Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. MATERIALS AND METHODS: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis. RESULTS: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I2 = 73.271) efficacy. CONCLUSIONS: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.

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.

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.

Development, characterization, and in vitro-in vivo evaluation of polymeric nanoparticles containing miconazole and farnesol for treatment of vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is caused mainly by the opportunistic fungus Candida albicans, and its yeast to hyphae transition is considered a major virulence factor. Farnesol is a molecule that inhibits yeast to hyphae transition. The increased incidence of VVC has influenced a need for developing new therapeutic strategies. The objective was to develop a mucoadhesive nanostructured system composed of miconazole and farnesol co-encapsulated within chitosan nanoparticles. The miconazole presented a minimal inhibitory concentration (MIC) of 1 µg/ml against C. albicans. The farnesol was capable of inhibiting yeast to hyphae transition at levels greater or equal to 300 µM. The combination of miconazole and farnesol showed no change in miconazole MIC. Chitosan nanoparticles containing miconazole and farnesol were prepared by ionic gelation and showed favorable characteristics for use on mucous membranes. They showed size variation and polydispersion index (PDI) after 30 days, but the efficiency of drug encapsulation was maintained. Regarding toxicity in cultured fibroblasts (BALB/c 3T3) the nanoparticles were considered nontoxic. The nanoparticles showed antifungal activity against the C. albicans strain used with MICs of 2.5 µg/ml and 2 µg/ml for nanoparticles containing miconazole or miconazole/farnesol, respectively. Nanoparticles containing farnesol inhibited yeast to hyphae transition at concentrations greater than or equal to 240 µM. The in vivo antifungal activity was assessed in the murine model for VVC. The results suggested that chitosan nanoparticles containing miconazole and farnesol were effective at inhibiting fungal proliferation. Additionally, chitosan nanoparticles containing farnesol were capable of decreasing the pathogenicity of infection, demonstrated through the absence of inflammation.

Tinea nigra palmaris: a clinical case in a rural Ethiopian hospital.

Tinea nigra is an infrequent, superficial fungal infection, mainly caused by Hortaea werneckii, which is still underreported in Ethiopia. An asymptomatic 62-year-old male patient sought a rural hospital of Ethiopia, showing dark plaques on the palms of both hands. A superficial mycosis was suspected and a direct light microscopic mycological examination from skin scrapings revealed short brownish hyphae. To our knowledge, this is the first case of tinea nigra from the Ethiopian highlands. This may be due to the actual rarity of the condition or to underreporting.

Figurate erythematous lesion by Microsporum canis in immunosuppressed patient.

Dermatophytes are fungi capable of invading keratinized tissues. Isolation of the fungus with the culture is essential to guide the treatment, because there are more resistant species like Microsporum canis. The chronic use of corticosteroids leads to the deregulation of immunity, promoting atypical manifestations of infections. Topical antifungal therapy is often insufficient, requiring systemic medications. We describe the case of a patient undergoing systemic corticosteroid therapy with a large figurate lesion who presented complete response to exclusively topical treatment.

Figurate erythematous lesion by Microsporum canis in immunosuppressed patient

Abstract: Dermatophytes are fungi capable of invading keratinized tissues. Isolation of the fungus with the culture is essential to guide the treatment, because there are more resistant species like Microsporum canis. The chronic use of corticosteroids leads to the deregulation of immunity, promoting atypical manifestations of infections. Topical antifungal therapy is often insufficient, requiring systemic medications. We describe the case of a patient undergoing systemic corticosteroid therapy with a large figurate lesion who presented complete response to exclusively topical treatment.

Methylene Blue-Mediated Photodynamic Inactivation Followed by Low-Laser Therapy versus Miconazole Gel in the Treatment of Denture Stomatitis.

PURPOSE: Photodynamic therapy (PDT) appears to be an effective method for the in vitro and in vivo inactivation of Candida spp., but no clinical trials in this context have yet been conducted. The aim of this study was to compare the effect of oral miconazole gel to PDT combined with low-power laser (LPL) therapy in the treatment of denture stomatitis. MATERIALS AND METHODS: Forty participants with clinical and microbiological diagnoses of type II denture stomatitis were randomly allocated to two treatment groups (PDT and miconazole gel), each with 20 individuals. The PDT group was submitted to one session of methylene blue-mediated PDT plus two sessions of low-laser therapy twice a week for 15 days. The miconazole group was submitted to the drug four times a day for 15 days. RESULTS: Forty percent of the patients achieved clinical and microbiological resolution of denture stomatitis after methylene blue-mediated photodynamic inactivation followed by low-laser therapy. The cure rate associated with miconazole was 80% (p < 0.05). Fifteen days after the end of treatment, the recurrence rate was 25% in patients treated with PDT combined with LPL therapy and 12.5% in patients treated with miconazole. CONCLUSION: Miconazole gel provides better results than a protocol combining methylene blue-mediated PDT and LPL therapy in the treatment of type II denture stomatitis.

Estabilidad de la crema reformulada de nitrato de miconazol al 2 % / Stability of reformulated 2 % miconazol nitrate cream

INTRODUCCIÓN: la Empresa Productora Roberto Escudero Díaz, llevó a cabo la reformulación de la crema de nitrato de miconazol al 2 por ciento, por incumplimiento de algunas especificaciones de calidad y contaminaciones microbiológicas de varios lotes industriales, por lo que hubo que realizar cambios mayores a la composición de la formulación registrada. OBJETIVO: determinar la estabilidad de la nueva formulación de nitrato de miconazol crema al 2 por ciento, para determinar su período de validez. MÉTODOS: se realizaron los estudios según las regulaciones vigentes. Se emplearon tres lotes elaborados a escala piloto, envasados en tubos comprimibles de aluminio por 25 g. Se emplearon como métodos analíticos una técnica por cromatografía líquida de alta resolución y una por cromatografía en capa delgada previamente validadas para estos propósitos. Se consideraron dos temperaturas de almacenamiento: 30 ± 2 ºC (vida de estante) y 40 ± 2 ºC (estabilidad acelerada). Se determinaron los parámetros: propiedades organolépticas, pH, área de extensibilidad, valoración, contenido de sustancias relacionadas y/o productos de degradación, y además se evaluó la calidad de la formulación desde el punto de vista microbiológico. RESULTADOS: desde el punto de vista químico, los lotes evaluados mostraron contenidos superiores al 98 por ciento de analito y niveles muy bajos de sustancias relacionadas, independientemente del lote y la temperatura de almacenamiento. No se detectaron manchas adicionales por cromatografía en capa delgada atribuibles a posibles productos de degradación. La extensibilidad mostró un decrecimiento normal debido a la estructuración progresiva del sistema, y el pH también disminuyó discretamente pero dentro de los límites propuestos. Además se comprobó la elevada estabilidad microbiológica del medicamento a los 12 meses. CONCLUSIONES: la crema es estable química, física y microbiológicamente a temperatura ambiente durante 12 meses, por lo que se propone este tiempo como período de validez provisional(AU)

INTRODUCTION: Roberto Escudero Diaz drug producing company is carrying out the reformulation of 2 percent miconazole nitrate cream due to non-compliance with some quality specifications and the microbiological contamination of several industrial batches, so it was required to make major changes in the registered formulation composition. OBJECTIVE: to determine the stability of the new 2 percent miconazol nitrate cream formulation to verify its validity period. METHODS: the studies followed the regulations in force. Three pilot-scaled batches, packed in 25 g aluminum tubes, were used. The analytical methods were high resolution liquid chromatography technique and thin layer chromatography, being both methods previously validated for these purposes. The selected storage temperatures were 30 ± 2 °C (shelf life) and 40 ± 2 ºC (accelerated stability). The estimated parameters included organoleptic properties, pH, extensibility area, titration, content of related substances and/or degradation products in addition to evaluating the quality of formulation from the microbiological viewpoint. RESULTS: from the chemical viewpoint, the evaluated batches showed contents over 98 percent of analyte and very low levels of related substances, regardless of batch and the storage temperature. The thin layer chromatography did not detect any additional stain attributed to possible degradation products. The extensibility showed normal decrease resulting from progressive structuring of the system and the pH also lowered within the set limits. The microbiological stability of the drug was proved to be high after 12 months. CONCLUSIONS: the cream was chemically, physically and microbiologically stable at room temperature for 12 months, so this is the term suggested as the temporary validity period(AU

Evaluation of different treatment methods against denture stomatitis: a randomized clinical study.

OBJECTIVE: The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). STUDY DESIGN: Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. RESULTS: Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. CONCLUSIONS: U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.

Validación del método para control de la calidad del nitrato de miconazol en una nueva crema al 2 % / Validation of a quality control method of a new 2 percent miconazole nitrate cream

Objetivo: validar el método para control de la calidad del nitrato de miconazol en una nueva crema al 2 por ciento. Métodos: se realizó la validación según los parámetros exigidos para la categoría I y considerando la metodología y los criterios de aceptación vigentes en Cuba. Una vez validado, se aplicó al análisis de los tres lotes elaborados a escala piloto. Resultados: los resultados fueron satisfactorios, cumpliendo en todos los parámetros los límites establecidos. El método fue lineal, exacto y preciso en el rango de 10 a 30 mg/g y no hubo interferencias de ninguno de los componentes de la nueva formulación. Los lotes presentaron correcta dosificación, sin diferencias estadísticamente significativas entre las réplicas y los lotes analizados. Conclusiones: El método evaluado resulta válido para el objetivo con el cual se propuso(AU)

Objective: to validate a quality control method for a 2 percent new miconazole nitrate cream. Methods: the validation was made following the category I parameters and taking into account the methodology and acceptance criteria in force in Cuba. Once validated, the analysis of the three batches was applied on pilot scale. Results: the results were satisfactory since they fulfilled all the set parameters. The method was linear, accurate and precise in the 10-30 mg/g range. there was no interference from any of the components of the new formulation. The batches presented correct dosing, without any statistically significant differences between replicas and analyzed batches. Conclusions: the evaluated method proved to be valid for the stated purpose(AU)

Eficacia, tolerancia y seguridad de una combinación de metronidazol, miconazol, centella asiática, polimixina y neomicina en cápsula blanda para uso vaginal en el tratamiento de la vaginosis bacteriana / Efficacy, tolerability, and safety of a combination including metronidazole, miconazole, Gotu kola, polymixin, and neomycin in soft vaginal capsules for the treatment of bacterial vaginosis

Introducción: La vaginosis bacteriana (VB) es un síndrome polimicrobiano, en la cual la flora dominante de lactobacilos normales es sustituida por una flora polimicrobiana. La prevalencia de VB en Perú varía entre 27 y 43,7%. El Centro de Control y Prevención de Enfermedades (DCD) sugiere el tratamiento de VB en mujeres sintomáticas con metronidazol oral/gel o clindamicina crema. Se planteó en el presente estudio evaluar la eficacia, tolerancia y seguridad de la combinación de metronidazol, miconazol, centella asiática, polimixina y neomicina en cápsula blanda para el tratamiento de VB. Material y Métodos: El presente estudio de tipo abierto, observacional, prospectivo, permitió evaluar la eficacia, tolerancia y seguridad en la aplicación de la combinación de metronidazol, miconazol, centella asiática, polimixina y neomicina en cápsula blanda. Resultados: Se incluyó a 61 pacientes con edad promedio de 29.28 años (rango 18-48) de las cuales 93,4% tenía historia previa de flujo vaginal anormal. Se realizaron dos visitas durante el estudio, la primera para diagnóstico e inicio de tratamiento y la segunda de control post tratamiento. Tres pacientes no tuvieron segunda visita y 8 no tenían registrada toda la información para definir la respuesta terapéutica. La segunda visita se realizó a los 21 días en promedio. Los principales signos y síntomas en la primera visita de diagnóstico fueron flujo vaginal (100,0%), disconfort vaginal (85,2%), dispareunia (70,5%) y dolor abdominal bajo (57,4%), las cuales disminuyeron en forma significativa (p<0,05) a la segunda visita post tratamiento. La prueba de aminas resultó positiva en el 93,4% de los casos en la primera visita y en el 15,5% de los casos en la segunda visita (p<0,05). De la población inicial de estudio, solo 53 mujeres son evaluables para eficacia terapéutica...

Introduction: Bacterial vaginosis (BV) is a polymicrobial syndrome, in which the normal dominant flora consisting in Lactobacillus is replaced by polymicrobial flora. The prevalence of BV in Peru varies between 27 and 43.7%. The Centers for Disease Control and Prevention suggest therapy for BV in symptomatic women should include oral/gel metronidazole or clindamycin cream. We proposed in this study to evaluate the efficacy, tolerability and safety of the combination of metronidazole, miconazole, Gotu kola (Centella asiatica), polymixin, and neomycin in soft capsules, for the treatment of BV. Material and Methods: This investigation was an open, observational, and prospective study, which allowed us to evaluate the efficacy, tolerability and safety of the aforementioned combined therapy administered in soft capsules. Results: The study included 61 patients with a mean age of 29.28 years (range, 18-48) and 93.4% had a history of abnormal vaginal discharge. Two visits took place during the study, the first for making the diagnosis and initiating therapy, and the second was the post-treatment control. Three patients did not have a second visit and 8 did not record all the information required to define the therapeutic response. The second visit took place after 21 days on average. The main signs and symptoms at the first visit were vaginal discharge at diagnosis (100.0%), vaginal discomfort (85.2%), dyspareunia (70.5%) and lower abdominal pain (57.4%), which were significantly reduced (p <0.05) in the second visit after treatment. The amine test was positive in 93.4% of cases in the first visit and in 15.5% of cases in the second visit (p <0.05). From the initial population in the study, only 53 women are evaluable for efficacy. An overall response rate in 44 women (83.02%) was achieved with the soft capsule combination treatment. Adverse events were reported in only one case...

Double-blind study with topical Isoconazole and Terbinafine for the treatment of one patient with bilateral Tinea nigra plantaris and suggestions for new differential diagnosis.

The authors report a case of bilateral Tinea nigra plantaris treated through a double-blind study with the topical antifungal agents Isoconazole and Terbinafine. The objective of the study was to clinically compare the efficacy of these two topical antifungal agents on days 10, 20 and 30 of the treatment. No significant clinical differences were found, as all the plantar lesions regressed completely by the end of the treatment. Our conclusion was that in the case reported, the topical antifungal agents Isoconazole and Terbinafine demonstrated identical efficacy as a clinical cure. We also suggest the inclusion of injuries caused by arthropods of the Diplopoda Class in the differential diagnosis of Tinea nigra plantaris, due to the persistent acral hyperpigmentation.

Ricinus communis treatment of denture stomatitis in institutionalised elderly.

This study compared the effectiveness of Ricinus communis (RC) with Nystatin (NYS) and Miconazole (MIC) in the treatment of institutionalised elderly with denture stomatitis (DS). They (n = 30) were randomly distributed into three groups: MIC, NYS or RC. Clinical and mycological evaluations were performed prior to the use of the antifungal (baseline) and repeated after 15 and 30 days of treatment. The sample was clinically examined for oral mucosal conditions. Standard photographs were taken of the palate, and the oral candidiasis was classified (Newton's criteria). Mycological investigation was performed by swabbing the palatal mucosa, and Candida spp. were quantified by counting the number of colony-forming units (cfu mL⁻¹). The clinical and mycological data were analysed, respectively by Wilcoxon and Student's t-test (α = 0.05). Significant improvement in the clinical appearance of DS in the MIC and RC groups was observed between the 1st and 3rd collections (MIC - P = 0.018; RC - P = 0.011) as well as between the 2nd and 3rd collections (MIC - P = 0.018; RC - P = 0.011). Neither groups showed a statistically significant reduction in cfu mL⁻¹ at any time. Although none of the treatments decreased the cfu mL⁻¹, it was concluded that Ricinus communis can improve the clinical condition of denture stomatitis in institutionalised elderly patients, showing similar results to Miconazole.

[Generalized cutaneous candidiasis in newborn at term]. / Candidiasis cutánea generalizada en recién nacido a término.

INTRODUCTION: Cutaneous candidiasis is a disease that affects children as well as adults. The presentation may be localized or systemic, and with multiple etiological agents. The most prevalent infecting species in children differs from that of the adult. OBJECTIVE: A case is presented where a congenital cutaneous candidiasis was transmitted to the child during birth. MATERIALS AND METHODS: A full term newborn was exposed to a subclinical vaginal candidiasis infection, and 24 hr after birth, developed congenital cutaneous candidiasis. The etiological agent was Candida albicans, and was associated with sepsis and respiratory distress. Blood cultures, cutaneous biopsy of vesicular lesions, blood tests and lumbar puncture were performed. RESULTS: Biochemistry and blood count showed a CRP of 5.7 mg/dl, leukocytosis with left shift and mild anemia. After 24 hr, the blood analyses showed an increase in a CRP (7.8 mg/dl) and increased progressively for three days; consequently, a lumbar puncture was performed. Blood culture was positive for Staphylococcus aureus. Cutaneous biopsy confirmed the cutaneous candidiasis. CONCLUSIONS: The early diagnosis is essential to prevent complications derived by the Candida albicans in newborns.

Candidiasis cutánea generalizada en recién nacido a término / Generalized cutaneous candidiasis in newborn at term

Introducción. La candidiasis cutánea es una enfermedad que afecta tanto a población infantil como adulta. Las forma de presentación puede ser localizada o sistémica y el agente etiológico múltiple, siendo las especies infecciosas de Candida albicans más prevalentes en niños. Objetivo. Presentar un caso de candidiasis cutánea congénita cuya causa aparente fue la transmisión vertical durante el parto. Material y metodología. Se describe el caso de un recién nacido a término expuesto a una candidiasis vaginal subclínica, que desarrolló una candidiasis cutánea congénita por C. albicans asociada a sepsis y dificultad respiratoria en las primeras 24 horas de vida. Se practicaron hemocultivos, biopsia cutánea de las lesiones pápulopústulo-vesiculosas, análisis de sangre y punción lumbar. Resultados. En la bioquímica y el hemograma se encontró una proteína C reactiva de 5,7 mg/dl, leucocitosis con desviación a la izquierda y anemia leve. A las 24 horas, en el control se encontró una proteína C reactiva (7,82 mg/dl) que fue en aumento progresivo durante tres días, por lo que se practicó punción lumbar. El hemocultivo fue positivo para Staphylococcus aureus. La biopsia cutánea dio como resultado histológico la candidiasis cutánea. Conclusiones. El diagnóstico precoz es fundamental para prevenir complicaciones derivadas del cuadro producido por C. albicans en neonatos.

Introduction. Cutaneous candidiasis is a disease that affects children as well as adults. The presentation may be localized or systemic, and with multiple etiological agents. The most prevalent infecting species in children differs from that of the adult. Objective. A case is presented where a congenital cutaneous candidiasis was transmitted to the child during birth. Materials and methods. A full term newborn was exposed to a subclinical vaginal candidiasis infection, and 24 hr after birth, developed congenital cutaneous candidiasis. The etiological agent was Candida albicans, and was associated with sepsis and respiratory distress. Blood cultures, cutaneous biopsy of vesicular lesions, blood tests and lumbar puncture were performed. Results. Biochemistry and blood count showed a CRP of 5.7 mg/dl, leukocytosis with left shift and mild anemia. After 24 hr, the blood analyses showed an increase in a CRP (7.8 mg/dl) and increased progressively for three days; consequently, a lumbar puncture was performed. Blood culture was positive for Staphylococcus aureus. Cutaneous biopsy confirmed the cutaneous candidiasis. Conclusions. The early diagnosis is essential to prevent complications derived by the Candida albicans in newborns.

Contact dermatitis caused by dimethylfumarate in Argentina.

For the first time in Argentina, we describe an outbreak of contact dermatitis. New pairs of shoes caused intense pruritus, pain, and eruption, followed by edema, blisters, and a severe negative impact on the epidermal barrier of the feet. We identify dimethylfumarate as the causal agent and suggest an analytical method for its fast identification.