Vulvovaginal Candidiasis Research Articles

Development of Novel Women's Friendly Antifungal Microemulsion Loaded Gel for Vulvovaginal Infections

Aim: The research was carried out to develop the microemulsion-loaded gel of curcu-min, alkylpolyglucoside, and tea tree oil to treat vulvovaginal candidiasis infection. Methods: Screening of oils, surfactants, and co-surfactants was done based on solubility studies and the construction of pseudo-ternary phase diagrams with curcumin. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex-vivo studies were carried out using Franz diffusion cells. The antifungal activity of microemulsion-loaded hydrogel was evaluated using the cup plate method using Candida albicans ATCC 10231 in glucose yeast agar medium. Results: The selected micro-emulsion consisted of curcumin 35μg/mL, IPM+TTO (1:1) 0.1 mL, Milcoside 100 + Acconon MC 8-2 EP NF 0.6-0.3 mL, phosphate buffer pH 4 160 mL showed maximum thermodynamic stability and exhibited lowest particle size and highest intensity. The viscosity of microemulsion-loaded gel was 11.2 pa.s. The surface tension of the microemulsion was measured by tensiometer and was found to be 26.07 mN/m. Antimicrobial susceptibility test-ing assay was done according to NCCLs assay protocol, and the EC50 value of our formulation was found to be 0.4465 μg/mL. In-vitro drug release and ex-vivo permeation studies showed 67.9% release in 420 minutes and 83.02% release in 360 minutes, respectively. An in-vitro irrita-tion study concluded that there was no redness or irritation on goat mucosa. Conclusion: The texture analysis test showed adhesiveness at -172.46 g s at - 4.60 adhesive force, and the peak load was 13.40 g. The microemulsion-loaded gel formulation can be a promis-ing alternative to the marketed formulations available for vaginal yeast infections.

An update on the pathogenesis and ethnopharmacological therapeutic approaches of vulvovaginal candidiasis

AbstractIn the era of globalization, the concept of world health needs to be practiced where a significant consideration should be given to women health. Of many issues, the most common and under-rated is vulvovaginal candidiasis (VVC); a superficial to invasive mucosal infection of lower reproductive tract in women, primarily caused by commensal yeast Candida. The inability of conventional drugs in triumphing the VVC has made researchers to review the potential of traditional medicines. The present review aimed to highlight the problem and concerns of women related to VVC, covering all aspects of disease development, host response, conventional drug failure, and possibilities of formulating phytomolecule based VVC therapy. The health and disease issues in women are considerably severe, especially for those living in impoverished conditions. Any dysbiosis in vaginal microbiome disturbs the harmony between residing microbes and leads to commencement of VVC. Lactobacillus is key care-taker microbe that keeps check on over growth of Candida by various means. However, Candida have evolved numerous virulence traits to overcome the governance of Lactobacillus as well as host immune system. The present review comprehensively outlined the virulence, and pathogenicity of Candida along with its interaction with host immune system. The review has also highlighted the current conventional drugs and their drawbacks, along with potential of ethnopharmacological phytoactive molecules as future therapies for defining the therapeutic management of the disease. Graphical Abstract

Formulation of Emulgels Containing Clotrimazole for the Treatment of Vaginal Candidiasis

Vaginal candidiasis poses significant health concerns that affect approximately 75% of women globally and often leads to discomfort and a decrease in quality of life. Traditional treatments, despite their effectiveness, may cause discomfort and adverse effects, such as vaginal discharge, bleeding, and dryness, promoting the exploration of alternative formulations. In this study, we aimed to develop a novel therapeutic approach for the treatment of vaginal candidiasis utilizing oleic acid containing emulgels made from thermoresponsive poloxamer-based hydrogels. These emulgels were designed to provide a sustained release of clotrimazole, an antifungal agent. Incorporating oleic acid enhanced the drug’s solubility and contributed to vaginal health. The formulations were characterized by their rheological properties, in vitro release, mucoadhesion, and spreadability. We conducted rheological measurements on the hydrogels that served as the base for the emulgels, as well as on the emulgels themselves. The emulgels exhibited continuous rheological behavior with changing temperatures, making them suitable for storage at room temperature. With an increasing HPMC content, we achieved enhanced mucoadhesion, which is beneficial for formulations used in body cavities. Moreover, in vitro release studies revealed sustained drug release profiles, which can be adjusted by varying the ratios of poloxamers and HPMC. These findings suggest that the developed emulgels offer a promising therapeutic option for vaginal candidiasis, addressing both the symptoms and the treatment of discomfort.

Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application.

Integrating Clinical and Microbiological Expertise to Improve Vaginal Candidiasis Management.

Vaginal candidiasis (VC) is a prevalent condition among women of reproductive age and poses a significant global public health challenge. However, the disease is often diagnosed and treated without mycological information. We investigated the epidemiology, laboratory diagnostics, and antifungal susceptibility of VC. We included 300 women from Çukurova University Obstetrics and Gynecology outpatient clinic in Adana, Türkiye. Participants underwent a health survey and provided vaginal swab samples for microscopic examination and fungal culture. The microscopic analysis involved wet-mount and gram-stained slides, whereas fungal identification involved CHROMAgar Candida, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and real-time polymerase chain reaction high-resolution melting analysis (RT-PCR HRMA). Antifungal susceptibility tests were conducted at pH 7 and 4 using the CLSI document M44-A2. Of the 106 women with positive fungal cultures, 86.8% were diagnosed with VC, whereas 13.2% showed Candida colonization. Among those with VC, 55.4% had acute and 44.6% had recurrent VC; a family history of allergies increased the risk for both types. We recovered 115 yeast isolates, predominantly C. albicans, C. glabrata, and C. krusei. Diagnostic accuracy of CHROMAgar Candida was 91.3% for the most common isolates, and HRMA was consistent in differential diagnosis. Antifungal resistance varied with pH; susceptibility to fluconazole, itraconazole, and ketoconazole decreased at pH 4, whereas susceptibility to miconazole increased. Our findings underscore the need for a diagnostic algorithm and enhanced collaboration between clinicians and microbiologists to improve VC management. Recommendations include using Gram staining, CHROMAgar Candida, MALDI-TOF MS, and antifungal susceptibility tests at both pH levels.

Effective correction of manifestations of vaginal microflora disorders

Pathological vaginal discharge is one of the main reasons for visiting gynecologists. Despite the abundance of drugs, not all are compliant and quickly effective for pronounced itching and swelling in the introitus area. One of the most common causes of pathological leukemia is vaginal infections, which are represented by three main clinical forms: bacterial vaginosis (BV) – up to 50% of all cases; vulvovaginal candidiasis (CVV) – 20–25% and trichomonas vaginitis (TV) – 15–20% of cases, respectively. In this regard, retrospective analysis shows that patients with BV, KV, TV most often actively turn to a gynecologist or venereologist However, the fact that the cause of pathological whites in more than 30% of cases can be a mixed infection creates problems in treatment with the use of monodrugs (many relapses up to 40% or more). Therefore, for their treatment, it is considered rational to use the concept of the etiotropic approach, based on the local effect of combined vaginal drugs. The role of a combined topical drug, including those with a rapid anesthetic effect, was evaluated. Neo-Penotran Forte L is a logical combination of antibacterial agents and a local anesthetic used to treat manifest forms of vaginal infections and provide rapid relief of intolerable symptoms.

Evaluation of the Vaginal Panel Realtime PCR kit (Vircell, SL) for diagnosing vaginitis: A comparative study with routinely used diagnostics.

Vaginitis is a prevalent clinical disorder associated with several adverse health consequences, prompting women to seek medical care. In this study we evaluate the Vaginal Panel Real-Time PCR kit (qPCR test) against routinely used diagnostics for detection of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis. A total of 1011 vaginal swab specimens were analyzed. The routinely diagnostic methods for BV was Gram stain-based Nugent score. VVC presence was detected by culture, and Candida species were identified using MALDI-TOF MS. Trichomonas vaginalis was identified by culture in a selective medium. Molecular analyses were conducted on the MagXtract® 3200 System and analyzed using the CFX96™ Real-Time PCR Detection System. The sensitivity, specificity, positive predictive value, and negative predictive value of the qPCR test compared to the reference method for BV diagnosis was 93.1%, 88.8%, 90.1% and 92.2%, respectively, with a Kappa value of 0.82. For Candida species, sensitivity, specificity, positive predictive value, and negative predictive value were 96.0%, 98.4%, 95.3%, and 98.7%, respectively. The qPCR test detected 32 additional positive samples for Candida not reported by the routinely used diagnostics. For trichomoniasis, the qPCR test identified T. vaginalis in fifteen specimens, despite no microscopic detection in cultured specimens. Our results demonstrate that the Vaginal Panel Real-Time PCR kit shows optimal concordance with routinely used diagnostics for diagnosing vaginitis. Furthermore, enhancing detection of T. vaginalis. However, further validation studies are necessary to confirm its full diagnostic accuracy. The use of nucleic acid amplification tests (NAATs) provides rapid and accurate diagnosis, crucial for early detection and treatment of vaginitis.

Detection of Mutated erg11 and fks1 Genes among Resistant Candida Species Isolated in Pregnant Women in Mbarara, Uganda

Background: Vulvovaginal candidiasis is estimated to range between 35-60% among pregnant women worldwide. The emergency of anti-fungal resistance in Candida species against azoles and caspofungin is a rising concern because there is a limited range of choices of antifungals to be used in pregnant women with low toxicity. In Uganda, the burden of vulvovaginal candidiasis is estimated to be 48%. However, there is limited data regarding in vitro phenotypic and genotypic anti-fungal susceptibility patterns among candida species isolated from pregnant women. Thus, this study aimed to screen for the two mutated famous erg11 and fks1 genes that lead to anti-fungal resistance among clinical candida isolates. Methods: A cross-sectional study involving 90 Candida species isolates previously collected from a larger study carried out from Mbarara regional referral hospital. Phenotypic susceptibility methods (Kirby-Bauer and minimum inhibitory concentration) while Polymerase chain reaction method and gel electrophoresis were used for detection of the amplified mutated ERG11 and FKS1 genes. Mean and chi-square tests were used to evaluate the associations of resistance patterns between resistant and susceptible isolates. Results: Out of the 90 Candida isolates recovered, 56% were Candida albicans, C.glabrata were 31.11% (28/90), C. parapsilosis and C.famata accounted for 4.44% (4/90) each, C. krusei accounted for 3.33% (3/90) while C. tropicalis accounted for 1.11% (1/90). All the Candida isolates were susceptible to caspofungin while fluconazole resistance was 34.4%. The FKS1 mutated gene was not detected in randomly selected caspofungin susceptible isolates. The ERG11 mutated gene was detected in 80.6% of the fluconazole-resistant isolates and 87.5% of the isolates with intermediate activity towards fluconazole. Conclusion: This study provides evidence that mutated erg11 gene causes reduced fluconazole drug susceptibility (p-value 0.001). Susceptible dose dependence should not be ignored as it may be associated with ERG11 gene mutation leading to resistance to fluconazole.

Effects of intravaginal curcumin gels combined with electroporation on vulvovaginal candidiasis

ObjectiveTo provide a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis (VVC) caused by Candida albicans. MethodsTemperature-sensitive in situ gels (ISG) were prepared using poloxamers 407 and 188 as matrices. The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29°C and gelation time of 2.5 min. ResultsElectroporation increased the transmucosal permeability of the model drug, doxorubicin and improved the antifungal effects of curcumin. In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG. In vivo pharmacodynamic experiments showed that, compared to the model group, curcumin ISG with electroporation inhibited the growth of Candida albicans, alleviated vaginal mucosal edema, and reduced the inflammatory response. ConclusionCurcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.

Kushen Gel Combined with Antifungal Drugs for the Treatment of Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Kushen Gel Combined with Antifungal Drugs for the Treatment of Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Long-term outcomes of prolonged fenticonazole therapy in patients with recurrent vulvovaginal candidiasis

Long-term outcomes of prolonged fenticonazole therapy in patients with recurrent vulvovaginal candidiasis

Highlight signatures of vaginal microbiota and metabolome contributed to the occurrence and recurrence of vulvovaginal candidiasis.

This study enhances our knowledge of the vaginal microbiota dynamics and the role of associated metabolites in individuals with vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis through shotgun sequencing and multi-omics analysis. The relationship between metabolites and vaginal microbiota and disease state was revealed. The accumulation of L-glutamate generated in glycogen metabolism, which is governed by Lactobacillus iners or bacterial vaginosis-associated bacteria, may contribute to the incidence and recurrence of VVC. Such insights have the potential to impact the treatment and prevention strategies for these common yet distressing conditions, potentially leading to targeted therapies and improved patient outcomes.

Fungal disease incidence and prevalence in Iraq – Preliminary estimates

BackgroundThe surveillance of serious and superficial skin fungal infections in Iraq has not been conducted. Limited information exists on their incidence and prevalence. ObjectivesThis study aimed to analyze, compute and estimate the prevalence and burden of fungal infections, as no previous data is available and no studies has been attempted in Iraq. MethodsIn the present study the data were collected and reviewed from published data on epidemiology of fungal infections nationally, internationally, from unpublished postgraduate master and PhD theses, hospital records and private clinic records. External sources of data from other countries were used for diseases which lacked sufficient local data. ResultsWe estimated 985,628 annual serious infections comprising of 2.26 % of the total population. When including superficial fungal infections group of the skin, this rises to 2,075,113 infections at 4.76 % of the total population. The most common serious and skin infections were recurrent Candida vaginitis, fungal rhinosinusitis and tinea capitis comprising 61.5 %, 21.8 %, and 22.4 % of all infections although the total incidence of superficial fungal infections was also high at 1,071,485. Respiratory fungal disease is also common comprising 14.0 % of infections. We predicted the following annual burden per 100,000; oral candidiasis at 247.9, esophageal candidiasis at 6.04, candidemia at 5.0, Candida peritonitis at 0.75, recurrent Candida vaginitis at 5461, allergic bronchopulmonary aspergillosis at 35, severe asthma with fungal sensitisation at 46, invasive aspergillosis at 7.9, chronic pulmonary aspergillosis at 11.7, chronic fungal rhinosinusitis at 496, mucormycosis at 0.99, fungal keratitis at 14.0, and total dermatophytosis at 1631, the most severe being tinea capitis at 366. Many of these estimates were made with data sourced from other nations, so additional data from Iraq is required to validate or modify these estimates. ConclusionRecurrent Candida vaginitis, fungal rhinosinusitis, and tinea capitis are considered to be the most frequent fungal diseases present in Iraq.

Identifying changes in vaginal fluid using SERS: Advancing diagnosis of vulvovaginal candidiasis

Vaginal infections, medically termed vaginitis, encompass a spectrum of symptomatic presentations arising from disturbances within the vaginal microflora. The conventional diagnostic approach relies on microscopic examination of wet preparation of vaginal discharge, considered the ‘gold standard’ in clinical practice. Complementary to this, culture-based methodologies are often employed to reinforce diagnostic accuracy. However, challenges such as subjectivity in result interpretation, resource-intensive requirements regarding skilled personnel, and reagent utilization underscore the need for alternative diagnostic strategies.In this article, we demonstrate surface-enhanced Raman spectroscopy (SERS) and partial least squares regression (PLSR) techniques to elucidate the molecular signatures present in vaginal fluids, accounting for various influencing factors, including disruptions in the natural microflora, vaginal irrigation practices, and contraceptive usage. Furthermore, we investigated the spectral manifestations associated with vulvovaginal candidiasis (VVC) relative to control samples. Each clinical specimen underwent meticulous characterization encompassing microbial composition, pH levels, purity, and other pertinent parameters.Our findings unveil significant associations between extraneous inflammatory factors such as vaginal irrigation and diminished sample purity with alterations in SERS signals. Conversely, the day of the menstrual cycle phase exhibits negligible influence on spectral profiles. Notably, VVC samples demonstrated diverse spectral responses correlating with the abundance of pathogenic bacteria. These explorations hold promise in paving the path towards developing a novel intrinsic framework for the diagnosis of vaginitis.

Three-Dose Antifungal Treatment Improves the Efficacy for Severe Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is a prevalent gynecological infection characterized by high incidence and recurrent episodes, causing significant distress in women. This study aims to assess the effectiveness of different clotrimazole and fluconazole treatment regimens for severe vulvovaginal candidiasis (SVVC). A retrospective analysis was conducted on 1303 cases of SVVC among first-time visitors to the gynecology outpatient department at Peking University Shenzhen Hospital between January 2013 and December 2022. Vaginal secretions were systematically collected for fungal culture, with species identification conducted using Chromogenic culture medium and API Candida test reagents. Mycological cure rates were assessed at days 7–14, days 25–35, and day 35 to 6 months after treatment. The three-dose clotrimazole regimen demonstrated significantly higher mycological cure rates (85.7%, 80.0% and 74.6% at three follow-up periods, respectively) compared to the two-dose clotrimazole regimen (76.0%, 61.6%, and 59.8%, all P < 0.05). The three-dose fluconazole regimen showed no significant difference to three-dose clotrimazole regimen, with cure rates of 82.8%, 79.3%, and 75.9% (all P > 0.05). The two-dose fluconazole regimen had cure rates of 74.3%, 56.4% and 51.1%, with no significant difference from two-dose clotrimazole regimen at days 7–14 and 25–35, but lower than three-dose fluconazole regimen at days 25–35 and 35 to 6 months. The three-dose clotrimazole regimen demonstrated higher cure rates in Candida albicans and non-albicans Candida SVVC cases than two-dose regimen. These findings suggest that three-dose antifungal regimens may be more efficacious than two-dose regimens for SVVC. The three-dose clotrimazole regimen could serve as a promising alternative for SVVC management.

Effects and Mechanisms of Lactobacillus Probiotics in Maintaining Women’s Vaginal Health: A Review

Probiotics are beneficial living microorganisms. They are useful to vaginal health when consumed in suitable doses. The dominant species included in probiotics are Lactobacillus. We can get these microbes naturally or commercially utilize them as functional food. Lactobacillus species form 70% of inhabitant bacteria in females compared to other warm-blooded animals. The prevalent Lactobacillus species are L. crispatus, L. gasseri, L. iners and L. jensenii. Because of the development of antibiotic resistance mechanisms, the beneficial relationship between humans and probiotics has been discussed for several years. Lactobacillus prevents the attachment of pathogens by using several mechanisms, for example, by increasing estrogen levels, production of lactic acid, lowering pH 4.0-4.5 to provide an acidic environment, release of hydrogen peroxide, bacteriocins and bacteriocins-like substances, adhesion and colonization properties. Lactobacillus prevent the entry and attachment of pathogenic bacteria, thus not only helping to control and manage different gynecological conditions like bacterial vaginosis, endometriosis, vulvovaginal candidiasis and genitourinary syndrome of menopause but also infections that can spread through sexual contacts such as gonorrhea, chlamydia, genital herpes, Human papillomavirus infections (HPV). Overall, the use of probiotics in improving vaginal health is beneficial, easy and cost-effective but the use of probiotics in HPV clearance is not quite beneficial. So, more work should be done on HPV preventive vaccines.

Pulsatilla suppository prevents recurrent vulvovaginal candidiasis in a rat model via the TLR/MyD88/NLRP3 signaling pathway

Fungal infection caused by Candida albicans is a serious health problem, and as drug resistance worsens, new sources for therapeutic compounds are needed. Traditional Chinese medicine represents a wealth of such sources, and can be designed as suppositories for the treatment of recurrent vulvovaginal candidiasis (RVVC). This study aimed to develop a Pulsatilla suppository containing the n-butanol extract of Pulsatilla decoction (BEPD) to treat RVVC. A Pulsatilla suppository containing BEPD was prepared, and its performance, weight, drug content, dissolution time and percentage, stability, toxicology, and pharmacodynamics were evaluated. Biological compatibility tests and clinical evaluations were performed in female Sprague–Dawley rats. The Pulsatilla suppository melted completely within 30 min. In vitro anti-C. albicans activity, stability changes, and toxicology tests indicated stability and safety in the rats. Compared with RVVC model rats, high-dose BEPD suppository (40, 60 mg/kg) can significantly reduce the vaginal fungal load of rats, relieve neutrophil infiltration, reduce the content of TLR/MyD88 pathway-related proteins, and reduce the expression of inflammatory factors such as NLRP3, demonstrating the efficacy of the Pulsatilla suppository in RVVC.

Rapid Molecular Diagnostics in Vulvovaginal Candidosis.

Vulvovaginal candidosis (VVC) is a common condition among women, with current diagnostic methods relying on clinical evaluation and laboratory testing. These traditional methods are often limited by the need for specialized training, variable performance, and lengthy diagnostic processes, leading to delayed treatment and inappropriate antifungal use. This review evaluates the efficacy of molecular diagnostic tools for VVC and provides guidance on their application in clinical practice. A literature search was conducted using PubMed to identify studies evaluating rapid diagnostic tests specifically for vulvovaginal Candida isolates. Inclusion criteria focused on studies utilizing molecular diagnostics for the detection of Candida species in VVC. Articles discussing non-vaginal Candida infections, non-English studies, and animal or in vitro research were excluded. Twenty-three studies met the inclusion criteria, predominantly evaluating nucleid acid amplification tests/polymerase chain reaction (NAAT/PCR) assays and DNA probes. PCR/NAAT assays demonstrated high sensitivity and specificity (>86%) for VVC diagnosis, outperforming conventional diagnostic methods. Comparatively, DNA probes, while simpler, exhibited lower sensitivity. The included studies were mostly observational, with only one randomized controlled trial. Emerging diagnostic technologies, including artificial intelligence and integrated testing models, show promise for improving diagnostic precision and clinical outcomes. Molecular diagnostics offer a significant improvement in VVC management, though traditional methods remain valuable in resource-limited settings.

Clotrimazole-induced shifts in vaginal bacteriome and lipid metabolism: insights into recovery mechanisms in vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant proportion of women worldwide, with recurrent episodes leading to detrimental effects on quality of life. While treatment with clotrimazole is common, the specific alterations it evokes in the vaginal bacteriome and metabolome were previously underexplored. In this prospective study, we enrolled reproductive-age women diagnosed with single VVC and conducted comprehensive analyses of vaginal fungi, bacteriome, and metabolome before and after local clotrimazole treatment. We observed a significant reduction in Candida albicans and notable improvements in vaginal cleanliness. Advanced sequencing revealed substantial shifts in the vaginal bacteriome, with an increase in Lactobacillus-dominant communities post-treatment. Our findings identified 17 differentially abundant bacterial species, including notable decreases in pathogenic anaerobes such as Gardnerella vaginalis, Dialister micraerophilus, and Aerococcus christensenii, suggesting a restoration of a healthier microbial balance. Furthermore, metabolomic analysis revealed significant changes in 230 metabolites, particularly within lipid metabolism pathways, with marked downregulation of lipid-related compounds linked to inflammation. Correlation studies indicated a strong interplay between lipid metabolites and specific bacterial species, emphasizing the influence of clotrimazole treatment on microbial and metabolic interactions. Importantly, predictive models using microbiota and metabolite signatures demonstrated high accuracy in distinguishing pre- and post-treatment states. This research highlights clotrimazole's dual role in effectively clearing Candida infection and promoting a healthier vaginal microenvironment, paving the way for novel microbial and metabolomic-based diagnostic approaches to enhance VVC management and understand its underlying mechanisms.

Development of synergistic antifungal in situ gel of miconazole nitrate loaded microemulsion as a novel approach to treat vaginal candidiasis

Limited solubility is the main cause of the low local availability of anti-candidiasis drug, miconazole nitrate (MN). The study’s objective was to develop and characterize microemulsion (ME) based temperature-triggered in situ gel of MN for intravaginal administration to enhance local availability and antifungal activity. The solubility of MN was initially studied in different oils, surfactants, and co-surfactants. Then, pseudo-ternary phase diagrams were constructed to select the best ratio of various components. The ME formulations were characterized by thermodynamic study, droplet size, polydispersity index (PDI), viscosity, and in-vitro antifungal mean inhibition zone (MIZ). Selected MEs were incorporated into different in situ gel bases using a combination of two thermosensitive polymers (poloxamer (PLX) 407 and 188), with 0.6% of hydroxypropyl methylcellulose (HPMC K4M) and gellan gum (GG) as mucoadhesive polymer. ME-based gels (MG) were investigated for gelation temperature, gelation time, viscosity, spreadability, mucoadhesive strength, in vitro release profile, and MIZ test. Furthermore, the optimum MG was assessed for in vivo animal irritation test and FESEM investigation. Tea tree oil, lavender oil, tween 80, and propylene glycol (PG) were chosen for ME preparation for the optimal formulation; formulation ME7 and ME10 were chosen. After incorporation of the selected formulation into a mixture of P407 and P188 (18:2% w/w) with 0.6% mucoadhesive polymer, the resultant MG formulation (MG1) revealed optimum gelation temperature (33 ± 0.01℃) and appropriate viscosity with enhanced sustained release (98%) and retention through sheep vaginal mucosa, MG1 exhibited a better MIZ compared to the 2% MN gel formulation and the marketed MN product, and no rabbit vagina irritation. In conclusion, the miconazole nitrate-loaded MG-based formula sustained the duration of action and better antifungal activity than the marketed miconazole nitrate formulation.