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Candida spp. are members of the human mucosal microbiota that can cause opportunistic diseases ranging from superficial infections to life-threatening invasive candidiasis. In humans, the most common infection caused by Candida spp. is vulvovaginal candidiasis (VVC), which affects >70% of women at least once in their lifetime. Of those women, ∼5%–10% develop recurrent VVC (RVVC). In this review, we summarize our current understanding of the host and fungal factors that contribute to susceptibility to VVC and RVVC. We synthesize key findings that support the notion that disease symptoms are driven by neutrophil-associated dysfunction and immunopathology and describe how antifungal immune mechanisms in the vagina are distinct from other mucosal barrier sites. Finally, we highlight key, unanswered research areas within the field that can help us better understand the immunopathogenesis of this infection and facilitate the development of novel preventive, therapeutic, and/or vaccination strategies to combat these common, poorly understood diseases. Vulvovaginal candidiasis is the most common fungal disease in humans. MacAlpine and Lionakis synthesize the host, microbiome, and fungal factors that alter susceptibility to acute and recurrent vaginal yeast infections. They highlight recent advancements in antifungal treatment and vaccination and offer an outlook for the field of vaginal fungal immunology. [ABSTRACT FROM AUTHOR]

Background: Vulvovaginitis is common in women of reproductive age group characterized by purulent white discharge. The incidence of vulvovaginitis has risen recently due to the resistance of Candida species to commonly used antifungal agents and recurrent infections. Objective: The study aimed to determine the prevalence, associated factors, and antifungal susceptibility patterns of vaginal candidiasis among pregnant women attending Bule Hora University Teaching Hospital. Methods: A hospital-based cross-sectional study was conducted from May 2023 to August 2023. Using systematic random sampling, 317 pregnant women participated in the study. Sabouraud Dextrose Agar and Chromogenic Candida Differential Agar were used to isolate and identify Candida species from clinical samples. Antifungal susceptibility was performed using a modified disc diffusion method. Epi data version 4.6 was used for data entry and Statistical Packages for Social Sciences version 25 was used for statistical analysis. A P-value < 0.05 was declared statistically significant. Result: The prevalence of vaginal candidiasis was 26.8% (95%, CI 21.9–31.72%). History of using contraceptives (AOR = 5.03, 95%CI, 1.21–11.37), past vaginal candidiasis (AOR = 6, 95%CI, 1.61–12.92), pregnant women infected with human immunodeficiency virus (HIV) (AOR = 4.24, 95%CI, 1.23–14.14), diabetic mellitus (AOR = 2.17, 95%CI, 1.02–4.64), history of antibiotic use (AOR = 3.55, 95%CI, 1.67–12.75), pregnant women in third trimester (AOR = 8.72, 95%CI, 1.30–23.07), were the significantly associated factors for vaginal candidiasis. The study revealed that itraconazole, amphotericin B, and miconazole were the most effective antifungal drugs for all Candida isolates. Conclusion: The present study has identified a high prevalence of vaginal candidiasis among pregnant women. The isolated Candida species showed resistance to fluconazole, ketoconazole, and clotrimazole. Therefore, healthcare providers should increase awareness of the risks of Candida infections to reduce Candida species among pregnant women. Physicians should prescribe suitable medications based on antifungal drug test outcomes to treat pregnant women with vaginal candidiasis. [ABSTRACT FROM AUTHOR]

Background & Objectives: Genotypic identification of the etiologic agents of vaginal candidiasis (VC) is of significance in epidemiologic studies and in the establishment of adequate treatment protocol. The aim of this study was to determine the antifungal susceptibility and gene diversity of C. albicans isolated from a group of Jordanian women with VC. Methods: A total of 312 isolates of candida species, recovered from women with vaginal candidiasis who attended gynecology clinics affiliated to three major private hospitals in Amman over a period of five months (July 2020 to December 2020) were included in this study. The isolated Candida were characterized by phenotypic and genotypic means. Genotypic studies were performed using specific PCR primers of the rDNA and RPS genes. Susceptibility testing of all C. albicans isolates was conducted following the National Committee for Clinical Laboratory Standards and E-test strips. Results: Candida albicans was the most dominant Candida spp. that caused VC among the studied population. C. albicans isolates were found to be of three different subtypes at the 25S rDNA gene. All isolates belonged to genotypes A, B and C while genotypes D and E were not detected. The diversity of C. albicans was higher on the basis of RPS region where the use of two markers (P-I and P-II) resulted in the identification of nine distinct C. albicans subtypes. The sensitivity testing revealed variations in the susceptibility of various genotypes to different antifungal drugs. Genotype A isolates were more susceptible to fluconazole, flucytosine and ketoconazole than genotypes B and C. Conclusion: Candida albicans incriminated as etiologic agents of vaginitis among Jordanian women exhibited relationship between various genotypes and antifungal drugs. [ABSTRACT FROM AUTHOR]

Vaginal candidiasis (VC), a common recurrent gynaecological disorder affects almost 70% of women. Development of resistance to anti-fungal agents exacerbates the need for new treatments against Candida infections. The objective of the current work was to develop ethosomal vesicles (EVs) and EV hydrogel of Butea monosperma seed oil (BMSO) for treatment of vaginal candidiasis, as BMSO has demonstrated fungicidal and bactericidal activities. EVs, formulated by ethanol injection-sonication method, used Phospholipon®90G and ethanol as excipients and were optimized by Box-Behnken design (BBD). BMSO (X1), phospholipid (X2) and ethanol concentration (X3) were selected as input variables, while vesicle size (Y1), polydispersity index (PDI) (Y2) and percent entrapment efficiency (%EE) (Y3) were taken as response variables. The size of optimized EVs determined by dynamic light scattering technique was found to be 249 ± 2.6 nm; PDI was 0.301 ± 0.013; %EE determined by high-speed centrifugation method was 53.84 ± 1.98%. Field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HR-TEM) unveiled vesicles of rhombic dodecahedral shape with smooth, sealed structure. The EVs, incorporated into carbopol gel, demonstrated non-Newtonian behaviour on a rotary type rheometer. Minimal inhibitory concentration (MIC) determination by broth microdilution method revealed MIC of EVs and hydrogel to be 2.5 times less, as compared to BMSO against Candida albicans (C.albicans). Anti-candidal activities determined using agar well diffusion method demonstrated better zone of inhibition for hydrogel vis-a-vis BMSO. Pharmacodynamic evaluation conducted on Balb/c female mice manifested a comparable decrease in fungal burden by EVs and EV hydrogel to marketed clotrimazole. Histopathology of vaginal tissue of treated groups showed no or mild inflammation with normal skin structure. The results disclosed EVs and EV hydrogel to possess better anti-fungal activity vis-a-vis BMSO and can be explored as potential alternative herbal product for VC. [ABSTRACT FROM AUTHOR]

Abstract Background Vulvovaginitis is common in women of reproductive age group characterized by purulent white discharge. The incidence of vulvovaginitis has risen recently due to the resistance of Candida species to commonly used antifungal agents and recurrent infections. Objective The study aimed to determine the prevalence, associated factors, and antifungal susceptibility patterns of vaginal candidiasis among pregnant women attending Bule Hora University Teaching Hospital. Methods A hospital-based cross-sectional study was conducted from May 2023 to August 2023. Using systematic random sampling, 317 pregnant women participated in the study. Sabouraud Dextrose Agar and Chromogenic Candida Differential Agar were used to isolate and identify Candida species from clinical samples. Antifungal susceptibility was performed using a modified disc diffusion method. Epi data version 4.6 was used for data entry and Statistical Packages for Social Sciences version 25 was used for statistical analysis. A P-value

Abstract Background Vaginal candidiasis (VC) commonly affects pregnant women. Traditionally, clotrimazole vaginal tablets (CLO) have been the cornerstone of management. However, sertaconazole ovules (SER) offer a novel topical antimycotic option. This double-blinded, randomized trial evaluated the efficacy of single-dose SER and CLO in treating acute VC during pregnancy. Methods From June 2020 to May 2021, this trial recruited pregnant women aged ≥ 18 years with VC symptoms (abnormal vaginal discharge and/or vulvar/vaginal itching) confirmed by microscopy. Participants with ≥ 4 VC episodes in the prior year, immunocompromised status, or imidazole contraindications and those who were absent at the 2-week follow-up were excluded. Participants were randomized to receive either 300 mg SER or 500 mg CLO. Evaluations 2 weeks after the initial medication administration included clinical cure (self-reported resolution of all symptoms), microscopic cure (pseudohyphal absence), patient satisfaction, side effects, and time to clinical cure. Participants with persistent VC received weekly SER doses until delivery. Assessments of recurrence and pregnancy outcomes were done. Results The analysis included 96 participants (48 per group, mean age 27.4 ± 7.4 years, gestational age at diagnosis 22.9 ± 6.4 weeks). Without statistical significance, SER achieved a higher clinical cure rate (62.5% vs 50%, p = 0.217; a mean difference of 12.5%, 95%CI: -17.5% to 42.5%; and a rate ratio of 1.25, 95%CI: 0.71 to 2.23) and a lower microscopic cure (47.9% vs. 62.5%, p = 0.151; a mean difference of -14.6%, 95%CI: -44.3% to 15.1%; and a rate ratio of 0.77, 95%CI: 0.43 to 1.37). The two groups had comparable times to clinical cure (SER: 3.1 ± 1.8 days, CLO: 3.4 ± 2.7 days; p = 0.848) and substantial satisfaction rates (SER: 66.7%, CLO: 60.4%; p = 0.753). No side effects were reported. Of 60 participants who gave birth at Siriraj Hospital, there were no significant differences in pregnancy outcomes. Repeated SER dosing eradicated symptoms and enhanced the microscopic cure rate. Recurrence was observed in four SER and two CLO participants within 1–2 months. Conclusion In the treatment of acute VC during pregnancy, 300 mg SER and 500 mg CLO exhibited comparable efficacy in terms of clinical and microscopic cure rates, satisfaction, side effects, time to clinical cure, recurrence rates, and pregnancy outcomes. Trial registration TCTR20190308004 (registration date March 8, 2019).

This review aims to evaluate efficacy and drug treatment options in cases of vaginal and vulvar candidiasis associated with diabetes. We conducted an exhaustive literature review, looking at relevant clinical trials, meta-analyses, and clinical experiences. Patients with candidiasis and diabetes mellitus were included in a clinical case study to assess their response to treatment. Antifungals such as fluconazole and clotrimazole have been effective in treating candidiasis, but success has been influenced by glucose control levels. Proper diabetes management, along with antifungal therapy, resulted in decreased recurrences. Treatment of candidiasis in a diabetic context requires an integrated approach, including antifungal therapy and adequate management of diabetes. Strict blood glucose control plays a crucial role in preventing recurrences and improving the quality of life of affected patients. Further studies are needed to better understand the complex interactions between diabetes and candidiasis, paving the way for the development of more personalized and effective treatment strategies.

Purpose: The purpose of this study was to develop fluconazole microsponges loaded bioadhesive film, rolled into a torpedo-shaped capsule, to achieve ease of application and reduce application frequency for the treatment of vulvovaginal candidiasis. This was accomplished by using biodegradable polymer blend specifically designed to cater the busy lifestyle of working women. Methods: Microsponges were prepared using the quasi-emulsion solvent diffusion method. Herein, fluconazole: ethyl cellulose (1:2.5, 1:3, 1:3.5) and polyvinyl alcohol (used as the external phase) were dissolved in dichloromethane (12.5, 15, 17.5 ml). Three-level, two-factor full-factorial design optimized the above process. Next, the developed microsponges were thoroughly evaluated for entrapment efficiency, drug release and antimicrobial study. Lastly, film was developed which was made up of blend of bioadhesive polymers, namely pectin and xanthan gum. Subsequently, film was rolled into a torpedo-shaped capsule shell. Results: The spherical-shaped porous microsponges exhibited a notable entrapment efficiency (94.17%), size 14.68 μm and rapid drug release of 91.1 ± 1.54% within 10 h. Further, bioadhesive film revealed thickness 92 μm, folding endurance 440, moisture content 5.66 ± 0.51% w/w, and good tensile strength to withstand vaginal pressure and remarkable zone of inhibition against Candida albicans (19.1 mm). Conclusion: Fluconazole microsponges loaded bioadhesive film, rolled into a torpedo-shaped capsule, exhibited an excellent aesthetic appearance. Moreover, strong bioadhesivity ensured a high efficacy in combating disease. [ABSTRACT FROM AUTHOR]

ARTICLE HIGHLIGHTS - Lactic acid bacteria have potential to control candidiasis or Candida albicans. - The novelty of this study is to advance the potential of lactic acid bacteria to control candidiasis infection in human, with a view to develop novel LAB-based probiotic candidates with capability to inhibit/prevent infection by C. albicans, the causative agent of candidiasis. ABSTRACT The main aims of this research were to isolate and identify potential lactic acid bacteria (LAB) inhibitory to Candida albicans. The LAB sources were kimchi, honey and vaginal secrete of healthy women. They were isolated with a view to develop a novel alternative method with reduced use of antifungal agents in the treatment of patients infected by such fungal pathogen. Isolation of the LABs was conducted by applying dilution spread method on de Mann Rogosa Sharpe agar (MRSA) medium supplemented with bromo cresol purple (BCP) indicator. Once purified, they were tested for antagonism against C. albicans in dual culture assays. LAB isolates that showed significant inhibition against the pathogen were identified using 16s rDNA sequences and their sequences were aligned with those of known sequences deposited at the Gene Bank (http://www.ncbi.nlm.nih.gov). The results showed that 46 among more than 100 LABs isolated in this study significantly inhibited the growth of C. albicans in the in vitro dual culture assays, and all showed resistance property to antifungal agent (fluconazole). This indicated that they all have potential to be synergically applied with reduced use of fluconazole in the therapy. The most potential isolates (10 isolates) were closely related to three LAB species, namely Lactobacillus paracasei, Lacticaseibacillus paracasei, and Pediococcus pentosaceus, based on their 16s rDNA sequence similarities with those deposited in the GenBank.

Abstract Background Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). Objectives This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. Methods The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. Results Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. Conclusion The current findings highlight FA’s potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Background: Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). Objectives: This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. Methods: The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. Results: Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. Conclusion: The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis. [ABSTRACT FROM AUTHOR]

Currently, the high incidence of fungal infections among females has resulted in outstanding problems. Candida species is related with multidrug resistance and destitute clinical consequences. Chitosan-albumin derivatives with more stability exhibit innate antifungal and antibacterial effects that boost the activity of the drug without inflammatory impact. The stability and sustained release of Fluconazole in mucosal tissues can be ensured by encapsulating in protein/polysaccharide nanocomposites. Thus, we developed chitosan-albumin nanocomposite (CS-A) loaded with Fluconazole (Flu) antifungals against vaginal candidiasis. Various ratios of CS/Flu (1:1, 1:2, 2:1) were prepared. Thereafter, the CS-A-Flu nanocomposites were qualified and quantified using FT-IR, DLS, TEM, and SEM analytical devices, and the size range from 60 to 100 nm in diameter was attained for the synthesized nanocarriers. Afterward, the antifungal activity, biofilm reduction potency, and cell viability assay were performed for biomedical evaluation of formulations. The minimum inhibitory concentration) and minimum fungicidal concentration on Candida albicans were attained at 125 ng/μL and 150 ng/μL after treatment with a 1:2 (CS/Flu) ratio of CS-A-Flu. The biofilm reduction assay indicated that biofilm formation was between 0.05 and 0.1% for CS-A-Flu at all ratios. The MTT assay also exhibited excellent biocompatibility for samples, about 7 to 14% toxicity on human HGF normal cells. These data have indicated that CS-A-Flu would be a promising candidate against Candida albicans. [ABSTRACT FROM AUTHOR]

This article from the Romanian Journal of Oral Rehabilitation discusses the use of gynecological drug treatments for vaginal and vulvar candidiasis in individuals with diabetes and oral pathology. It emphasizes the importance of glucose control and an integrated approach to treatment. The document also provides information on diagnosing and treating candidiasis, highlighting the need for proper blood glucose control and collaboration between healthcare professionals. Additionally, there are lists of articles and references related to oral health, dentistry, dermatology, and other specific topics, providing valuable information for researchers and professionals in these fields. [Extracted from the article]

The human microbiome exhibits intricate populations across the body, with the vaginal tract serving as an ecosystem characterized by the prevalence of the genus Lactobacillus. Disruptions in the vaginal microbiota, which are frequently linked to variables such as sexual activity, hormonal fluctuations, and excessive use of antibiotics, can result in vaginal dysbiosis and the development of diseases such as bacterial vaginosis (BV) and candidiasis. Lactobacillus species, owing to their capacity to create an acidic environment through the production of lactic acid, have a key function within this complex microbial community: they inhibit the growth of harmful microorganisms. This study aimed to investigate the genomic characteristics of L. rhamnosus LR6, a newly discovered strain isolated from the vaginal microbiota of 20 healthy women to assess its potential as a vaginal probiotic. We performed a comparative investigation of the genetic traits of L. rhamnosus using 45 publicly available genomes from various sources. We evaluated the genetic characteristics related to carbohydrate utilization, adhesion to host cells, and the presence of bacteriocin clusters. A comprehensive study was conducted by integrating in silico evaluations with experimental techniques to authenticate the physiological characteristics of strain LR6. We further used a rat model to assess the impact of L. rhamnosus LR6 administration on the changes in the gastrointestinal tract and the vaginal microbiome. The assessments revealed a significantly high inhibitory activity against pathogens, enhanced adherence to host cells, and high lactic acid production. Rat experiments revealed changes in both the fecal and vaginal microbiota; in treated rats, Firmicutes increased in both; Lactobacillaceae increased in the fecal samples; and Enterobacteriaceae decreased but Enterococcaceae, Streptococcaceae, and Morganellaceae increased in the vaginal samples. The study results provide evidence of the genetic characteristics and probiotic properties of LR6, and suggest that oral administration of L. rhamnosus LR6 can alter both gut and vaginal microbiome. Collectively, these findings establish L. rhamnosus LR6 as a highly promising candidate for improving vaginal health. [ABSTRACT FROM AUTHOR]

Background We compared the rate, type and severity of vulvovaginitis in women who are practicing internal vaginal douching (IVD) or not while using an intrauterine contraceptive device (IUCD). It is a cross-sectional study on 604 consecutive attendees of the outpatient clinics using IUCD for at least 6 months prior to recruitment. Eligible participants were divided into two groups: group 1 (302 women) performing IVD and group 2 (302 women) not practicing this habit (NIVD). The frequency of vaginal infections in IUCD users who perform IVD compared to women who were abstaining from this habit was our primary outcome. Results They are IUCD users who were practicing IVD more frequent history of vaginal infection (VI) compared with NIVD-IUCD users [260 (88.1%) versus 151(43.4%); respectively] (P < 0.001). Current diagnosis of VI was significantly higher in IVD group (275; 91.05%) compared to NIVD group (115; 38.1%) (P < 0.001). Bacterial vaginosis was the most common infection (287; 47.5%) followed by candida vulvovaginitis (278; 46.03%). Moreover, both types of infections were significantly more common in IVD. Conclusion The use of IUCD may not increase occurrence of vulvovaginitis, but IVD does increase vaginal infection rate either with or without IUCD use. When vaginal infection happens with IUCD, BV is the most common type of infection followed by Candida albicans. [ABSTRACT FROM AUTHOR]

Abstract Background We compared the rate, type and severity of vulvovaginitis in women who are practicing internal vaginal douching (IVD) or not while using an intrauterine contraceptive device (IUCD). It is a cross-sectional study on 604 consecutive attendees of the outpatient clinics using IUCD for at least 6 months prior to recruitment. Eligible participants were divided into two groups: group 1 (302 women) performing IVD and group 2 (302 women) not practicing this habit (NIVD). The frequency of vaginal infections in IUCD users who perform IVD compared to women who were abstaining from this habit was our primary outcome. Results They are IUCD users who were practicing IVD more frequent history of vaginal infection (VI) compared with NIVD-IUCD users [260 (88.1%) versus 151(43.4%); respectively] (P

Worldwide, 40 to 50% of women suffer from reproductive tract infections. Most of these infections are mixed infections, are recurrent and difficult to treat with antimicrobials or antifungals alone. For symptomatic relief of infections, oral antimicrobial therapy must be combined with topical therapy. The purpose of this work is to optimize and develop a polyelectrolyte complex (PEC) of chitosan/anion for the formulation of posaconazole- and probiotic-loaded vaginal hydrogel inserts with prolonged release and significant mucoadhesion. PECs were prepared using chitosan as cationic and carrageenan, pectin and polycarbophil as anionic polymers via a lyophilization technique. PEC formation was confirmed by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry, by observing changes in its surface, physical and thermal properties. The probiotic, Lactobacillus casei, was added to the PEC during the lyophilization process and the effect on the probiotic viability was studied. The PECs were further compressed along with posaconazole to form hydrogel inserts and optimized using a 32 full-factorial design. The hydrogel inserts were assessed for swelling behavior, drug release, in vitro mucoadhesion and in vitro antifungal activity. The chitosan–pectin hydrogel insert demonstrated excellent mucoadhesion (1.25 N), sustained drug release (88.2 ± 2.4% in 8 h) and a swelling index of 154.7%. The efficacy of hydrogel inserts was evaluated using in vitro study with a co-culture of Lactobacillus casei and Candida albicans. This study revealed an increase in Lactobacilli casei count and a significant drop in the viable count of Candida albicans (4-log reduction in 24 h), indicating the effectiveness of hydrogel inserts in alleviating the fungal infection. Overall, our study demonstrated the potential of the hydrogel insert for preventing vaginal infection and restoring normal vaginal microbiota. [ABSTRACT FROM AUTHOR]

Candida albicans-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 in vivo models. [ABSTRACT FROM AUTHOR]

The exploration of the interference prompted by commensal bac-teria over fungal pathogens is an interesting alternative to develop new ther-apies. In this work we scrutinized how the presence of the poorly studied vag-inal species Lactobacillus gasseri affects relevant pathophysiological traits of Candida albicans and Candida glabrata. L. gasseri was found to form mixed biofilms with C. albicans and C. glabrata resulting in pronounced death of the yeast cells, while bacterial viability was not affected. Reduced viability of the two yeasts was also observed upon co-cultivation with L. gasseri under plank-tonic conditions. Either in planktonic cultures or in biofilms, the anti-Candida effect of L. gasseri was augmented by acetate in a concentration-dependent manner. During planktonic co-cultivation the two Candida species counter-acted the acidification prompted by L. gasseri thus impacting the balance be-tween dissociated and undissociated organic acids. This feature couldn’t be phenocopied in single-cultures of L. gasseri resulting in a broth enriched in acetic acid, while in the co-culture the non-toxic acetate prevailed. Altogether the results herein described advance the design of new anti-Candida thera-pies based on probiotics, in particular, those based on vaginal lactobacilli spe-cies, helping to reduce the significant burden that infections caused by Can-dida have today in human health.

Candida albicans-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 in vivo models.

Introduction: Vaginal candidiasis refers to a fungal infection that causes irritation, discharge, and intense itchiness of the vagina. This study assessed the factors associated with Vaginal Candidiasis among pregnant women at Kawaala Health Centre IV, Kampala district while specifically seeking to assess the knowledge on vaginal candidiasis health-seeking habits associated with vaginal candidiasis among pregnant women. Methodology: The study adopted a cross-sectional and descriptive research design with both qualitative and quantitative approaches where a pretested questionnaire designed based on the specific objectives was used to collect data. Findings: The majority 55% were between 26-33 years, marital status, the majority 50% of the respondents were cohabiting, 50% of the respondents had attained a primary level of education, religion, Catholic-dominated 51%, majority 78% of respondents had ever heard about vaginal candidiasis, majority 63% of respondents knew that they had vaginal candidiasis after being tested in the hospital, majority 62% of had ever heard about vaginal candidiasis testing, Majority 56% of respondents revealed that they knew the health seeking habits associated with vaginal candidiasis and Majority 54%of respondents reported that consultation with a general practitioner was the health seeking habits they knew. Conclusion: The study therefore concluded that more than 70%) of the respondents had ever heard about vaginal candidiasis, some of the health-seeking habits associated with vaginal candidiasis among pregnant women such other after being tested in the hospital and by observing signs and symptoms. This indicates that the respondents had a good awareness of health-seeking habits associated with vaginal candidiasis among pregnant women. Recommendations: The government should employ more health workers such that the majority go for outreach services in different areas so that they sensitize women about vaginal candidiasis among pregnant women. Its complications and how they can avoid its services.

Background: Vaginal candidiasis is a most common fungal infection of vagina, second most common after bacterial vaginosis. Candida albicans is the most common species constituting 85-90% of cases, producing symptoms and signs of vaginal candidiasis. With the introduction of antifungal drugs, the causative agents of candida infections shifted from C. albicans to other species. Aims and objectives: To find the prevalence of Candida species in outdoor patients (OPD) along with the pattern of sensitivity, resistance to antifungal agents and to compare the efficacy of single dose of vaginal fenticonazole with standard dose of clotrimazole. Material and methods: In a single center (SSG Hospital, Vadodara), randomized, controlled study was initiated with patients of vaginal candidiasis who were diagnosed either by wet mount preparation or by culture technique in OPD. Two randomized groups were assigned using opaque sealed envelope method. Group A was treated with single dose vaginal fenticonazole while group B with vaginal clotrimazole for six days. Results: Vaginal candidiasis was more prevalent in age group of 21-30 years. Candida glabrata was found to be most prevalent identified species among outdoor patients. During follow-up, improvement of symptoms and satisfaction score was significant in fenticonazole group. Clinically, improvement in signs of vaginal candidiasis even with positive wet mount smear on follow-up was not statistically significant between two groups. Conclusions: The results demonstrate that treatment with single dose of fenticonazole was statistically significant in terms of improvement in symptoms and satisfaction score, compared to clotrimazole treatment. The resistance pattern of antifungal agents is helpful in treatment plan. [ABSTRACT FROM AUTHOR]

Objectives: Female population frequently seeks medical consultation for the vaginal candidiasis. Voriconazole (VOR) is a BCS class II antifungal drug with low aqueous solubility and hence inclusion complex was formulated using Hydroxypropyl-β-cyclodextrin (HPβCD). The complex was incorporated into mucoadhesive vaginal tablet using Chitosan and Hydroxypropyl Methyl Cellulose (HPMC K100). Materials and Methods: A 3² full factorial design was employed for sustained release tablet using Design expert® software. Results: Scanning Electron Microscopy (SEM) results indicated the complex formation between the drug and HPβCD. The batches showed 39.68±1.2 to 72.31±1.4% of drug release for 4 hr while for 8 hr it was from 77.23±1.5 to 99.82±1.1%. Therefore, the sustained release of drug was achieved for 8 hr. The tablet batches had swelling % from 228.51±12 to 323.11±8% and mucoadhesive strength from 1131.02±49 to 2302.12±55 dyne/cm². In the in vitro antifungal activity study, a higher zone of inhibition was observed for the inclusion complex-based tablet (34±0.3 mm) as compared to plain drug tablet (25±0.4 mm). Conclusion: Therefore, the inclusion complex-based vaginal tablet could be formulated successfully by employing 3² full factorial design for increased residence of drug at the vaginal site of infection and for improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Voriconazole (VOZ) is an antifungal drug having poor aqueous solubility. VOZ nanostructured lipid carrier (VNLC) was prepared by using melt emulsification followed by ultrasonication technique. The VNLCs were optimized by 32 full factorial design using Design-Expert® software. The optimized VNLC had a particle size, zeta potential and entrapment efficiency of 205.8 nm, −27.1 mV and 78.85%, respectively. The optimized VNLC was further loaded in thermosensitive in situ gel. In vitro release studies of VNLC gel showed sustained release of the drug (98.84 ± 1.26%) for up to 24 h. The ex vivo permeation studies showed higher penetration for the VNLC gel as compared to plain VOZ gel. The in vitro antifungal assay showed higher efficacy of VNLC than that of plain VOZ. The HET-CAM test of the VNLC gel showed no irritation and thus was found to be suitable for vaginal administration. Thus, it can be concluded that the developed VNLC gel showed a sustained release pattern with higher drug localization in the vaginal tissue and thus can offer improved treatment of vaginal candidiasis. [ABSTRACT FROM AUTHOR]

Background: Candida albicans represents the most abundant opportunistic strain. Candida tropicalis, Candida glabrata, Candida krusei, Candida parapsilosis and Candida lusitaniae may also mount infection under opportunistic conditions. The presence of candidal infection in the vagina is specified as a vaginal candidiasis. During pregnancy, vaginitis is more common, and there is a high chance of recurrent infection. In pregnancy, higher level of estrogen enhances the attachment of yeast cells to vaginal mucosa due to which woman are more susceptible to yeast infection. Aim: The aim of the study was to determine the fungal burden of candidiasis in pregnant and non-pregnant ladies at a tertiary care centre in central region of Nepal. Methods: The study was conducted after receiving the approval from the Institutional Review Committee of Chitwan Medical College and Teaching Hospital (CMCTH). The recent study was carried in 150 women of child bearing age group visiting the Department of Gynecology and obstetrics at CMCTH during a period of 6 months from October 2020 to January 2021. The isolates were subjected to microscopy, culture and identification. Results: Among 150 samples processed in our microbiology laboratory during the study period, 41.7% of non-pregnant ladies were found to be positive for Candida sp. and 55.5% of the pregnant ladies were positive for Candida species. Conclusions: The ladies of child bearing age group are at high risk of vaginal candidiasis in Central region of Nepal. The present study shows that age and pregnancy both influences the colonization of fungi in women.

Vaginal candidiasis (VC) is an emerging global hardly treated health issue affecting millions of women worldwide. In this study, the nanoemulsion consisting of clotrimazole (CLT), rapeseed oil, Pluronic F-68, Span 80, PEG 200, and lactic acid was prepared using high-speed and high-pressure homogenization. Yielded formulations were characterized by an average droplet size of 52–56 nm, homogenous size distribution by volume, and a polydispersity index (PDI) < 0.2. The osmolality of nanoemulsions (NEs) fulfilled the recommendations of the WHO advisory note. NEs were stable throughout 28 weeks of storage. The stationary and dynamic (USP apparatus IV) pilot study of the changes of free CLT over time for NEs, as well as market cream and CLT suspension as references, were conducted. Test results of the changes in the amount of free CLT released from the encapsulated form were not coherent; in the stationary method, NEs yielded up to 27% of the released CLT dose within 5 h, while in the USP apparatus IV method, NEs released up to 10% of the CLT dose. NEs are promising carriers for vaginal drug delivery in the treatment of VC; however, further development of the final dosage form and harmonized release or dissolution testing protocols are needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 μm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect (p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis. [ABSTRACT FROM AUTHOR]

Introduction: Irrational antifungals prescription results in inappropriate use of antifungals, leading to emergence of antifungal resistance. Aim: To determine the prescription patterns of antifungal agents in Gynaecology and Oncology Departments of the tertiary hospital in Tanzania. Materials and Methods: This was a retrospective hospital-based study involving files of patients who attended Gynaecology and Oncology Department of Bugando Medical Centre between January 2017 to December 2017. All files of patients with fungal infections were analysed. The analysis of the data was done from January 2018 to August 2018. Checklist was used to collect information such as clinical diagnosis, age, name of antifungal, number of antifungals, dosage form and dose frequency. Descriptive analysis was done using STATA version 13.0. Results: A total of 1,070 files of patients who attended Gynaecology and Oncology Departments in the year 2017 were retrieved, of which 860 (80.4%) were from patients who attended Gynaecology Department. A total of 156 (14.6%) files out of 1,070 were of patients with fungal infections. Of the patients from gynaecology 116 (n=860, 13.48%) had fungal infection. While of the patients from oncology 40 (n=210, 19.1%) had fungal infection. The most common fungal infection diagnosed were vaginal candidiasis 112 (96.6%) and oral candidiasis 33 (82.5%) from gynaecology and oncology department, respectively. Common antifungal prescribed were azoles (clotrimazole 56.9% in gynaecology and fluconazole 30% in oncology). The prevalence of irrational antifungal prescription in gynaecology and oncology departments was 22.4% (26/116) and 20% (8/40), respectively. Conclusion: About one in five antifungal prescriptions for vaginal candidiasis in gynaecology and oral candidiasis in oncology are irrational as evidenced in standard treatment guideline. Clinicians should adhere to the national standard treatment guidelines in order to reduce irrational prescriptions of antifungal agents.

Vaginal candidiasis is a common form of infection in women caused by Candida species. Due to several drawbacks of conventional treatments, the current research is attempted to formulate and optimize a miconazole nitrate-loaded in situ spray gel for vaginal candidiasis. The stimuli-responsive (pH and thermo-responsive) polymers selected for the in situ gel were chitosan and poloxamer 407, respectively, whereas hydroxypropyl methylcellulose (HPMC) was introduced in the formulation to further improve the mucoadhesive property. The dispersion of each polymer was carried out using the cold method, whereas the optimization of the formulation was achieved using Box-Behnken statistical design considering viscosity and gelation temperature as dependent variables. Present design achieved the optimized outcome with HPMC, poloxamer and chitosan at 0.52% (w/v), 18.68% (w/v) and 0.41% (w/v), respectively. Evaluation of drug-excipients compatibility was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermogravimetric analysis where the results showed the absence of any chemical interaction between the polymers and drug component. The optimized formulation showed gelation temperature at 31°C allowing in situ phase transition in a vaginal environment; pH of 4.21 is suitable for use in the vaginal cavity, and appropriate viscosity (290 cP) at storage temperature (below 30°C) would allow spraying at ease, whereas strong mucoadhesive force (22.4±0.513 g) would prevent leaking of the formulation after application. The drug release profile showed sustained release up to 24 h with a cumulative drug release of 81.72%, which is significantly better than the marketed miconazole nitrate cream. In addition, an improved antifungal activity could be correlated to the sustained release of the drug from the formulation. Finally, the safety of the formulation was established while tested on HaCaT cell lines. Based on our findings, it could be concluded that the in situ hydrogel formulation using stimuli-responsive polymers could be a viable alternative to the conventional dosage form that can help to reduce the frequency of administration with ease of application to the site of infection, thus will provide better patient compliance. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and objectives: Boswellia serrata is an important medicinal plant with strong antioxidant activity. The present study was designed to evaluate the effects of Boswellia vaginal gel on apoptosis and oxidative damage in vaginal mucosal cells of women with vaginal candidiasis. Methods: Ninety-five women with vaginal candidiasis were enrolled in the clinical trial and received the gel for seven consecutive nights. The clinical symptoms of the disease including vaginal secretion, pain, itching, unpleasant odor, and dyspareunia were recorded. Vaginal discharges were collected before and after treatment for the assessment of malondialdehyde (MDA) and total antioxidant capacity (TAC) using TBAR and FRAP methods, respectively. Expression of Bax, Bcl2, and Caspases-3 genes was surveyed by RT-PCR. Results: Gel therapy significantly decreased the frequency of pain, burning, itching, dyspareunia and secretion compared to the baseline (p

Worldwide, 40 to 50% of women suffer from reproductive tract infections. Most of these infections are mixed infections, are recurrent and difficult to treat with antimicrobials or antifungals alone. For symptomatic relief of infections, oral antimicrobial therapy must be combined with topical therapy. The purpose of this work is to optimize and develop a polyelectrolyte complex (PEC) of chitosan/anion for the formulation of posaconazole- and probiotic-loaded vaginal hydrogel inserts with prolonged release and significant mucoadhesion. PECs were prepared using chitosan as cationic and carrageenan, pectin and polycarbophil as anionic polymers via a lyophilization technique. PEC formation was confirmed by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry, by observing changes in its surface, physical and thermal properties. The probiotic, Lactobacillus casei, was added to the PEC during the lyophilization process and the effect on the probiotic viability was studied. The PECs were further compressed along with posaconazole to form hydrogel inserts and optimized using a 32 full-factorial design. The hydrogel inserts were assessed for swelling behavior, drug release, in vitro mucoadhesion and in vitro antifungal activity. The chitosan–pectin hydrogel insert demonstrated excellent mucoadhesion (1.25 N), sustained drug release (88.2 ± 2.4% in 8 h) and a swelling index of 154.7%. The efficacy of hydrogel inserts was evaluated using in vitro study with a co-culture of Lactobacillus casei and Candida albicans. This study revealed an increase in Lactobacilli casei count and a significant drop in the viable count of Candida albicans (4-log reduction in 24 h), indicating the effectiveness of hydrogel inserts in alleviating the fungal infection. Overall, our study demonstrated the potential of the hydrogel insert for preventing vaginal infection and restoring normal vaginal microbiota.

Introduction: Due to the increasing prevalence of candidiasis infections and the increase in drug resistance to common antifungal drugs, it is necessary to find natural anti-candidiasis compounds. Therefore, this study was performed with aim to compare the effect of vaginal solution of alum (alum) with clotrimazole cream in the treatment of vaginal candidiasis in women of childbearing age. Methods: This randomized clinical trial study was performed in 2020 on 72 women referred to East Ahvaz Health Center No. 1 with complaint of clinical signs of candida vaginitis. The tools were a demographic and midwifery information questionnaire and a checklist of observations and examinations. The subjects were randomly divided into two groups receiving clotrimazole 1% vaginal cream and white alum solution for 7 days. Data were collected before and after treatment and were analyzed by SPSS software (version 21) and Chi-square and Fisher's exact tests. P 0.05). After the intervention, there was a statistically significant difference between the two groups in terms of vulvar and vaginal itching and vaginal discharge, so that in the alum solution group, the amount of itching and vaginal discharge was significantly less than the clotrimazole vaginal cream group (p < 0.05). However, the two groups were the same in terms of improvement of other symptoms and did not show a statistically significant difference (P > 0.05). Conclusion: The alum vaginal solution and clotrimazole vaginal cream similarly improved candidiasis vaginitis in women of childbearing age. However, before using this solution as an alternative treatment, further studies are recommended to prove its effectiveness and safety.

The incidence of candida infections is on the increase globally, with laboratories not performing speciation and susceptibility testing routinely. This study aims to speciate and determine the susceptibility profile of yeast isolates recovered from urogenital specimens. A total of 115 female participants with signs and symptoms of urogenital tracts infection attending various clinics in University of Benin Teaching Hospital Benin City, Nigeria were recruited for this study. A total of 55 mid-stream urine and 60 high vaginal swabs and or endocervical swabs were collected from the participants and processed to recover yeast isolates. The yeast isolates were identified and susceptibility test performed using standard techniques. The prevalence of candiduria - 54.55% and vaginal candidiasis - 63.33%, did not differ significantly (P = 0.4426). Age did not significantly affect the prevalence of candiduria and vaginal candidiasis (P = 0.0525 and P = 0.2194, respectively). Candida albicans was the most prevalent yeast isolate recovered from urine and genital specimens. Amphotericin B and nystatin were the most active antifungal agents while fluconazole was the least active. High prevalence of yeast urogenital tract infections was observed in this study. [ABSTRACT FROM AUTHOR]

The incidence of candida infections is on the increase globally, with laboratories not performing speciation and susceptibility testing routinely. This study aims to speciate and determine the susceptibility profile of yeast isolates recovered from urogenital specimens. A total of 115 female participants with signs and symptoms of urogenital tracts infection attending various clinics in University of Benin Teaching Hospital Benin City, Nigeria were recruited for this study. A total of 55 mid-stream urine and 60 high vaginal swabs and or endocervical swabs were collected from the participants and processed to recover yeast isolates. The yeast isolates were identified and susceptibility test performed using standard techniques. The prevalence of candiduria - 54.55% and vaginal candidiasis - 63.33%, did not differ significantly (P = 0.4426). Age did not significantly affect the prevalence of candiduria and vaginal candidiasis (P = 0.0525 and P = 0.2194, respectively). Candida albicans was the most prevalent yeast isolate recovered from urine and genital specimens. Amphotericin B and nystatin were the most active antifungal agents while fluconazole was the least active. High prevalence of yeast urogenital tract infections was observed in this study.

Despite being recognized as the “gold standard” for treating azole-resistant vulvovaginal candidiasis, amphotericin B (AmB), an amphoteric molecule, has not been widely used due to serious issues with solubility and permeability. In light of the aforementioned, the objective of the present study was to increase AmB's therapeutic efficacy by formulating it into an o/w nanoemulsion (AmB-NE) system. Furthermore, to facilitate AmB-NE's retention within the vaginal cavity, it was loaded into a mixture of Carbopol® 974P and Aloe vera-based gel (CA gel). Briefly, in the present study, a kinetically stable batch of formulated AmB-NE having a globule size of 76.52 ± 3.11 nm, PDI of 0.342 ± 0.032, and zeta potential of -22.32 ± 0.88 mV was incorporated into the CA gel base. This AmB-NE loaded gel (AmB-NE gel) exhibited a non-Fickian/anomalous diffusion from the hydrophilic matrix. The texture analysis of AmB-NE gel revealed that the prepared gel was a non-drip, soft, easy to spread, and sufficiently cohesive gel that could reside in the vaginal cavity, which was confirmed by our ex-vivo retention test, which revealed that AmB-NE loaded gel could stay in the vaginal cavity for approximately 11 h. Ex-vivo skin permeation studies revealed that AmB-NE is 4.26 times more permeable than AmB-coarse gel, implying that AmB-NE facilitates AmB entry into the vaginal epithelial layers. Furthermore, in-vivo vaginal lavage studies revealed that AmB-NE gel permeated 7.03-fold more than AmB-coarse gel. Prepared AmB-NE gel was stable in refrigerated condition and showed no histopathological toxicity. Thus, the present study suggests that AmB-NE gel could eliminate the existing problem of AmB and that it could serve as an alternative option to treat vulvovaginal candidiasis.

ABSTRACT Vaginal candidiasis is a medical condition characterized by the overgrowth of Candida spp. in the vaginal cavity with complex recurrent pathogenicity as well as tolerance to antifungal therapy and hence is awaiting more safe and effective treatments. This work aimed to assess the potential antifungal activity of galloylquinic acid compounds (GQAs) from Copaifera lucens leaves against vaginal Candida albicans. The antifungal susceptibility test was performed against 20 isolates of multidrug-resistant (MDR) C. albicans using agar diffusion and broth microdilution assays. The results showed that GQAs exhibited strong antagonistic activity against the test isolates, with inhibition zone diameters ranging from 26 to 38 mm and low MICs (1 to 16 μg/mL) as well as minimum fungicidal concentrations (2 to 32 μg/mL). The MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay confirmed the safety of GQAs against the Vero cell line, showing a 50% inhibitory concentration (IC50) of 168.17 mg/mL. A marked difference in the growth pattern of the treated and untreated pathogens was also observed, where a concentration-dependent reduction in the growth rate occurred. Moreover, a pronounced fungicidal effect was demonstrated 6 h after treatment with 1× the minimum fungicidal concentration (MFC), as evidenced by time-kill assays, where the number of survivors was decreased a 6-fold. GQAs effectively inhibited and eradicated about 80% of C. albicans biofilm at 6 μg/mL and 32 μg/mL, respectively. Interestingly, GQAs disturbed the fungal membrane integrity, induced cell lysis, and reduced the virulence factors (proteinase and phospholipase) as well as the catalase activity. Moreover, the ergosterol content in the plasma membrane decreased in a concentration-dependent manner. Additionally, the altered mitochondrial membrane potential was associated with an increased release of cytochrome c from mitochondria to the cytosol, suggesting the initiation of early apoptosis in GQA-treated cells. Transcriptional analysis revealed that all test genes encoding virulence traits, including SAP1, PLB1, LIP1, HWP1, and ALS1, were markedly downregulated in GQA-treated cells compared to the control. The in vivo murine model of vaginal candidiasis further confirmed the therapeutic activity of GQAs (4 mg/kg of body weight) against C. albicans. This work comprehensively evaluated the antifungal, antivirulence, and antibiofilm activities of GQAs against C. albicans isolates using in vitro and in vivo models, providing molecular-level insights into the antifungal mechanism of action and experimental evidence that supports the potential use of GQAs for the treatment of vaginal candidiasis. IMPORTANCE Our work presents a new perspective on the potential use of GQAs as safe and highly effective phytochemicals against MDR C. albicans. This microorganism colonizes the human vaginal epithelium, causing vaginal candidiasis, a condition characterized by recurrent pathogenicity and tolerance to traditional antifungal therapy. Based on the results of in vitro tests, our study reports GQAs antifungal modes of action. These compounds exhibited an anticandidal effect by deactivating the fungal hydrolytic enzymes, reducing ergosterol content in the plasma membrane, altering the potential of the mitochondrial membrane, and inducing apoptosis. Additionally, GQAs showed high activity in eradicating the biofilm formed by the fungus via the downregulation of HWP1, ALS, SAP, PLB, and LIP genes, which are constitutively expressed in the biofilm. In an in vivo murine model of vaginal candidiasis, GQAs further demonstrated strong evidence of their effectiveness as an antifungal therapy. In this regard, our findings provide novel insights into the potential therapeutic use of these phytoactive molecules for vaginal candidiasis treatment.

Introduction: Irrational antifungals prescription results in inappropriate use of antifungals, leading to emergence of antifungal resistance. Aim: To determine the prescription patterns of antifungal agents in gynaecology and oncology departments of the tertiary hospital in Tanzania. Materials and Methods: This was a retrospective hospital-based study involving files of patients who attended gynaecology and oncology department of Bugando Medical Centre between January 2017 and December 2017. All files of patients with fungal infections were analysed. Checklist was used to collect information such as clinical diagnosis, age, name of antifungal, number of antifungals, dosage form and dose frequency. Descriptive analysis was done using STATA version 13.0. Results: A total of 1,070 files of patients who attended gynaecology and oncology departments in the year 2017 were retrieved, of which 860 (80.4%) were from patients who attended gynaecology department. A total of 156 (14.6%) files out of 1,070 were of patients with fungal infections. Of the patients from gynaecology 116 (n=860, 13.48%) had fungal infection. While of the patients from oncology 40 (n=210, 19.1%) had fungal infection. The most common fungal infection diagnosed were vaginal candidiasis 112 (96.6%) and oral candidiasis 33 (82.5%) from gynaecology and oncology department, respectively. Common antifungal prescribed were azoles (clotrimazole 56.9% in gynaecology and fluconazole 37.5% in oncology). The prevalence of irrational antifungal prescription in gynaecology and oncology departments was 22.4% (26/116) and 20% (8/40), respectively. Conclusion: About one in five antifungal prescriptions for vaginal candidiasis in gynaecology and oral candidiasis in oncology are irrational as evidenced in standard treatment guideline. Clinicians should adhere to the national standard treatment guidelines in order to reduce irrational prescriptions of antifungal agents. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the additive effect of intra-vaginal gentian violet (GV) on a single dose oral 200 mg fluconazole for acute vaginal candidiasis (VC). Women aged ≥18 years who had VC were randomly allocated to receive either fluconazole 200 mg (group 1, FLU, N = 90); or the fluconazole with GV (group 2, FLU + GV, N = 93). Outcome measures were 2-week clinical cure rate, conversion of positive fungal culture, time-to-cure, side effects, satisfaction and symptomatic recurrence within 2 months. No significant difference of participants' characteristics was observed. They were 32.4 ± 8.7 year-old and non-obese. Participants receiving FLU + GV had higher clinical cure rates (81.7% vs. 74.4%, p=.236); lower recurrence rate (19.4% vs. 30.0%, p=.097); shorter time-to-cure (3.1 vs. 4.0 days, p=.013); but lower culture conversion rate (74.2% vs. 80.0%, p=.351). Participants in both groups reported high satisfaction and none had severe adverse events. In conclusion, the addition of GV results in a shorter time-to-cure but not cure rate. Clinical trial registration: TCTR20180917003 (http://thaiclinicaltrials.org/show/TCTR20180917003).Impact StatementWhat is already known on this subject? The efficacy of fluconazole for acute vaginal candidiasis is limited to 75-90% due to drug resistance and non-albicans Candida. Gentian violet (GV) has long been used for mucosal candidiasis; and is recommended as the second line treatment for women with recurrent vulvovaginal candidiasis (RVVC).What do the results of this study add? Adding GV to a single oral 200 mg fluconazole results in a quicker resolution of symptoms of acute VC but not cure rate. The participants' satisfaction and acceptance are high. Lifestyle modification, particularly reduction of sugar-rich diet, associates with the higher culture-based cure rate.What are the implications of these findings for clinical practice and/or further research? As GV is widely and easily accessible, and speculum examination with or without microscopy is the main diagnostic tool of VC; the single application of GV seems doable in real-life practice. This simple anti-septic solution can accelerate symptom resolution. However, the proper frequency of GV application should be further explored. As importantly, lifestyle modification should always be included in counselling session to optimise treatment outcome. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes and is an independent risk factor for vaginal dysbiosis. Understanding the vaginal microbiota in health and disease is essential to screen, detect, and manage complications of pregnancy. Therefore, the aims of the present study were to assess and compare vaginal dysbiosis in pregnancy in women with and without GDM and examine its impact on perinatal outcomes in our population. Methods: The present study was a prospective cohort study recruiting pregnant women. The subjects were divided into two groups (GDM and non-GDM) and were followed until delivery to assess fetomaternal outcomes. Vaginal samples were collected at 24-28 weeks and 34-38 weeks for Nugent scoring and determination of bacterial and fungal species. Results: The study recruited 502 pregnant women, with a final assessment of 320 mother-infant pairs (GDM n = 134; non-GDM n = 186). We found a significant association of vaginal dysbiosis with GDM and adverse perinatal outcomes. Significant differences were also seen in status of infection and its trimester-wise changes in relation to hyperglycemia. Conclusion: By defining an association of vaginal dysbiosis with GDM and its correlation with perinatal outcomes, the present study calls for exploitation of this potential association as a new target in the prevention and treatment of GDM and in alleviating their undesired maternal and infant outcomes. [ABSTRACT FROM AUTHOR]

Background & aim: Vaginal candidiasis infection is the second most common disease after bacterial vaginitis, affecting about 75% of women at least once in their lifetime. 85 to 90% of these infections are caused by Candida albicans species. Various factors, including genetic and immunology factors, play an important role in the development of this disease . Interleukin 19 is one of the important cytokines in the immune system and has several polymorphisms in the promoter region. The aim of the present study was to determine the association between IL-19 gene polymorphisms (rs2243191 and rs1028181) and recurrent candidiasis vulvovaginitis. Methods: The present case-control study was performed on 100 patients with recurrent vaginal candidiasis and 110 healthy individuals during 2016-2019. Five mL venous blood was taken from each participant and transferred to a tube containing EDTA anticoagulant. Genomic DNA was isolated using a special kit; the PCR chain reaction was performed by ARMS method and data were analysed in patients and control subjects using Chi square test and SPSS software. Results: The results of the present study revealed that no significant difference was seen in frequency of GG, AG and AA genotypes in the position of both rs2243191 and rs1028181 IL-19 gene in both patients and the control group (P> 0.05). Also, no significant difference was observed in frequency of both A and G alleles in the mentioned positions between patients and the control group (P> 0.05). Conclusion: No significant association between IL-19 gene polymorphism at positions (rs2243191 T / C and rs1028181-513T / C) and recurrent vulvovaginal candidiasis was observed.

Vaginal candidiasis (VC) is an emerging global hardly treated health issue affecting millions of women worldwide. In this study, the nanoemulsion consisting of clotrimazole (CLT), rapeseed oil, Pluronic F-68, Span 80, PEG 200, and lactic acid was prepared using high-speed and high-pressure homogenization. Yielded formulations were characterized by an average droplet size of 52–56 nm, homogenous size distribution by volume, and a polydispersity index (PDI) < 0.2. The osmolality of nanoemulsions (NEs) fulfilled the recommendations of the WHO advisory note. NEs were stable throughout 28 weeks of storage. The stationary and dynamic (USP apparatus IV) pilot study of the changes of free CLT over time for NEs, as well as market cream and CLT suspension as references, were conducted. Test results of the changes in the amount of free CLT released from the encapsulated form were not coherent; in the stationary method, NEs yielded up to 27% of the released CLT dose within 5 h, while in the USP apparatus IV method, NEs released up to 10% of the CLT dose. NEs are promising carriers for vaginal drug delivery in the treatment of VC; however, further development of the final dosage form and harmonized release or dissolution testing protocols are needed.

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti- Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 μm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect (p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis.

Aims: The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; placebo, n = 39) and the potential benefits on quality of life. Methods and Results: The lactobacilli putative probiotic (SynForU‐HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8‐weeks in a randomized, double‐blind, placebo‐controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week‐4 and week‐8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week‐4 and continued after week‐8 (P < 0·05), accompanied by reduced symptoms for burning after week‐8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week‐4 (P = 0·010) and continued after week‐8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week‐8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week‐4 and week‐8 (P < 0·05). Patients consuming lactobacilli showed higher defecation times per week at week‐4 (P = 0·010) and week‐8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy‐induced constipation. Conclusions: Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC. Significance and Impact of the Study: The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug‐resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae‐related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin‐17A (IL‐17A); however, the levels of interleukin‐8 (IL‐8) and interleukin‐1β (IL‐1β) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL‐17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC. [ABSTRACT FROM AUTHOR]