Lived experience of medical management in recurrent vulvovaginal candidiasis: a qualitative study of an uncertain journey.

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is experienced by up to 10% of pre-menopausal women globally, yet there is limited research exploring the perspective of women living with this challenging condition. METHODS: Semi-structured interviews with Australian women experiencing RVVC were conducted between April-July 2021. Interviews were transcribed verbatim, and qualitative interpretative phenomenological analysis (IPA) was conducted. RESULTS: Ten RVVC patients were interviewed. IPA revealed an uncertain journey living with RVVC for all participants ranging from initial symptoms and difficulties in obtaining a diagnosis, the trial and error of symptom management, to the overall debilitating impact of living with a personal and intimate health condition. Four key themes were identified: Theme 1 outlined challenges and delays in diagnosis and clinically appropriate management. Theme 2 found that health care professional (HCP) knowledge limitations impacted RVVC management. Theme 3 illustrated the consequences of a lack of HCP support leading to self-referral and self-education. Theme 4 details the significant emotional and psycho-social repercussions of RVVC. CONCLUSIONS: This debilitating, life-long disease has a prolonged effect on women both physically and psychologically. Living with RVVC seems an uncertain journey that, to a large degree, women feel they must navigate alone. While resilience and self-empowerment were noted, better support through evidence-based treatment options, educated and evidence-informed HCPs and a sympathetic social support network is needed to decrease the disease burden. Future clinical management guidelines and patient support need to consider the findings of this study.

Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k).

Approximately 70-75% of women will have vulvovaginal candidosis (VVC) at least once in their lifetime. In premenopausal, pregnant, asymptomatic and healthy women and women with acute VVC, Candida albicans is the predominant species. The diagnosis of VVC should be based on clinical symptoms and microscopic detection of pseudohyphae. Symptoms alone do not allow reliable differentiation of the causes of vaginitis. In recurrent or complicated cases, diagnostics should involve fungal culture with species identification. Serological determination of antibody titres has no role in VVC. Before the induction of therapy, VVC should always be medically confirmed. Acute VVC can be treated with local imidazoles, polyenes or ciclopirox olamine, using vaginal tablets, ovules or creams. Triazoles can also be prescribed orally, together with antifungal creams, for the treatment of the vulva. Commonly available antimycotics are generally well tolerated, and the different regimens show similarly good results. Antiseptics are potentially effective but act against the physiological vaginal flora. Neither a woman with asymptomatic colonisation nor an asymptomatic sexual partner should be treated. Women with chronic recurrent Candida albicans vulvovaginitis should undergo dose-reducing maintenance therapy with oral triazoles. Unnecessary antimycotic therapies should always be avoided, and non-albicans vaginitis should be treated with alternative antifungal agents. In the last 6 weeks of pregnancy, women should receive antifungal treatment to reduce the risk of vertical transmission, oral thrush and diaper dermatitis of the newborn. Local treatment is preferred during pregnancy.

Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis: a systematic review and recommendations for future trial designs.

BACKGROUND: Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES: We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY: We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA: There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS: The authors independently extracted data. MAIN RESULTS: All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS: Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT: Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.

Blue light therapy to treat candida vaginitis with comparisons of three wavelengths: an in vitro study.

Anti-fungal blue light (ABL) therapies have been widely studied to treat various microbial infections in the literature. The blue light with wavelengths ranging from 400 to 470 nm has been reported to be effective to inhibit various kinds of bacteria and fungi. The existing studies usually report the viability rates of the pathogens under the irradiation of the blue light with different dosage parameters. However, to the best of our knowledge, there is still no work especially focusing on studying the effect of ABL therapies on treating candida vaginitis, where it is important to study the viability of both the Candida albicans (C. albicans) and the human vaginal epithelial cells. It is the purpose of this work to conduct ABL experiments on both of these two cells, analyze the effects, and determine the best ABL wavelength out of three candidates, i.e., 405-nm, 415-nm, and 450-nm wavelength. The viability rates of the C. albicans and the human vaginal epithelial cells irradiated by the three blue LED light sources were measured, whose irradiance (power density) were all set to 50 mW/cm2. The dynamic viability models of the C. albicans and the epithelial cells were built based on the experimental data. Moreover, in this work, we also built a functional relationship between the viability of these two types of cells, by which we further compared the effects of the blue light irradiation on both the C. albicans and vaginal epithelial cells. The experimental data showed that when an approximately 80% inhibiting rate of the C. albicans was achieved, the survival rates of the epithelial cells were 0.6700, 0.7748, and 0.6027, respectively for the treatment by the 405-nm, 415-nm, and 450-nm wavelength light. On the other hand, by simulating the functional relationship between the viability of the two types of cells, the survival rates of the epithelial cells became 0.5783, 0.6898, and 0.1918 respectively using the 405-nm, 415-nm and 450-nm wavelength light, when the C. albicans was completely inhibited. Therefore, both the experimental data and the model simulation results have demonstrated that the 415-nm light has a more effective anti-fungal result with less damage to the epithelial cells than the 405-nm and 450-nm light.

Probiotics for oral and vulvovaginal candidiasis: A review.

Dermatologists commonly prescribe medications such as antibiotics and corticosteroids that can increase the risk for candidiasis. Though conventional antifungals are often effective against candidiasis, they are not without side effects and species of Candida are gaining resistance. Probiotics help treat conditions such as post-antibiotic diarrhea and infectious diarrhea, and thus have the potential to help with Candida infections, as well. For this reason, we provide an overview of therapies prescribed in dermatology that may increase the risk for candidiasis, and we review the literature on whether probiotics are useful in the treatment and prevention of oral and vulvovaginal candidiasis to help dermatologists treating the condition be better informed about their supplemental use with conventional antifungals.

Probiotics and vaginal microecology: fact or fancy?

BACKGROUND: Probiotics are live microorganisms that, when administered in adequate amounts, should confer a health benefit to the host. Media sources tend to present probiotics as an appealing health promotion method able to prevent or treat a wide variety of clinical conditions. In obstetrics and gynaecology, Lactobacilli species are mainly used to restore the physiologic vaginal microbiota in order to treat bacterial vaginosis and vulvovaginal candidiasis (VVC) and prevent preterm birth. DISCUSSION: Several RCTs investigated the potential benefits of probiotics in gynaecological and obstetrics conditions. For all potential indications, recent specific meta-analyses have been published. Considering vulvovaginal candidiasis in non-pregnant women, probiotics slightly improved the short-term clinical and mycological cure, and reduced the 1-month relapse. However, no important impact of probiotic use was observed on long-term clinical or mycological cure. Similarly, the addition of probiotics to metronidazole for the treatment of bacterial vaginosis was not shown to provide any additional benefit. In obstetrics, using probiotics during pregnancy neither decreased nor increased the risk of preterm birth before 34 weeks or before 37 weeks. Similarly, no benefits emerged for gestational diabetes, preterm premature rupture of membrane, and small and large for gestational age infants. CONCLUSION: Despite increasing marketing of probiotics for the treatment of vulvovaginal candidiasis and prevention of preterm birth robust evidence demonstrating a beneficial effect is scarce. Moreover, there was considerable heterogeneity among the different studies in terms of route of administration, strain/s of probiotic adopted, and length of probiotic use. Before recommending the systematic use of probiotics to treat bacterial vaginosis and VVC and prevent preterm birth, high-quality research is needed. Professional medical associations should issue recommendations defining if, when, and how probiotics should be used for gynaecological disorders.

A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC. Methods: This exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC. Results: The study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B- and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). The analysis of evaluable patients, which combined patients aged <40 years (77%) and ≥40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099). Conclusions: In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged <40 years. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC. Clinical Trials Registration: NCT01926028.

Probiotics for vulvovaginal candidiasis in non-pregnant women.

BACKGROUND: Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and recovering the normal vaginal microbiota, and their potential ability to resist Candidas give rise to the concept of using probiotics for the treatment of VVC. OBJECTIVES: To assess the effectiveness and safety of probiotics for the treatment of vulvovaginal candidiasis in non-pregnant women. SEARCH METHODS: We searched the following databases to October 2017: Sexually Transmitted Infections Cochrane Review Group's Specialized Register, CENTRAL, MEDLINE, Embase and eight other databases. We searched in following international resources: World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, Web of Science and OpenGrey. We checked specialty journals, reference lists of published articles and conference proceedings. We collected information from pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomized controlled trials (RCT) using probiotics, alone or as adjuvants to conventional antifungal drugs, to treat VVC in non-pregnant women. Trials recruiting women with recurrent VVC, coinfection with other vulvovaginal infections, diabetes mellitus, immunosuppressive disorders or taking immunosuppressant medication were ineligible for inclusion. Probiotics were included if they were made from single or multiple species and in any preparation type/dosage/route of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and quality and extracted data. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Ten RCTs (1656 participants) met our inclusion criteria, and pharmaceutical industry funded none of these trials. All trials used probiotics as adjuvant therapy to antifungal drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR) 1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969 participants, 7 studies, low quality evidence) and decreased relapse rate at one month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low quality evidence). However, this effect did not translate into a higher frequency of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to 1.33, 172 participants, 1 study, very low quality evidence; three months after treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI 0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one study, very low quality evidence). Probiotics use did not increase the frequency of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low quality evidence). We found no eligible RCTs for outcomes as time to first relapse, need for additional treatment at the end of therapy, patient satisfaction and cost effectiveness. AUTHORS' CONCLUSIONS: Low and very low quality evidence shows that, compared with conventional treatment, the use of probiotics as an adjuvant therapy could increases the rate of short-term clinical and mycological cure and decrease the relapse rate at one month but this did not translate into a higher frequency of long-term clinical or mycological cure. Probiotics use does not seem to increase the frequency of serious or non-serious adverse events. There is a need for well-designed RCTs with standardized methodologies, longer follow-up and larger sample size.

Selection of Lactobacillus strains as potential probiotics for vaginitis treatment.

Lactobacilli are the dominant bacteria of the vaginal tract of healthy women, and imbalance of the local microbiota can predispose women to acquire infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). Although antimicrobial therapy is generally effective, there is still a high incidence of recurrence and increase of microbial resistance due to the repetitive use of antimicrobials. Thus, it has been suggested that administration of probiotics incorporating selected Lactobacillus strains may be an effective strategy for preventing vaginal infections. Accordingly, the in vitro probiotic potential of 23 lactobacilli isolated from the vaginal ecosystem of healthy women from Cuba was evaluated for use in BV and VVC treatments. Eight strains were selected based on their antagonist potential against Gardnerella vaginalis, Candida albicansor both. In vitro assays revealed that all these strains reduced the pathogen counts in co-incubation, showed excellent adhesive properties (biofilm formation and auto-aggregation), were able to co-aggregate with G. vaginalis and C. albicans, yielded high amounts of hydrogen peroxide and lactic acid and demonstrated high adhesion rates to epithelial HeLa cells. Interference tests within HeLa cells showed that all strains were able to reduce the adherence of pathogens by exclusion or displacement. Lactobacilli were able to inhibit HeLa cell apoptosis caused by pathogens when the cells were incubated with the probiotics prior to challenge. These results suggest that these strains have a promising probiotic potential and can be used for prevention or treatment of BV and VVC.

The In Vitro Effectiveness of Lactobacillus fermentum Against Different Candida Species Compared With Broadly Used Azoles.

GOALS: To investigate the possible use of Lactobacillus strains in the prophylaxis and/or adjuvant therapy of acute vulvovaginal candidiasis and other vaginal infections sustained by Candida yeasts. BACKGROUND: The incidence of Candida infections has substantially increased in recent years. Treatment of vaginal infections with lactobacilli has a long tradition, starting with Döderlein's description of the vaginal microbiota. MATERIALS AND METHODS: We assessed the activity of serially diluted fluconazole and miconazole (from 3 ng/mL to 1 mg/mL) against Candida strains. Serial dilutions of the azoles were prepared in Sabouraud Dextrose Broth in the presence of Candida strains. Broths were incubated under aerobic condition at 30°C, and the optical density was measured at 560 nm. Minimum inhibitory concentration was defined as the lowest concentration of the antibiotic that completely inhibited visible growth. RESULTS: An evident resistance to the azoles used was recorded for all species of Candida, with the exception of Candida parapsilosis. For this species, a minimum inhibitory concentration ≤1 mg/mL was obtained, thus confirming the slight sensitivity to fluconazole and miconazole.All Lactobacillus strains tested, namely LF5, LF09, LF10, and LF11, have the ability to significantly inhibit the growth of the five species of Candida of at least 4 logarithms. Furthermore, the best result obtained with miconazole on C. parapsilosis is still 2 logarithms lower. CONCLUSIONS: The use of beneficial bacteria, especially lactobacilli, could be regarded as a good alternative for the prevention and treatment of Candida infections.

Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery.

BACKGROUND: Genital tract infection is associated with preterm birth (before 37 weeks' gestation). Screening for infections during pregnancy may therefore reduce the numbers of babies being born prematurely. However, screening for infections may have some adverse effects, such as increased antibiotic drug resistance and increased cost of treatment. OBJECTIVES: To assess the effectiveness of antenatal lower genital tract infection screening and treatment programs for reducing preterm birth and subsequent morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 7) and reference lists of retrieved reports. SELECTION CRITERIA: We included all published and unpublished randomised controlled trials in any language that evaluated any described methods of antenatal lower genital tract infection screening compared with no screening. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked for accuracy. MAIN RESULTS: One study (4155 women at less than 20 weeks' gestation) met the inclusion criteria. The intervention group (2058 women) received infection screening and treatment for bacterial vaginosis, trichomonas vaginalis and candidiasis; the control group (2097 women) also received screening, but the results of the screening program were not revealed and women received routine antenatal care. The rate of preterm birth before 37 weeks' gestation was significantly lower in the intervention group (3% versus 5% in the control group) with a risk ratio (RR) of 0.55 (95% confidence interval (CI) 0.41 to 0.75; the evidence for this outcome was graded as of moderate quality). The incidence of preterm birth for infants with a weight equal to or below 2500 g (low birthweight) and infants with a weight equal to or below 1500 g (very low birthweight) were significantly lower in the intervention group than in the control group (RR 0.48, 95% CI 0.34 to 0.66 and RR 0.34; 95% CI 0.15 to 0.75, respectively; both graded as moderate quality evidence). Based on a subset of costs for preterm births of < 1900 g, the authors reported that for each of those preterm births averted, EUR 60,262 would be saved. AUTHORS' CONCLUSIONS: There is evidence from one trial that infection screening and treatment programs for pregnant women before 20 weeks' gestation reduce preterm birth and preterm low birthweight. Infection screening and treatment programs are associated with cost savings when used for the prevention of preterm birth. Future trials should evaluate the effects of different types of infection screening programs.

Effect of asymptomatic vaginal colonization with Candida albicans on pregnancy outcome.

INTRODUCTION: Vaginal infection is a major causative factor of preterm delivery. The present study was performed to evaluate the effect of asymptomatic vaginal colonization with Candida albicans at early gestation on pregnancy outcome. MATERIAL AND METHODS: From 2005 to 2014, a total of 8447 women with singleton pregnancies between 10(+0) and 16(+0) gestational weeks were routinely subjected to an antenatal infection screen-and-treat program. Vaginal smears were Gram-stained and microscopically evaluated, and data were retrospectively analyzed. Women exposed to Candida received clotrimazole and were re-tested after 4-6 weeks. Treatment was repeated in case of recurrence. Women with normal or intermediate vaginal flora were considered as non-exposed. Bacterial vaginosis and trichomoniasis were assessed and treated as well. Descriptive data analysis, chi-squared testing and multiple regression analysis with adjustment for potential confounders were performed. Rates of asymptomatic vaginal infections, preterm delivery and low birthweight served as the main outcomes measures. RESULTS: A normal or intermediate flora was found in 6708 (79.4%) of the screened women; 1142 women (13.5%) showed asymptomatic C. albicans infection. Of this group, 185 women (2.2%) had a recurrence of Candida on vaginal smears. Compared with the non-exposed women with normal or intermediate flora, those with recurrent candidiasis had higher rates of preterm delivery (11.9% vs. 9.5%) and of low birthweight (10.8% vs. 8.0%), as confirmed in the multiple model (p = 0.02). CONCLUSIONS: Recurrent asymptomatic vaginal colonization with Candida in early pregnancy is associated with preterm delivery and low birthweight. Routine screening and consequent treatment for candidiasis could improve pregnancy outcomes.

Does removal of CU-IUD in patients with biofilm forming candida really maintain regression of clinical symptoms?

OBJECTIVE: To evaluate whether symptoms and recurrence would differ with and without Cu-IUD removal in patients with concomitant biofilm forming Candida spp. METHODS: The data of 270 consecutive patients wearing TCu380A Cu-IUD were evaluated. Among these patients, 100/270 were found to have Candida spp. isolated from the tail of Cu-IUD or vaginal samples. These patients were investigated in four groups: Group 1 (n = 24; Biofilm (+), Cu-IUD removed), Group 2 (n = 14; Biofilm (+), Cu-IUD not removed), Group 3 (n = 29; Biofilm (-), Cu-IUD removed), Group 4 (n = 33; Biofilm (-), Cu-IUD not removed). Patients in each group were followed for clinical signs and symptoms for 8-16 months and compared to each other. RESULTS: Symptoms, physical findings and candida positivity have decreased statistically significantly in Group 1 one year after removal of Cu-IUD (95.8% vs. 4.2%, p < 0.01; 95.8% vs. 4.2%, p < 0.01; 100% vs. 8.3%, p < 0.01 respectively). In Group 2, symptoms, physical findings and candida positivity have decreased after follow-up, but without a statistical significance. In Group 3, all the parameters have decreased, but only decrease in candida positivity has reached statistical significance (100% vs. 48.3%, p < 0.01). In Group 4 - as in Group 1- symptoms, physical findings and candida positivity have decreased statistically significantly (48.5% vs. 18.2%, p = 0.01; 72.7% vs. 48.5%, p = 0.05; 100% vs. 51.5%, p < 0.01 respectively). CONCLUSION: Biofilm forming microorganisms should be considered in the management of vaginal infections or symptoms for safer use of intrauterine devices.

Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a slow-release vaginal product be useful for prevention of recurrent vulvovaginal candidiasis?: A clinical study.

OBJECTIVE: To assess the effectiveness of the association of 2 specific strains, Lactobacillus fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02 (DSM 21717), specifically formulated in slow-release effervescent tablets, in patients with recurrent vulvovaginal candidiasis. STUDY DESIGN: The study was a clinical trial of 58 women diagnosed with recurrent VVC (≥4 culture-confirmed episodes in a 12-mo period). All patients were given 200 mg of fluconazole orally as an induction dose for 3 alternate days during the first treatment week. Afterward, the patients were given a new product formulated in slow-release vaginal tablets containing at least 0.4 billion live cells of each of lactobacillus L. fermentum LF10 and L. acidophilus LA02 (first phase of the prophylactic period), on alternate days for 10 consecutive nights. Patients who were still free of symptoms were given 1 vaginal tablet every week for the next 10 weeks (second phase of the prophylactic period). Patients asymptomatic after the total duration of the observation phase (7 mo) were considered as responders. RESULTS: During the second 10-week prophylactic phase, 49 of 57 (86.0%) patients remained free of clinical recurrence, whereas symptomatic VVC occurred in 8 patients (14.0%). During the 7-month follow-up, 42 patients of 49 (85.7%) were symptom free at the end of the protocol, whereas clinical recurrences occurred in 7 women (14.3%). Overall, 42 of 58 women enrolled in the study (72.4%) experienced no clinical recurrence throughout the 7-month observation phase (responders). CONCLUSIONS: This study strengthens the evidence supporting the use of specific lactobacilli with well-demonstrated activities associated with the creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by Candida.

Future perspective of probiotics in dermatology: an old wine in new bottle.

Probiotics are live microbial food supplements that are beneficial to the host health when administered in adequate amounts. Probiotics do have an exciting concept in digestive functions, but these live microbes have wider applicability as evidenced by gut-brain-skin axis theory given 80years back. However, the details regarding use of probiotics for dermatological indications ranging from atopic dermatitis to acne and sexually transmitted infections is dispersed in the literature, herein we have tried to focus all under one heading. Overall, probiotics seem to be promising and safe therapeutic modality, but the evidence as of now, from the available published data is low. This review will stimulate readers to carry out well designed, larger population based trials, so as to validate its use in dermatology practice.

A molecular view on the interference established between vaginal Lactobacilli and pathogenic Candida species: Challenges and opportunities for the development of new therapies.

Vaginal infectious diseases caused by viruses and bacteria have been linked to the occurrence of dysbiosis, that is, a reduction in the abundance of the normally dominating vaginal Lactobacillus species. Mucosal infections in the vagina and/or vulva caused by Candida species, usually known as vulvovaginal candidiasis (or VVC), are among the leading causes of diseases in the vaginal tract. The existence of a clear link between the occurrence of dysbiosis and the development of VVC is still unclear, although multiple observations point in that direction. Based on the idea that vaginal health is linked to a microbiota dominated by lactobacilli, several probiotics have been used in management of VVC, either alone or in combination with antifungals, having obtained different degrees of success. In most cases, the undertaken trials resorted to lactobacilli species other than those indigenous to the vaginal tract, although in vitro these vaginal species were shown to reduce growth, viability and virulence of Candida. In this paper we overview the role of lactobacilli and Candida in the vaginal micro- and myco-biomes, while discussing the results obtained in what concerns the establishment of interference mechanisms in vivo and the environmental factors that could determine that. We also overview the molecular mechanisms by which lactobacilli species have been shown to inhibit pathophysiology of Candida, including the description of the genes and pathways determining their ability to thrive in the presence of each other. In a time where concerns are increasing with the emergence of antifungal resistance and the slow pace of discovery of new antifungals, a thorough understanding of the molecular mechanisms underneath the anti-Candida effect prompted by vaginal lactobacilli is of utmost importance to assure a knowledge-based design of what can be a new generation of pharmaceuticals, eventually focusing therapeutic targets other than the usual ones.

The role of probiotics as adjunct treatment in the prevention and management of gynecological infections: An updated meta-analysis of 35 RCT studies.

OBJECTIVE: The present study aims to conduct a comprehensive meta-analysis of randomized controlled trials (RCTs) investigating the efficacy of probiotics as an adjunct treatment for preventing and treating gynecological infections. MATERIALS AND METHODS: The study adopted a systematic review of scientific databases including PubMed, Cochrane, and EMBASE, using defined MeSH terms. The inclusion and exclusion criteria were set to refine the search, with the data extraction and quality assessment being conducted by two independent investigators. RESULTS: A total of 35 articles, comprising 3751 patients, were included in the meta-analysis. The application of probiotics demonstrated a notable increase in the cure rates of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) as compared to control groups. A significant BV cure rate (OR: 5.972; 95% CI: 2.62-13.59; p-value: 0.01) was noted with probiotic use, which was even more pronounced when used as an adjunctive treatment with antibiotics (OR: 2.504; 95% CI: 1.03-6.06; p-value: 0.04). Additionally, probiotic use significantly reduced the recurrence rates of BV (OR: 0.34; 95% CI: 0.167-0.71; p-value: 0.004). For VVC, a significant increase in the cure rate was observed in the probiotic group (OR: 3.425; 95% CI: 2.404-4.879; p-value: 0.01), along with a lower recurrence rate (OR: 0.325; 95% CI: 0.175-0.606; p-value: 0.01). CONCLUSION: Our findings underscore the potential role of probiotics as a beneficial adjunctive treatment for gynecological infections, indicating an improved cure rate and decreased recurrence. However, additional well-designed studies are necessary to corroborate these findings.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

The Role of Probiotics in the Treatment of Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis.

Background: Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of probiotics in the treatment of vulvovaginal candidiasis. Methods: A comprehensive search of databases including PubMed, Scopus, Cochrane, Scientific Information Database (SID), IranMedex, and Google Scholar search engine was performed. The search was conducted from inception to 1 October 2022, to identify published English or Persian language randomized control trials (RCTs) of women with vulvovaginal candidiasis who received probiotics as medical treatment. The quality of the included studies was assessed using the Oxford Center for Evidence Based Medicine checklist All statistical analyses were performed using Comprehensive Meta-analysis (CMA) version 2. Results: Six RCTs were included in this review. The results showed that treatment with probiotic was not different from placebo regarding the rate of positive culture (OR: 1.12; 95% CI: 0.390 to 3.26, P=0.825); treatment with probiotic was more effective compared to placebo regarding the rate of recurrence. (OR: 0.14; P= 0.01; 95 % CI: 0.028-0.7). Conclusion: Probiotics have a beneficial effect in the treatment of women with vulvovaginal candidiasis. Our results provide evidence for an alternative treatment modality for vaginal candidiasis using probiotics.

Effectiveness of the association of 2 probiotic strains formulated in a slow release vaginal product, in women affected by vulvovaginal candidiasis: a pilot study.

BACKGROUND: Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis after bacterial vaginosis, and it is diagnosed in up to 40% of women with vaginal complaints in the primary care setting. Among Candida spp., Candida albicans is the most common infectious agent. The treatment of choice for uncomplicated VVC is achieved with single-dose or short-course therapy in over 90% of cases. Several topical and oral drugs are available, without evidence for superiority of any agent or route of administration. In any case, most classic treatments are unable to significantly offer a protection against possible recurrences. In recent years, probiotics are emerging as a new strategy to counteract VVC. In fact, they are well known for their ability to lower intravaginal pH, thus establishing a barrier effect against many types of yeasts. Some strains are also able to exert additional and more focused antagonistic activities mediated by specific molecules such as hydrogen peroxide and bacteriocins. For example, Lactobacillus fermentum LF5 (CNCM I-789) was successfully tested in 4 human trials involving a total of 340 women reporting VVC at enrollment. In any case, the way used to deliver probiotics to the vaginal environment represents a crucial point. The aim of this work was to first select 1 or more probiotic strains in vitro with an antagonistic activity on Candida yeasts and then to perform an in vivo human pilot study using an association of the most promising and active bacteria. METHODS: For this purpose, 2 probiotic strains Probiotical S.p.A (Italy) were selected based on their strong in vitro inhibition activity toward 4 particular Candida species, namely C. albicans, Candida glabrata, Candida parapsilosis, and Candida krusei and subsequently tested in a human intervention pilot trial involving 30 women with VVC. The probiotics used, L. fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02 (DSM 21717), were administered by means of slow release effervescent vaginal tablets (ActiCand 30 product). The main endpoint was the assessment of the establishment and maintenance of a barrier effect against Candida yeasts in women suffering from VVC. Thirty female subjects who were diagnosed with VVC by both microscopic examination and yeast culture were enrolled in the study and directed to apply a vaginal tablet once a day for 7 consecutive nights, followed by 1 tablet every 3 nights for a further 3-week application (acute phase) and, finally, 1 tablet per week to maintain a long-term vaginal colonization against possible recurrences. A medical examination of each patient was performed at enrollment (d0), at the end of the first 4 weeks of treatment (d28), and at the end of the second month of relapse prevention (d56). The visual and microscopic examination was always accompanied by microbiological analyses of vaginal swabs to assess the presence of Candida. A statistical comparison was made between d28, or d56, and d0, and between d56 and d28 to quantify the efficacy against possible recurrences. RESULTS: The administration of the product ActiCand 30 was able to significantly solve Candida yeast symptoms after 28 days in 26 patients out of 30 (corresponding to 86.6%, P<0.001). At the end of the second month, recurrences were recorded, albeit not particularly serious, in only 3 out of 26 patients (11.5%, P=0.083) who were found to have fully healed at the end of the first month of treatment. This is a further confirmation of the long-term barrier effect exerted by the product. CONCLUSIONS: VVC has a very high incidence as 70% to 75% of women report at least 1 episode during the life. Many treatments are currently available but, despite a relatively high effectiveness in the relief of symptoms typically associated with acute infections, they are generally unable to offer a long-term protective barrier against possible recurrences. This study demonstrated the ability of ActiCand 30 to not only solve Candida infections in a very high percentage of women, but also to exert a long-term physiological defense due to the colonization of vaginal microbiota and adhesion of the mucosa to the epithelial cells. The special formulation of ActiCand 30, consisting of slow release effervescent vaginal tablets, is able to mediate 2 types of barrier effects, the first represented by the formation of an anaerobic environment due to the release of CO2 and the second guaranteed by the colonization and adhesion to the vaginal epithelium of the 2 probiotics L. fermentum LF10 and L. acidophilus LA02.