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Pharmaceutical Research Feb 2023Vulvovaginal candidiasis (VVC) is an opportunistic and endogenous infection caused by a fungus of the Candida genus, which can cause pruritus, dysuria, vulvar edema,... (Review)
Review
Vulvovaginal candidiasis (VVC) is an opportunistic and endogenous infection caused by a fungus of the Candida genus, which can cause pruritus, dysuria, vulvar edema, fissures and maceration of the vulva. The treatment of vaginal candidiasis is carried out mainly by antifungal agents of azole and polyene classes; however, fungal resistance cases have been often observed. For this reason, new therapeutic agents such as essential oils, probiotics and antimicrobial peptides are being investigated, which can be combined with conventional drugs. Local administration of antimicrobials has also been considered to allow greater control of drug delivery and reduce or avoid undesirable systemic adverse effects. Conventional dosage forms such as creams and ointments result in reduced residence time in the mucosa and non-sustained and variable drug delivery. Therefore, advanced solid formulations such as intravaginal rings, vaginal films, sponges and nanofibers have been purposed. In these systems, polymers in different ratios are combined aiming to achieve a specific drug release profile and high mucoadhesion. Overall, a more porous matrix structure leads to a higher rate of drug release and mucoadhesion. The advantages, limitations and technological aspects of each dosage form are discussed in detail in this review.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Candida; Drug Delivery Systems; Drug Compounding; Candida albicans
PubMed: 36451068
DOI: 10.1007/s11095-022-03441-5 -
Drugs of Today (Barcelona, Spain : 1998) Apr 2022Worldwide, effective management of vulvovaginal candidiasis (VVC) continues to serve as a major therapeutic goal with numerous unmet drug treatment challenges. After 3... (Review)
Review
Worldwide, effective management of vulvovaginal candidiasis (VVC) continues to serve as a major therapeutic goal with numerous unmet drug treatment challenges. After 3 decades of azole drug dominance, with few recent new antifungal agents and little progress in VVC management, the first-in-class oral triterpenoid glucan synthase inhibitor agent ibrexafungerp has emerged in the treatment of acute VVC. After reviewing existing treatment standards and unmet needs, the pharmacology, pharmacokinetics, antimicrobial activity and clinical efficacy of ibrexafungerp are reviewed in this article together with phase III clinical trial results and drug safety. The projected role and status of ibrexafungerp are reviewed together with perspectives of its future development and role in the treatment of VVC.
Topics: Antifungal Agents; Candidiasis, Vulvovaginal; Female; Glycosides; Humans; Triterpenes
PubMed: 35412529
DOI: 10.1358/dot.2022.58.4.3381586 -
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 -
Current Drug Targets 2020Female genital tract infections have a high incidence among different age groups and represent an important impact on public health. Among them, vaginitis refers to... (Review)
Review
Female genital tract infections have a high incidence among different age groups and represent an important impact on public health. Among them, vaginitis refers to inflammation of the vulva and/or vagina due to the presence of pathogens that cause trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Several discomforts are associated with these infections, as well as pregnancy complications and the facilitation of HIV transmission and acquisition. The increasing resistance of microorganisms to drugs used in therapy is remarkable, since women report the recurrence of these infections and associated comorbidities. Different resistant mechanisms already described for the drugs used in the therapy against Trichomonas vaginalis, Candida spp., and Gardnerella vaginalis, as well as aspects related to pathogenesis and treatment, are discussed in this review. This study aims to contribute to drug design, avoiding therapy ineffectiveness due to drug resistance. Effective alternative therapies to treat vaginitis will reduce the recurrence of infections and, consequently, the high costs generated in the health system, improving women's well-being.
Topics: Animals; Anti-Infective Agents; Candidiasis, Vulvovaginal; Drug Resistance, Microbial; Female; Humans; Trichomonas Infections; Trichomonas vaginalis; Vaginitis
PubMed: 32753007
DOI: 10.2174/1389450121666200804112340 -
Ethiopian Journal of Health Sciences Sep 2023Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of probiotics in the treatment of vulvovaginal candidiasis.
METHODS
A comprehensive search of databases including PubMed, Scopus, Cochrane, Scientific Information Database (SID), IranMedex, and Google Scholar search engine was performed. The search was conducted from inception to 1 October 2022, to identify published English or Persian language randomized control trials (RCTs) of women with vulvovaginal candidiasis who received probiotics as medical treatment. The quality of the included studies was assessed using the Oxford Center for Evidence Based Medicine checklist All statistical analyses were performed using Comprehensive Meta-analysis (CMA) version 2.
RESULTS
Six RCTs were included in this review. The results showed that treatment with probiotic was not different from placebo regarding the rate of positive culture (OR: 1.12; 95% CI: 0.390 to 3.26, P=0.825); treatment with probiotic was more effective compared to placebo regarding the rate of recurrence. (OR: 0.14; P= 0.01; 95 % CI: 0.028-0.7).
CONCLUSION
Probiotics have a beneficial effect in the treatment of women with vulvovaginal candidiasis. Our results provide evidence for an alternative treatment modality for vaginal candidiasis using probiotics.
Topics: Candidiasis, Vulvovaginal; Probiotics; Humans; Female; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38784519
DOI: 10.4314/ejhs.v33i5.18 -
The Annals of Pharmacotherapy Jan 2023To review the pharmacology, efficacy, and safety of ibrexafungerp in the management of vulvovaginal candidiasis (VVC). (Review)
Review
OBJECTIVE
To review the pharmacology, efficacy, and safety of ibrexafungerp in the management of vulvovaginal candidiasis (VVC).
DATA SOURCES
Literature was sought using PubMed (1966-February 2022) and EMBASE (1973-February 2022), and clinicaltrials.gov. Search terms included ibrexafungerp, SCY-078, and VVC.
STUDY SELECTION AND DATA EXTRACTION
All studies including humans and published in English with data assessing the efficacy and safety of ibrexafungerp for the treatment of VVC were evaluated.
DATA SYNTHESIS
A phase 2 dose-finding study found ibrexafungerp had similar efficacy to fluconazole in the clinical cure of VVC (51.9% vs 58.3%, respectively). Two phase 3 clinical trials demonstrated ibrexafungerp had statistical superiority over placebo for clinical cure in moderate to severe VVC ( < 0.001 and = 0.023, respectively). The most frequently reported adverse reactions in the clinical trials were gastrointestinal-related symptoms. To date, data comparing efficacy of ibrexafungerp and topical imidazoles in the treatment of VVC are nonexistent.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Topical imidazoles and oral fluconazole are effective for the treatment of uncomplicated VVC. Due to increased resistance, limited fluconazole coverage for non- species, and potential for significant drug interactions associated with fluconazole use, alternative treatments for VVC are needed. Ibrexafungerp is a new oral triterpenoid antifungal agent indicated for the treatment of VVC. Additional clinical trials are needed to evaluate long-term safety data as well as efficacy and safety in specialty populations.
CONCLUSION
Ibrexafungerp, a recently approved triterpenoid antifungal agent, is an effective and well-tolerated option for the treatment of VVC.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Fluconazole; Antifungal Agents; Triterpenes; Imidazoles
PubMed: 35502451
DOI: 10.1177/10600280221091301 -
BMJ (Clinical Research Ed.) Jun 2020
Topics: Antifungal Agents; Candida; Candidiasis, Vulvovaginal; Female; Humans; Microbiological Techniques; Nonprescription Drugs; Practice Guidelines as Topic; Recurrence; Young Adult
PubMed: 32513647
DOI: 10.1136/bmj.m1995 -
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 -
The Journal of Obstetrics and... Jul 2022To provide an overview of clinical, immunological, and mycological aspects of vulvovaginal candidiasis (VVC). (Review)
Review
AIM
To provide an overview of clinical, immunological, and mycological aspects of vulvovaginal candidiasis (VVC).
METHODS
A literature search was conducted to find relevant articles about different aspects of VVC. Related data from retrieved articles were summarized in different headings.
RESULTS
VVC has a global distribution and Candida albicans is the leading cause of infection except for specific patient groups like postmenopausal, diabetic, or immunocompromised women. VVC has a range of clinical presentations, accordingly, its diagnosis should be based on clinical examination coupled with laboratory investigations. The best therapeutic regimen depends on the patient's conditions and the causative agent. Moreover, factors like drug resistance of the causative agents and different mutations in the immunity-related genes could affect the treatment outcome.
CONCLUSION
As a globally distributed disease, VVC needs further attention, especially in areas related to the treatment failure and recurrence of the disease.
Topics: Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Female; Humans; Treatment Outcome
PubMed: 35445492
DOI: 10.1111/jog.15267 -
American Journal of Health-system... Dec 2022The pharmacology, microbiology, pharmacokinetics, pharmacodynamics, efficacy, safety, and role of ibrexafungerp in the treatment of fungal infections are reviewed.
PURPOSE
The pharmacology, microbiology, pharmacokinetics, pharmacodynamics, efficacy, safety, and role of ibrexafungerp in the treatment of fungal infections are reviewed.
SUMMARY
Ibrexafungerp is the first triterpenoid antifungal. Similarly to echinocandins, it inhibits the synthesis of 1,3-β-d-glucan. However, it binds to a different site on the enzyme than echinocandins, resulting in limited cross-resistance. Ibrexafungerp exerts concentration-dependent fungicidal activity against Candida species and retains in vitro activity against most fluconazole-resistant strains. It is also active against Aspergillus species. Ibrexafungerp has been shown to be safe and effective in the treatment of vulvovaginal candidiasis caused by Candida albicans in phase 2 and phase 3 clinical trials. It is approved for vulvovaginal candidiasis in adult and postmenarchal pediatric females and is given as two 150-mg tablets orally, administered 12 hours apart. Ibrexafungerp is contraindicated in pregnancy. The most commonly reported adverse reactions were diarrhea, nausea, abdominal pain, dizziness, and vomiting. Ibrexafungerp should be avoided with strong or moderate CYP3A inducers, and the dose should be reduced with strong CYP3A inhibitors. Ibrexafungerp may be useful for patients who are not able to receive fluconazole or prefer oral therapy for the treatment of vulvovaginal candidiasis. However, it is more expensive than the 150-mg tablet of generic fluconazole, which is the current standard of care for vulvovaginal candidiasis. Clinical trials are ongoing for recurrent and complicated vulvovaginal candidiasis as well as invasive candidiasis and pulmonary aspergillosis.
CONCLUSION
Ibrexafungerp is an alternative to fluconazole for the treatment of vulvovaginal candidiasis in nonpregnant females. It has the potential to be useful for recurrent and complicated vulvovaginal candidiasis as well as certain invasive fungal infections.
Topics: Adult; Pregnancy; Female; Humans; Child; Antifungal Agents; Fluconazole; Candidiasis, Vulvovaginal; Triterpenes; Echinocandins
PubMed: 36083109
DOI: 10.1093/ajhp/zxac256