Development of biopolymer films loaded with fluconazole and thymol for resistant vaginal candidiasis.

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.

Patients with recurrent vulvovaginal candidiasis exhibit a decrease in both the fungicidal activity of neutrophils and the proliferation of peripheral blood mononuclear cells.

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is an important and underestimated fungal infection. OBJECTIVE: We aimed to determine the fungicidal and proliferative capacities of neutrophils and peripheral blood mononuclear cells (PBMCs), respectively and the clinical and microbiological characteristics of a cohort of Colombian patients diagnosed with RVVC. METHODS: A cross-sectional study was conducted. A total of 66 women were included (40 diagnosed with RVVC and 26 healthy women [HW]). Demographic and clinical data were recorded. Vaginal fluid samples were obtained for isolation, identification and antifungal susceptibility testing of Candida species using selective culture media and the Vitek 2.0® system. Blood samples were also obtained to evaluate cell subpopulations; furthermore, neutrophils and PBMCs were isolated to determine their fungicidal and proliferative capacities, respectively. RESULTS: The median age was 29 (IQR: 34-23) for RVVC and 24 (IQR: 30-23) for HW. Only two species of the genus Candida were identified: Candida albicans (92.5%) and Candida lusitaniae (7.5%). Resistance to fluconazole, voriconazole, flucytosine and amphotericin B was observed on six C. albicans isolates and one C. lusitaniae isolate. Only the family history of vulvovaginal candidiasis was associated with RVVC occurrence. The RVVC group exhibited a significantly higher number of neutrophils but with lower fungicidal activity in comparison to HW; likewise, PBMCs from RVVC patients presented a lower proliferation index when stimulated with C. albicans. CONCLUSION: Contrary to what has been reported worldwide, in Colombian patients with RVVC, C. albicans was the main isolated species without increased antifungal resistance. The diminished fungicidal and proliferative capacities of neutrophils and PBMCs, respectively, could suggest a possible alteration in the innate and adaptive immune responses.

Molecular epidemiology of Candida africana isolates collected from vagina swabs in French Guiana.

Previous molecular studies have shown that Candida africana corresponds to the clade 13 of Candia albicans. It has been mostly involved in vulvovaginal candidiasis worldwide but few data exist in South America. The aim of our study was to investigate the prevalence of C. africana in women living in French Guiana. For this, we first set up a fluorescent-intercalating-dye-real time Polymerase Chain Reaction (PCR) targeting the hyphal wall protein 1 gene. The test was applied to 212 C. albicans isolates collected from May to August 2019 from vaginal swabs, allowing the identification of six women harboring C. africana (eight isolates). The in vitro susceptibility of these eight isolates to six antifungal drugs was also evaluated. No demographics or clinical-specific features could be demonstrated. Genetic diversity of those isolates was analyzed through multilocus sequence typing and showed that diploid sequence type 182 was predominant (n = 6) and allowed the report of a new diploid sequence type.

Candida africana, the clade 13 of C. albicans, is characterized by specific genetic and phenotypic traits. Using a new molecular technique, we report a high prevalence of C. africana in vaginal swabs from patients living in French Guiana. The worldwide predominant genotype was detected in all but one patient.

Role of vulvovaginal candidiasis infection in infertility: systematic review and meta-analysis.

OBJECTIVE: To evaluate the relationship between fungal infection in the female genital tract and infertility. DATA SOURCES: A systematic review was carried out, and the search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane Library databases until August 2022. The search strategy used standardized keywords such as "candidiasis" and "infertility," combined with their respective synonyms. The search was limited to human studies, with no language restrictions. STUDY ELIGIBILITY CRITERIA: Primary articles that evaluated women of reproductive age with and without infertility and related to the presence or absence of candidiasis were included. STUDY APPRAISAL AND SYNTHESIS METHODS: For the analyses, the odds ratio association measure was used with a confidence interval of 95% using RevMan software (version 5.4). RESULTS: Eight studies, published between 1995 and 2021 in different countries around the world, were included in this systematic review. Two studies were excluded after sensitivity analysis. A total of 909 participants were included in the group of infertile women and 2363 women in the control group. The age of the evaluated women varied between 18 and 50 years. The random effect model was used and showed no significant difference when comparing candidiasis between fertile and infertile women (odds ratio: 1.44; 95% confidence interval 0.86, 2.41 p= 0.17). CONCLUSIONS: There was no association between candidiasis and female sterility.

Uso dos antifúngicos no tratamento da candidíase vulvovaginal: uma revisão integrativa / Use of antifungals in the treatment of vulvovaginal candidiasis: an integrative review

Objective: To identify scientific evidence available in the literature and analyze the action of antifungal drugs used for the treatment of vulvovaginal candidiasis. Methods:Integrative literature review conducted in the databases Medline/PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SCOPUS and VHL; with the descriptors "woman", "antifungal agents"; "vulvovaginal candidiasis". Results:Ten scientific articles published between 1983 and 2020 were obtained. Of these, four were developed in Iran; followed by Mexico, England, Taiwan, Thailand, Denmark, and the United States. In terms of methodological design, most studies are clinical trials (n=8), and two are cross-sectional studies. Regarding the level of evidence, eight are level II, and only two investigations are level IV. Concerning the antifungal drugs used in the treatment, there was a predominance of clotrimazole (n=4; efficacy ranging from 42.4% to 98.3%), followed by econazole (n=2; efficacy between 39% and 89%), combined or not with another antifungal drug. Conclusion: The use of clotrimazole stands out, as it is highly effective in the treatment of vulvovaginal candidiasis. This study contributes to the advancement of knowledge and improvement of the clinical practice of nursing and other health professionals. It is expected that these results will encourage further studies and update clinical practices.Descriptors:Women;Antifungal Agents;Candidiasis, Vulvovaginal

Objective: To identify scientific evidence available in the literature and analyze the action of antifungal drugs used for the treatment of vulvovaginal candidiasis. Methods: Integrative literature review conducted in the databases Medline/PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SCOPUS and VHL; with the descriptors "woman", "antifungal agents"; "vulvovaginal candidiasis". Results:Ten scientific articles published between 1983 and 2020 were obtained. Of these, four were developed in Iran; followed by Mexico, England, Taiwan, Thailand, Denmark, and the United States. In terms of methodological design, most studies are clinical trials (n=8), and two are cross-sectional studies. Regarding the level of evidence, eight are level II, and only two investigations are level IV. Concerning the antifungal drugs used in the treatment, there was a predominance of clotrimazole (n=4; efficacy ranging from 42.4% to 98.3%), followed by econazole (n=2; efficacy between 39% and 89%), combined or not with another antifungal drug. Conclusion:The use of clotrimazole stands out, as it is highly effective in the treatment of vulvovaginal candidiasis. This study contributes to the advancement of knowledge and improvement of the clinical practice of nursing and other health professionals. It is expected that these results will encourage further studies and update clinical practices.Descriptors:Women;Antifungal Agents;Candidiasis, Vulvovaginal

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

Successful treatment of experimental murine vulvovaginal candidiasis with gentian violet.

Aim: This study evaluated the antifungal efficacy of gentian violet (GV) in an experimental vulvovaginal candidiasis (VVC) model. Materials & methods: In vitro susceptibility and cytotoxicity assays were performed to validate the antifungal potential and safety of GV. The antifungal efficacy was then evaluated in vivo through comparative analysis of the fungal burden following treatment with GV or nystatin, as well as assessment of the vaginal tissue by histology and electron microscopy. Results: GV demonstrated a safe antifungal profile against C. albicans, with a significant decrease in fungal burden and an improvement in the inflammatory process evaluated histologically. Conclusion: The results of this study motivate further assessment of GV as a promising alternative for VVC therapy.

Antibiofilm potential of Annona muricata L. ethanolic extract against multi-drug resistant Candida albicans.

ETNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Annona muricata L. (soursop) include treatment for cancer, fungal infections, and inflammatory diseases. Its phytoconstituents, mainly acetogenins and alkaloids, are associated with therapeutic activity and clinical application is currently under investigation. However, the application of phytotherapy to treat diseases caused by fungal biofilms, such as vulvovaginal candidiasis (VVC), is still limited. AIM OF THE STUDY: To investigate the activity of the ethanolic extract of A. muricata leaves (AML) against biofilms formed by multiresistant Candida albicans (ATCC® 10231) both in vitro and in a VVC experimental model. MATERIAL AND METHODS: C. albicans biofilms were grown and their adhesion, proliferation, development, and matrix composition studied by spectrophotometry, scanning electron microscopy (SEM), whole slide imaging (WSI), and biochemical assays without or with AML treatment. In parallel, in vivo experiments were conducted using a murine model of infection treated with different concentrations of the extract and nystatin. Fungal burden and histological changes were investigated. RESULTS: The proliferation and adhesion of C. albicans biofilms were significantly reduced as confirmed by SEM and WSI quantitative analyses. Furthermore, the concentration of carbohydrates, proteins and DNA was reduced in the biofilm matrix. In vivo assays demonstrated that AML was able to reduce the fungal burden and the inflammatory process. CONCLUSIONS: The findings further emphasized the therapeutic and scientific potential of AML, thus encouraging its future use in the treatment of VVC.

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.

Species and antifungal susceptibility profile of agents causing vulvovaginal candidiasis in a military population: a cross-sectional study.

Military women on active duty are exposed to constant physical and mental demands, which may predispose them to some infection risks, including vulvovaginal candidiasis (VVC), a pathology considered a global public health problem. To monitor the prevalent and emerging pathogens in VVC, this study aimed to evaluate the distribution of yeast species and their in vitro antifungal susceptibility profile. We studied 104 vaginal yeast specimens obtained during routine clinical examinations. The population was attended at the Medical Center of the Military Police, São Paulo, Brazil, and was divided into two groups: infected patients (VVC) and colonised patients. Species were identified by phenotypic and proteomic methods (MALDI-TOF MS) and susceptibility to eight antifungal drugs, including azoles, polyenes, and echinocandins, was determined using microdilution broth. Candida albicans stricto sensu was found to be the most frequently isolated species (55%), but we observed a considerable rate of other Candida species isolates (30%), including Candida orthopsilosis stricto sensu only in the infected group. There were also other rare genera such as Rhodotorula, Yarrowia, and Trichosporon (15%), of which Rhodotorula mucilaginosa was the most prevalent in both groups. Fluconazole and voriconazole had the highest activity against all species in both groups. Candida parapsilosis was the most susceptible species, except for amphotericin-B in the infected group. Of note, we observed unusual resistance in C. albicans. Our results have allowed us to compile an epidemiological database on the etiology of VVC to support the empirical treatment and improve the health care of military women.

Vulvovaginal candidiasis (VVC) is an infection caused by fungi, mainly Candida albicans. Our results show that fungi other than C. albicans can cause VVC. So, our findings may help to choose the most appropriate treatment, as some may be resistant, to improve the quality of life of military women.

Advanced Solid Formulations For Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is an opportunistic and endogenous infection caused by a fungus of the Candida genus, which can cause pruritus, dysuria, vulvar edema, fissures and maceration of the vulva. The treatment of vaginal candidiasis is carried out mainly by antifungal agents of azole and polyene classes; however, fungal resistance cases have been often observed. For this reason, new therapeutic agents such as essential oils, probiotics and antimicrobial peptides are being investigated, which can be combined with conventional drugs. Local administration of antimicrobials has also been considered to allow greater control of drug delivery and reduce or avoid undesirable systemic adverse effects. Conventional dosage forms such as creams and ointments result in reduced residence time in the mucosa and non-sustained and variable drug delivery. Therefore, advanced solid formulations such as intravaginal rings, vaginal films, sponges and nanofibers have been purposed. In these systems, polymers in different ratios are combined aiming to achieve a specific drug release profile and high mucoadhesion. Overall, a more porous matrix structure leads to a higher rate of drug release and mucoadhesion. The advantages, limitations and technological aspects of each dosage form are discussed in detail in this review.

Aspectos da abordagem terapêutica sobre candidíase vulvovaginal / Aspects of the therapeutic approach to vulvovaginal candidiasis / Aspectos del abordaje terapéutico de la candidiasis vulvovaginal

A candidíase vulvovaginal, é uma infecção da vulva e vagina causada por vários tipos de Candida spp. Essa patologia afeta 75% de todas as mulheres pelo menos uma vez durante a vida, ocorrendo com mais frequência durante a idade fértil. A transmissão dessa infeção fúngica ocorre por meio de contato com mucosas e secreções em pele de portadores ou doentes, contato sexual, água contaminada e transmissão vertical. Alguns outros sintomas característicos mais vistos em casos de CVV, são lesões brancas, cremosas e planas, sendo mais intensos no período pré-menstrual, quando a acidez vaginal aumenta. numerosos antifúngicos estão disponíveis no mercado, os quais são encontrados para administração oral na forma de comprimidos ou, para uso tópico, na forma de cremes, loções, comprimidos vaginais, supositórios e tampões revestidos. O objetivo geral do trabalho foi analisar através da revisão de literatura, tratamentos convencionais e alternativos para abordagem terapêutica da Candidíase Vulvovaginal contextuando a mesma, utilizando definições, dados epidemiológicos e sua sintomatologia frente à sociedade. O presente trabalho é uma revisão integrativa, que teve a coleta de dados realizada de março de 2021 a outubro de 2021 nas bases de dados Lilacs, Scielo, Google acadêmico, A busca resultou em 902 artigos, dos quais 14 atenderam ao critério de inclusão. A busca por tratamentos frente a candidíase vulvovaginal tem se mostrado ampla de acordo com os artigos selecionadas. Concluímos que a patologia candidíase vulvovaginal, vem apresentando resistência em algumas abordagens terapêuticas, assim como algumas mulheres não aderem há algum tipo de tratamento, devido à falta de conhecimento sobre a patologia.

Vulvovaginal candidiasis is an infection of the vulva and vagina caused by various types of Candida spp. This condition affects 75% of all women at least once in their lifetime, occurring more frequently during their childbearing years. The transmission of this fungal infection occurs through contact with mucous membranes and secretions on the skin of patients or patients, sexual contact, contaminated water and vertical transmission. Some other characteristic symptoms more seen in cases of VVC are white, creamy and flat lesions, being more intense in the premenstrual period, when the vaginal acidity increases. numerous antifungals are available on the market which are available for oral administration in tablet form or, for topical use, in the form of creams, lotions, vaginal tablets, suppositories and coated tampons. The general objective of the work was to analyze, through a literature review, conventional and alternative treatments for the therapeutic approach of Vulvovaginal Candidiasis in its context, using definitions, epidemiological data and its symptoms in society. The present work is an integrative review, which had data collection carried out from March 2021 to October 2021 in the Lilacs, Scielo, Google academic databases. The search resulted in 902 articles, of which 14 met the inclusion criteria. The search for treatments against vulvovaginal candidiasis has been shown to be wide according to the selected articles. We conclude that the vulvovaginal candidiasis pathology has been showing resistance in some therapeutic approaches, as well as some women do not adhere to any type of treatment, due to lack of knowledge about the pathology.

La candidiasis vulvovaginal es una infección de la vulva y la vagina cau- sada por diversos tipos de Candida spp. Esta afección afecta al 75% de las mujeres al menos una vez en la vida, siendo más frecuente durante la edad fértil. La transmisión de esta infección fúngica se produce por contacto con mucosas y secreciones de la piel de pacientes o enfermos, contacto sexual, agua contaminada y transmisión vertical. Otros síntomas característicos más observados en los casos de CVV son las lesiones blancas, cremosas y planas, siendo más intensas en el período premenstrual, cuando aumenta la acidez vaginal. Existen en el mercado numerosos antifúngicos disponibles para adminis- tración oral en forma de comprimidos o, para uso tópico, en forma de cremas, lociones, comprimidos vaginales, supositorios y tampones recubiertos. El objetivo general del tra- bajo fue analizar, a través de una revisión bibliográfica, los tratamientos convencionales y alternativos para el abordaje terapéutico de la Candidiasis Vulvovaginal en su contexto, utilizando definiciones, datos epidemiológicos y su sintomatología en la sociedad. El pre- sente trabajo es una revisión integradora, que tuvo recolección de datos realizada de marzo de 2021 a octubre de 2021 en las bases de datos académicas Lilacs, Scielo, Google. La búsqueda resultó en 902 artículos, de los cuales 14 cumplieron los criterios de inclu- sión. La búsqueda de tratamientos contra la candidiasis vulvovaginal se ha mostrado am- plia según los artículos seleccionados. Concluimos que la patología de la candidiasis vul- vovaginal viene mostrando resistencia en algunos abordajes terapéuticos, así como algu- nas mujeres no se adhieren a ningún tipo de tratamiento, debido al desconocimiento de la patología.

Actividad de fosfolipasas y proteasas en aislamientos de especies de Candida colonizadoras y causantes de vulvovaginitis en mujeres gestantes / Phospholipase and proteinase activities of isolatesof colonizing Candida spp. causing vulvovaginitis in pregnant women

Introducción. Las proteasas y las fosfolipasas son factores de virulencia de Candida spp. que cumplen un papel importante en la invasión de los tejidos. Entre los factores relacionados con el huésped, se encuentran algunos asociados con las características ambientales y otros con la colonización. Objetivo. Determinar la actividad de fosfolipasas y proteasas en aislamientos de especies colonizadoras y patógenas de Candida spp., aisladas de mujeres gestantes de Cartagena de Indias. Materiales y métodos. Se determinó la actividad de fosfolipasas y proteasas en 56 aislamientos mediante degradación del sustrato y cálculo del coeficiente de actividad enzimática. Se compararon las actividades de fosfolipasas y proteasas, entre los aislamientos colonizadores y los patógenos. Resultados. La actividad de la fosfolipasa fue "muy alta" (< 0,69) en 34 aislamientos e, igualmente, la de la proteasa en 14. No hubo diferencias significativas al comparar las actividades de las fosfolipasas y de las de las proteasas, entre los aislamientos colonizadores y los patógenos. Conclusiones. La actividad de las fosfolipasas predominó como factor de virulencia en los aislamientos estudiados. No obstante, no se encontró una diferencia significativa entre los grupos de aislamientos colonizadores y los patógenos, en cuanto a las actividades de fosfolipasas y proteasas.

Introduction. Proteases and phospholipases are virulence factors of Candida spp. that play an important role in tissue invasion. Among the factors related to the host some are associated with environmental characteristics and others with Candida colonization. Objectives. To determine phospholipase and protease activities in colonizing and pathogenic strains, isolated from pregnant women in Cartagena de Indias. Materials and methods. Phospholipase and protease activity was determined in 56 isolates, evaluating substrate degradation and calculating the enzyme activity coefficient. Phospholipase and protease activities were compared between colonizing and pathogenic strains. Results. "Very high" (<0.69) phospholipase and protease activity was found in 34 and 14 isolates, respectively. There was no significant difference when comparing phospholipase and protease activities between colonizing and pathogenic isolates. Conclusions. Phospholipase activity predominated as a virulence factor in the studied strains, but no significant difference was found between colonizing and pathogenic strains for phospholipase and protease activities.

Lycopene, Mesoporous Silica Nanoparticles and Their Association: A Possible Alternative against Vulvovaginal Candidiasis?

Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region known as vulvovaginal candidiasis (VVC). This pathology is, in fact, one of the main C. albicans clinical manifestations, changing from a colonizer to a pathogen. The increase in VVC cases and limited antifungal therapy make C. albicans an increasingly frequent risk in women's lives, especially in immunocompromised patients, pregnant women and the elderly. Therefore, it is necessary to develop new therapeutic options, especially those involving natural products associated with nanotechnology, such as lycopene and mesoporous silica nanoparticles. From this perspective, this study sought to assess whether lycopene, mesoporous silica nanoparticles and their combination would be an attractive product for the treatment of this serious disease through microbiological in vitro tests and acute toxicity tests in an alternative in vivo model of Galleria mellonella. Although they did not show desirable antifungal activity for VVC therapy, the present study strongly encourages the use of mesoporous silica nanoparticles impregnated with lycopene for the treatment of other human pathologies, since the products evaluated here did not show toxicity in the in vivo test performed, being therefore, a topic to be further explored.

High Presence of NETotic Cells and Neutrophil Extracellular Traps in Vaginal Discharges of Women with Vaginitis: An Exploratory Study.

Infectious vaginitis is a microbiological syndrome of great importance in public health that affects millions of women worldwide. However, no studies have explored the phenomenon of the production of the neutrophil extracellular traps (NETs) that are released into the female reproductive tract in these pathologies. This study aimed to determine the presence of NETosis in vaginal discharges of women with bacterial vaginosis, candidiasis, and trichomoniasis by characterizing NETs. Extracellular DNA with neutrophil elastase and citrullinated histones was identified to confirm the NET components (n = 10). The concentration, phenotypes of NETs, and number of NETotic cells were determined. The results showed an increase in NETotic cells in women with Candida albicans (CA) and Trichomonas vaginalis (TV) and an increase in NETs in TV-induced vaginitis. Samples of CA- and TV-infected women showed different NET phenotypes (diffNETs, sprNETs, and aggNETs); diffNETs were found in high concentrations in samples with CA and were increased in three types of NETs in TV infections. Samples with intermediate microbiota and bacterial vaginosis showed increased NETotic cells while the intermediate microbiota presented a higher concentration of NETs. Therefore, alterations in the microbiota and the presence of fungal and parasitic infections are important stimuli for the activation and induction of NETosis, and their cytotoxic effects could enhance tissue damage.

Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections.

BACKGROUND: Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: This study was conducted to evaluate the efficacy and safety of oral oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode. STUDY DESIGN: Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks. RESULTS: In the induction phase, oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the OTESECONAZOLE/oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group. CONCLUSION: In participants with recurrent vulvovaginal candidiasis, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.

Bioactive compounds with antifungal activity against pathogens isolated from pregnant woman: Gallesia integrifolia (garlic wood) is a promising treatment for vulvovaginal candidiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves, bark, and roots of Gallesia integrifolia are consumed in folk medicine through infusion, decoction, and topical preparation by crushing because of its pharmacological properties in several peripheral system disorders, including microbial infections. The presence of various molecules in different parts of the plant likely confers this species' fungicidal action, but scientific evidence is lacking. Vulvovaginal candidiasis mainly affects women of reproductive age. When left untreated, it can cause pregnancy complications. Currently available antifungals often cause undesirable side effects. New alternative therapeutic strategies based on medicinal plants have been proposed. AIM: To investigate the antifungal activity of G. integrifolia against vulvovaginal candidiasis secretion in pregnant women. MATERIALS AND METHODS: Antifungal activity was determined by the minimum inhibitory concentration (MIC), determined by broth microdilution method using Candida spp (NEWP1210), C. albicans (CCCD-CC001), C. tropicalis (CCCD-CC002) standard and clinical isolates from pregnant women with vulvovaginal candidiasis. Nystatin and fluconazole were used as positive controls. The chemical composition of essential oils that were extracted from leaves, flowers, and fruits of G. integrifolia was determined by gas chromatography coupled to mass spectrometry. Reverse docking was used to suggest a possible target in Candida. Conventional docking was used to identify the most probable compound that inhibits fungal growth. RESULTS: A total of 24 compounds were identified, accounting for ∼99% of volatile constituents in the essential oils. Leaves of G. integrifolia contained 3,5-dithiahexanol-5,5-dioxide (40.93%), flowers contained methionine ethyl ester (46.78%), and fruits contained 2,8-dithianonane (54.01%) as the most abundant compounds. The MICs of essential oils of leaves, flowers, and fruits of G. integrifolia against standard strains of Candida spp, C. albicans, and C. tropicalis ranged from 13.01 to 625.00 µg/mL. The essential oil of flowers more effectively inhibited Candida spp. Essential oils of leaves and flowers were similar to fluconazole against C. albicans. Essential oils of flowers and fruits were similar to fluconazole against C. tropocalis. In Candida yeast species that were isolated from vaginal secretion samples from pregnant patients, the MICs of leaves and flowers ranged from 52.08 to 5000.00 µg/mL. The essential oil of leaves (277.77 µg/mL) was the most active against C. albicans. No significant differences were found between the essential oils of leaves and flowers against C. glabrata. Docking simulations suggested that phytol in leaves and flowers was responsible for the antimicrobial effect. CONCLUSION: The present results suggest the potential therapeutic use of G. integrifolia, especially its leaves and flowers, against Candida and vulvovaginal candidiasis.

A novel nanotechnological mucoadhesive and fast-dissolving film for vaginal delivery of clotrimazole: design, characterization, and in vitro antifungal action.

Pullulan (PUL) films containing pomegranate seed oil and Eudragit® RS100 nanocapsules loaded with clotrimazole (CTZ-NC-PUL) were developed to treat vulvovaginal candidiasis (VVC). Our findings showed that the nanocapsule average diameter was around 163 ± 4 nm, with polydispersity index values of up to 0.1 ± 0.01 and positively charged zeta potential (+ 43.5 ± 0.7 mV). The pH was in the acid range (5.14 ± 0.12) and encapsulation efficiency was around 99.6%; CTZ nanoencapsulation promoted higher homogeneity values for the film (91%), and the stability studies displayed no changes in the drug content after 120 days for the CTZ-NC-PUL under refrigerated conditions. All formulations were considered non-irritant, and CTZ-NC-PUL promoted a controlled release of the drug (60% in 24 h) compared to CTZ-PUL (100% in 8 h). The permeation results corroborate the drug release, where higher CTZ amounts were found in the mucosa and receptor medium for CTZ-PUL (21.02 and 4.46 µg/cm2). The films were fast dissolving (10 min), and CTZ-NC-PUL presented higher mucoadhesive properties; the antifungal activity against Candida albicans was maintained, and the in vitro efficacy of the film was proved. In conclusion, CTZ-NC-PUL formulation was considered promising and suitable for vaginal application against candida-related infections.

Factores de riesgo asociados al trabajo de parto pretérmino en gestantes del Hospital Universitario Maternidad Nuestra Señora de la Altagracia septiembre-diciembre 2018 / Risk factors associated to preterm labor in pregnant patients in teaching Hospital Maternidad Nuestra Señora de la Altagracia September-December 2018

Objetivo: Determinar los factores de riesgo asociados al trabajo de parto pre-término en gestantes del Hospital Universitario Maternidad Nuestra Señora de la Altagracia, periodo septiembre­diciembre 2018. Método: se realizó un estudio retrospectivo, descriptivo y de corte transversal, con una muestra de 52 mujeres. Los datos obtenidos fueron procesados con el sistema Epi-info 7.0. Resultados: el estudio muestra que entre los factores de riesgo más relevantes se encuentra la multiparidad, mostrando que el 65.4 % tuvieron un número mayor a dos embarazos, de las cuales se encontró que el 52.9 % tienen historia de abortos. Otros factores de riesgo asociados a partos prematuros es la enfermedad obstétrica relacionada, con mayor relevancia la anemia, con un 31.6 %, seguida por las infecciones urinarias con un 17.5 %. Conclusión: el estudio demuestra que dentro de los factores de riesgo asociados a partos pretérminos se encuentran la anemia con un 31.6 % y las infecciones urinarias con un 17.5 %, además el 48.1 % de las pacientes tenían una edad gestacional que rondaba entre 33 y 36 semanas de gestación.

Objective: Determine the risk factors associated to preterm labor in pregnant patients in ''Hospital Maternidad Nuestra Señora de la Altagracia'' in Santo Domingo, September­December 2018. Methods: It is a descriptive, retrospective, and a cross-sectional study, with a sample of 52 women. The data collected was processed with the system Epi-info 7.0. Results: The study shows that multiparity is one of the most relevant risk factors for preterm delivery, showing that 65.4% had a number equal or greater than 2 pregnancies, of which 52.9% had a history of abortion. Others risk factors related to preterm delivery is a concomitant diseases within the pregnancy, being the anemia the most relevant with 31.6% and follow up by urinary tract infections with 17.5%. Conclusion: The study shows that within the risk factors associated with preterm delivery, anemia is within 31.6% and the urinary tract infections are 17.5%, Also related to preterm delivery we have the gestational age which was around 33 ­ 36 weeks in 48.1% of the preterm deliveries.