Even though Candida albicans commonly colonizes on most mucosal surfaces including the vaginal and gastrointestinal tract, it can cause candidiasis as an opportunistic infectious fungus. The emergence of resistant Candida strains and the toxicity of anti-fungal agents have encouraged the development of new classes of potential anti-fungal agents. Sclareol, a labdane-type diterpene, showed anti-Candida activity with a minimum inhibitory concentration of 50 μg/mL in 24 h based on a microdilution anti-fungal susceptibility test. Cell membrane permeability with propidium iodide staining and mitochondrial membrane potential with JC-1 staining were increased in C. albicans by treatment of sclareol. Sclareol also suppressed the hyphal formation of C. albicans in both liquid and solid media, and reduced biofilm formation. Taken together, sclareol induces an apoptosis-like cell death against Candida spp. and suppressed biofilm and hyphal formation in C. albicans. Sclareol is of high interest as a novel anti-fungal agent and anti-virulence factor.

Visceral leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania donovani and Leishmania infantum that is endemic not only in East African countries, but also in Asia, regions of South America and the Mediterranean Basin. For the pharmacological control of this disease, there is a limited number of old and, in general, poorly adherent drugs, with a multitude of adverse effects and low oral bioavailability, which favor the emergence of resistant pathogens. Pentavalent antimonials are the first-line drugs, but due to their misuse, resistant Leishmania strains have emerged worldwide. Although these drugs have saved many lives, it is recommended to reduce their use as much as possible and replace them with novel and more friendly drugs. From a commercial collection of anti-infective drugs, we have recently identified nifuratel-a nitrofurantoin used against vaginal infections-as a promising repurposing drug against a mouse model of visceral leishmaniasis. In the present work, we have tested combinations of miltefosine-the only oral drug currently used against leishmaniasis-with nifuratel in different proportions, both in axenic amastigotes from bone marrow and in intracellular amastigotes from infected Balb/c mouse spleen macrophages, finding a potent synergy in both cases. In vivo evaluation of oral miltefosine/nifuratel combinations using a bioimaging platform has revealed the potential of these combinations for the treatment of this disease.

Data on the epidemiology and the antifungal susceptibility of Candida species infections in Malaysia is still limited. The study aimed to review and compare studies reporting the prevalence of Candida species and antifungal susceptibility of Candida infections in Peninsular Malaysia. Data from 22 studies published between 2009 and 2018. Data was collected using National Center for Biotechnology Information and Google Scholar using the keywords "Candida and Malaysia." Around 19 Candida species were identified in a total of 35,608 Candida isolates analyzed in these studies. In most studies examined, C. albicans (66.3%) was the predominant species, followed by C. glabrata (11.7%), C. parapsilosis (10.7%), C. tropicalis (9.5%), and C. krusei (1.19%). Vaginal swabs yielded the most isolates, followed by the respiratory system, urine, blood, oral, pus, and other locations. The demographic, racial, and gender data were recorded only in two studies. Totally, eight studies examined 396 isolates for antifungal susceptibility to common antifungal medications. The average antifungal susceptibility of isolates and efficacy of drugs in these studies ranged between 45 and 99% for most common antifungal drugs. Caspofungin had the highest susceptibility at 99%, whereas itraconazole had the lowest at only 45%. Overall, this review provided a comprehensive summary of all the current research on predominant Candida species in Peninsular Malaysia.

This work aimed to evaluate poly(pseudo)rotaxanes (PPRs) potential for vaginal antifungal delivery. For this, PPRs containing terbinafine (TB) 2 % were obtained using two small surfactants, Kolliphor® RH40 and Gelucire® 48/16, and different α-cyclodextrin (α-CD) concentrations (5 and 10 %). PPRs were characterized by their physicochemical characteristics, irritation, and mucoadhesion capabilities. Formulations' performance was assessed in a vertical penetration model, which uses ex vivo entire porcine vagina. Conventional penetration experiments with excised vaginal tissue were performed as a control. Results showed all formulations were non-irritant according to the HET-CAM test. Furthermore, PPRs with 10 % αCD showed superior mucoadhesion (p < 0.05). Conventional horizontal penetration studies could not differentiate formulations (p > 0.05). However, PPRs with 10 % αCD presented a better performance in vertical ex vivo studies, achieving higher drug penetration into the vaginal mucosa (p < 0.05), which is probably related to the formulation's prolonged residence time. In addition, the antifungal activity of the formulations was maintained against Candida albicans and C. glabrata cultures. More importantly, the formulation's viscosity and drug delivery control had no negative impact on the antifungal activity. In conclusion, the best performance in a more realistic model evidenced the remarkable potential of PPRs for vaginal drug delivery.

The objective of this research is to formulate lyophilized fluconazole-loaded nanocellulose-gellan scaffolds cross-linked using trisodium trimetaphosphate as a vaginal drug delivery system. The effect of polymers (nanocellulose and gellan gum) and cross-linking agents on drug release and mucoadhesive strength were determined by approaching a two-factor three-level central composite experimental design. The optimal formulation of the fluconazole-loaded cross-linked rice or wheat nanocellulose-gellan based scaffolds comprised of the concentration of polymers (4.91 % w/v or 4.99 % w/v) and trisodium trimetaphosphate (16.43 % w/v or 15.83 % w/v), respectively. The infrared spectra confirmed the cross-linking of nanocellulose and gellan gum while the thermal graph revealed the higher thermal stability of cross-linked scaffolds. The diffractogram of the scaffolds unveiled their amorphous nature while the electron micrographs depict the porous nature of the fluconazole-loaded nanocellulose-gellan scaffolds. The phosphorylated cross-linked nanocellulose-gellan scaffolds represent more swelling (8-fold higher), porosity (>83 %), tensile strength (>34 MPa), and mucoadhesive strength (>1940 mN), and less enzymatic degradation rate over the non cross-linked scaffolds. The optimal batch of cross-linked nanocellulose-gellan scaffolds provided a sustained release of 99 % of fluconazole over 24 h with 1.19-fold higher ex-vivo vaginal permeation over the native scaffolds. In addition, the phosphorylated nanocellulose-gellan based scaffolds exhibit improved antifungal activity and non-cytotoxicity.

Candida vulvovaginitis is characterized by the appearance of inflammatory changes in the vaginal and vulvar epithelium secondary to infection with Candida species. The purpose of this study was to analyze and compare the clinical, microbiological, and histopathological aspects of pregnant and non-pregnant patients, symptomatic or asymptomatic in the case of candida vaginitis and to correlate the microscopic aspects with the symptoms before applying the local treatment with Nystatin. The study presents a retrospective analysis of the management of vaginitis in 166 pregnant or non-pregnant patients during 2021-2022. We observed the structure of the Malpighian squamous epithelium without keratinization present on the vaginal mucosa and the structure of the subepithelial connective tissue, which shows increased numerical values of inflammatory and vascular cellularity in the case of candida vaginitis symptomatic compared to asymptomatic ones. We noticed also in the microscopic study that in cases of asymptomatic patients before treatment, the number of inflammatory cells and blood vessels situated immediately under the epithelium was significantly lower compared to their number in symptomatic patients before treatment. Analyzing the results obtained after the administration of the treatment proposed by us, we can say that local Nystatin treatment is beneficial and safe for pregnant and non-pregnant patients and is a good alternative for patients with recurrent vulvovaginal candidiasis.

Benzoxazepines constitute a significant class of organic compounds extensively described in the literature. Several derivatives with pharmacological properties have been produced due to the semi-rigid azepine scaffold, which allows for the addition of other heteroatoms. This study investigated the possible antifungal effect and antioxidant activity of 2,3-dihydro-1,5-benzoxazepines. The antifungal effect was investigated using the broth dilution assay, while the antioxidant property was determined using the ABTS and DPPH scavenging tests. The results indicated that the 2,3-dihydro-1,5-benzoxazepine derivatives had antifungal properties and could be working via its fungicidal and biofilm inhibitory properties. It was also realized that it had synergistic effects when administered concomitantly with standard antifungal drugs. The antioxidant effects were high with 2,2-dimethyl-4-[(E)-2-(4-methylphenyl)ethenyl]-2,3-dihydro-1,5-benzoxazepine (1) compared to the other derivatives. It could be concluded that 2,3-dihydro-1,5-benzoxazepines could possess fungicidal and possible antioxidant properties. And hence could serve as new drug leads in discovering novel drugs that could help manage fluconazole-resistant vulvovaginal candidiasis.

The inappropriate use of antifungals is associated with greater antimicrobial resistance, costs, adverse events, and worse clinical outcomes. The aim of this study was to determine prescription patterns and approved and unapproved indications for systemic antifungals in a group of patients in Colombia. This was a cross-sectional study on indications for the use of systemic antifungals in outpatients from a drug dispensing database of approximately 9.2 million people affiliated with the Colombian Health System. Sociodemographic, pharmacological, and clinical variables were considered. Descriptive, bivariate, and multivariate analyses were performed. A total of 74,603 patients with antifungal prescriptions were identified; they had a median age of 36.0 years (interquartile range: 22.0-53.0 years), and 67.3% of patients were women. Fluconazole (66.5%) was the most prescribed antifungal for indications such as vaginitis, vulvitis, and vulvovaginitis (35.0%). A total of 29.3% of the prescriptions were used in unapproved indications. A total of 96.3% of ketoconazole users used the medication in unapproved indications. Men (OR: 1.91; CI95%: 1.79-2.04), <18 years of age (OR: 1.20; CI95%: 1.11-1.31), from the Caribbean region (OR: 1.26; CI95%: 1.18-1.34), with chronic obstructive pulmonary disease (OR: 1.80; CI95%: 1.27-2.54), prescriptions made by a general practitioner (OR: 1.17; CI95%: 1.04-1.31), receiving comedications (OR: 1.58; CI95%: 1.48-1.69), and the concomitant use of other antimicrobials (OR: 1.77; CI95%: 1.66-1.88) were associated with a higher probability that the antifungal was used for unapproved indications; deep mycosis (OR: 0.49; CI95%: 0.41-0.58), prescribing fluconazole (OR: 0.06; CI95%: 0.06-0.06), and having diabetes mellitus (OR: 0.33; CI95%: 0.29-0.37), cancer (OR: 0.13; CI95%: 0.11-0.16), or HIV (OR: 0.07; CI95%: 0.04-0.09) reduced this risk. Systemic antifungals were mostly used for the management of superficial mycoses, especially at the gynecological level. In addition, more than a quarter of patients received these medications in unapproved indications, and there was broad inappropriate use of ketoconazole.

Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region known as vulvovaginal candidiasis (VVC). This pathology is, in fact, one of the main C. albicans clinical manifestations, changing from a colonizer to a pathogen. The increase in VVC cases and limited antifungal therapy make C. albicans an increasingly frequent risk in women's lives, especially in immunocompromised patients, pregnant women and the elderly. Therefore, it is necessary to develop new therapeutic options, especially those involving natural products associated with nanotechnology, such as lycopene and mesoporous silica nanoparticles. From this perspective, this study sought to assess whether lycopene, mesoporous silica nanoparticles and their combination would be an attractive product for the treatment of this serious disease through microbiological in vitro tests and acute toxicity tests in an alternative in vivo model of Galleria mellonella. Although they did not show desirable antifungal activity for VVC therapy, the present study strongly encourages the use of mesoporous silica nanoparticles impregnated with lycopene for the treatment of other human pathologies, since the products evaluated here did not show toxicity in the in vivo test performed, being therefore, a topic to be further explored.

Vulvovaginal candidiasis (VVC) is an opportunistic and endogenous infection caused by a fungus of the Candida genus, which can cause pruritus, dysuria, vulvar edema, fissures and maceration of the vulva. The treatment of vaginal candidiasis is carried out mainly by antifungal agents of azole and polyene classes; however, fungal resistance cases have been often observed. For this reason, new therapeutic agents such as essential oils, probiotics and antimicrobial peptides are being investigated, which can be combined with conventional drugs. Local administration of antimicrobials has also been considered to allow greater control of drug delivery and reduce or avoid undesirable systemic adverse effects. Conventional dosage forms such as creams and ointments result in reduced residence time in the mucosa and non-sustained and variable drug delivery. Therefore, advanced solid formulations such as intravaginal rings, vaginal films, sponges and nanofibers have been purposed. In these systems, polymers in different ratios are combined aiming to achieve a specific drug release profile and high mucoadhesion. Overall, a more porous matrix structure leads to a higher rate of drug release and mucoadhesion. The advantages, limitations and technological aspects of each dosage form are discussed in detail in this review.

Cellulose sponges with compressibility and resilience are an ideal packaging material for fruits with fragile skin. Here, a soft and elastic all-cellulose sponge (CS) with a hierarchical cellular structure was fabricated, where the long molecular chain cellulose constructed major pores, the cellulose at nanoscale acted as an elastic nanofiller to fill the gaps of long molecular chain cellulose fibers and constructed minor pores. With these two kinds of pores, this structure can absorb strain hierarchically. The sponge can protect fruits from mechanical damage when dropped or repeated vibration. Furthermore, the CS modified with chlorogenic acid (C-CGAS) had excellent antibacterial and antifungal abilities. Therefore, C-CGAS could extend the storage time of strawberries to 18 days without any microbial invasion, which is the longest storage time reported thus far. This study provides a new idea for the preparation of polymer sponges and a new design for the development of antimicrobial packaging materials.

In recent years, clinicians and doctors have become increasingly interested in fungal infections, including those affecting the mucous membranes. Vulvovaginal candidiasis (VVC) is no exception. The etiology of this infection remains unexplained to this day, as well as the role and significance of asymptomatic vaginal Candida colonization. There are also indications that in the case of VVC, standard methods of determining drug susceptibility to antifungal drugs may not have a real impact on their clinical effectiveness-which would explain, among other things, treatment failures and relapse rates. The aim of the study was to verify the promising results obtained previously in vitro using standard methods, in a newly developed ex vivo model, using tissue fragments of the mouse vagina. The main goal of the study was to determine whether the selected ultrashort cyclic lipopeptides (USCLs) and their combinations with fluconazole at specific concentrations are equally effective against Candida forming a biofilm directly on the surface of the vaginal epithelium. In addition, the verification was also performed with the use of another model for the study of microorganisms (biofilms) in vitro-the BioFlux system, under microfluidic conditions. The obtained results indicate the ineffectiveness of the tested substances ex vivo at concentrations eradicating biofilm in vitro. Nevertheless, the relatively most favorable and promising results were still obtained in the case of combination therapy-a combination of low concentrations of lipopeptides (mainly linear analogs) with mycostatic fluconazole. Additionally, using BioFlux, it was not possible to confirm the previously obtained results. However, an inhibiting effect of the tested lipopeptides on the development of biofilm under microfluidic conditions was demonstrated. There is an incompatibility between the classic in vitro methods, the newer BioFlux method of biofilm testing, offering many advantages postulated elsewhere, and the ex vivo method. This incompatibility is another argument for the need, on the one hand, to intensify research on the pathomechanism of VVC, and, on the other hand, to verify and maybe modify the standard methods used in the determination of Candida susceptibility.

Objective - to determine the sensitivity of Gardnerella vaginalis to fenticonazole to justify the feasibility of using this mainly antifungal drug for local treatment of BV in cases when it is a multifactorial disease caused by Gardnerella vaginalis and Candida spp. simultaneously.; We observed 98 women with infections of the urogenital tract at the ages of 20 to 49. At the first stage of the study, we analyzed the results of laboratory data on pathological discharge from the urogenital system of these patients. 36 (%) of the examined women had Gardnerella vaginalis in the vaginal discharge. At the second stage of the study, the sensitivity of Gardnerella vaginalis to fenticonazole was determined.; The resistance to fenticonazole was registered in 1 case (2.7%). In the remaining 35 patients Gardnerella vaginalis was not stable to fenticonazole. High sensitivity to this substance was found in 22 of them (61.2%). Respectively, low sensitivity was registered in 13 people from the observation group (36.1%).; Gardnerella vaginalis is the main constituent and a marker of bacterial vaginosis. The elimination of this very microorganism is of paramount importance for its treatment. In 35 studied patients (97.3%) Gardnerella vaginalis, which was isolated by culture from vaginal discharge, had sensitivity to fenticonazole. Moreover, in 22 of them (61.2%) the sensitivity was high, and low in 13 (36.1%). Candida spp. was found in 17 (47.1%) of 36 patients with bacterial vaginosis. It is appropriate to use fenticonazole as a means of local treatment during complex therapy of women with bacterial vaginosis that improves its compliance.

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. STATEMENT OF SIGNIFICANCE: A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.

Resistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in Nicotiana benthamiana. Griffithsin has well characterized broad spectrum antiviral activity and has demonstrated potent in vitro activity against multiple strains of Candida, including C. albicans. We have been working to incorporate Q-GRFT into topical microbicide products to prevent HIV-1 and HSV-2 transmission. The goal of this study was to evaluate the efficacy of a prototype Q-GRFT dosage form in prophylactic and therapeutic murine models of vaginal candidiasis, through microbiologic, histopathologic, and immune studies. In a preventive model, in comparison with infected controls, Q-GRFT treatment resulted in a lower fungal burden but did not alter the number of vaginal neutrophils and monocytes. In a therapeutic model, Q-GRFT enhanced fungal clearance when compared with infected untreated controls. Finally, histopathology demonstrated lower vaginal colonization with C. albicans following Q-GRFT treatment. Our results demonstrate that Q-GRFT has significant preventive and therapeutic activity in vaginal candidiasis offering additional benefit as a topical microbicide for prevention of HIV-1 and HSV-2 transmission.

To explore the mechanism of vulvovaginal candidiasis (VVC) recurrence. A total of 127 strains of Candida albicans (C. albicans) were collected, including 58, 40, and 29 strains from the recurrent vulvovaginal candidiasis (RVVC), VVC, and asymptomatic carrier (AC), respectively. The strains' virulence such as in vivo hypha formation rate, germ tube formation rate, biofilm formation ability, and sensitivity to five common antifungals were detected. The in vivo hypha formation rates of C. albicans from the RVVC (55.2%) and VVC (40.0%) were significantly higher than that from the AC (0%) (P < .001). The median germ tube formation rate of the RVVC was 88.2%, which was higher than that of the VVC and AC (59.9% and 65.6%), respectively (P < .001). The median absorbance of the biofilm formation test for strains in the RVVC was 0.380, considerably higher than that in the VVC and AC (0.246 and 0.254) (P < .001). The drug sensitivity rate of the strains to 5-fluorocytosine and itraconazole and the ratio of strains sensitive to all the five antifungals in the VVC group were lower than those in the RVVC and AC groups. In conclusion, the virulence of strains from the RVVC is stronger than that of strains from the VVC and AC, the antifungal resistance rate of strains from the RVVC group is lower than that of strains from the VVC group. So, it is suitable to argue that the strains' virulence is one of the mechanisms for the relapse of RVVC, rather than its antifungal resistance.

Antimicrobial resistance remains a worldwide issue with a major clinical and economic impact, leading to exceeding mortality, increased frequency of hospitalization and a great burden on the healthcare systems. Vulvovaginitis, especially when due to mixed infections, has emerged as a condition for which appropriate selection of antimicrobial therapy and proper antimicrobial stewardship programs (ASPs) may contribute to minimizing the resistance development. This review discusses the appropriateness of selecting treatment for vulvovaginitis in order to reduce the development of resistance in gynecological practice. Narrative review based on a selection of literature performed according to the Authors' experience and a MEDLINE search using the following keywords: "vaginitis" OR "Candida" OR "fungal infection" AND "antifungal therapy". No limits were applied, but papers were selected for inclusion in this narrative review according to their relevance to the topic, as judged by the Authors. Worldwide, antimicrobial treatment in gynecology and ASPs focuses on prescribing systemic and expensive antifungal drugs, while treatment selection should consider several factors. Recently, topical azoles have been recommended as suitable alternatives to oral systemic azoles, given their similar efficacy in limiting clinical recurrence. In particular, fenticonazole has already been proposed as an alternative to systemic antifungal drugs to limit the onset of resistance. Optimizing the selection of antimicrobial treatment can help reduce the development of resistance in gynecological practice. Given its wide action spectrum and ability to exert antimicrobial activity against fungi, bacteria and mixed infections, fenticonazole may be considered a suitable first-line, empiric therapy for vaginal and mixed infections, avoiding alteration of intestinal microflora and minimizing the risk of selection of drug-resistant microbial strains.

Lactobacillus spp. generally dominate the vaginal microbiota and prevent pathogen adhesion and overgrowth, including Candida spp., by various mechanisms. Although Candida spp. can be commensal, in certain conditions they can become pathogenic, causing vulvovaginal candidiasis. The insurgence of candidiasis is related to the expression of Candida virulence factors, including morphologic switching and biofilm formation. Germ tubes, pseudohyphae, and hyphae promote Candida tissue invasion, biofilms increase persistence and are often resistant to antifungals and host immune response. Here, we explored the inhibitory activity of vaginal Lactobacillus strains belonging to Lactobacillus crispatus, Lactobacillus gasseri, Limosilactobacillus vaginalis, and Lactiplantibacillus plantarum species towards Candida virulence factors. With the aim to investigate the interrelation between mode of growth and functionality, supernatants were collected from lactobacilli planktonic cultures and, for the first time, from adherent ones, and were evaluated towards Candida dimorphic switching and biofilm. Candida biofilms were analyzed by multiple methodologies, i.e., crystal violet staining, MTT assay, and confocal microscopy. Lactobacillus supernatants reduce Candida switching and biofilm formation. Importantly, L. crispatus supernatants showed the best profile of virulence suppression, especially when grown in adherence. These results highlight the role of such species as a hallmark of vaginal eubiosis and prompt its employment in new probiotics for women's health.

Objective: Compare demographics, treatment, and follow-up rates for patients with complaints of vulvovaginitis suggestive of candida infection evaluated via e-visit, face-to-face (F2F) visits, or nurse-administered phone protocol. Methods: Manual review of 150 vaginitis visits of each visit type (e-visit, F2F, and phone protocol) completed between May 5, 2018 through January 31, 2020 by Mayo Clinic patients residing in Minnesota. Outcomes: Comparison between the three visit types of patient characteristics, treatment rates, type of treatment, follow-up rates, and types of follow-up. Results: Patients utilizing phone visits were significantly older than those seeking care via e-visit (p < 0.0001) or F2F (p = 0.001) and were more likely to be treated with oral fluconazole than those treated by e-visit (p < 0.0001) or F2F (p < 0.0001) encounters. Patients were significantly less likely to receive fungal directed treatment at a F2F visit than an e-visit (p < 0.0001) or phone encounter (p < 0.0001). There was no significant difference in follow-up rates between the three groups. Conclusion: Virtual visits (non-F2F) for suspected vulvovaginal candidiasis are unlikely to result in more follow-up visits than F2F encounters; however, prescriptions for antifungals are significantly higher with virtual visits.

Vulvovaginal candidiasis (VVC), which is most frequently caused by Candida albicans, is a common problem worldwide. Despite the fact that extensive epidemiological studies have been performed, the cause of recurrent VVC (RVVC) remains uncertain. The aims of this work were to compare the genotypes of C. albicans strains causing different conditions of VVC, and explore the relationship between the drug resistance and genotype of C. albicans strains. In our study, we collected 649 independent strains from VVC patients in China. Isolates were tested for in vitro susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin in accordance with the Clinical Laboratory Standards Institute (CLSI) document M27-A3. Genotyping was performed using PCR targeting specific CAI locus marker. C. albicans is the main pathogen of VVC, but the proportion of non-candida albicans (NAC) infection is also increasing, and we also found increased cases of mixed infection. Some C. albicans are resistant to multiple drugs. The strains with the genotypes including 16-16, 18-18 and 22-22 was likely to be the dominant genotype of uncomplicated VVC (p < 0.05). The genotypes of complicated VVC are mainly distributed in 30-45, 33-45, 32-46 and 39-45. Strains of 30-45, 32-45, 30-47 and 30-46 genotypes showed resistance to fluconazole, itraconazole, voriconazole and amphotericin B respectively. Our work suggests that the dominant genotypes with higher repeat number of C. albicans strains were more prevalent in patients with RVVC and drug-resistant strains, however, strains with uncomplicated VVC were more likely to distribute in homozygous. Identification of specific genotypes that correlate with different conditions of VVC and drug resistant is also of diagnostic and therapeutic significance.

Recurrent vulvovaginal candidosis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. A long-term prophylactic maintenance regimen with antifungals is often necessary. In most clinical practice guidelines, oral fluconazole is recommended as the first-line treatment. Although clinical resistance to antifungal agents remains rare, overexposure to azoles may increase the development of fluconazole-resistant C. albicans strains. In addition, non-albicans Candida species are frequently dose-dependent susceptible or resistant to fluconazole and other azoles, and their prevalence is rising. Available therapeutic options to treat such fluconazole-resistant C. albicans and low susceptibility non-albicans strains are limited. Ten experts from different European countries discussed problematic issues of current RVVC diagnosis and treatment in two audiotaped online sessions and two electronic follow-up rounds. A total of 340 statements were transcribed, summarized, and compared with published evidence. The profile of patients with RVVC, their care pathways, current therapeutic needs, and potential value of novel drugs were addressed. Correct diagnosis, right treatment choice, and patient education to obtain adherence to therapy regimens are crucial for successful RVVC treatment. As therapeutic options are limited, innovative strategies are required. Well- tolerated and effective new drugs with an optimized mechanism of action are desirable and are discussed. Research into the impact of RVVC and treatments on health-related quality of life and sex life is also needed.