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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 -
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 -
Frontiers in Public Health 2020The microbiome of the female genital tract may undergo changes in pregnancy due to metabolic, endocrinological, and immunological alterations. These dysbiotic states may... (Review)
Review
The microbiome of the female genital tract may undergo changes in pregnancy due to metabolic, endocrinological, and immunological alterations. These dysbiotic states may cause infections which may ascend upwards to the feto-placental unit or may be seeded hematogenously. These low grade and often low virulent infectious states lead to chronic inflammatory states and maybe associated with adverse maternal and neonatal outcome. Organisms have been isolated from amniotic fluid and placentae from women delivering pre-term; however the possibility of contamination cannot be conclusively ruled out. Common vaginal dysbiotic states often cause symptoms that are overlooked and often untreated. Vulvovaginal Candidiasis (VVC), Bacterial Vaginosis (BV), and Trichomonas Vaginitis (TV) are the commonly occurring dysbiotic states leading to vaginal infective states in pregnancy. With the advent of novel technologies like Next Generation sequencing (NGS), it will soon be possible to comprehensively map the vaginal microbiome and assess the interplay of each microbial state with their effects in pregnancy. This may open new avenues for antibiotic recommendations, probiotics and potential alternate therapies for dysbiotic states leading to pregnancy complications.
Topics: Candidiasis, Vulvovaginal; Dysbiosis; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Trichomonas Vaginitis; Vaginosis, Bacterial
PubMed: 32612969
DOI: 10.3389/fpubh.2020.00225 -
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 -
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 -
The Australasian Journal of Dermatology Aug 2023The incidence and prevalence of recalcitrant cutaneous fungal infections is on the rise. Terbinafine-resistant Trichophyton has not only been widespread in India, but... (Review)
Review
The incidence and prevalence of recalcitrant cutaneous fungal infections is on the rise. Terbinafine-resistant Trichophyton has not only been widespread in India, but has also been reported in countries spread throughout the globe. Strains of yeasts such as Malassezia and Candida, which exist both as commensals and as pathogens to the human skin, have also been found to develop resistance to antifungals. Non-dermatophyte moulds which can colonize and infect damaged nails are especially difficult to treat, not only due to resistance, but also because of poor drug penetration of hard keratin. Psychosocial factors such as the indiscriminate broad-spectrum antifungal use in agriculture and in medicine, and poor adherence to hygienic measures to break the chain of infection contribute to the development of antifungal resistance. Such environments encourage fungi to develop various resistance mechanisms to withstand antifungal treatment. These include: (a) alteration of the drug target, (b) increasing efflux of drug/metabolites, (c) inactivation of drug, (d) bypass mechanisms or substitution of the pathway affected by the drug, (e) stress adaptation mechanisms and (f) biofilm formation. Understanding of such mechanisms and how they arise are crucial for development of new ways to prevent or overcome resistance. Novel antifungal treatments have recently been approved in the United States of America for treatment of vulvovaginal candidiasis. Ibrexafungerp (enfumafungin derivative) and oteseconazole (tetrazole) differ from their respective related drug classes of echinocandins and triazoles by having different structures, which lend these medicines advantage compared to traditional treatment by having a different binding site and more selectivity for fungi respectively. Other drugs designed to circumvent the known mechanisms of antifungal resistance are also at various phases of development. Concurrent measures at an institutional and individual level to address and limit inappropriate antifungal use to reduce development of antifungal resistance should be undertaken in a concerted effort to address this epidemic.
Topics: Female; Humans; Antifungal Agents; Echinocandins; Dermatomycoses; Terbinafine; Candidiasis, Vulvovaginal
PubMed: 37387447
DOI: 10.1111/ajd.14115 -
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 -
Frontiers in Cellular and Infection... 2022
Topics: Female; Humans; Candidiasis, Vulvovaginal
PubMed: 36339342
DOI: 10.3389/fcimb.2022.999967 -
The Journal of Obstetrics and... Dec 2022Vulvovaginal candidiasis (VVC), is a common fungal infection that remains a global concern. The objectives of this study were molecular identification and assessment of...
AIM
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Humans; Female; Candidiasis, Vulvovaginal; Antifungal Agents; Iran; Fluconazole; Cross-Sectional Studies; Drug Resistance, Fungal; Microbial Sensitivity Tests; Candida albicans
PubMed: 36184563
DOI: 10.1111/jog.15442 -
Current Problems in Pediatric and... Jul 2020Vulvovaginitis, referring to inflammation of the vulva and vagina, is a commonly reported concern among adolescents and young women presenting for gynecologic care.... (Review)
Review
Vulvovaginitis, referring to inflammation of the vulva and vagina, is a commonly reported concern among adolescents and young women presenting for gynecologic care. Symptoms of vulvovaginitis may include vaginal discharge, odor, itching, pain, dysuria, skin irritation, burning, and dyspareunia. Vulvovaginitis may result from infectious or non-infectious causes. Bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis represent the three most common infectious causes of vulvovaginitis in adolescents and young adults. Additionally, non-infectious causes such as the presence of a foreign body in the vagina, chemical irritants, douching, and poor hygiene may also lead to symptoms of vulvovaginitis. A thorough history in combination with the appropriate physical examination and laboratory evaluation is necessary to identify the cause of a patient's symptoms. Importantly, adolescent patients should be given the opportunity to speak privately with the provider without a parent or guardian present in the room, particularly when gathering the sexual history. Appropriate anticipatory guidance and counseling should be provided once a diagnosis has been made, and prevention of future episodes of vulvovaginitis should be discussed.
Topics: Anti-Infective Agents; Candidiasis, Vulvovaginal; Female; Humans; Sexual Behavior; Sexually Transmitted Diseases; Vagina; Vulvovaginitis
PubMed: 32778468
DOI: 10.1016/j.cppeds.2020.100836