Treatment Of Vulvovaginal Candidiasis Research Articles

Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant Candida albicans and the Dectin-1 Signaling Pathway Activation.

Vulvovaginal candidiasis (VVC) is an infectious disease caused by Candida species, which affects millions of women worldwide every year. The resistance to available antifungal drugs for clinical treatment is a growing problem. The treatment of refractory VVC caused by azole-resistant Candida is still facing challenges. However, research on new antifungal drugs is progressing slowly. Although a lot of reports on new antifungal drugs, only three new antifungal drugs (Isavuconazole, ibrexafungerp, and rezafungin) and two new formulations of posaconazole were marketed over the last decade. Chinese botanical medicine has advantages in the treatment of drug-resistant VVC, such as outstanding curative effects and low adverse reactions, which can improve patients’ comfort and adherence to therapy. Kangbainian lotion (KBN), a Chinese botanical formulation, has achieved very good clinical effects in the treatment of VVC. In this study, we investigated the antifungal and anti-inflammatory effects of KBN at different doses in fluconazole-resistant (FLC-resistant) VVC model mice. We further studied the antifungal mechanism of KBN against FLC-resistant Candida albicans (C. albicans) and the anti-inflammatory mechanism correlated with the Dectin-1 signaling pathway. In vivo and in vitro results showed that KBN had strong antifungal and anti-inflammatory effects in FLC-resistant VVC, such as inhibiting the growth of C. albicans and vaginal inflammation. Further studies showed that KBN inhibited the biofilm and hypha formation, reduced adhesion, inhibited ergosterol synthesis and the expression of ergosterol synthesis-related genes ERG11, and reduced the expression of drug-resistant efflux pump genes MDR1 and CDR2 of FLC-resistant C. albicans in vitro. In addition, in vivo results showed that KBN reduced the expression of inflammatory factor proteins TNF-α, IL-1β, and IL-6 in vaginal tissues, and inhibited the expression of proteins related to the Dectin-1 signaling pathway. In conclusion, our study revealed that KBN could ameliorate vaginal inflammation in VVC mice caused by FLC-resistance C. albicans. This effect may be related to inhibiting the growth of FLC-resistance C. albicans and Dectin-1 signaling pathway activation.

Therapeutic Potential of Perillaldehyde in Ameliorating Vulvovaginal Candidiasis by Reducing Vaginal Oxidative Stress and Apoptosis.

Vulvovaginal candidiasis (VVC) is one of the most frequent diseases induced by Candida albicans (C. albicans) during pregnancy, which results in enormous pain to women and their partners in daily life. Perillaldehyde (PAE), a natural monoterpenoid, has significant anti-microbial, anti-inflammatory and anti-oxidation effects. Reactive oxygen species (ROS) are key factors for the host to resist the invasion of fungi. However, excess ROS can cause additional damage independent of the pathogen itself, and the mechanism of ROS in VVC has not been investigated. In this murine study, we revealed that C. albicans infection increased the expression of NADPH oxidase 2 (NOX2) and the content of malonaldehyde (MDA). C. albicans inhibited the activity of antioxidant enzymes in the vagina, including superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase (HO-1), which were returned to normal levels after treatment with PAE. Furthermore, PAE inhibited the activities of Keap1 and promoted Nrf2 transfer from cytoplasm to nucleus, which were mediated by excessive accumulation of ROS in the VVC mice. In this study, we also indicated that PAE inhibited the apoptosis of vagina cells via Caspase 9- Caspase 7-PARP pathway and prevented the release of IL-1ꞵ in VVC mice. In summary, this study revealed that the treatment of VVC in mice with PAE might be mediated by inhibition of ROS, and established the therapeutic potential of PAE as an antifungal agent for the treatment of VVC.

Comparison of the effect of miconazole and clotrimazole in the treatment of vulvovaginal candidiasis among women seen in a tertiary medical center from 2016 to 2020

Comparison of the effect of miconazole and clotrimazole in the treatment of vulvovaginal candidiasis among women seen in a tertiary medical center from 2016 to 2020

Novel Antifungals for the Treatment of Vulvovaginal Candidiasis: Where Are We?

Vulvovaginal candidiasis (VVC) is a common health-related issue and the second most common cause of vaginitis. Previously, azole antifungals were the mainstay of VVC treatment. Additionally, boric acid and nystatin have been used topically for management of VVC. Despite being effective and well tolerated by most patients, the use of azoles may be limited in some cases. Currently, two new antifungal agents have received US Food and Drug Administration approval for use in the management of VVC. In this article, we briefly review treatment regimens used for the management of VVC over the past decade, the newly approved agents and their possible clinical application, and future treatment considerations.

Chamomile Extract versus Clotrimazole Vaginal Cream in Treatment of Vulvovaginal Candidiasis: A Randomized Double-Blind Control Trial.

ObjectivesVulvovaginal candidiasis (VVC) treatment is advised for all women due to its symptoms and complications. In this study, the standard treatment, clotrimazole, was compared with chamomile extract cream in outpatient clinics.MethodsWe recruited 73 women with VVC, who were randomly allocated into two groups, clotrimazole versus chamomile extract cream. After two weeks of treatment with the same criteria, cheese-like vaginal discharge, itching and burning sensations, strawberry cervix, and recovery percentage was evaluated.ResultsThirty patients in each group were analyzed. There was no significant difference in age and number of pregnancies between groups (p = 0.85 and 0.09, respectively). Comparing before and after treatment, cheese like discharge (p < 0.001), itching (p < 0.001), burning (p < 0.001) had significantly improved in both groups. Further, the recovery percentage was not significantly different between groups (88.9% vs 75% in the chamomile vs clotrimazole groups, respectively).ConclusionChamomile is as effective as clotrimazole in VVC treatment; a higher percentage of women who used this medication recovered, although this did not reach significance. In addition, no complications were reported in either group.

Pharmacokinetics and Pharmacodynamics of Ibrexafungerp.

On 2 June, 2021, the US Food and Drug Administration approved ibrexafungerp (formerly MK-3118 and SCY-078) for the treatment of vulvovaginal candidiasis, also known as vaginal yeast infection. Ibrexafungerp is the first drug approved in a novel antifungal class in more than two decades, and the Food and Drug Administration’s decision was based on positive results from two pivotal phase III studies in which oral ibrexafungerp proved both safe and effective in patients with vulvovaginal candidiasis. The decision was also based on substantial preclinical and clinical work in both the pharmacokinetics and pharmacodynamics of ibrexafungerp. This paper reviews that research and looks ahead to explore how this novel antifungal agent may be used in the future to address the expanding problem of drug-resistant mycotic infections.

Design of transfersomal nanocarriers of nystatin for combating vulvovaginal candidiasis; A different prospective

The objective of this study was to prepare and evaluate Nystatin (NYS) loaded transfersomes to achieve better treatment of vulvovaginal candidiasis. Nystatin transferosomes were formulated utilizing thin film hydration method. A 32 full factorial design was employed to evaluate the effect of different formulation variables. Two independent variables were chosen; the ratio between lecithin surfactant (X1) was set at three levels (10–40), and the type of surfactants (X2) was set at three levels (Span 60, Span 85 and Pluronic F-127). The dependent responses were; entrapment efficiency (Y1: EE %), vesicles size (Y2: VS) and release rate (Y3: RR). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high NYS encapsulation efficiency ranging from 97.35 ± 0.03 to 98.01 ± 0.20% whereas vesicle size ranged from 194.8 ± 20.42 to 400.8 ± 42.09 nm. High negative zeta potential values indicated good stability of the prepared formulations. NYS release from transfersomes was biphasic and the release pattern followed Higuchi’s model. The optimized formulation (F7) exhibited spherical morphology under transmission electron microscopy (TEM). In-vitro and in-vivo antifungal efficiency studies revealed that the optimized formula F7 exhibited significant eradication of candida infestation in comparison to free NYS. The results revealed that the developed NYS transfersomes could be a promising drug delivery system to enhance antifungal efficacy of NYS.

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.

Antifungal activity of Ocimum gratissimum L., Lantana camara L. & Pteleopsis suberosa Engl. & Dies used in the treatment of vulvovaginal candidiasis in Benin

BackgroundVulvovaginal candidiasis is a widespread mycotic infection that affects a large proportion of women of childbearing age. Its management in traditional medicine is based on the use of medicinal plants. This study aimed to evaluate the antifungal activity of Ocimum gratissimum L., Lantana camara L. and Pteleopsis suberosa Engl. & Diels used in the treatment of vulvovaginal candidiasis in Benin.ResultsThe data obtained from the in vitro antifungal test show that the strains tested (ATCC 90028 and two clinical strains: 1MA and 3MA) were more sensitive to aqueous extracts with a better effect for Pteleopsis suberosa. This potential of the tested extracts correlated with their richness in total polyphenols. The extract of the Pteleopsis suberosa was very active on the inhibition of the reference strain ATCC 90028. On the clinical strains (1MA and 3MA) the aqueous extract of Pteleopsis suberosa showed a better MIC on the 1MA strain. In vivo model, inoculation of 100 µL of the concentrated Candida albicans suspension 1.5 × 105 UFC/mL induced the candidiasis of the female Wistar rat. The treatment with the aqueous extract of Pteleopsis suberosa, like fluconazole (reference drug), significantly reduced Candida albicans infection at a dose of 100 mg/kg after 1, 7 and 13 days of treatment.ConclusionThis study revealed the potential antifungal of the Ocimum gratissimum, Lantana camara and Pteleopsis suberosa. Pteleopsis suberosa has better antifungal activity in vitro and in vivo. These observations justify the use of their medicinal plant in the traditional treatment of vulvovaginal candidiasis in Benin.

Treatment of vulvovaginal candidiasis in preparation programs for in vitro fertilization

Vulvovaginal candidiasis (VVC) is considered as the second most common cause of vaginitis after bacterial vaginosis. About three quarters of women of reproductive age have a history of at least one episode of VVC, and about a half of women have two or more episodes. Candida albicans is responsible for85% to 90% of vulvovaginal candidiasis. There are uncomplicated and complicated forms of VVC. Uncomplicated forms are not severe cases caused by C. albicans. Complicated forms are cases caused by other Candida species, severe cases, cases that develop during pregnancy or associated with other diseases such as diabetes mellitus or immunosuppressive conditions. Reccurent cases are also complicated ones. Therapeutic schemes should depend on the form of the VVC. Short-term topical therapy or a single oral dose are effective in 90% of uncomplicated cases. Complicated forms of VVC require longer treatment. Oral fluconazole can be administered three times with a break of 72 hours. Topical azoles can be administered daily for at least 1 week. So, sertaconazole in the form of suppositories is used once intravaginally. The data on the use of probiotics in the treatment of VVC today are contradictory and heterogeneous. Treatment of VVC during pregnancy, especially in the first trimester, may be associated with adverse perinatal outcomes. On the other hand, during pregnancy, VVC can be more severe than in non-pregnant women, especially in the second half of pregnancy. In addition, the risk of transmission to a newborn is about 50%. Thus, the identification and treatment of VVC is one of the important tasks in pregnancy planning, including assisted reproduction.

Data on Safety of Intravaginal Boric Acid Use in Pregnant and Nonpregnant Women: A Narrative Review.

Intravaginal boric acid (IBA) represents one of the only options available to treat azole-resistant vulvovaginal candidiasis (VVC) and is included as part of multiple national guidelines (including the United Kingdom and the United States) for the treatment of VVC or recurrent bacterial vaginosis. Novel products using IBA are under development for treatment and suppression of VVC and bacterial vaginosis. Use of over-the-counter or clinician-prescribed IBA in reproductive-aged women is already widespread and may increase further if drug resistance in VVC rises. However, IBA is not a Food and Drug Administration-approved drug, and safety data are sparse. Given these factors, it is important to understand the currently available data on the safety of IBA use. Herein, we set out to synthesize human and animal data (converting, where appropriate, dose and serum values to standard units to facilitate comparison) to answer 2 key questions: (1) What are the data on the safety of IBA use for women? and (2) What are the data on the safety of IBA use in pregnancy? We find that, despite gaps, available data suggest IBA use is safe, at least when used in doses commonly described in the literature as being prescribed by clinicians. Information on harms in pregnancy is limited, and data remain insufficient to change current guidelines, which recommend IBA avoidance in pregnancy.

Development of bifunctional vaginal suppositories by joint use terconazole and probiotic for treatment and prophylaxis of vulvovaginal candidiasis

Objective The objective of this article is the creation and investigation of bifunctional suppositories that are endowed with antifungal and probiotic properties intended for the treatment of vulvovaginal candidiasis (VVC) and colonization of the vaginal cavity by powerful lactobacilli. Materials and methods Freeze-dried Lactobacillus delbrueckii MH10 was used as a probiotic, which is an active producer of H2O2 isolated from a healthy woman’s vagina. Hydrophilic PEG 4000/400, amphiphilic Suppocire AP, and lipophilic Novata ABPH bases were used for the preparation of vaginal suppositories and each included 80 mg terconazole and 25 mg (∼109 CFU) lactobacilli. The release kinetic of active agents from suppositories was studied using the British Pharmacopeia’s basket dissolution method, and the physicochemical properties were studied using known methods. Bioadhesion of suppositories was evaluated by flow rate from polyacrylamide substrate inclined at 60°. Antagonism of lactobacillus against fungi was studied using the disk diffusion method and joint cultivation in simulated vaginal fluid. Results The release rate of active ingredients from the suppositories was PEG 4000/400 > Suppocire AP > Novata ABPH in decreasing order. Suppositories made of Suppocire AP possessed higher adhesion ability to artificial mucosa and longer shelf life. It was revealed that during joint cultivation L. delbrueckii MH10 kills more than 90% of C. albicans population. Conclusions Due to its physicochemical, biopharmaceutical, and bioadhesive properties, the base Suppocire AP is preferable for manufacturing vaginal bifunctional suppositories. Lactobacilli kill C. albicans by coaggregating and direct releasing hydrogen peroxide onto target cells.

Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis.

This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303)

BackgroundCurrent treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC.MethodsPatients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4).ResultsPatients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity.ConclusionsIbrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

Ibrexafungerp: First Approval.

Ibrexafungerp (BREXAFEMME®) is an orally active triterpenoid antifungal drug being developed by SCYNEXIS, Inc. for the treatment of fungal infections. The inhibition of β-1,3-D glucan synthetase by ibrexafungerp compromises the integrity of fungal cell walls. Ibrexafungerp has been recently approved for the treatment of vulvovaginal candidiasis (VVC), and it is the first novel antifungal drug class to be approved in more than 20 years. Development for the treatment of recurrent VVC and invasive fungal infections is ongoing. This article summarizes the milestones in the development of ibrexafungerp leading to this first approval for the treatment of VVC in adult and postmenarchal paediatric females.

Effect of Propolis on the Adhesion Index, Morphology and Viability of Candida albicans Cells on Biofilm Formation

About 70-75% of reproductive women have experienced vulvovaginal candidiasis at least once and 40-45% will have recurrences. Candida albicans is the most etiology of vulvovaginal candidiasis and is able to form biofilm that can lead to antifungal resistances and recurrences. One of the natural products that have an antibiofilm effect is propolis. This study expected that propolis from Lawang can be the one of antibiofilm agent candidates to antifungi resistant cases. This study aimed to know the antibiofilm effect of propolis ethanol extract to cell adhesion index, morphology, and viability of Candida albicans cell on biofilm formation. The adhesion index was counted on 100 epithelial cells under light microscopy (1000x). Morphology was seen using light microscopy (400x). Cell viability was examined by CFU assay. At 12.5% concentration of propolis ethanol extract, adhesion index decreased (p=0,000) and hyphal growth was inhibited. Colony growth decreased at 2.5% concentration and was not seen at 10% concentration of propolis ethanol extract (p=0,000). This results indicated that propolis ethanol extract can decrease adhesion index, failed the Candida albicans morphology transition from yeast to hyphal, and decreased Candida albicans cell viability on biofilm formation. Propolis ethanol extract is likely to be one of alternatives to recurrent vulvovaginal candidiasis treatment, especially caused by Candida albicans biofilm formation.

Effect of Propolis on the Adhesion Index, Morphology and Viability of Candida albicans Cells on Biofilm Formation

About 70-75% of reproductive women have experienced vulvovaginal candidiasis at least once and 40-45% will have recurrences. Candida albicans is the most etiology of vulvovaginal candidiasis and is able to form biofilm that can lead to antifungal resistances and recurrences. One of the natural products that have an antibiofilm effect is propolis. This study expected that propolis from Lawang can be the one of antibiofilm agent candidates to antifungi resistant cases. This study aimed to know the antibiofilm effect of propolis ethanol extract to cell adhesion index, morphology, and viability of Candida albicans cell on biofilm formation. The adhesion index was counted on 100 epithelial cells under light microscopy (1000x). Morphology was seen using light microscopy (400x). Cell viability was examined by CFU assay. At 12.5% concentration of propolis ethanol extract, adhesion index decreased (p=0,000) and hyphal growth was inhibited. Colony growth decreased at 2.5% concentration and was not seen at 10% concentration of propolis ethanol extract (p=0,000). This results indicated that propolis ethanol extract can decrease adhesion index, failed the Candida albicans morphology transition from yeast to hyphal, and decreased Candida albicans cell viability on biofilm formation. Propolis ethanol extract is likely to be one of alternatives to recurrent vulvovaginal candidiasis treatment, especially caused by Candida albicans biofilm formation.

P-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis

Vulvovaginal candidiasis (VVC) is an extremely common type of vaginal infection, which is mainly caused by Candida albicans. However, non-albicans Candida species are frequently more resistant to conventional antifungal agents and can represent up to 30% of cases. Due to side effects and increasing antifungal resistance presented by standard therapies, phenolic compounds, such as p-coumaric acid (p-CA), have been studied as molecules from natural sources with potential antifungal activity. p-CA is a poorly water-soluble compound, thus loading it into liquid crystals (LCs) may increase its solubility and effectiveness on the vaginal mucosa. Thereby, here we propose the development of mucoadhesive liquid crystalline systems with controlled release of p-CA, for the local treatment of VVC. Developed LCs consisted of fixed oily and aqueous phases (oleic acid and cholesterol (5:1) and poloxamer dispersion 16%, respectively), changing only the surfactant phase components (triethanolamine oleate (TEA-Oleate) or triethanolamine (TEA), the latter producing TEA-Oleate molecules when mixed with oleic acid). Systems were also diluted in artificial vaginal mucus (1:1 ratio) to mimic the vaginal environment and verify possible structural changes on formulations upon exposure to the mucosa. From the characterization assays, p-CA loaded TEA-Oleate systems presented mucoadhesive profile, liquid crystalline mesophases, well-organized structures and pseudoplastic behaviour, which are desirable parameters for topical formulations. Moreover, they were able to control the release of p-CA throughout the 12 h assay, as well as decrease its permeation into the vaginal mucosa. p-CA showed antifungal activity in vitro against reference strains of C. albicans (SC5314), C. glabrata (ATCC 2001) and C. krusei (ATCC 6258), and exhibited higher eradication of mature biofilms than amphotericin B and fluconazole. In vivo experiments demonstrated that the formulations reduced the presence of filamentous forms in the vaginal lavages and provided an improvement in swelling and redness present in the mice vaginal regions. Altogether, here we demonstrated the potential and feasibility of using p-CA loaded liquid crystalline systems as a mucoadhesive drug delivery system for topical treatment of VVC.

VULVOVAGINAL CANDIDOSIS IN WOMEN AND GIRLS OF PUBLIC AGE. LITERATURE REVIEW.

Introduction. The article presents data on the prevention, diagnosis and treatment of vulvovaginal candidiasis in women and adolescent girls. The history of the study of fungi of the genus Candida began since the time of Hippocrates, however, the direct defeat of the lower genital area by this fungus was first described in their doctoral works by Frank (1830) and Hirschfeld (1859). As the term "candidiasis" was adopted by the All-Russian Society of Dermatologists in 1957, the first to study the microstructure of the Candida fungus and the effect of antimycotic drugs on it was the famous Russian scientist IM Romanenko [1]. According to many authors, vulvovaginal candidiasis occupies one of the leading places in the structure of gynecological morbidity. This pathology occurs in more than 25% of all cases of vulvovaginitis in adolescent girls and 35% in women [2,3]. F.Blostina and co-authors believe that a feature of vulvovaginal candidiasis is the prevalence and high risk of recurrence, 4 out of 10 women experience this pathology in their lives, while the purity of recurrence within one year reaches 23% [4]. Prilepskaya V.N. in his works notes that inflammatory diseases of the lower genital tract significantly increase the risk of developing urogenital infections, and as a consequence can cause infertility and premature birth [5,6]. Unfortunately, despite the high interest of researchers in this pathology, many authors believe that the true incidence of vulvovaginal candidiasis is not known, due to the high percentage of self-medication of women, which significantly worsens and complicates the consequences of this disease.

Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis.

BackgroundAzoles are the most common antifungal drugs used in the treatment of vulvovaginal candidiasis (VVC). The frequency of azole-resistant Candida isolates has increased dramatically in the last two decades. Here, we assessed the antifungal activity of a combination of fluconazole (FLZ) and methanolic extract of ginger (Meth-Gin) against drug-resistant vulvovaginal candidiasis (VVC) in a murine model.MethodsThe in vitro activity of FLZ or a combination of FLZ and Meth-Gin was determined against Candida albicans by the agar well diffusion, macrodilution, time-kill and the biofilm eradication methods. The therapeutic efficacy of the formulations was assessed by analyzing the fungal load, pro-inflammatory cytokines, percent apoptotic cells and the histological changes in the vaginal tissues of the mice. Moreover, the renal toxicity the drug formulation was evaluated by analyzing the levels of the blood urea nitrogen (BUN) and creatinine.ResultsThe results of in vitro study demonstrated that FLZ did not show any activity against C. albicans, whereas a combination of FLZ and Meth-Gin demonstrated greater activity as shown by the data of the zone of growth inhibition, MIC and time-kill assay. FLZ or Meth-Gin treatment could not completely cure VVC, whereas a combination of FLZ and Meth-Gin was greatly effective in the treatment of VVC. The vaginal tissue from mice of the infected control group had the highest fungal load of 155370 ± 20617 CFUs. Treatment with FLZ at a dose of 40 mg/kg reduced the fungal load to 120863 ± 10723 CFUs. Interestingly, the mice treated with a combination of FLZ (40 mg/kg) and Meth-Gin (200 mg/kg) had a fungal load of 256 ± 152 CFUs. Besides, FLZ and Meth-Gin combination effectively reduced the pro-inflammatory cytokines (IL-1β, TNF-α and IL-17) and the percentage of apoptotic cells in the vaginal tissues. Likewise, the histological analysis revealed the epithelial necrosis, shedding and ulceration in the vaginal tissue, whereas treatment with FLZ and Meth-Gin combination reversed the histopathological changes in the vaginal epithelium and lamina propria.ConclusionThe findings of the current study suggest that the co-administration of Meth-Gin and FLZ may have a potential therapeutic effect in the treatment of azole-resistant candidiasis.