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Journal of Clinical Medicine Aug 2023Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse... (Review)
Review
Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse treatment regimens are developed; the newest ones include oteseconazole and ibrexafungerp. Here, we focus on the most up-to-date recommendations regarding VVC treatment, as well as novel treatment options. Topical and oral azoles are the drugs of choice in uncomplicated mycosis. The efficacy of probiotics and substances such as TOL-463 and chlorhexidine is indicated as satisfactory; however, there are no relevant guidelines. Although the majority of researchers agree that the treatment of non-albicans VVC should be long-lasting, the recommendations are inconsistent. Another clinical problem is the treatment of VVC with azole intolerance or resistance, for which literature proposes the use of several drugs including oteseconazole, ibrexafungerp, and voriconazole. The treatment schedules for recurrent VVC include mainly fluconazole; however, alternative options such as immunotherapeutic vaccine (NDV-3A) or designed antimicrobial peptides (dAMPs) were also described. We also focused on VVC affecting pregnant women, which is a substantial challenge in clinical practice, also due to the heterogeneous relevant guidelines. Thus far, few precise recommendations are available in the literature. Future studies should focus on atypical VVC forms to elucidate the inconsistent findings.
PubMed: 37629418
DOI: 10.3390/jcm12165376 -
Probiotics and Antimicrobial Proteins Oct 2023Vaginitis is a common problem in women. Candida albicans is responsible for more than 85% of vaginal fungal infections. The aim of this study was to compare the effects... (Randomized Controlled Trial)
Randomized Controlled Trial
Vaginitis is a common problem in women. Candida albicans is responsible for more than 85% of vaginal fungal infections. The aim of this study was to compare the effects of probiotic and fluconazole on the treatment and recurrence of vulvovaginal candidiasis (VVC). This triple-blinded randomized controlled trial was conducted on 80 married women, aged 18-49 years, with VVC, as confirmed by clinical and laboratory diagnosis. The participants were allocated into two groups using blocked randomization method. The fluconazole-treated group received a single dose of fluconazole (150 mg) supplemented with 30 placebo capsules of probiotic, and the probiotic-treated group got 30 probiotic capsules containing 1 × 10 CFU/g LA-5 with 1 fluconazole placebo capsule. The samples were taken from patients to evaluate the vaginal pH and microbiological tests before, 30-35 days, and 60-65 days after starting the treatment. The signs and symptoms were assessed before the intervention and the first and second follow-ups. Chi-square, Fisher's exact, independent t, and ANCOVA tests were then used for data analysis. There was no statistically significant difference between the two groups (p = 0.127) in the frequency of negative culture 30-35 days after starting the treatment, but the frequency of negative culture 60-65 days after starting treatment in the fluconazole group was significantly higher than that of the probiotic group (p = 0.016). The abnormal discharge and vulvovaginal erythema in the first and second follow-ups and also pruritus in the second follow-up in the fluconazole group were significantly lower than those in the probiotic group (p < 0.05). There was, however, no statistically significant difference in burning, frequent urination, dysuria, and dyspareunia between the groups (p > 0.05). Lactobacillus acidophilus supplementation had an effect similar to that of fluconazole in treating most symptoms of VVC, but it was less effective than the latter in preventing recurrence. Trial Registration: Iranian Registry of Clinical Trials (IRCT): IRCT20110826007418N5. Date of registration: 3 March 2021; URL: https://en.irct.ir/trial/50819 ; Date of first registration: 10 March 2021.
Topics: Humans; Female; Fluconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Capsules; Iran; Probiotics
PubMed: 36198994
DOI: 10.1007/s12602-022-09997-3 -
Science Translational Medicine Dec 2023causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by , which, in this setting, triggers nonprotective...
causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by , which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation, releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.
Topics: Female; Humans; Animals; Mice; Candidiasis, Vulvovaginal; Zinc; Vagina; Candida albicans; Inflammation
PubMed: 38055800
DOI: 10.1126/scitranslmed.adi3363 -
Journal of Midwifery & Women's Health 2024
Topics: Humans; Female; Candidiasis, Vulvovaginal; Antifungal Agents; Pregnancy
PubMed: 38738848
DOI: 10.1111/jmwh.13650 -
PLoS Pathogens Nov 2023
Topics: Female; Humans; Candidiasis, Vulvovaginal; Recurrence; Antifungal Agents
PubMed: 37948448
DOI: 10.1371/journal.ppat.1011684 -
Microorganisms Jan 2024Among the infectious causes of vulvovaginal symptoms, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) dominate. Apart from infrequent mixed infections, both... (Review)
Review
Among the infectious causes of vulvovaginal symptoms, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) dominate. Apart from infrequent mixed infections, both are considered independent and caused by unrelated pathogenic mechanisms. Clinical experience, however, is strongly suggestive that in some populations these infections are linked with recurrent BV (RBV) serving as the dominant etiopathogenic trigger for development of recurrent VVC (RVVC) with profound clinical and therapeutic consequences. The biologic basis for this critical interrelationship is discussed and suggests that as a consequence of BV dysbiosis, and not necessarily because of antibiotics prescribed, immune defenses are compromised, neutralizing vaginal yeast tolerance. The consequent BV-induced vaginal proinflammatory environment predisposes to mixed infection or consecutive episodes of post-treatment VVC. Recurrent BV and repeated antimicrobial drug exposure also predispose to acquired fluconazole resistance in isolates, contributing to refractory vulvovaginal candidiasis.
PubMed: 38257934
DOI: 10.3390/microorganisms12010108 -
The Nurse Practitioner Sep 2023Vaginitis symptoms are among the most common reasons for patients to seek acute gynecological care. NPs who care for women and other patients with vaginas need to be... (Review)
Review
Vaginitis symptoms are among the most common reasons for patients to seek acute gynecological care. NPs who care for women and other patients with vaginas need to be up-to-date on diagnosis and treatment of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Two new antifungal medications for VVC are available. This article reviews vaginal physiology and provides an overview of VVC and RVVC pathophysiology, diagnosis, and treatment options.
Topics: Humans; Female; Fluconazole; Candidiasis, Vulvovaginal; Vagina; Critical Care
PubMed: 37643144
DOI: 10.1097/01.NPR.0000000000000095 -
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... 2023
Topics: Female; Humans; Vagina; Vaginosis, Bacterial
PubMed: 37928184
DOI: 10.3389/fcimb.2023.1292815 -
Current Research in Microbial Sciences 2024Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the... (Review)
Review
Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the β-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including and spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the genes, primarily mutations in . In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.
PubMed: 38873590
DOI: 10.1016/j.crmicr.2024.100245