miconazole [92.25% (1 107/1 200)] and clotrimazole [87.17% (1 046/1 200)]. All strains had higher resistance to fluconazole [69.17% (830/1 200)], while itraconazole was 50.83% (610/1 200). (3) There was no significant difference between candida albicans and non-candida albicans in drug sensitivity to nystatin (P=0.315) and miconazole (P=0.425). (4) Candida albicans and non-candida albicans showed different sensitivity to clotrimazole, fluconazole and itraconazole, respectively. Compared with non-candida albicans, candida albicans showed higher sensitivity to clotrimazole [susceptibility rate: 73.01% (165/226) vs 90.45% (881/974); P<0.001] and higher resistance to fluconazole [resistance rate: 50.88% (115/226) vs 73.41% (715/974); P<0.001]. Although the drug sensitivity of itraconazole was not high, the susceptibility rate of candida albicans to itraconazole was slightly higher than that of non-candida albicans [37.68% (367/974) vs 23.89% (54/226)], and the drug resistance rate was lower [49.28% (480/974) vs 57.52% (130/226)]. Conclusions: The sensitivity of 1 200 strains of candida to 5 antifungal drugs is significantly different, the sensitivity rate of nystatin, miconazole and clotrimazole are higher, but the resistance rate of fluconazole and itraconazole are higher. The sensitivity of candida albicans and non-candida albicans to the same drug is also significantly different. It is suggested that in clinical diagnosis and treatment, we should pay attention to the identification of candida and drug sensitivity test, so as to select antifungal drugs rationally.

Effectiveness of redcore lotion in patients with vulvovaginal candidiasis: a systematic review and Meta-analysis.

OBJECTIVE: To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of randomized controlled trials. METHODS: A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019. Randomized controlled trials in the treatment for VVC were included; only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included. Relative risk (RR) and 95% confidence intervals (CI) were used in the Meta-analysis. RESULTS: Seven studies involving 768 patients suffering from VVC were identified; 468 of the patients were pregnant women (60.9%). Combination group (Redcore lotion plus miconazole) was more effective in reduCIng symptomatic episodes of VVC than miconazole alone, with respect to cure rate (RR, 1.31; 95% CI, 1.09-1.57; P = 0.01), fungal culture negative rate (RR, 1.21; 95% CI, 1.04-1.41; P = 0.01), and effective rate (RR, 1.18; 95% CI, 1.05-1.35; P = 0.01). Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate (RR, 1.48; 95% CI, 1.16-1.88, P < 0.01), fungal culture negative rate (RR, 1.26; 95% CI; 1.09-1.47; P < 0.01), and effective rate (RR, 1.25; 95% CI, 1.10-1.42; P < 0.01). Additionally, the observed risk of adverse events was lower in the combination medication group (RR, 0.30; 95% CI, 0.14-0.65; P < 0.01). CONCLUSIONS: Though overall quality of individual studies was low, Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.

The efficacy of a novel topical spray composed of sodium benzoate, alcohol and botanical oils for the treatment of Malassezia dermatitis in dogs - a split body, randomised, blinded study.

BACKGROUND: Treatment of Malassezia pachydermatis dermatitis can be performed by systemic or topical route. As M. pachydermatis is located on the stratum corneum, topical therapy alone may be sufficient to resolve the infection. Owing to systemic antifungal resistance and adverse effects, topical treatment alone may improve treatment outcome. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of a topical spray composed of sodium benzoate, alcohol and botanical oils, compared to a shampoo containing 2% chlorhexidine gluconate and 2% miconazole nitrate for the treatment of Malassezia pachydermaitis dermatitis in dogs. ANIMALS: Sixteen client owned dogs diagnosed with symmetrical interdigital lesions as a result of secondary Malassezia dermatitis. METHODS: The study design was prospective, randomised and single-blinded, using a split body protocol. Malassezia yeasts were determined by cytology at the inclusion day (day0) and after treatment (day14). All dogs were treated during 14 days with both shampoo at one paw and spray on the other paw. RESULTS: At day 14 a reduction of Malassezia dermatitis was shown at both paws. No statistical difference was demonstrated between treatment with shampoo or spray. CONCLUSIONS AND CLINICAL IMPORTANCE: We could not show a difference in efficacy between application of the test spray once daily and the topical use of 2%miconazole/2%chlorhexidine shampoo every other day. No adverse effects were reported.

Contexte - Le traitement de la dermatite à Malassezia peut être réalisé par voie systémique ou topique. Comme M. pachydermatis est situé sur la couche cornée, un traitement topique seul peut suffire à résoudre l'infection. En raison de résistance antifongique systémique et d'effets indésirables, le traitement topique seul peut améliorer les résultats du traitement. Hypothèses/Objectifs - Évaluer l'efficacité d'un spray topique composé de benzoate de sodium, d'alcool et d'huiles végétales, par rapport à un shampooing contenant 2 % de gluconate de chlorhexidine et 2 % de nitrate de miconazole pour le traitement de la dermatite à Malassezia chez le chien. Animaux - Seize chiens appartenant à des clients ont reçu un diagnostic de lésions interdigitées symétriques à la suite d'une dermatite à Malassezia secondaire. Méthodes - La conception de l'étude était prospective, randomisée et en simple aveugle. Les levures Malassezia ont été évaluées par cytologie au jour de l'inclusion (jour0) et après traitement (jour14). Tous les chiens ont été traités pendant 14 jours avec du shampooing sur une patte et un spray sur l'autre patte. Résultats - Au jour 14, une réduction de la dermatite à Malassezia a été observée aux deux pattes. Aucune différence statistique n'a été mise en évidence entre le traitement shampooing ou spray. Conclusions et importance clinique - Nous n'avons pas pu montrer de différence d'efficacité entre l'application du spray test une fois par jour et l'utilisation topique du shampooing 2%miconazole/2%chlorhexidine tous les deux jours. Aucun effet indésirable n'a été signalé.

Introducción- el tratamiento de la dermatitis por Malassezia pachydermatis se puede realizar por vía sistémica o tópica. Como M. pachydermatis se encuentra en el estrato córneo, la terapia tópica sola puede ser suficiente para resolver la infección. Debido a la resistencia antifúngica sistémica y los efectos adversos, el tratamiento tópico podría mejorar los resultados terapeúticos. Hipótesis/Objetivos - Evaluar la eficacia de un spray tópico compuesto por Benzoato de Sodio, alcohol y aceites botánicos, en comparación con un champú que contiene gluconato de clorhexidina al 2% y nitrato de miconazol al 2% para el tratamiento de la dermatitis por M. Paquydermatis en perros. Animales- dieciséis perros de propietarios particulares diagnosticados con lesiones interdigitales simétricas como resultado de una dermatitis secundaria por Malassezia. Métodos- el diseño del estudio fue prospectivo, al azar y simple ciego, utilizando un protocolo de cuerpo dividido. La presencia de levaduras Malassezia se determinó mediante citología el día de inclusión (día 0) y después del tratamiento (día 14). Todos los perros fueron tratados durante 14 días con champú en una pata y spray en la otra pata. Resultados- en el día 14 se mostró una reducción de la dermatitis por Malassezia en ambas patas. No se demostró diferencia estadística entre el tratamiento con champú o spray. Conclusiones e importancia clínica- no pudimos demostrar una diferencia en la eficacia entre la aplicación del aerosol a prueba una vez al día y el uso tópico de champú con miconazol al 2%/clorhexidina al 2% en días alternos. No se detectaron efectos adversos.

Contexto - O tratamento da dermatite por Malassezia pachydermatis pode ser realizado por via sistêmica ou tópica. Como a M. pachydermatis fica localizada no estrato córneo, a terapia tópica unicamente pode ser suficiente para resolver a infecção. Devido à resistência antifúngica e aos efeitos adversos, terapia tópica em monoterapia pode melhorar o resultado do tratamento. Hipótese/Objetivos - Avaliar a eficácia de um spray tópico contendo benzoato de sódio, álcool e óleos botânicos, comparado a um shampoo de gluconato de clorexidina a 2% e nitrato de miconazol a 2% para o tratamento de dermatite por Malassezia pachydermaitis em cães. Animais - Dezesseis cães de clientes diagnosticados com lesões interdigitais simétricas resultantes de infecção secundária por Malassezia. Métodos - O delineamento do estudo foi prospectivo, randomizado e simples-cego, utilizando um protocolo de corpo dividido. As leveduras identificadas como Malassezia foram determinadas por citologia no dia da inclusão (dia 0) e após o tratamento (dia 14). Todos os cães foram tratados por 14 dias com shampoo em uma pata e spray na outra. Resultados - No dia 14, observou-se um declínio na dermatite por Malassezia em ambas as patas. Não houve diferença estatística entre o tratamento com shampoo ou spray. Conclusões e importância clínica - Não pudemos encontrar diferenças na eficácia entre a aplicação do spray teste uma vez ao dia e o uso tópico de um shampoo contendo 2%miconazol/2%clorexidine em dias alternados. Não foram relatados efeitos adversos.

A preliminary study of suppression of candida infection by miconazole mucoadhesive tablets in oral or oropharyngeal cancer patients undergoing radiotherapy.

Elevated numbers of candida in the oral cavity often lead to oral candidiasis development in patients undergoing radiotherapy for oral or oropharyngeal cancer. This study aimed to verify the effect of miconazole mucoadhesive tablets on suppression of oral candida infection during radiotherapy. For this preliminary interventional study, miconazole mucoadhesive tablets were attached to the oral mucosa for 14 days from when grade 2 oral mucositis appeared in patients with oral or oropharyngeal cancer receiving radiotherapy, and the incidence of oral candidiasis was investigated. Various clinical factors were examined; univariate and multivariate Cox regression analyses were performed to investigate and compare the efficacy of this drug in preventing oral candidiasis with results of our previous study as historical control. Miconazole mucoadhesive tablets were administered to 18 patients, and oral candidiasis was observed in one patient (5.6%) after treatment completion. Among 144 historical control patients, 43 (29.9%) developed oral candidiasis. Multivariate Cox regression showed that miconazole mucoadhesive tablets significantly reduced oral candidiasis development during radiotherapy (p = 0.049, Hazard ratio 0.136, 95% confidence interval 0.019-0.994). This preliminary study suggests the efficacy of miconazole mucoadhesive tablets in preventing oral candidiasis in oral or oropharyngeal cancer patients treated with radiotherapy.Trial registration: Japan Registry of Clinical Trials (jRCT), jRCTs071190023. Registered 3 September, 2019.

Dermatophytosis caused by Trichophyton benhamiae in a dog.

Trichophyton benhamiae was diagnosed in a 9-year-old female dog by histopathological evaluation, fungal culture and confirmation by sequencing of the internal transcribed spacer region of ribosomal DNA. Successful therapy was achieved with itraconazole, bathing with miconazole and chlorhexidine shampoo, and topical application of sodium hypochlorite as a rinse.

Trichophyton benhamiae a été diagnostiqué chez une chienne de 9 ans par examen histopathologique, culture fongique et confirmation par séquençage de la région ITS (internal trasbcriber spacer) de l'ADN ribosomique. Une guérison thérapeutique a été obtenue par de l'itraconazole, des shampooings de miconazole et chlorhexidine et application topique d'hypochlorite de sodium en rinçage.

Trichophyton benhamiae foi diagnosticado em uma cadela de 9 anos através de avaliação histopatológica, cultura de fungos e confirmação por sequenciamento da região espaçadora transcrita interna do DNA ribossomal. Sucesso terapêutico foi obtido com o uso de itraconazol, banho com shampoo à base de miconazol e clorexidina e aplicação tópica de hipoclorito de sódio.

Se diagnosticó infección por Trichophyton benhamiae en una perra de 9 años mediante evaluación histopatológica, cultivo de hongos y confirmación mediante secuenciación de la región espaciadora transcrita interna del DNA ribosómico. Se logró un tratamiento exitoso con itraconazol, baños con champú de miconazol y clorhexidina y aplicación tópica de hipoclorito de sodio como enjuague.

Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections.

A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 µg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 µg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.

Antimycotic Treatment of Oral Candidiasis in Warfarin Users.

PURPOSE: Azole antimycotics and nystatin oral solution are used to treat oral candidiasis. Azoles inhibit cytochrome (CYP) P450-dependent metabolism of warfarin, which could increase the anticoagulant effect of warfarin. Nystatin is not expected to interfere with warfarin metabolism, but current data are conflicting. With this study, we aimed to explore the potential drug-drug interactions between warfarin and azole antimycotics used in the treatment of oral candidiasis, that is, systemic fluconazole, miconazole oral gel, and nystatin oral solution. METHODS: By linking clinical data on international normalized ratio (INR) measurements with administrative data on filled prescriptions of warfarin and antimycotics during 2000-2015, we explored INR changes in warfarin users relative to initiation of systemic fluconazole (n = 413), miconazole oral gel (n = 330), and nystatin oral solution (n = 399). RESULTS: We found a significant increase in mean INR of 0.83 (95% confidence interval [CI] 0.61-1.04) and 1.27 (95% CI 0.94-1.59) following initiation of systemic fluconazole and miconazole oral gel, respectively. Also, the proportion of patients experiencing an INR-value above 5 was increased after initiation of fluconazole (from 4.3% to 15.3%) and miconazole (from 5.5% to 30.1%). INR was unaffected by initiation of nystatin oral solution (mean change 0.08; 95% CI -0.10 to 0.25). CONCLUSION: Initiation of systemic fluconazole and miconazole oral gel was associated with increased INR in warfarin users. A similar association was not found for nystatin oral solution, which thus appears to be the safest alternative when treating oral candidiasis in warfarin users.

Antifungal drug miconazole ameliorated memory deficits in a mouse model of LPS-induced memory loss through targeting iNOS.

Alzheimer's disease (AD) is closely related to neuroinflammation, and the increase in inflammatory cytokine generation and inducible nitric oxide synthase (iNOS) expression in the brain of a patient with AD is well known. Excessive cytokines can stimulate iNOS in microglia and astroglia and overproduce nitric oxide, which can be toxic to neurons. The disease-gene-drug network analysis based on the GWAS/OMIM/DEG records showed that miconazole (MCZ) affected AD through interactions with NOS. Inhibiting iNOS can reduce neuroinflammation, thus preventing AD progression. To investigate the prophylactic role of antifungal agent in the AD development, a lipopolysaccharide-induced memory disorder mouse model was used, and cognitive function was assessed by Morris water maze test and passive avoidance test. MCZ treatment significantly attenuated cognitive impairment, suppressed iNOS and cyclooxygenase-2 expression, and activation of astrocyte and microglial BV2 cells, as well as reduced cytokine levels in the brains and lipopolysaccharide-treated astrocytes and microglia BV2 cells. In further mechanism studies, Pull-down assay and iNOS luciferase activity data showed that MCZ binds to iNOS and inhibited transcriptional activity. Our results suggest that MCZ is useful for ameliorating the neuroinflammation-mediated AD progression by blocking iNOS expression.

Cutaneous candidiasis - an evidence-based review of topical and systemic treatments to inform clinical practice.

Cutaneous candidiasis is a common skin disease, and several treatments have been investigated within the last fifty years. Yet, systematic reviews are lacking, and evidence-based topical and systemic treatment strategies remain unclear. Thus, the aim of this review was to summarize efficacy and adverse effects of topical and oral therapies for cutaneous candidiasis in all age groups. Two individual researchers searched PubMed and EMBASE for 'cutaneous candidiasis' and 'cutaneous candidiasis treatment', 'intertrigo', 'diaper dermatitis' and 'cheilitis'. Searches were limited to 'English language', 'clinical trials' and 'human subjects', and prospective clinical trials published in abstracts or articles were included. In total, 149 studies were identified, of which 44 were eligible, comprising 41 studies of 19 topical therapies and four studies of three systemic therapies for cutaneous candidiasis. Topical therapies were investigated in infants, children, adolescents, adults and elderly, while studies of systemic therapies were limited to adolescents and adults. Clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated similar efficacy with complete cure rates of 73%-100%. Single-drug therapy was as effective as combinations of antifungal, antibacterial and topical corticosteroid. Four studies investigated systemic therapy, and oral fluconazole demonstrated similar efficacy to oral ketoconazole and topical clotrimazole. Limitations to this review were mainly that heterogeneity of studies hindered meta-analyses. In conclusions, clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated equal good efficacy and mild adverse effects similar to combinations of antifungal, antibacterial and topical corticosteroids. Oral fluconazole was as effective as topical clotrimazole and is the only commercially available evidence-based option for systemic treatment of cutaneous candidiasis.