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PloS One 2020Recurrent vulvovaginal candidiasis (RVVC) causes significant morbidity. Candida albicans is the main pathogen associated with both sporadic and recurrent candidiasis....
OBJECTIVES
Recurrent vulvovaginal candidiasis (RVVC) causes significant morbidity. Candida albicans is the main pathogen associated with both sporadic and recurrent candidiasis. Due to unsatisfactory treatment effect, the impact of chlorhexidine digluconate and fluconazole alone or in combination on C. albicans and biofilm was investigated.
METHODS
Vaginal C. albicans isolates from 18 patients with recurrent candidiasis and commensals from 19 asymptomatic women were isolated by culture. Crystal violet, XTT and colony forming unit assay were used to analyze the effect of chlorhexidine digluconate and fluconazole on growth of C. albicans, formation of new and already established, mature, biofilm.
RESULTS
Fluconazole reduced the growth of planktonic C. albicans. However, in established biofilm, fluconazole had no effect on the candida cells and was not able to disperse and reduce the biofilm. By contrast, chlorhexidine digluconate had a direct killing effect on C. albicans grown both planktonically and in biofilm. Chlorhexidine digluconate also dispersed mature biofilm and inhibited formation of new biofilm. No major differences were observed between commensal isolates and candida causing recurrent vulvovaginitis with respect to biofilm or growth after chlorhexidine digluconate treatment.
CONCLUSION
Biofilm is a problem in patients with recurrent vulvovaginal candidiasis reducing the effect of antifungal treatment. Development of new treatment strategies are urgently needed to decrease the recurrences. In already established biofilm, chlorhexidine digluconate dispersed the biofilm and was more effective in eradicating candida compared to fluconazole. Future treatment strategy may thus be a combination of chlorhexidine digluconate and fluconazole and prophylactic use of chlorhexidine digluconate to prevent biofilm formation and restrict infections.
Topics: Adult; Antifungal Agents; Biofilms; Candida; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Chlorhexidine; Female; Fluconazole; Humans; Microbial Sensitivity Tests; Vagina
PubMed: 32941438
DOI: 10.1371/journal.pone.0238428 -
PloS One 2018Vaginal candidiasis is a common disorder in women of childbearing age, caused primarily by the dimorphic fungus Candida albicans. Since C. albicans is a normal commensal... (Clinical Trial)
Clinical Trial
Vaginal candidiasis is a common disorder in women of childbearing age, caused primarily by the dimorphic fungus Candida albicans. Since C. albicans is a normal commensal of the vaginal mucosa, a long-standing question is how the fungus switches from being a harmless commensal to a virulent pathogen. Work with human subjects and in mouse disease models suggests that host inflammatory processes drive the onset of symptomatic infection. Fungal cell wall molecules can induce inflammation through activation of epithelial and immune receptors that trigger pro-inflammatory cytokines and chemokines, but pathogenic fungi can evade recognition by masking these molecules. Knowledge about which cell wall epitopes are available for immune recognition during human infection could implicate specific ligands and receptors in the symptoms of vaginal candidiasis. To address this important gap, we directly probed the surface of fungi present in fresh vaginal samples obtained both from women with symptomatic Candida vaginitis and from women that are colonized but asymptomatic. We find that the pro-inflammatory cell wall polysaccharide β-glucan is largely masked from immune recognition, especially on yeast. It is only exposed on a small percentage of hyphal cells, where it tends to co-localize with enhanced levels of chitin. Enhanced β-glucan availability is only found in symptomatic patients with strong neutrophil infiltration, implicating neutrophils as a possible driver of these cell wall changes. This is especially interesting because neutrophils were recently shown to be necessary and sufficient to provoke enhanced β-glucan exposure in C. albicans, accompanied by elevated immune responses. Taken together, our data suggest that the architecture of C. albicans cell wall can be altered by environmental stress during vaginal candidiasis.
Topics: Adult; Candida albicans; Candidiasis, Vulvovaginal; Epitopes; Female; Fungal Polysaccharides; Humans; Hyphae; Middle Aged; Neutrophil Infiltration; Neutrophils
PubMed: 30063729
DOI: 10.1371/journal.pone.0201436 -
Obstetrics and Gynecology Dec 2021To compare the performance of vaginitis diagnosis based on clinical assessment to molecular detection of organisms associated with bacterial vaginosis, vulvovaginal... (Comparative Study)
Comparative Study
OBJECTIVE
To compare the performance of vaginitis diagnosis based on clinical assessment to molecular detection of organisms associated with bacterial vaginosis, vulvovaginal candidiasis, and Trichomonas vaginalis using a vaginal panel assay.
METHODS
This cross-sectional diagnostic accuracy study included 489 enrolled participants from five collection sites where those with vaginitis symptoms had a vaginal assay swab collected during their visit and a clinical diagnosis made. The swab was later sent to a separate testing site to perform the vaginal panel assay. Outcome measures include positive, negative, and overall percent agreement (and accompanying 95% CIs) of clinical assessment with the vaginal panel assay. P<.05 was used to distinguish significant differences in paired proportions between the vaginal panel assay and clinical diagnosis, using the McNemar test. Inter-rater agreement between the two diagnostic approaches was determined using Cohen's kappa coefficient.
RESULTS
Clinical diagnosis had a positive percent agreement with the vaginal panel assay of 57.9% (95% CI 51.5-64.2%), 53.5% (95% CI 44.5-62.4%), and 28.0% (95% CI 12.1-49.4%) for bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis, respectively. Negative percent agreement for clinical diagnosis was 80.2% (95% CI 74.3-85.2%), 77.0% (95% CI 72.1-81.4%), and 99.8% (95% CI 98.7-99.9%), respectively. Sixty-five percent (67/103), 44% (26/59), and 56% (10/18) of patients identified as having bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis by assay, respectively, were not treated for vaginitis based on a negative clinical diagnosis. Compared with the assay, clinical diagnosis had false-positive rates of 19.8%, 23.0%, and 0.2% for bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis, respectively. Significant differences in paired proportions were observed between the vaginal panel assay and clinical diagnosis for detection of bacterial vaginosis and T vaginalis.
CONCLUSION
The vaginal panel assay could improve the diagnostic accuracy for vaginitis and facilitate appropriate and timely treatment.
FUNDING SOURCE
Becton, Dickinson and Company.
Topics: Adolescent; Adult; Aged; Biological Assay; Candidiasis, Vulvovaginal; Cross-Sectional Studies; Female; Humans; Middle Aged; Physical Examination; Prospective Studies; Reproducibility of Results; Specimen Handling; Trichomonas Vaginitis; Vagina; Vaginitis; Vaginosis, Bacterial; Young Adult
PubMed: 34736269
DOI: 10.1097/AOG.0000000000004592 -
Mycopathologia Jun 2022A total of 244 Candida albicans isolates recovered from vulvovaginal candidiasis (VVC) patients in Suzhou, Eastern China, were investigated. According to CLSI documents...
A total of 244 Candida albicans isolates recovered from vulvovaginal candidiasis (VVC) patients in Suzhou, Eastern China, were investigated. According to CLSI documents M27-A4 and M59-3ed/M60-2ed, the MIC geometric means of nine antifungals in increasing order were micafungin (0.048 mg/L), anidulafungin (0.132 mg/L), caspofungin (0.19 mg/L), itraconazole (0.23 mg/L), posaconazole (0.25 mg/L), voriconazole (0.28 mg/L), 5-flucytosine (0.44 mg/L), amphotericin B (0.49 mg/L) and fluconazole (2.01 mg/L) respectively. Of note, 6.5% (16/244) C. albicans isolates showed resistance mainly to anidulafungin (mono-echinocandin resistance), while voriconazole had the lowest susceptibility rate of 34.8% (85/244), followed by fluconazole 59.4% (145/244), respectively. All isolates were genotyped by allelic combination of 3 microsatellite markers (CEF3, CAIII and LOC4). A total of 129 different allelic genotypes were identified, in which seven different clades were recognized with a discriminatory power of 0.96. Genotypes A-D were present in 35% of the isolates. In conclusion, decrease in antifungal drug susceptibility to C. albicans isolates from VVC is alarming. Our findings revealed the genetic diversity of C. albicans isolates among VVC patients and provided insights into the molecular epidemiology of Candida infections in China.
Topics: Anidulafungin; Antifungal Agents; Candida; Candida albicans; Candidiasis, Vulvovaginal; Drug Resistance, Fungal; Female; Fluconazole; Genotype; Humans; Microbial Sensitivity Tests; Voriconazole
PubMed: 35072854
DOI: 10.1007/s11046-022-00616-x -
Virulence Jan 2017
Topics: Candida; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Humans; Saccharomyces cerevisiae
PubMed: 27580424
DOI: 10.1080/21505594.2016.1230580 -
Revista Da Associacao Medica Brasileira... Feb 2022
Meta-Analysis
Topics: Administration, Oral; Antifungal Agents; Candidiasis, Vulvovaginal; Female; Humans; Recurrence; Vagina
PubMed: 35239893
DOI: 10.1590/1806-9282.20210916 -
Clinical Infectious Diseases : An... Jul 2022Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis.
METHODS
Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10).
RESULTS
Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events.
CONCLUSIONS
Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis.
CLINICAL TRIALS REGISTRATION
NCT03253094.
Topics: Administration, Oral; Antifungal Agents; Candidiasis, Vulvovaginal; Female; Fluconazole; Glycosides; Humans; Triterpenes
PubMed: 34555149
DOI: 10.1093/cid/ciab841 -
Clinical Infectious Diseases : An... Jun 2022Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC.
METHODS
Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4).
RESULTS
Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity.
CONCLUSIONS
Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.
Topics: Antifungal Agents; Azoles; Candidiasis, Vulvovaginal; Female; Glycosides; Humans; Triterpenes
PubMed: 34467969
DOI: 10.1093/cid/ciab750 -
MBio Mar 2024can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and...
can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and vulvovaginal candidiasis (VVC), which is the most frequent manifestation of candidiasis. Epithelial cell invasion by hyphae is accompanied by the secretion of candidalysin, a peptide toxin that causes epithelial cell cytotoxicity. During vaginal infections, candidalysin-driven tissue damage triggers epithelial signaling pathways, leading to hyperinflammatory responses and immunopathology, a hallmark of VVC. Therefore, we proposed blocking candidalysin activity using nanobodies to reduce epithelial damage and inflammation as a therapeutic strategy for VVC. Anti-candidalysin nanobodies were confirmed to localize around epithelial-invading hyphae, even within the invasion pocket where candidalysin is secreted. The nanobodies reduced candidalysin-induced damage to epithelial cells and downstream proinflammatory responses. Accordingly, the nanobodies also decreased neutrophil activation and recruitment. mathematical modeling enabled the quantification of epithelial damage caused by candidalysin under various nanobody dosing strategies. Thus, nanobody-mediated neutralization of candidalysin offers a novel therapeutic approach to block immunopathogenic events during VVC and alleviate symptoms.IMPORTANCEWorldwide, vaginal infections caused by (VVC) annually affect millions of women, with symptoms significantly impacting quality of life. Current treatments are based on anti-fungals and probiotics that target the fungus. However, in some cases, infections are recurrent, called recurrent VVC, which often fails to respond to treatment. Vaginal mucosal tissue damage caused by the peptide toxin candidalysin is a key driver in the induction of hyperinflammatory responses that fail to clear the infection and contribute to immunopathology and disease severity. In this pre-clinical evaluation, we show that nanobody-mediated candidalysin neutralization reduces tissue damage and thereby limits inflammation. Implementation of candidalysin-neutralizing nanobodies may prove an attractive strategy to alleviate symptoms in complicated VVC cases.
Topics: Humans; Female; Candidiasis, Vulvovaginal; Quality of Life; Single-Domain Antibodies; Candida albicans; Candidiasis; Inflammation; Fungal Proteins
PubMed: 38349176
DOI: 10.1128/mbio.03409-23 -
Genitourinary Medicine Oct 1994To determine whether zinc deficiency in serum or vulvovaginal secretion is a risk factor for recurrent vulvovaginal candidiasis. (Clinical Trial)
Clinical Trial
OBJECTIVE
To determine whether zinc deficiency in serum or vulvovaginal secretion is a risk factor for recurrent vulvovaginal candidiasis.
DESIGN
Prospective and controlled study.
SETTING
Department of Dermatology, University of Vienna.
SUBJECTS
21 women who had experienced at least three documented episodes of acute vulvovaginal candidiasis within the previous 12 months. Fifteen women without anamnesis of vulvovaginal candidiasis as a control group.
INTERVENTIONS
Blood samples were drawn for measurement of plasma zinc levels. Lavage of the vagina and ectocervix was performed with sterile saline solution for measurement of cervicovaginal zinc levels.
MAIN OUTCOME MEASURES
Zinc levels of serum and cervicovaginal secretions were determined by flame atomic absorption spectrophotometry.
RESULTS
We found no significant difference in the mean zinc concentration of plasma and cervicovaginal secretions between the recurrent vulvovaginal candidiasis and the control group. (p value for serum = 0.71, p value for secretion = 0.80). Zinc levels of plasma and cervicovaginal secretions showed no correlation (patient group: r = -0.05, control group: r = -0.07).
CONCLUSION
It is well known that zinc not only exerts a major impact on different immune functions, but also participates in growth and morphogenesis of Candida albicans. Our results could not confirm the previous hypothesis that zinc deficiency of serum is a risk factor in recurrent vulvovaginal candidiasis. It is possible that the local zinc level of cervicovaginal secretions essentially influences antifungal activity of third generation azole antimycotics.
Topics: Adult; Candidiasis, Vulvovaginal; Cervix Uteri; Female; Humans; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Spectrophotometry, Atomic; Vagina; Zinc
PubMed: 8001939
DOI: 10.1136/sti.70.5.308