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Heliyon Apr 2024This study aims to evaluate the efficacy and safety associated with ibrexafungerp in the treatment of vulvovaginal candidiasis infection patients.
BACKGROUND
This study aims to evaluate the efficacy and safety associated with ibrexafungerp in the treatment of vulvovaginal candidiasis infection patients.
METHODS
We conducted a comprehensive search of the PubMed, Embase, Cochrane Library, and Clinical Trials databases up to December 25, 2022. The primary outcomes were clinical cure rate and mycological eradication rate, whereas the secondary outcomes were the risk of an adverse events.
RESULTS
In total of four studies encompassing 880 patients diagnosed with vulvovaginal candidiasis (VVC) were included in the analysis. The findings demonstrated that ibrexafungerp exhibited superior clinical cure ratio (RR = 1.33 [1.07, 1.66]), mycological eradication rate (RR = 1.72 [1.00, 2.95]), and overall success ratio (RR = 1.64 [0.92, 2.92]) when compared to the fluconazole/placebo in the treatment of VVC. Furthermore, patients treated with ibrexafungerp demonstrated significantly higher clinical cure rates, mycological eradication, and overall success ratio compared to those receiving other treatments for vulvovaginal candidiasis caused by . When ibrexafungerp was compared to fluconazole/placebo, the duration of any treatment-related treatment-emergent adverse events (TEAE), nausea, and diarrhea during therapy was significantly longer.
CONCLUSION
In summary, the use of ibrexafungerp was linked to superior clinical cure ratio, and mycological eradication when compared to fluconazole/placebo.
PubMed: 38628772
DOI: 10.1016/j.heliyon.2024.e28776 -
BMC Infectious Diseases Aug 2023Genital tract infections pose a public health concern. In many low-middle-income countries, symptom-based algorithms guide treatment decisions. Advantages...
BACKGROUND
Genital tract infections pose a public health concern. In many low-middle-income countries, symptom-based algorithms guide treatment decisions. Advantages notwithstanding, this strategy has important limitations. We aimed to determine the infections causing lower genital tract symptoms in women, evaluated the Kenyan syndromic treatment algorithm for vaginal discharge, and proposed an improved algorithm.
METHODS
This cross-sectional study included symptomatic non-pregnant adult women presenting with lower genital tract symptoms at seven outpatient health facilities in Nairobi. Clinical, socio-demographic information and vaginal swabs microbiological tests were obtained. Multivariate logistic regression analyses were performed to find predictive factors for the genital infections and used to develop an alternative vaginal discharge treatment algorithm (using 60% of the dataset). The other 40% of data was used to assess the performance of each algorithm compared to laboratory diagnosis.
RESULTS
Of 813 women, 66% had an infection (vulvovaginal candidiasis 40%, bacterial vaginosis 17%, Neisseria gonorrhoea 14%, multiple infections 23%); 56% of women reported ≥ 3 lower genital tract symptoms episodes in the preceding 12 months. Vulvovaginal itch predicted vulvovaginal candidiasis (odds ratio (OR) 2.20, 95% CI 1.40-3.46); foul-smelling vaginal discharge predicted bacterial vaginosis (OR 3.63, 95% CI 2.17-6.07), and sexually transmitted infection (Neisseria gonorrhoea, Trichomonas vaginalis, Chlamydia trachomatis, Mycoplasma genitalium) (OR 1.64, 95% CI 1.06-2.55). Additionally, lower abdominal pain (OR 1.73, 95% CI 1.07-2.79) predicted sexually transmitted infection. Inappropriate treatment was 117% and 75% by the current and alternative algorithms respectively. Treatment specificity for bacterial vaginosis/Trichomonas vaginalis was 27% and 82% by the current and alternative algorithms, respectively. Performance by other parameters was poor to moderate and comparable between the two algorithms.
CONCLUSION
Single and multiple genital infections are common among women presenting with lower genital tract symptoms at outpatient clinics in Nairobi. The conventional vaginal discharge treatment algorithm performed poorly, while the alternative algorithm achieved only modest improvement. For optimal care of vaginal discharge syndrome, we recommend the inclusion of point-of-care diagnostics in the flowcharts.
Topics: Adult; Female; Humans; Kenya; Vaginosis, Bacterial; Reproductive Tract Infections; Candidiasis, Vulvovaginal; Cross-Sectional Studies; Gonorrhea; Communicable Diseases; Genital Diseases, Female
PubMed: 37608250
DOI: 10.1186/s12879-023-08442-2 -
European Journal of Pharmaceutical... Sep 2023Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy...
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.
Topics: Humans; Female; Mice; Animals; Miconazole; Candidiasis, Vulvovaginal; Hyaluronic Acid; Antifungal Agents; Candida albicans; Nanoparticles
PubMed: 37379779
DOI: 10.1016/j.ejps.2023.106508 -
Mycoses Jul 2023Recurrent vulvovaginal candidiasis (RVVC), despite its worldwide prevalence, has limited treatment options; and a long-term prophylactic regimen utilising fluconazole is... (Review)
Review
BACKGROUND
Recurrent vulvovaginal candidiasis (RVVC), despite its worldwide prevalence, has limited treatment options; and a long-term prophylactic regimen utilising fluconazole is the dominant choice.
OBJECTIVES
An increase in fluconazole resistance is reported, and little information is available about the reversibility of resistance status following the withdrawal of fluconazole.
METHODS
Repeated antifungal susceptibility tests (ASTs) for fluconazole at a median interval of 3 months between them were evaluated in women with refractory or recurrent VVC patients at the Vaginitis clinic from 2012 to 2021 (10 years) and performed at pH 7 and pH 4.5 using the broth microdilution tests based on the CLSI M27-A4 reference method.
RESULTS
Of 38 patients with long-term follow-up with repeat ASTs, 13 patients (13/38, 34.2%) tested at pH 7.0 remained susceptible to fluconazole with MIC ≤2 μg/mL. Nineteen patients (19/38, 50%) remained resistant to fluconazole with MIC ≥8 μg/mL, whereas four (4/38, 10.5%) changed from susceptible to resistant and two (2/38, 5.2%) changed from resistant to susceptible over time. At pH 4.5, among the 37 patients with repeated MIC values, nine (9/37, 24.3%) remained susceptible to fluconazole and 22 (22/37, 59.5%) remained resistant. Three isolates (3/37, 8.1%) changed from susceptible to resistant, while 3 (3/37, 8.1%) changed from resistant to susceptible over time.
CONCLUSION
Fluconazole susceptibility in Candida albicans vaginal isolates obtained longitudinally in women with RVVC remains stable with rare reversal of resistance despite azole avoidance.
Topics: Humans; Female; Fluconazole; Candida albicans; Antifungal Agents; Candidiasis, Vulvovaginal; Longitudinal Studies; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 36866967
DOI: 10.1111/myc.13582 -
Reproductive Sciences (Thousand Oaks,... Dec 2023Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are the most common lower genital tract infections in reproductive women. In recent years,...
Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are the most common lower genital tract infections in reproductive women. In recent years, the research on its pathogenesis mainly focuses on vaginal local immunity and IL-17 as key factors in adaptive immunity, attracting much attention. However, the role of IL-17 in local immunity in VVC and RVVC is poorly understood. At the same time, neutrophils are considered the most effective way to control and eliminate candidal infection and have a controversial role in VVC and RVVC. In this study, we built a mouse RVVC model. After analyzing the vaginal lavage solution of RVVC mice with an inflammatory factor antibody chip and ELISA, we found that IL-17 may play a protective role in RVVC. The experiment of constructing RVVC mice with different concentrations of IL-17 using halofuginone and comparing the vaginal fungi load and vaginal epithelial damage verified that IL-17 had a protective effect in RVVC. In addition, in vitro and in vivo studies found that IL-17 can promote neutrophil apoptosis and recruit neutrophils in the vagina. The neutrophils in the vagina can secrete IL-17 in an autocrine manner. These two may be why IL-17 plays a protective role in RVVC. In summary, the study suggests that IL-17-mediated regulation of neutrophil function is involved in host immune response to RVVC, which helps us to further understand the potential mechanism of IL-17 in RVVC.
Topics: Female; Humans; Animals; Mice; Candidiasis, Vulvovaginal; Candida albicans; Neutrophils; Interleukin-17; Vagina; Recurrence
PubMed: 37438557
DOI: 10.1007/s43032-023-01291-z -
Expert Review of Anti-infective Therapy May 2024In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs... (Review)
Review
INTRODUCTION
In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections.
AREAS COVERED
In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients.
EXPERT OPINION
We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.
Topics: Humans; Candida; Antifungal Agents; Female; Candidiasis, Vulvovaginal; Microbial Sensitivity Tests; Drug Resistance, Fungal; Azoles; Species Specificity; Practice Guidelines as Topic
PubMed: 38720183
DOI: 10.1080/14787210.2024.2347953 -
Journal of Ethnopharmacology Jan 2024Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during...
ETHNOPHARMACOLOGICAL RELEVANCE
Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during the Qing dynasty. It has been used extensively to treat vulvovaginal candidiasis (VVC). However, despite its effectiveness, the mechanism of action remains unknown.
AIM OF THE STUDY
To elucidate the mechanism by which LXD relieves VVC via the Toll-like receptor/MyD88 pathway and activation of the NLRP3 inflammasome.
MATERIALS AND METHODS
Female Kunming mice (n = 96) were randomly divided into six groups: control, VVC model, LXD (10/20/40 mL/kg), and positive drug fluconazole. Mice were vaginally administered Candida albicans (C. albicans) solution (20 μL; 1 × 10 colony-forming units/mL), suspended for 5 min, and observed daily for changes in their condition. Continuous dilution was used to determine the number of colony-forming units. Gram, periodic acid-Schiff, Papanicolaou, and hematoxylin and eosin staining were used to determine the extent of infection. Enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of proinflammatory cytokines IL-1β and IL-18. TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 protein expression were determined using western blotting.
RESULTS
C. albicans infection destroyed the integrity of the vaginal mucosa, increased fungal burden and the influx of neutrophils into the vaginal cavity, and promoted the secretion of proinflammatory cytokines. C. albicans stimulated the expression of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 in vaginal tissue. Fungal burden, hyphal formation, and C. albicans adhesion were reduced in the 20 and 40 mL/kg LXD groups. Hematoxylin and eosin staining showed that inflammation was reduced and the stratum corneum had recovered in the 20 and 40 mL/kg LXD groups. LXD (20 and 40 mL/kg) significantly reduced IL-1β, IL-18 levels and the number of neutrophils in vaginal lavage and decreased TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 expression.
CONCLUSIONS
This study systematically demonstrated the therapeutic effect of LXD on protein expression and pathological conditions in VVC mice. The results showed that LXD could eliminate the invasion of vaginal hyphae in mice, reduce the recruitment of neutrophils, and reduce the expression of TLR/MyD88 pathway-related proteins and NLRP3 inflammasome. The above results clearly indicate that LXD may profoundly regulate NLRP3 inflammasome through the TLR/MyD88 pathway and play a therapeutic role in VVC.
Topics: Mice; Humans; Female; Animals; Candidiasis, Vulvovaginal; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Myeloid Differentiation Factor 88; Interleukin-18; NF-kappa B; Toll-Like Receptor 2; Toll-Like Receptor 4; Eosine Yellowish-(YS); Hematoxylin; Candida albicans; Cytokines; Caspases
PubMed: 37390876
DOI: 10.1016/j.jep.2023.116869 -
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 -
Journal of Lower Genital Tract Disease Jul 2023The authors investigate the incidence of clinical and mycological resistance of Candida albicans vulvovaginitis (VVC) at the Jefferson Vulvovaginal Health Center. They...
OBJECTIVE
The authors investigate the incidence of clinical and mycological resistance of Candida albicans vulvovaginitis (VVC) at the Jefferson Vulvovaginal Health Center. They also review their experience with boric acid in the treatment of fluconazole-resistant VVC.
METHODS
The authors conducted a retrospective chart review of all patients with C. albicans VVC diagnosed at the Jefferson Vulvovaginal Health Center between November 2019 and December 2021. Patients with clinically defined fluconazole resistance were identified. Information about demographics, in vitro susceptibility testing, and treatment outcomes with boric acid was obtained.
RESULTS
Of 970 patients with vaginal C. albicans isolates, 71 (7.3%) with clinically defined fluconazole-resistant C. albicans infections were identified. Relevant demographics included 45.1% African American, 43.7% aged younger than 30 years, and 43.7% with body mass index less than 25. Of the 71 patients, 58 (81.7%) received vaginal boric acid treatment. The mycological and clinical cure rates were 85.7% and 73.7%, respectively. After successful boric acid treatment and negative yeast cultures, 14.3% of patients had a mycological recurrence within 3 months. Of 31 isolates with antifungal susceptibility testing, 83.9% (26/31) were found to have minimal inhibitory concentration results consistent with fluconazole resistance.
CONCLUSIONS
In a tertiary care vulvovaginal health center, fluconazole-resistant Candida albicans VVC is by no means uncommon and usually responds in the short term to treatment with boric acid. However, in the absence of maintenance boric acid, recurrence of culture-positive VVC is likely.
Topics: Female; Humans; Aged; Fluconazole; Candida albicans; Antifungal Agents; Retrospective Studies; Candidiasis, Vulvovaginal; Referral and Consultation
PubMed: 36961480
DOI: 10.1097/LGT.0000000000000733 -
3 Biotech Nov 2023The ineffectiveness of azole drugs in treating Vulvovaginal Candidiasis (VVC) and Recurrent Vulvovaginal Candidiasis (RVVC) due to antifungal resistance of non-albicans...
The ineffectiveness of azole drugs in treating Vulvovaginal Candidiasis (VVC) and Recurrent Vulvovaginal Candidiasis (RVVC) due to antifungal resistance of non-albicans Candida has led to the investigation of inorganic nanoparticles with biological activity. Silver nanoparticles (AgNPs) are important in nanomedicine and have been used in various products and technologies. This study aimed to develop a vaginal cream and assess its in vitro antimicrobial activity against strains, specifically focusing on the synergy between AgNPs and miconazole. AgNPs were synthesized using glucose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer in varying amounts (0.50, 0.25, and 0.10 g). The AgNPs were characterized using UV-Visible (UV-Vis) and Fourier-Transform Infrared (FT-IR) spectroscopies, X-Ray Diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Energy Dispersive X-Ray Analysis (EDX). Fifty strains of were used to evaluate the synergistic activity. AgNPs synthesized with 0.5 g SDS had an average size of 77.58 nm and a zeta potential of -49.2 mV, while AgNPs with 0.25 g showed 91.22 nm and -47.2 mV, respectively. AgNPs stabilized with 0.1 g of SDS were not effective. When combined with miconazole, AgNPs exhibited significant antifungal activity, resulting in an average increase of 80% in inhibition zones. The cream developed in this study, containing half the miconazole concentration of commercially available medication, demonstrated larger inhibition zones compared to the commercial samples.
PubMed: 37810191
DOI: 10.1007/s13205-023-03776-9