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BMC Infectious Diseases Nov 2023The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and...
BACKGROUND
The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and explore the correlation between HPV infection and vaginal microecology imbalance and the occurrence of intrauterine adhesion (IUA).
METHODS
A total of 479 women were enrolled in the study, including 259 in the normal group and 220 in the IUA group. Vaginal microecological and HPV analyses were performed on all participants. Significant differences between the two groups were analyzed, and Spearman correlation analysis was performed.
RESULTS
The incidence of IUA in patients between 31 and 40 years of age was high. The I-II degree of vaginal cleanliness in the IUA group was significantly lower than that in the normal group, and the number of III-IV degree was significantly higher than that in the normal group. Moreover, the incidences of VVC (vulvovaginal candidiasis) and vaginal disorders and infections with HPV 16 and HPV 52 subtypes were significantly higher in the IUA group than in the normal group. The incidence of high-risk HPV infection combined with vaginal disorders in the IUA group was higher than that in the normal group. Correlation analysis showed that the occurrence of IUAs was positively correlated with HPV infection and negatively correlated with PH and vaginal microecological imbalance.
CONCLUSION
The HPV infection rate and vaginal microecology disorders affect the occurrence of IUAs. For patients with IUAs, control of the HPV infection rate and the prevention of vaginal microecological disorders should be improved.
Topics: Female; Humans; Cross-Sectional Studies; East Asian People; Papillomavirus Infections; Uterine Diseases; Vagina; Vaginal Diseases; Tissue Adhesions; China
PubMed: 38012631
DOI: 10.1186/s12879-023-08659-1 -
Antimicrobial Agents and Chemotherapy Dec 2023Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against spp., spp., and... (Randomized Controlled Trial)
Randomized Controlled Trial
Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against spp., spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD, = 42), and multiple ascending dose (MAD, = 28) study was conducted in healthy Chinese subjects from March to October 2022. There were three cohorts in the SAD stage (300, 600, and 1,500 mg) and two cohorts in the MAD stage [450 mg once daily (QD) for 7 days; a loading dose of 750 mg twice daily (BID) for the first 2 days followed by a maintenance dose of 750 mg QD for consecutive 5 days]. Eligible participants in each cohort were randomly assigned in a 6:1 ratio to receive either ibrexafungerp or placebo orally. The primary objectives were to evaluate the safety and tolerability. The secondary objective was to evaluate PK parameters, including C, AUC, and t. A total of 70 healthy Chinese subjects were enrolled in the study. The mean (SD) age was 29.0 (6.32), and 55.7% were male. All treatment-emergent adverse events (TEAEs) were mild or moderate. There were no serious adverse events, and no subjects were discontinued from the study due to TEAEs. All TEAEs were recovered or resolved. The most common TEAEs were diarrhea, abdominal pain, and nausea. In the SAD stage, C, and AUC increased in an approximately dose-proportional manner in the dose range of 300-1,500 mg. The mean t was within 18.29-21.30 hours. In the MAD stage, an accumulation of exposure (C and AUC) was observed following multiple doses. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of ibrexafungerp in healthy Chinese subjects.
Topics: Adult; Humans; Male; Female; Area Under Curve; Double-Blind Method; Healthy Volunteers; Triterpenes; Dose-Response Relationship, Drug
PubMed: 37971243
DOI: 10.1128/aac.01075-23 -
Molecules (Basel, Switzerland) Oct 2023In the present work, a series of -terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration...
In the present work, a series of -terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration (MIC) for each compound in fluconazole (FLU)-sensitive (S1) and FLU-resistant (S2) strains of (). The most active compounds in the MIC screen were CHB4 and CHB6, which were then evaluated for cytotoxicity in human cervical cancer cells (KB-3-1) and found to be selective for fungi. Next, CHB4 and CHB6 were investigated for skin irritation using a reconstructed 3D human epidermis and both compounds were considered safe to the epidermis. Using a mouse model of vulvovaginal candidiasis (VVC), CHB4 and CHB6 both exhibited antimycotic efficacy by reducing yeast colonization of the vaginal tract, alleviating injury to the vaginal mucosa, and decreasing the abundance of myeloperoxidase (MPO) expression in the tissue, indicating a reduced inflammatory response. In conclusion, CHB4 and CHB6 demonstrate antifungal activity in vitro and in the mouse model of VVC and represent two new promising antifungal agents.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Fluconazole; Candida albicans; Vagina; Microbial Sensitivity Tests
PubMed: 37959796
DOI: 10.3390/molecules28217377 -
PLoS Pathogens Nov 2023
Topics: Female; Humans; Candidiasis, Vulvovaginal; Recurrence; Antifungal Agents
PubMed: 37948448
DOI: 10.1371/journal.ppat.1011684 -
Biofilm Dec 2023Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by in...
BACKGROUND
Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC.
METHODS
Vaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with -specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate growth in the human vagina. The presence of biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated biofilms to fluconazole at the peak serum concentration was evaluated.
RESULTS
species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole.
CONCLUSIONS
In summary, our study provides direct evidence to support the presence of biofilms in RVVC and an important role of biofilm formation in disease persistence.
PubMed: 37941804
DOI: 10.1016/j.bioflm.2023.100162 -
Frontiers in Cellular and Infection... 2023
Topics: Female; Humans; Vagina; Vaginosis, Bacterial
PubMed: 37928184
DOI: 10.3389/fcimb.2023.1292815 -
Heliyon Nov 2023Recurrent Vulvovaginal Candidiasis (RVVC) is defined as 3 or more episodes of symptomatic Vulvovaginal Candidiasis (VVC) within a year. Out of 75 % of women with VVC,...
BACKGROUND
Recurrent Vulvovaginal Candidiasis (RVVC) is defined as 3 or more episodes of symptomatic Vulvovaginal Candidiasis (VVC) within a year. Out of 75 % of women with VVC, this debilitating infection is experienced by 9 % of women. Although standard guidelines recommend oral and topical fluconazole as its treatment regimen, approval of another drug Oteseconazole has drawn the attention because of its better safety profile and lower recurrence rate by its use.
AIM
The purpose of our Meta-analysis is to evaluate the safety and efficacy of Oteseconazole (Vivjoa) (VT-1161) in the treatment of Recurrent Vulvovaginal Candidiasis (RVVC).
METHODOLOGY
Four databases namely PubMed, Google Scholar, Cochrane CENTRAL and Clinical Trial.gov were used from inception till June 2023. Studies that met the predefined inclusion criteria were statistically analyzed on RevMan (Version 5.4). A random effect model was used to pool the studies. A p value of less than 0.05 was considered significant and results were presented as Odds ratio with 95 % Confidence Intervals (CIs).
RESULT
The pooled analysis of our selected studies showed that Oteseconazole was associated with significantly reduced incidence of Recurrent Vulvovaginal Candidiasis (OR = 0.07; 95 % CI = 0.05-0.11; p < 0.00001, I = 0 %) through week 48. Additionally, Vivjoa has also been shown by our analysis to reduce incidence of RVVC through week 24. (OR = 0.05; 95 % CI = 0.03-0.09; p < 0.00001, I = 0 %) Furthermore, Oteseconazole was non-significantly associated with developing serious adverse effects during the treatment for Recurrent Vulvovaginal Candidiasis in comparison to the placebo (OR = 0.79; 95 % CI = 0.33-1.89; p = 0.60, I2 = 0 %).
CONCLUSION
The available evidence suggests Oteseconazole to be safer and more efficacious. However, limited patient population points towards the need of further large and dedicated trials for definitive conclusion.
PubMed: 37920530
DOI: 10.1016/j.heliyon.2023.e20495 -
Cureus Oct 2023Background Bacterial vaginosis (BV) is a ubiquitous vaginal discomfort and has overlapping symptoms with other reproductive tract infections. The World Health...
Background Bacterial vaginosis (BV) is a ubiquitous vaginal discomfort and has overlapping symptoms with other reproductive tract infections. The World Health Organization suggested a symptomatic approach for diagnosing BV with insufficient laboratory setup. However, due to symptom overlap, BV is often misled and ends up with injudicious drug application. Objective The study aims to identify the most relevant symptoms and behavioral risk factors associated with BV in tertiary healthcare settings in West Bengal, India. It also seeks to develop a scoring system based on clinical symptoms to screen for BV, especially when laboratory facilities are limited. Methodology The study is a retrospective case-control study involving 95 women of reproductive age. It employs both univariate and multivariate binary logistic regression models to identify risk factors and symptoms associated with BV. The study also compares these clinical symptoms with laboratory tests (Amsel's test) and attempts to create a scoring system for BV diagnosis. Key Findings Good menstrual hygiene and condom use were identified as key behavioral practices reducing the risk of BV. Four clinical symptoms, like malodor ( = 0.007), lower abdominal pain ( = 0.015), abnormal vaginal discharge ( = 0.071), and painful intercourse ( = 0.08), were identified as notable predictors. Based on these four symptoms, the scoring system showed a sensitivity of 88.2%, a specificity of 67.25%, and an overall accuracy of 74.7%. An additional diagnosis of vulvovaginal candidiasis (VVC) revealed that the odds of malodor (= 0.006) and burning sensation (= 0.011) increased significantly during co-infection.
PubMed: 37916250
DOI: 10.7759/cureus.46310 -
Frontiers in Cellular and Infection... 2023-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence,... (Review)
Review
-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence, development of resistance, and poor penetration into the biofilm matrix. Various predisposition factors are molecular drivers that lead to the dysbiosis of normal microflora of the vagina, upregulation of central metabolic pathways, morphogenesis, hyphal extension, adhesion, invasion, and biofilm formation leading to chronic infection and recurrence. Hence, it is crucial to understand the molecular mechanism behind the virulence pathways driven by those drivers to decode the drug targets. Finding innovative solutions targeting fungal virulence/biofilm may potentiate the antifungals at low concentrations without affecting the recurrence of resistance. With this background, the present review details the critical molecular drivers and associated network of virulence pathways, possible drug targets, target-specific inhibitors, and probable mode of drug delivery to cross the preclinical phase by appropriate models.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Candida albicans; Antifungal Agents; Vagina; Virulence
PubMed: 37900321
DOI: 10.3389/fcimb.2023.1245808 -
Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments.Microorganisms Sep 2023Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity... (Review)
Review
Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.
PubMed: 37894065
DOI: 10.3390/microorganisms11102407