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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 -
Frontiers in Cellular and Infection... 2022
Topics: Female; Humans; Candidiasis, Vulvovaginal
PubMed: 36339342
DOI: 10.3389/fcimb.2022.999967 -
PloS One 2023Cytolytic vaginosis (CV) is a little-known, controversial condition that is typically not considered for women presenting with vulvovaginitis symptoms. Objective: The... (Review)
Review
BACKGROUND
Cytolytic vaginosis (CV) is a little-known, controversial condition that is typically not considered for women presenting with vulvovaginitis symptoms. Objective: The objective of this scoping review was to identify and compile the global evidence on CV.
METHODS
A medical librarian searched Prospero, Wiley Cochrane Library, Ovid Embase, Ovid Medline, EBSCO CINAHL, ProQuest Dissertations and Theses Global, and Scopus, from inception to April 4, 2019 and updated to October 17, 2021. Studies were eligible if they discussed CV. Two independent reviewers conducted study selection and data extraction.
RESULTS
Sixty-four studies were identified, with 67% of studies (n = 43) published since 2007. Studies were from around the world, including the United States (28%, n = 18), Brazil (11%, n = 7), Portugal (11%, n = 7), and China (11%, n = 7). Fifty percent of studies (n = 32) were reviews; the remainder were observational; and of these, 78% (n = 25) were cross-sectional. The most frequent topics included: diagnosis (19%, n = 12), prevalence (17%, n = 11), and overview of CV (50%, n = 32). Evidence for prevalence in symptomatic women (median prevalence of 5%, interquartile range 3%-8%) was based only on 16% of studies (n = 10) with minimal evidence on prevalence in asymptomatic women and across different geographic regions. Microbiological findings, including abundant lactobacilli and fragmented epithelial cells, were found useful to distinguish between CV and vulvovaginal candidiasis, and Lactobacillus crispatus was noted to dominate the vaginal flora in women with CV. Most studies used subjective criteria to diagnose CV as the condition lacks gold-standard microscopic criteria. The suggested primary treatment (baking soda irrigations) was largely based on expert opinion, and there was minimal evidence on associations between CV and other conditions.
CONCLUSION
Knowledge gaps currently exist in all realms of CV research. Additional research is needed to confirm the validity of CV and ensure that women are diagnosed and treated effectively.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Vagina; Cell Death; Lactobacillus; Lactobacillus crispatus
PubMed: 36701339
DOI: 10.1371/journal.pone.0280954 -
Journal of Fungi (Basel, Switzerland) Aug 2021Recurrent vulvovaginal candidiasis (RVVC) is a relapsing vaginal fungal infection caused by species. The prevalence varies among age populations and can be as high as... (Review)
Review
Recurrent vulvovaginal candidiasis (RVVC) is a relapsing vaginal fungal infection caused by species. The prevalence varies among age populations and can be as high as 9%. Treatment options are limited, and in 57% of the cases, relapses occur within six months after fluconazole maintenance therapy, which is the current standard of care. The pathogenesis of RVVC is multifactorial, and recent studies have demonstrated that the vaginal microenvironment and activity of the immune system have a strong influence on the disease. Medical-grade honey (MGH) has protective, antimicrobial, and immunomodulatory activity and forms a putative alternative treatment. Clinical trials have demonstrated that honey can benefit the treatment of bacterial and -mediated vaginal infections. We postulate that MGH will actively fight ongoing infections; eradicate biofilms; and modulate the vaginal microenvironment by its anti-inflammatory, antioxidative, and immunomodulatory properties, and subsequently may decrease the number of relapses when compared to fluconazole. The MGH formulation L-Mesitran Soft has stronger antimicrobial activity against various species than its raw honey. In advance of a planned randomized controlled clinical trial, we present the setup of a study comparing L-Mesitran Soft with fluconazole and its practical considerations.
PubMed: 34436203
DOI: 10.3390/jof7080664 -
Romanian Journal of Morphology and... 2022Candida vulvovaginitis is characterized by the appearance of inflammatory changes in the vaginal and vulvar epithelium secondary to infection with Candida species. The...
Candida vulvovaginitis is characterized by the appearance of inflammatory changes in the vaginal and vulvar epithelium secondary to infection with Candida species. The purpose of this study was to analyze and compare the clinical, microbiological, and histopathological aspects of pregnant and non-pregnant patients, symptomatic or asymptomatic in the case of candida vaginitis and to correlate the microscopic aspects with the symptoms before applying the local treatment with Nystatin. The study presents a retrospective analysis of the management of vaginitis in 166 pregnant or non-pregnant patients during 2021-2022. We observed the structure of the Malpighian squamous epithelium without keratinization present on the vaginal mucosa and the structure of the subepithelial connective tissue, which shows increased numerical values of inflammatory and vascular cellularity in the case of candida vaginitis symptomatic compared to asymptomatic ones. We noticed also in the microscopic study that in cases of asymptomatic patients before treatment, the number of inflammatory cells and blood vessels situated immediately under the epithelium was significantly lower compared to their number in symptomatic patients before treatment. Analyzing the results obtained after the administration of the treatment proposed by us, we can say that local Nystatin treatment is beneficial and safe for pregnant and non-pregnant patients and is a good alternative for patients with recurrent vulvovaginal candidiasis.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Nystatin; Retrospective Studies; Neoplasm Recurrence, Local; Vagina
PubMed: 36588489
DOI: 10.47162/RJME.63.3.05 -
SAGE Open Medicine 2022Vulvovaginal candidiasis is a common infection associated most often with the overgrowth of the fungal species . Although most women will have at least one episode of... (Review)
Review
Vulvovaginal candidiasis is a common infection associated most often with the overgrowth of the fungal species . Although most women will have at least one episode of vulvovaginal candidiasis in their lifetime, some will experience recurrent infections. Recurrent vulvovaginal candidiasis can significantly impact quality of life, causing both physical and psychological symptoms, and poses a substantial financial burden for women and the health care system. Acute vulvovaginal candidiasis infections are often diagnosed symptomatically by clinicians or self-diagnosed by patients themselves; this can result in over- and underdiagnosis, as well as misdiagnosis, and has the potential to lead to ineffective treatment and incomplete infection resolution. Clinical diagnosis should include confirmatory laboratory tests, including microscopy and fungal culture, especially in women with a history of recurrent vulvovaginal candidiasis, who are more likely than women with vulvovaginal candidiasis to be infected with less-common species or with azole-resistant strains. With proper diagnosis, most acute vulvovaginal candidiasis episodes can be successfully treated; however, women with recurrent vulvovaginal candidiasis may require long-term maintenance therapy. US-based guidelines recommend ⩽6 months of maintenance fluconazole treatment, but infection recurs in up to 50% of women treated. There are currently no US Food and Drug Administration-approved treatments for recurrent vulvovaginal candidiasis; however, several promising treatments for recurrent vulvovaginal candidiasis are in development.
PubMed: 36105548
DOI: 10.1177/20503121221115201 -
Drug Design, Development and Therapy 2023Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year... (Review)
Review
Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.
Topics: Pregnancy; Female; Humans; Candidiasis, Vulvovaginal; Fluconazole; Antifungal Agents; Triterpenes; Candida albicans; Azoles; Polyenes
PubMed: 36785761
DOI: 10.2147/DDDT.S339349 -
Indian Journal of Sexually Transmitted... 2021Vaginal candidiasis is one of the most common vaginal infections in women of reproductive age group caused by species of fungi, a normal inhabitant of vagina.
BACKGROUND
Vaginal candidiasis is one of the most common vaginal infections in women of reproductive age group caused by species of fungi, a normal inhabitant of vagina.
AIMS
The aim is to study the culture characteristics, species prevalence, and drug sensitivity of vulvovaginal candidiasis (VVC) among females with genital pruritus and discharge per vaginum who are proved to have infection by a vaginal smear study.
MATERIALS AND METHODS
A prospective study was done on female patients aged 18 years attending the Sexually Transmitted Diseases Clinic of the Department of Dermato-Venereo-Leprology (DVL), Tirunelveli Medical College, with complaints of genital pruritus and vaginal discharge over a period of 1½ years from 2013 to 2015. After clinical examination, vaginal discharge was smeared for wet mount, potassium hydroxide mount, and Gram stain. Those with pseudohyphae were chosen for culture, speciation, and drug sensitivity.
RESULTS
The most common age group affected was 18-35 years. The most common predisposing factor was HIV infection-induced immunosuppression (48.7%), followed by antibiotic usage and diabetes mellitus. Clinical presentation of VVC was similar in HIV-positive and HIV-negative patients. Recurrent VVC makes up 12% of total cases with most common species being whereas among the non-. Drug sensitivity pattern of showed the highest sensitivity to nystatin 85.7%, followed by triazoles (75%-85%) with ketoconazole being more resistant (40%-60%), and was similar in and non-.
LIMITATIONS
Exclusion of unmarried and pregnant women and lack of follow-up were limitations in our study.
CONCLUSIONS
According to our study, elimination of predisposing factors, speciation of fungus, and treatment based on drug sensitivity pattern will reduce the incidence of VVC.
PubMed: 34765939
DOI: 10.4103/ijstd.IJSTD_49_18 -
Frontiers in Microbiology 2020The ability of spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC)... (Review)
Review
The ability of spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of spp. Other studies have employed RNA sequencing to identify differences in the 1,245 genes involved in surface and invasive cellular metabolism regulation. systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation () in specific strains. Murine VVC models are used to study infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript.
PubMed: 33262741
DOI: 10.3389/fmicb.2020.544480 -
Mycopathologia Dec 2023Mucosal and invasive candidiasis can be challenging to treat in the setting of drug intolerance, antifungal resistance, drug-drug interactions, or host immune status.... (Review)
Review
Mucosal and invasive candidiasis can be challenging to treat in the setting of drug intolerance, antifungal resistance, drug-drug interactions, or host immune status. Antifungals with novel mechanisms of action and distinct pharmacokinetic/pharmacodynamic properties have been developed in recent years. Rezafungin is an echinocandin with high-tissue penetration and an extended half-life that allows for once-weekly administration, making it a convenient treatment option for invasive candidiasis while obviating the need for central catheter placement. Ibrexafungerp is an oral glucan synthase inhibitor that is active against most echinocandin-resistant Candida species. At present, it is approved for the treatment of acute vulvovaginal candidiasis and is under investigation as an oral step-down therapy following initial treatment with an echinocandin for cases of invasive candidiasis. Oteseconazole is a long-acting tetrazole that exhibits a higher affinity for the fungal enzyme CYP51, resulting in a potentially lower risk of drug-drug interactions and side effects compared to other azoles. It is currently approved for the treatment of recurrent vulvovaginal candidiasis. Fosmanogepix has a novel mechanism of action and potent activity against several Candida strains resistant to other antifungals. Due to its considerable bioavailability and tissue penetration, it holds promise as a potential treatment option in patients with invasive candidiasis, including those with chorioretinitis or meningitis. Results from clinical trials and observational studies will further delineate the role of these agents in the management of candidiasis. As the usage of these novel antifungals becomes widespread, we expect to acquire a greater understanding of their efficacy and potential benefits.
Topics: Female; Humans; Antifungal Agents; Candidiasis, Vulvovaginal; Echinocandins; Candida; Candidiasis, Invasive
PubMed: 37470902
DOI: 10.1007/s11046-023-00759-5