Vulvovaginal Candidiasis Patients Research Articles

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300mg or matching placebo for 1day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CTR20220918.

A multicentre, randomized, double blind, placebo controlled pilot study to evaluate the efficacy and safety of colloidal Nano silver gel (SilverSol) in the treatment of bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis

The study evaluated the efficacy and safety of colloidal nano silver gel (SilverSol Vagigel) (A patented technology from American Biotech Labs, USA) in combination with 0.2% lactic acid in the female subjects for the treatment of vaginal infections.This study was a multicenter, randomized, double-blind, placebo-controlled pilot study in which post-menarchal female subjects between 18 and 65 years of age clinically diagnosed with bacterial vaginosis and vulvovaginal candidiasis were enrolled. The participants were randomized to receive treatment with SilverSol Vagigel or placebo (vehicle) gel (both treatments as one 4 gm application inserted into the vagina with an applicator device, once daily at bedtime for internal use and 2 gm gel for local application to the vulva and vagina for external use twice daily for a period of 14 days). The primary endpoint evaluated was the proportion of subjects achieving clinical cure. The secondary endpoint was the proportion of subjects achieving microbiological cure at the end of the study visit. A total of 57 subjects were randomized in the study out of which 38 subjects were randomized in SilverSol Vagigel arm and 19 subjects were randomized in placebo arm. SilverSol Vagigel significantly improved cure rates of vaginal infections compared to placebo. The proportion of subjects achieving clinical cure of vaginal infections was higher i.e., 33 (86.84%) subjects in SilverSol Vagigel arm compared to 07 (41.18%) subjects in Placebo gel arm (p-value: 0.0009). The clinical cure rate with SilverSol Vagigel was 81.82% (P=0.1758) for bacterial vaginosis and 92.59% (P=0.0010) for vulvovaginal candidiasis patients at the end of the study. Overall SilverSol Vagigel treatment resulted in a significantly higher microbial cure of vaginal infections (P=0.0028) compared to placebo, with a microbial cure rate of 100% for bacterial vaginosis (P=0.0330) and 85.19% for vulvovaginal candidiasis (P=0.0097). No adverse events were reported in subjects treated with SilverSol Vagigel.Colloidal Nano Silver Gel (SilverSol Vagigel) was effective and safe in treating bacterial vaginosis and vulvovaginal candidiasis.

Vaginal homeostasis features of Vulvovaginal Candidiasis through vaginal metabolic profiling.

Vulvovaginal candidiasis (VVC) is an inflammatory disease primarily infected by Candida albicans. The condition has good short-term treatment effects, high recurrence, and seriously affects the quality of life of women. Metabolomics has been applied to research a variety of inflammatory diseases. In the present study, the vaginal metabolic profiles of VVC patients and healthy populations (CTL) were explored by a non-targeted metabolomics approach. In total, 211 differential metabolites were identified, with the VVC group having 128 over-expressed and 83 under-expressed metabolites compared with healthy individuals. Functional analysis showed that these metabolites were mainly involved in amino acid metabolism and lipid metabolism. In addition, network software analysis indicated that the differential metabolites were associated with MAPK signaling and NF-κB signaling. Further molecular docking suggested that linoleic acid can bind to the ACSL1 protein, which has been shown to be associated with multiple inflammatory diseases and is an upstream regulator of the MAPK and NF-κB signaling pathways that mediate inflammation. Therefore, our preliminary analysis results suggest that VVC has a unique metabolic profile. Linoleic acid, a significantly elevated unsaturated fatty acid in the VVC group, may promote VVC development through the ACSL1/MAPK and ACSL1/NF-κB signaling pathways. This study's findings contribute to further exploring the mechanism of VVC infection and providing new perspectives for the treatment of Candida albicans vaginal infection.

Antifungal Properties of Pinus eldarica and Pinus longifolia Fruit Extracts against Candida Species Isolated from Vulvovaginal Candidiasis Patients

Introduction:Candidiasis is a disease with serious problems in women. With the increasing drug resistance and risks of the drugs, we investigated the effect of different cone extracts of Pinus eldarica and Pinus longifolia against Candida species isolated from vulvovaginal candidiasis patients.Materials and Methods::Candida species isolated from 50 patients were identified by routine mycological methods, including morphology of corn mil agar, chromium agar, germination, and biochemical methods. The anti-candida properties of the extracts and essential oils of Pinus eldarica and Pinus longifolia were investigated using agar diffusion and microdilution test. The essential oil was then analyzed by Gas chromatography-mass spectrometry (GC-MS).Results:The major constituents of Pinus longifolia essential oil included 23.16% alpha-pinene, 2.59% beta-caryophyllene, 23.61% delta-3-carene, 0.24% carcin-4-hydroxy, 13.56% m-cymene, 0.45% alpha-humulene, and 2.12% junipene. The major constituents of Pinus eldarica essential oil included 29.13% alpha-pinene, 14.22% beta-caryophyllene, 11.70% delta-3-carene, -14.22% carcin-4-hydroxy, 4.29% beta-pinene, 3.59%, alpha humulene, and 8.86% junipene. The results of antifungal tests showed that aqueous, ethanolic, and methanolic extracts had a weak anti-candida effect. By changing the solvent and using petroleum ether solvent, it was found that petroleum ether extract and cone essential oil of Pinus longifolia and Pinus eldarica exhibited a relatively strong anti-candida effect.Discussion and Conclusion:Comparison of Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of four extracts of Pinus longifolia and Pinus eldarica against different Candida showed that the lowest MIC and MFC were related to essential oil, petroleum ether extract, methanolic extract, ethanolic extract, and aqueous extract, respectively.

Mycobiome Study Reveals Different Pathogens of Vulvovaginal Candidiasis Shape Characteristic Vaginal Bacteriome.

Vulvovaginal candidiasis (VVC) can alter the vaginal microbiome composition and structure, and this may be correlated with its variable treatment efficacy. Integrated analysis of the mycobiome and bacteriome in VVC could facilitate accurate diagnosis of infected patients and further decipher the characterized bacteriome in different types of VVC. Our mycobiome analysis determined two common types of VVC, which were clustered into two community state types (CSTs) featured by Candida glabrata (CST I) and Candida albicans (CST II). Subsequently, we compared the vaginal bacteriome in two CSTs of VVC and two other types of reproductive tract infections (RTIs), bacterial vaginosis (BV) and Ureaplasma urealyticum (UU) infection. The vaginal bacteriome in VVC patients was between the healthy and other RTIs (BV and UU) status, it bore the greatest resemblance to that of healthy subjects. While BV and UU patients have the unique vaginal microbiota community structure, which very different with healthy women. Compared with CST II, the vaginal bacteriome of CST I VVC was characterized by Prevotella, a key signature in BV. In comparison, CST II was featured by Ureaplasma, the pathogen of UU. The findings of our study highlight the need for co-analysis and simultaneous consideration of vaginal mycobiome and bacteriome in the diagnosis and treatment of VVC to solve common clinical problems, such as unsatisfactory cure rates and recurrent symptoms. IMPORTANCE Fungi headed by C. albicans play a critical role in VVC but are not sufficient for its occurrence, indicating the involvement of other factors, such as the vaginal bacteriome. We found that different CST correspond to different bacterial composition in patients with VVC, and this could underlie the alteration of vaginal microorganism environment in VVC patients. We believe that this correlation should not be ignored, and it may be related to the unsatisfactory treatment outcomes and high recurrence rate of VVC. Here, we provided evidence for associations between vaginal bacteriome patterns and fungal infection. Screening specific biomarkers for three common RTIs paves a theoretical basis for further development of personalized precision treatment.

The bacterial communities in vagina of different Candida species-associated vulvovaginal candidiasis

The incidence of vaginal infection caused by Candida species has considerably increased over the past two decades. Candida albicans is the main cause of vulvovaginal candidiasis (VVC); however, non-albicans Candida (NAC) species, such as Candida glabrata and Candida tropicalis, are now frequently identified in VVC patients. Although the vaginal microbiome (VMB) was well studied in Candida albicans-associated VVC patients, the fungal influence on bacterial communities of NAC species-associated VVC and potential microbial interplay contributing to VVC pathology remain elusive. We characterized VMB via Candida albicans and NAC species-associated VVC patients, as Candida albicans (CA, n = 16), Candida glabrata (CG, n = 16), Candida tropicalis (CT, n = 4), and recruiting healthy (CON, n = 20) women as references of dysbiosis and eubiosis. The bacterial diversity of the vagina in the CG group significantly declined. Further, all VVC patients have a higher abundance of Lactobacillus iners, especially for the CG group. Meanwhile, the predicted functions in all VVC are toned which may be associated with a disruption in the bacterial network. In conclusion, according to the taxonomic analysis, we found that the vaginal microbiome in C. glabrata-associated VVC women is different from that of other Candida species-associated VVC women, implying a different pathogenesis.

Improved treatment of vulvovaginal candidiasis with Clotrimazole plus probiotic Lacidophilin Vaginal Capsules: A prospective, real-world study

Clotrimazole has long been used to treat vulvovaginal candidiasis (VVC), yet the antibiotic resistance, adverse effects and recurrences still bring about a great challenge for the clinicians. To explore the effect of probiotic Lacidophilin Vaginal Capsules plus Clotrimazole Vaginal Tablets (500mg) in the treatment of uncomplicated VVC, a self-controlled real-world study was conducted. Twenty-seven women with a normal vaginal flora and 15 women with uncomplicated VVC were recruited. The patients were treated with the single dose of Clotrimazole Vaginal Tablets (500mg) supplemented with 2 Lacidophilin Vaginal Capsules for the following 7 days. The patients were prospectively examined 4 times and the time points were at m0 (the first visit), m1 (8-10 days after the first visit), m2 (30 days after the second visit) and m3 (30 days after the third visit). However, women in the healthy normal control group were examined just once at the first visit. The obtained vaginal secretions were examined by high-throughput sequencing. The mean age in healthy control group and case group was 28.63 ± 5.40y and 27.67 ± 3.33y, respectively. Finally, 46.67% (7/15) of patients were cured at the second visit, 61.54% (8/13) were cured at the third visit and eventually 72.73% (8/11) were cured. A total of 81 samples were sequenced, generating 1668 operation taxonomy units among all the samples. The bacterial composition of women in the healthy control group was exceedingly abundant and dominated by Lactobacillus, especially by Lactobacillus. crispatus, and followed by Lactobacillus. iners, Lactobacillus. jensenii and Gardneralla. On the contrary, the bacterial composition of women with VVC was relatively few and dominated by Lactobacillus. iners. During the process of treatment, the bacterial abundance of VVC patients was increased gradually. At the final visit, the abundance of vaginal flora was augmented further with the dominant bacteria being Lactobacillus. crispatus, followed by Lactobacillus. iners. Clotrimazole Vaginal Tablets plus probiotic Lacidophilin Vaginal Capsules could improve the effect in treating uncomplicated VVC. This improved effect was achieved perhaps through improving the composition of vaginal flora and restoring vaginal microecology.

871. Oral Ibrexafungerp Outcomes by Fungal Disease in Patients from an Interim Analysis of a Phase 3 Open-label Study (FURI)

Abstract Background There are limited oral treatment options for patients with fungal infections who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of, or with fungal disease refractory to, standard antifungal therapy. We present an interim analysis of patient outcomes from the FURI study by fungal disease type. Methods FURI patients are eligible for enrollment if they have proven or probable: severe mucocutaneous candidiasis, invasive candidiasis, chronic or invasive aspergillosis, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options (e.g., due to susceptibility), and continued IV antifungal therapy is clinically undesirable or unfeasible. Results An independent Data Review Committee (DRC) provided an assessment of treatment response for 113 enrolled patients in the FURI study from 27 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016–2021. Fifty-six patients (49.5%) had invasive candidiasis/candidemia, 32 (28.3%) had mucocutaneous candidiasis, 14 (12.4%) had vulvovaginal candidiasis (VVC), and 11 (9.7%) patients had aspergillosis. Upon DRC review, the percent of patients with complete or partial response, or for VVC, clinical improvement (defined as vulvovaginal signs and symptoms score ≤ 1) was 58.4%; stable disease was 23.9%; and 11.5% had disease progression (including 2 VVC patients not meeting the criteria for clinical improvement). There was 1 death due to underlying causes, and 6 outcomes were indeterminate. The table presents outcomes by disease type. Conclusion Analysis of 113 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options. Disclosures George R. Thompson, III, MD, Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Merck: Grant/Research Support|Pfizer: DSMB|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support Thomas King, MS MPH, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds Nkechi Azie, MD MBA FIDSA, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds David A. Angulo, MD, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds.

Genotyping of candida albicans isolates obtained from vulvovaginal candidiasis patients in Zanjan, Iran, based on ABC and RPS typing systems.

Genotyping of pathogenic microorganisms is important for epidemiological studies and the adoption of appropriate strategies to control infectious diseases. In this regard, the present study aimed to genotype Candida albicans strains isolated from vulvovaginal candidiasis (VVC) patients using combined ABC type (25SrDNA) and repetitive sequence (RPS) typing systems. using combined typing systems of ABC type (25SrDNA) and repetitive sequence (RPS). In total, 140 patients with VVC were investigated. Vaginal discharges were collected on Sabouraud dextrose agar and identified by CHROMagar. After species identification, a polymerase chain reaction system targeting 25S rDNA as well as ALT repeats in the RPS was designed to determine C. albicans genotypes. The dendrogram was constructed by zero-one matrix data based on the combination of ABC and RPS typing systems. Statistical analysis of data was performed in SPSS software (version 23). In total, 41 (29.3%) Candida isolates were obtained from 140 VVC patients. The most common Candida species that were identified included C. glabrata (56.1%) and C. albicans (39%). Genotype A3 with five isolates (31.25%) had the highest frequency, followed by B2/3 with three isolates (18.3%), A3/4, C3/4, and B3/4 with two isolates (12.5%), and C2/3 and C3 with one isolate (6.25%), respectively. No significant association was found between the genotypes and antifungal resistance (P<0.05). The results showed that non-albicans Candida species are more prevalent in VVC patients, compared to C. albicans. The results also indicated that ABC and RPS typings are useful for rapid genotyping and differentiation of C. albicans isolates in regional and small-scale studies.

In Vitro Antifungal Activity of Azoles and Other Antifungal Agents Against Pathogenic Yeasts from Vulvovaginal Candidiasis in China.

Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Biased Genotype Distributions of Candida albicans Strains Associated with 649 Clinical Vulvovaginal Candidiasis in China.

Vulvovaginal candidiasis (VVC), which is most frequently caused by Candida albicans, is a common problem worldwide. Despite the fact that extensive epidemiological studies have been performed, the cause of recurrent VVC (RVVC) remains uncertain. The aims of this work were to compare the genotypes of C. albicans strains causing different conditions of VVC, and explore the relationship between the drug resistance and genotype of C. albicans strains. In our study, we collected 649 independent strains from VVC patients in China. Isolates were tested for in vitro susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin in accordance with the Clinical Laboratory Standards Institute (CLSI) document M27-A3. Genotyping was performed using PCR targeting specific CAI locus marker. C. albicans is the main pathogen of VVC, but the proportion of non-candida albicans (NAC) infection is also increasing, and we also found increased cases of mixed infection. Some C. albicans are resistant to multiple drugs. The strains with the genotypes including 16-16, 18-18 and 22-22 was likely to be the dominant genotype of uncomplicated VVC (p < 0.05). The genotypes of complicated VVC are mainly distributed in 30-45, 33-45, 32-46 and 39-45. Strains of 30-45, 32-45, 30-47 and 30-46 genotypes showed resistance to fluconazole, itraconazole, voriconazole and amphotericin B respectively. Our work suggests that the dominant genotypes with higher repeat number of C. albicans strains were more prevalent in patients with RVVC and drug-resistant strains, however, strains with uncomplicated VVC were more likely to distribute in homozygous. Identification of specific genotypes that correlate with different conditions of VVC and drug resistant is also of diagnostic and therapeutic significance.

Vulvovaginal candidiasis in Iranian women: Molecular identification and antifungal susceptibility pattern.

Vulvovaginal candidiasis (VVC), is a common fungal infection that remains a global concern. The objectives of this study were molecular identification and assessment of the antifungal susceptibility profile of Candida species, causing VVC in southeast Iran. A cross-sectional investigation was carried out on 119 nonpregnant females suspected of VVC between February 2019 and May 2021. Yeast samples were characterized to the species level by conventional and molecular methods. All Candida isolates were examined for in vitro susceptibility profile to six conventional antifungal drugs using Clinical and Laboratory Standards Institute guidelines. Out of 119 subjects, 52 (43.7%) cases were affected by VVC, out of whom 11 (21.15%) cases had recurrent vulvovaginal candidiasis (RVVC). The species distribution was as follows; Candida albicans (n=21; 40.4%), C. glabrata (n=11; 21.2%), C. tropicalis (n=9; 17.3%), C. parapsilosis (n=5; 9.7%), C. africana (n=3; 5.7%), C. famata (n=1; 1.9%), C. lusitaniae (n=1; 1.9%), and C. dubliniensis (n=1; 1.9%). The resistance rate of Candida isolates to fluconazole, itraconazole, and voriconazole were 15.38%, 11.5%, and 3.8%, respectively. Resistance to fluconazole was obtained in 46% (5/11) of RVVC cases but only in 7% (3/41) of VVC cases. This study demonstrated that the majority of VVC cases were caused by non-albicans Candida species which also were resistant to some antifungal agents. Hence, our findings revealed the importance of conducting periodical epidemiological studies to determine changes in species distribution. Moreover, for effective management of treatment and infection, it is imperative to evaluate the susceptibility profiles of Candida species isolated from VVC patients.

P056 Oral Ibrexafungerp outcomes by fungal disease in patients from an interim analysis of a Phase 3 Open-label Study (FURI)

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMBackgroundThere are limited oral treatment options for patients with fungal infections who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of, or with fungal disease refractory to, standard antifungal therapy. We present an interim analysis of patient outcomes from the FURI study by fungal disease type.MethodsFURI patients are eligible for enrollment if they have proven or probable: severe mucocutaneous candidiasis, invasive candidiasis, chronic or invasive aspergillosis, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options (e.g., due to susceptibility), and continued IV antifungal therapy is clinically undesirable or unfeasible.ResultsAn independent Data Review Committee (DRC) provided an assessment of treatment response for 113 enrolled patients in the FURI study from 27 centers in US, UK, and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016-2021. A total of 56 patients (49.5%) had invasive candidiasis/candidemia, 32 (28.3%) had mucocutaneous candidiasis, 14 (12.4%) had vulvovaginal candidiasis (VVC), and 11 (9.7%) patients had aspergillosis.Upon DRC review, the percentage of patients with complete or partial response, or for VVC, clinical improvement (defined as vulvovaginal signs and symptoms score ≤ 1) was 58.4%; stable disease was 23.9%; and 11.5% had disease progression (including 2 VVC patients not meeting the criteria for clinical improvement). There was one death due to underlying causes, and six outcomes were indeterminate. Table 1 shows outcomes by disease type.ConclusionsAnalysis of 113 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options.

Kandughna Gana Varti in Vulvo Vaginalcandidiasis - A Case Series

Vulvovaginal candidiasis is an infection caused by yeast like micro organisms called candida albicans. It is the second most common cause of vaginitis affecting women of reproductive age group. It is most distressing and irritating to women, hampers their day to day life and makes them irritable, depressed, anxious and disturbs their interpersonal relationships including marital life. In vulvovaginal candidiasis patients complain of vaginal discharge with intense vulvovaginal pruritus. The pruritus is out of proportion to the discharge. The symptoms of vulvovaginal candidiasis appear similar to the symptoms of Slaishmiki yoni vyapath mentioned in Ayurvedic classics. It is due to the vitiation of Kapha caused by usage of Abishyandi aharas and has symptoms like Pichila yonisrava, Kandu, Alpa vedhana or Avedhana in Yoni. Topical treatments have great importance in the treatment of several gynecological conditions (Yoni vyapaths). Yoni varti or vaginal pessary is used to cleanse the vaginal walls and make the local environment more healthy. It acts directly on the vaginal mucosa and enables easier and target specific action. They are also hygroscopic in property and act in accordance with the drugs they contain. Kandughna gana varti have Tiktha, Kashaya rasa, Laghu, Ruksha guna, Krimighna, Kandughna and Kaphaghna properties and all the ingredients have potent antifungal action also. This facilitates faster absorption of drugs through vaginal mucosa and relieves the symptoms more quickly. A pilot study was conducted in 5 cases to assess the effect of Kandughna gana varti in vulvovaginal candidiasis. It was found to be effective in vaginal discharge and vulvovaginal pruritus.

Analysis of molecular resistance to azole and echinocandin in Candida species in patients with vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is considered the most common mucosal infection caused by Candida species. Azoles were considered the first-line treatment for VVC or recurrent vulvovaginal candidiasis (RVVC) in both healthy and immunocompromised populations. Recently, azole-resistant isolates, especially among non-albicans Candida samples have been encountered. This study aimed to evaluate the antifungal susceptibility profile of Candida spp. isolated from VVC or RVVC patients and assess the molecular resistance mechanism of Candida spp. to azole and echinocandin. Point mutation analysis was performed on the ERG11 and FKS candidate genes of azole- and caspofungin-resistant Candida albicans and Candida glabrata isolates. Real-time polymerase chain reaction was performed to gain insight into the differential expression of ERG11 mRNA. Variations in the amino acid D116E were observed in fluconazole- and itraconazole-resistant C. albicans strains, and changes in amino acid E517Q were observed only in fluconazole-resistant C. albicans strains. No polymorphisms were observed in the complete sequence alignment of the ERG11 gene in one azole-resistant C. glabrata isolate. The mutation triggered the changes in the amino acid serine in the reference gene FKS1 by the leucine at position 642 (S642L) of the isolates. In patients with persistent or recurrent infection, the choice of an antifungal agent is often challenging and requires monitoring of the antifungal susceptibility of the colonizing strain. C. albicans and C. glabrata isolates can be resistant to azole and caspofungin antifungal agents without mutations in the ERG 11 and HS1 regions of the FKS1 gene.

Oral Ibrexafungerp Outcomes in Subjects With Refractory Vulvovaginal Candidiasis From an Open-Label Study (FURI) [A122

INTRODUCTION: Ibrexafungerp, a novel one-day oral triterpenoid antifungal, was recently approved for the treatment of vulvovaginal candidiasis (VVC). Ibrexafungerp is a fungicidal with broad activity against Candida species, including fluconazole-resistant strains. We present data from an open-label Phase 3 study (FURI), which enrolled patients with refractory VVC utilizing a 3-day dose ibrexafungerp regimen. METHODS: FURI VVC subjects were included if they had proven or probable severe VVC, with evidence of treatment failure, intolerance, or toxicity to a currently approved standard-of-care antifungal treatment. Subjects with VVC received ibrexafungerp monotherapy given as oral doses of 375 mg twice daily every three days for a total of three dosing days (Day 1, Day 4, and Day 7). Global Response or Clinical Improvement, defined as complete or partial resolution of signs and symptoms with total vaginal signs and symptoms composite score&lt;1, without need for additional antifungal, was measured at Day 17. RESULTS: There were 14 VVC patients enrolled in FURI from 2019 to 2021. All patients had previously failed other therapies, including fluconazole, and were referred to an infectious disease specialist at a tertiary-care setting. Global response measured at Day 17 indicated that 12 patients (85.7%) had clinical improvement, one patient had partial improvement and one patient was deemed indeterminate. Adverse events for ibrexafungerp were predominantly gastrointestinal, with mild-to-moderate diarrhea, nausea, and abdominal pain. CONCLUSION: These results demonstrate the therapeutic potential of a 3-day dose of oral ibrexafungerp for the treatment of patients with VVC who have failed other treatments.

Candida albicans Multilocus Sequence Typing Clade I Contributes to the Clinical Phenotype of Vulvovaginal Candidiasis Patients

Candida albicans is the most frequent fungal species responsible for vulvovaginal candidiasis (VVC), which exhibits distinct genetic diversity that is linked with the clinical phenotype. This study aimed to assess the genotypes and clinical characteristics of different C. albicans isolates from VVC patients. Based on multilocus sequence typing (MLST), clade 1 was identified as the largest C. albicans group, which appeared most frequently in recurrent VVC and treatment failure cases. Further study of antifungal susceptibility demonstrated that MLST clade 1 strains presented significantly higher drug resistance ability than non-clade 1 strains, which result from the overexpression of MDR1. The mRNA and protein expression levels of virulence-related genes were also significantly higher in clade 1 isolates than in non-clade 1 isolates. Proteomic analysis indicated that the protein stabilization pathway was significantly enriched in clade 1 strains and that RPS4 was a central regulator of proteins involved in stress resistance, adherence, and DNA repair, which all contribute to the resistance and virulence of MLST clade 1 strains. This study was the first attempt to compare the correlation mechanisms between C. albicans MLST clade 1 and non-clade 1 strains and the clinical phenotype, which is of great significance for VVC classification and treatment.

Genotyping and Drug Resistance Profile of Clinical Isolates of Candida albicans from Vulvovaginal Candidiasis in the Eastern China

A total of 244 Candida albicans isolates recovered from vulvovaginal candidiasis (VVC) patients in Suzhou, Eastern China, were investigated. According to CLSI documents M27-A4 and M59-3ed/M60-2ed, the MIC geometric means of nine antifungals in increasing order were micafungin (0.048 mg/L), anidulafungin (0.132 mg/L), caspofungin (0.19 mg/L), itraconazole (0.23 mg/L), posaconazole (0.25 mg/L), voriconazole (0.28 mg/L), 5-flucytosine (0.44 mg/L), amphotericin B (0.49 mg/L) and fluconazole (2.01 mg/L) respectively. Of note, 6.5% (16/244) C. albicans isolates showed resistance mainly to anidulafungin (mono-echinocandin resistance), while voriconazole had the lowest susceptibility rate of 34.8% (85/244), followed by fluconazole 59.4% (145/244), respectively. All isolates were genotyped by allelic combination of 3 microsatellite markers (CEF3, CAIII and LOC4). A total of 129 different allelic genotypes were identified, in which seven different clades were recognized with a discriminatory power of 0.96. Genotypes A-D were present in 35% of the isolates. In conclusion, decrease in antifungal drug susceptibility to C. albicans isolates from VVC is alarming. Our findings revealed the genetic diversity of C. albicans isolates among VVC patients and provided insights into the molecular epidemiology of Candida infections in China.

Prevalência de casos de candidíase vulvovaginal no Amazonas, Brasil

Vulvovaginal candidiasis (VVC) is caused by abnormal growth of yeast on the female genital mucosa. We aimed to analyze the prevalence of VVC in Manaus, its association with pre-exposure factors and antifungal resistance. Study conducted in the public healthcare, involved 1226 women aged 13-84 years. The yeasts were isolated and identified using Candifast test. Symptomatic VVC patients were grouped in symptomatic with one episode in year (SVVC) and symptomatic with recurrent VVC (RVVC), had two or more episodes in year. The total vaginal yeast isolation occurred in 231 women (18.86%). Mixed resistance was observed in 39% of patients. The RVVC group (21.6%) had a higher percentage of positive test for Candida spp. than the symptomatic non-recurrent group (13%). The prevalence of non-albicans spp. demostrated the importance of identify the Candida spp. present in infected patients.

Evaluating the accuracy and diagnostic value of CFW and a new fluorescent reagents, fluorescent brightener 85, for the diagnosis of vulvovaginal candidiasis.

BackgroundVulvovaginal candidiasis (VVC) is a common vaginitis in females. The commonly used diagnostic method, 10% potassium hydroxide (KOH) smear microscopy, makes it not very easy to recognize fungi.MethodsVaginal secretions were collected from clinically suspected VVC patients and divided into four groups and examined using KOH, CFW (Calcofluor White), FB 85(fluorescent brightener 85), and culture. The data were statistically analyzed.ResultsIn total, 110 patients with suspected VVC were recruited. The positive rates of KOH, CFW, FB 85, and the culture method were 68.2%, 64.5%, 61.8%, and 77%, respectively. According to the McNemar test, there was no statistically significant difference between the KOH, CFW, and the FB 85 methods (p > 0.05). However, CFW had a shorter diagnosis time than the KOH method and had a statistically significant difference (p < 0.001). Moreover, CFW has the highest sensitivity, specificity, and accuracy. In morphological recognition, it was easier to recognize fungal structures with CFW and FB 85 than with the KOH.ConclusionsThe fluorescent method is a good method for the diagnosis of VVC. And the fungi can be found more quickly. Similar to CFW, FB 85 is also a potential good fluorescent reagent for the diagnosis of VVC and has potential value for application in clinical fungal infection diseases.