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Journal of Obstetrics and Gynaecology :... Dec 2023At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a... (Review)
Review
At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in , in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.
Topics: Female; Humans; Miconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; Nystatin; Candida albicans; Cytochrome P-450 Enzyme System
PubMed: 37029724
DOI: 10.1080/01443615.2023.2195001 -
Frontiers in Microbiology 2022"Unity in strength" is a notion that can be exploited to characterize biofilms as they bestow microbes with protection to live freely, escalate their virulence, confer... (Review)
Review
"Unity in strength" is a notion that can be exploited to characterize biofilms as they bestow microbes with protection to live freely, escalate their virulence, confer high resistance to therapeutic agents, and provide active grounds for the production of biofilms after dispersal. Naturally, fungal biofilms are inherently resistant to many conventional antifungals, possibly owing to virulence factors as their ammunitions that persistently express amid planktonic transition to matured biofilm state. These ammunitions include the ability to form polymicrobial biofilms, emergence of persister cells post-antifungal treatment and acquisition of resistance genes. One of the major disorders affecting vaginal health is vulvovaginal candidiasis (VVC) and its reoccurrence is termed recurrent VVC (RVVC). It is caused by the species which include and . The aforementioned species, notably is a biofilm producing pathogen and habitually forms part of the vaginal microbiota of healthy women. Latest research has implicated the role of fungal biofilms in VVC, particularly in the setting of treatment failure and RVVC. Consequently, a plethora of studies have advocated the utilization of probiotics in addressing these infections. Specifically, the excreted or released compounds of probiotics which are also known as postbiotics are being actively researched with vast potential to be used as therapeutic options for the treatment and prevention of VVC and RVVC. These potential sources of postbiotics are harnessed due to their proven antifungal and antibiofilm. Hence, this review discusses the role of biofilm formation in VVC and RVVC. In addition, we discuss the application of pro-, pre-, post-, and synbiotics either individually or in combined regimen to counteract the abovementioned problems. A clear understanding of the role of biofilms in VVC and RVVC will provide proper footing for further research in devising novel remedies for prevention and treatment of vaginal fungal infections.
PubMed: 35694318
DOI: 10.3389/fmicb.2022.787119 -
MBio Apr 2023The polymorphic fungus Candida albicans remains a leading cause of both invasive and superficial mycoses, including vulvovaginal candidiasis (VVC). Metabolic plasticity,...
The polymorphic fungus Candida albicans remains a leading cause of both invasive and superficial mycoses, including vulvovaginal candidiasis (VVC). Metabolic plasticity, including carbohydrate catabolism, confers fitness advantages at anatomical site-specific host niches. C. albicans possesses the capacity to accumulate and store carbohydrates as glycogen and can consume intracellular glycogen stores when nutrients become limited. In the vaginal environment, estrogen promotes epithelial glycogen accumulation and C. albicans colonization. However, whether these factors are mechanistically linked is unexplored. Here, we characterized the glycogen metabolism pathways in C. albicans and investigated whether these impact the long-term survival of C. albicans, both and during murine VVC, or virulence during systemic infection. SC5314 and 6 clinical isolates demonstrated impaired growth when glycogen was used as the sole carbon source, suggesting that environmental glycogen acquisition is limited. The genetic deletion and complementation of key genes involved in glycogen metabolism in Saccharomyces cerevisiae confirmed that and , as well as and , are essential for glycogen synthesis and catabolism in C. albicans, respectively. Potential compensatory roles for a glucoamylase encoded by were also explored. Competitive survival assays revealed that , Δ/Δ, and mutants exhibited long-term survival defects under starvation conditions and during vaginal colonization. A complete inability to catabolize glycogen () also rendered C. albicans significantly less virulent during disseminated infections. This is the first study fully validating the glycogen metabolism pathways in C. albicans, and the results further suggest that intracellular glycogen catabolism positively impacts the long-term fitness of C. albicans in nutrient deficient environments and is important for full virulence. Glycogen is a highly branched polymer of glucose and is used across the tree of life as an efficient and compact form of energy storage. Whereas glycogen metabolism pathways have been studied in model yeasts, they have not been extensively explored in pathogenic fungi. Using a combination of microbiologic, molecular genetic, and biochemical approaches, we reveal orthologous functions of glycogen metabolism genes in the fungal pathogen Candida albicans. We also provide evidence that extracellular glycogen poorly supports growth across the species and clinical isolates. Competitive fitness assays reveal that the loss of glycogen synthesis or catabolism significantly impacts survival during both starvation and the colonization of the mouse vagina. Moreover, a global glycogen catabolism mutant is rendered less virulent during murine invasive candidiasis. Therefore, this work demonstrates that glycogen metabolism in C. albicans contributes to survival and virulence in the mammalian host and may be a novel antifungal target.
Topics: Female; Humans; Animals; Mice; Candida albicans; Virulence; Candidiasis, Vulvovaginal; Antifungal Agents; Candidiasis, Invasive; Glycogen; Mammals
PubMed: 36840583
DOI: 10.1128/mbio.00046-23 -
Journal of Xenobiotics Jul 2023Vulvovaginitis with spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to...
Vulvovaginitis with spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to present challenges and the decision must balance the risk of fetal toxicity with the benefits to the fetus and mother. Starting from the idea that clotrimazole is the most recommended antifungal in candidal vaginitis in pregnancy, we tested the sensitivity of different species of spp. to other azoles, polyenes, and antimetabolites. This retrospective study (January to June 2019) assessed 663 pregnant women hospitalized for various pregnancy-related symptoms in which samples of phage secretion were taken. The laboratory results confirmed 21% of cases, indicating 140 positive mycologic samples. In this study, vaginal candidiasis was mostly related to the first trimester of pregnancy (53.57%,) and less related in the last trimester (17.14%). was the most frequent isolated strain in this study, accounting for 118 cases, followed by 16 strains of and 6 cases of . The highest sensitivity for was found in azoles, mostly in miconazole (93.2%), while was completely resistant to polyene with low sensitivity in antimetabolites and even in some azoles, such as fluconazole. In our study, higher resistance rates to flucytosine were found, with and exhibiting greater resistance than .
PubMed: 37489336
DOI: 10.3390/jox13030023 -
Pharmacology Research & Perspectives Oct 2021Lactobacilli are the predominant microorganisms of the healthy human vagina. A novel alternative for the prevention and treatment of female urogenital tract infections... (Review)
Review
Lactobacilli are the predominant microorganisms of the healthy human vagina. A novel alternative for the prevention and treatment of female urogenital tract infections (UGTI) is the inclusion of these microorganisms as active pharmaceutical ingredients in probiotic formulas, and more recently in female hygienic products. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host." A list of requirements must be considered during the development of probiotic product/formula for the female urogenital tract (UGT). This review aims to resume the requirements, probiotic characteristics, and clinical trial applied to determine the effect of probiotic and potentially probiotic strains on different woman's physiological and pathological conditions, and in preterm birth prevention. A revision of female hygienic products available in the world market is included, together with novel studies applying nanotechnology for Lactobacillus incorporation in hygienic products. Further studies and well-designed clinical trials are urgently required to complement the current knowledge and applications of probiotics in the female UGT. The use of probiotic formulas and products will improve and restore the ecological equilibrium of the UGT microbiome to prevent and treat UGTI in women under different conditions.
Topics: Candidiasis, Vulvovaginal; Carrier State; Cesarean Section; Delivery, Obstetric; Female; Feminine Hygiene Products; Genitalia, Female; Humans; Lactobacillus; Microbiota; Nanotechnology; Premature Birth; Probiotics; Streptococcal Infections; Streptococcus agalactiae; Trichomonas Vaginitis; Urinary Tract; Vagina; Vaginosis, Bacterial
PubMed: 34609059
DOI: 10.1002/prp2.787 -
Microorganisms May 2023Vulvovaginal candidiasis (VVC), which is primarily caused by , is an infection that affects up to 75% of all reproductive-age women worldwide. Recurrent VVC (RVVC) is... (Review)
Review
Vulvovaginal candidiasis (VVC), which is primarily caused by , is an infection that affects up to 75% of all reproductive-age women worldwide. Recurrent VVC (RVVC) is defined as >3 episodes per year and affects nearly 8% of women globally. At mucosal sites of the vagina, a delicate and complex balance exists between spp., host immunity and local microbial communities. In fact, both immune response and microbiota composition play a central role in counteracting overgrowth of the fungus and maintaining homeostasis in the host. If this balance is perturbed, the conditions may favor overgrowth and the yeast-to-hyphal transition, predisposing the host to VVC. To date, the factors that affect the equilibrium between spp. and the host and drive the transition from commensalism to pathogenicity are not yet fully understood. Understanding the host- and fungus-related factors that drive VVC pathogenesis is of paramount importance for the development of adequate therapeutic interventions to combat this common genital infection. This review focuses on the latest advances in the pathogenic mechanisms implicated in the onset of VVC and also discusses novel potential strategies, with a special focus on the use of probiotics and vaginal microbiota transplantation in the treatment and/or prevention of recurrent VVC.
PubMed: 37317186
DOI: 10.3390/microorganisms11051211 -
Heliyon Mar 2024Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and... (Review)
Review
Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and obstetric outcomes, including preterm delivery, sexually transmitted infections and pelvic inflammatory disease. Although effective control of VVC is achievable with the use of traditional treatment strategies (i.e., antifungals), the possibility of drug intolerance, treatment failure and recurrence, as well as the appearance of antifungal-resistant species remain critical challenges. Therefore, alternative therapeutic strategies against VVC are urgently required. In recent years, an improved understanding of the dysbiotic vaginal microbiota (VMB) during VVC has prompted the consideration of administering -biotics to restore the balance of the VMB within the context of VVC prevention and treatment. Here, we aim to summarize the current evidence of the anti- effects of probiotics, postbiotics and synbiotics and their potential use as an alternative/complementary therapy against VVC. Additionally, this review discusses advantages and challenges associated with the application of -biotics in VVC to provide guidance for their later use. We also review new developments in VVC therapy, i.e., vaginal microbiota transplantation (VMT) as an emerging live biotherapeutic therapy against VVC and discuss existing shortcomings associated with this nascent field, expecting to stimulate further investigations for introduction of new therapies against VVC.
PubMed: 38463778
DOI: 10.1016/j.heliyon.2024.e27239 -
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 -
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 -
Journal de Mycologie Medicale Nov 2022Vaginal infections are one of the most common reason for gynecological consultations. Many of them are the result of overgrowth of resident microorganisms. The clinical...
INTRODUCTION
Vaginal infections are one of the most common reason for gynecological consultations. Many of them are the result of overgrowth of resident microorganisms. The clinical symptoms of vulvovaginal candidiasis are nonspecific and an accurate diagnosis is a problem that often leads to inadequate treatment or delays in treatment. The lack of an exact and practical diagnostic method is a common cause of misdiagnosis.
AIM
To create a complex, quantitative method for the diagnosis of vulvovaginal candidiasis which to enables differentiation from vaginal fungal colonization.
MATERIAL AND METHODS
A total of 2306 vaginal samples were examined. Clinical, microbiological, epidemiological methods and statistical models are used.
RESULTS AND DISCUSSION
The proposed score system is a specific, sensitive and inexpensive method to routinely diagnose vulvovaginal candidiasis. Statistical processing of the obtained data shows the impact of the individual components on which the method is based: the presence of vaginal discharge, pruritus, direct microscopy and assessment of the fungal growth. The data analysis reveals good sensitivity (71%) and high specificity (98%) of the method. This allows accurate interpretation of the result of the clinical and microbiological examination of each patient.
CONCLUSION
The system for diagnosing vulvovaginal candidiasis is complex and based on quantitative indicators. The method can be used to differentiate vulvovaginal candidiasis from vaginal fungal colonization (the cut-off value is 5.5 points) and to more accurately interpret a Candida positive result from quantitative real-time PCR in asymptomatic patients or in women with mixed vaginal infection.
Topics: Humans; Female; Candidiasis, Vulvovaginal; Candida; Vagina
PubMed: 35717682
DOI: 10.1016/j.mycmed.2022.101302