Search Results (30)

Recurrent vulvovaginal candidosis (RVVC), defined as three or more episodes of vulvovaginal candidosis (VVC) within a 12-month period, is a common and debilitating condition that affects a significant percentage of reproductive-aged women, negatively impacting their quality of life. This review aimed to synthesize the most recent scientific data on the pathophysiological mechanisms triggering primary or idiopathic RVVC. Three databases (PubMed, Scopus, and Web of Science) were searched for studies published between 2014 and 2024. Twelve studies were included, covering prospective cohort, cross-sectional, and case–control studies conducted in different countries. The results indicate that recurrence may be related to both intrinsic characteristics of the pathogen, such as increased virulence attributes of Candida spp., and host immune system dysregulation, including alterations in Th1/Th17 and Th2/Treg cytokine levels, decreased levels of mannose-binding lectin (MBL), impaired neutrophil and lymphocyte function, and overexpression of CD163+ macrophages and NLRP3 inflammasome. Additionally, genetic factors, such as polymorphisms in the MBL2, IL-12, NLRP3, and TLR2 genes, are associated with increased susceptibility to RVVC. In conclusion, RVVC appears to involve a complex interaction between pathogen virulence and an altered host immune response, which reinforces the need for further investigations to develop personalized therapeutic strategies. Full article

Currently, the rising prevalence of resistant Candida species, particularly Candida albicans, as well as non-albicans isolates such as Candida glabrata and Candida krusei, represent challenges in their management. In this review, we aimed to explore the current management of fluconazole-resistant vulvovaginal candidiasis (FRVVC). Identified studies focused on alternative antifungal therapies, including boric acid, nystatin, and newer agents like oteseconazole and ibrexafungerp. The findings highlight the need for tailored treatment regimens, considering the variability in resistance patterns across regions. Unprofessional as well as professional overuse of antifungals for vulvovaginal symptoms that are not caused by Candida infections should be combatted and banned as much as possible. Instead of high-dose maintenance regimens using weekly doses of 150 to 200 mg of fluconazole for 6 months or longer, it is advisable to use an individualised degressive regimen (ReCiDiF regimen) in order to tailor the treatment of a particular patient to the lowest dosage possible to keep the diseases controlled. Additionally, this report underscores the impact of antibiotic use on the microbiota, which can raise the possibility of VVC and lead to fluconazole resistance, emphasizing the necessity for cautious antibiotic prescribing practices. Full article

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article

Background/Objectives: Vulvovaginal candidosis (VVC) is a common condition among women, with current diagnostic methods relying on clinical evaluation and laboratory testing. These traditional methods are often limited by the need for specialized training, variable performance, and lengthy diagnostic processes, leading to delayed treatment and inappropriate antifungal use. This review evaluates the efficacy of molecular diagnostic tools for VVC and provides guidance on their application in clinical practice. Methods: A literature search was conducted using PubMed to identify studies evaluating rapid diagnostic tests specifically for vulvovaginal Candida isolates. Inclusion criteria focused on studies utilizing molecular diagnostics for the detection of Candida species in VVC. Articles discussing non-vaginal Candida infections, non-English studies, and animal or in vitro research were excluded. Results: Twenty-three studies met the inclusion criteria, predominantly evaluating nucleid acid amplification tests/polymerase chain reaction (NAAT/PCR) assays and DNA probes. PCR/NAAT assays demonstrated high sensitivity and specificity (>86%) for VVC diagnosis, outperforming conventional diagnostic methods. Comparatively, DNA probes, while simpler, exhibited lower sensitivity. The included studies were mostly observational, with only one randomized controlled trial. Emerging diagnostic technologies, including artificial intelligence and integrated testing models, show promise for improving diagnostic precision and clinical outcomes. Conclusions: Molecular diagnostics offer a significant improvement in VVC management, though traditional methods remain valuable in resource-limited settings. Full article

Vulvovaginal candidosis (VVC) represents a frequent and cumbersome vaginal infection. Recurrent and/or persistent infections remain common among a significant number of patients despite the use of antifungals. Probiotics offer a promising adjunctive or alternative therapeutic strategy to antifungals in the management of VVC. We aimed to explore and thoroughly examine the various roles and potential applications of probiotics in VVC. A comprehensive literature search was conducted to identify relevant clinical trials and systematic reviews that examine the effectiveness of probiotics in the treatment and prevention of VVC and recurrent VVC (rVVC). Following the initial screening of 4563 articles, a total of 25 clinical studies and seven systematic reviews were finally included in this analysis. The studies reviewed provide a generally positive yet inconsistent view of the efficacy of probiotics in managing VVC, including clinical, mycological response, and prevention perspectives. Nonetheless, fluconazole remains more effective than probiotics in treating VVC, while the combination of the two seems to reduce recurrence and improve symptoms significantly. For prevention, probiotics seem to improve vaginal health and reduce symptoms, while safety and tolerability are consistently reported across the studies, affirming that probiotics represent a low-risk intervention. However, clear conclusions are difficult to establish since relative studies explore different clinical endpoints and follow-up times, variable populations are included, different probiotics are used, and diverse schedules and regimens are administered. We propose that future studies should study the benefit of probiotics in well-defined categories such as (1) treatment with acute probiotics instead of antifungals, (2) adjuvant probiotic therapy together or after antifungals, and (3) VVC recurrence prevention using probiotics. Full article

This study reports a peculiar case of systemic candidiasis infection associated with pulmonary aspergillosis in an apparently immunocompetent alpaca. A captive 7-year-old female alpaca exhibited respiratory symptoms, underwent treatment with benzylpenicillin and dexamethasone, and succumbed to the infection 40 days later. During the post-mortem examination, subcutaneous emphysema, widespread pneumonia with multiple suppurative foci, scattered necro-suppurative lesions throughout the renal and hepatic parenchyma were evident. Histopathological analysis of the collected tissues revealed multifocal mild lymphoplasmacytic chronic interstitial nephritis, necro-suppurative pneumonia with the presence of fungal hyphae, multifocal foci of mineralization, and fibrosis in the liver. Fungal cultures confirmed the growth of Aspergillus fumigatus from the lungs, and Candida albicans from the liver, kidney, and heart. The only recognizable risk factor for candidiasis and pulmonary aspergillosis in this case was prior corticosteroid and antibiotic therapy. Nevertheless, it is crucial to consider systemic candidosis and pulmonary aspergillosis as potential differential diagnoses in respiratory infections among camelids. Prolonged treatment with glucocorticoids and antibiotics should be avoided as it could represent a risk factor for the onset of pathologies caused by opportunistic fungi such as Candida spp. and Aspergillus spp. Full article

(1) Background: Vulvovaginal candidosis (VVC) is a major therapy issue due to its high resistance rate and virulence factors such as the ability to form biofilms. The possibility of combining commonly used antifungals with natural products might greatly improve therapeutic success. (2) Methods: A total of 49 vulvovaginal isolates, causative agents of recurrent VVC, were tested for their susceptibility to fluconazole, nystatin, and Melissa officinalis essential oil (MOEO). This examination included testing the antibiofilm potential of antifungals and MOEO and the determination of their types of interaction with mature biofilms. (3) Results: Antimicrobial testing showed that 94.4% of the Candida albicans isolates and all the Candida krusei isolates were resistant to fluconazole, while all strains showed resistance to nystatin. The same strains were susceptible to MOEO in 0.156–2.5 mg/mL concentrations. Additionally, the results revealed very limited action of fluconazole, while nystatin and MOEO reduced the amount of biofilm formed by as much as 17.7% and 4.6%, respectively. Testing of the combined effect showed strain-specific synergistic action. Furthermore, the lower concentrations exhibited antagonistic effects even in cases where synergism was detected. (4) Conclusions: This study showed that MOEO had a very good antibiofilm effect. However, combining MOEO with antimycotics demonstrated that the type of action depended on the choice of antifungal drugs as well as the applied concentration. Full article

Chronic hyperplastic candidiasis (CHC) presents a distinctive and relatively rare form of oral candidal infection characterized by the presence of white or white–red patches on the oral mucosa. Often mistaken for leukoplakia or erythroleukoplakia due to their appearance, these lesions display nonhomogeneous textures featuring combinations of white and red hyperplastic or nodular surfaces. Predominant locations for such lesions include the tongue, retro-angular mucosa, and buccal mucosa. This paper aims to investigate the potential influence of specific anatomical locations, retro-angular mucosa, on the development and occurrence of CHC. By examining the relationship between risk factors, we present an approach based on machine learning (ML) to predict the location of CHC occurrence. In this way, we employ Gradient Boosting Regression (GBR) to classify CHC lesion locations based on important risk factors. This estimator can serve both research and diagnostic purposes effectively. The findings underscore that the proposed ML technique can be used to predict the occurrence of CHC in retro-angular mucosa compared to other locations. The results also show a high rate of accuracy in predicting lesion locations. Performance assessment relies on Mean Squared Error (MSE), Root Mean Squared Error (RMSE), R-squared (R²), and Mean Absolute Error (MAE), consistently revealing favorable results that underscore the robustness and dependability of our classification method. Our research contributes valuable insights to the field, enhancing diagnostic accuracy and informing treatment strategies. Full article

Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, first from the anterior vulva and then from the upper third and right lateral wall of the vagina: 16 were with symptoms of vulvovaginal candidiasis and 17 were without characteristic symptoms; furthermore, the genus and species of each isolate were identified. In vitro susceptibility testing for fluconazole and clotrimazole was performed for all isolates. Candida albicans was the most common species (63.6%), followed by Rhodotorula spp. (51.5%), and then Candida parapsilosis (15.2%). Rhodotorula spp. and C. parapsilosis were more commonly associated with colonization, and C. albicans with infection. Rhodotorula spp. isolates presented a low susceptibility to fluconazole, with the MIC ranging from 32 to >64 µg/mL. Differences in susceptibility to fluconazole and clotrimazole between the pairs of vaginal and vulvar isolates were found for Candida albicans, Rhodotorula spp., and Nakaseomyces glabratus. The results suggest that different niches may impact the susceptibility profiles of the isolates, as well as their different clinical behaviors. Full article

Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years. Full article

Oral lichen planus (OLP) is an inflammatory condition of unknown cause that has been associated with concurrent candidal infection. Mucosal-associated invariant T (MAIT) cells express the T cell receptor TCRVα7.2 and are activated by riboflavin intermediates produced by microbes. The interaction between MAIT cells, Candida, and OLP is unknown. This study aimed to determine mucosal-associated T cell presence in OLP and whether the abundance of these cells changed due to the presence of either Candida or symptoms, using multiplex immunohistochemistry (mIHC). Ninety formalin fixed-paraffin-embedded (FFPE) tissue samples were assessed using mIHC for the cellular markers CD3, interleukin 18 receptor one (IL18R1), TCRVα7.2, CD161, CD8, and major histocompatibility complex class I-related (MR-1) protein. The samples were stratified into five groups on the basis of clinical (presence/absence of symptoms) and microbiological (presence/absence of Candida) criteria. Results demonstrated the presence of MAIT cell phenotypes in OLP inflammatory infiltrate within the connective tissue. Significant differences existed between different OLP groups with the percentage of log(CD3⁺ CD161⁺) and log(CD3⁺ TCRVα7.2⁺) positive cells (p < 0.001 and p = 0.005 respectively). Significant differences also existed with the relative abundance of triple-stained log(CD3⁺ CD161⁺ IL18R1⁺) cells (p = 0.004). A reduction in log(CD3⁺ CD161⁺ IL18R1⁺) cells was observed in lesional tissue of patients with symptomatic OLP with and without Candida when compared to controls. When present in OLP, MAIT cells were identified within the connective tissue. This study demonstrates that mIHC can be used to identify MAIT cell phenotypes in OLP. Reduced percentage of log(CD3⁺ CD161⁺ IL18R1⁺) cells seen in symptomatic OLP with and without Candida suggests a role for these cells in OLP pathogenesis. Full article

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings. Full article

Bacterial vaginosis (BV) is a common infection characterized by an imbalance in the vaginal microbiome. Alongside the extensive research for effective therapies, treatment recommendations for symptomatic BV with antibiotics have been developed and are currently available. However, the recurrence of BV remains a considerable challenge given that about 60% of women experience BV relapse within six months after initial treatment. In addition, clear guidelines on the treatment of asymptomatic BV during pregnancy or for BV mixed infections are still missing. Lactic acid has been put forward as a potential treatment or for prophylaxis of BV due to its ability to restore the imbalance of the vaginal microbiota and to promote the disruption of vaginal pathogenic bacterial biofilms, which might trigger BV recurrence. This review evaluates the clinical evidence regarding the efficacy and prophylactic potential of lactic acid in BV through a systematic literature search. In addition, a treatment regimen consisting of lactic acid as a standalone treatment or in combination with current recommended therapies for practice is suggested based on these findings and stratified according to BV severity, pregnancy status, and coincidence with vulvovaginal candidosis (VVC) or trichomoniasis. Full article

Previous studies have revealed that Candida albicans isolates involved in chronic vulvovaginal candidosis (cVVC) phenotypically express less virulent traits than clinical isolates involved in sporadic infections. In this study, we aimed to further explore this finding by studying the behaviour of those same clinical isolates in in-vitro models of infection. Eighteen clinical Candida albicans isolates were collected from women suffering sporadic (eight isolates) or chronic infections (ten isolates). Adhesion to HeLa cells (human cervical cancer epithelial cell line) and resistance to phagocytosis by RAW 264.7 cells (murine macrophages cell line) were tested in-vitro. In addition, phenotypic expression of virulence factors related with either adhesion or resistance to phagocytosis was tested in-vitro. Results indicated that yeast isolates involved in sporadic infection adhered in a higher proportion of HeLa cells than those of chronic infections, which was related with their ability to produce biofilm (p < 0.05). The ability to evade phagocytosis was related to an elevated production of proteases (p < 0.05) by chronic isolates, while sporadic isolates’ resistance to phagocytosis was related to a higher hydrophobicity of cell walls (p < 0.05). We conclude that the evasion of macrophage-mediated phagocytosis related to the production of proteases might be an important factor involved in the recurrence of vulvovaginal candidosis infection. Full article

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects. Full article