Candidiasis Research Articles

Assessment of Denture’s Continuous Wearing as a Factor Predisposing to Chronic Atrophic Candidiasis in a Sample of Lebanese Denture Wearers: A Clinico-microbiological Study

Background: Chronic atrophic candidiasis (CAC), commonly referred to as denture stomatitis, is the most prevalent multifactorial, chronic inflammatory oral condition amongst denture wearers. Denture’s continuous wearing is considered a risk factor predisposing to CAC. The aim of this study was to evaluate this factor and its relationship with the occurrence of CAC in a Lebanese population. Material and Methods: Two hundred ninety (161 women, 129 men; age range 40-80 years) were selected for this study. Swab samples from the palate and the palatal surfaces of the upper dentures of these patients were collected and examined mycologically. Denture’s continuous wearing and colonization by Candida albicans were evaluated. Results: In this sample of 290 patients, 85 (29.31%) wear their dentures continuously and 170 (58.62%) exhibited clinically and microbiologically CAC. With respect to the patient’s age, 41 out of the 65 patients (63.07%) aged between 40 and 60 years showed CAC against 129 (57.33%) who are older than 60. Conclusion: This study supports previous findings that denture continuous use of denture is a significant factor that contributes to CAC.

Synthesis and characterization of novel Schiff base ligands and their Cu (II), Zn (II), Co (II), and Ni (II) complexes: DNA binding, antibacterial activity, and docking studies

In this paper, we describe the process of synthesizing and characterizing of cu (II), Ni (II), Co (II) and Zn (II) coordination compounds of 4,4’-((1E,1’E) -((4chloro-1,2phenylene) bis(azanylylidine)bis (methanylylidine)) bis (naphthalene-2-ol) [CAMD] Schiff base. Elemental analysis, molar conductance, spectral data (FT-IR, 1H NMR & 13C NMR, UV-visible, EPR, XRD and mass spectra), and thermogravimetric analysis (TGA) were used to establish their formation and validate their structures. All the complexes obtained as monomeric structure and the metal center moieties are four-coordinated with square planar geometry, according to the spectral analysis. Thermogravimetric analysis (TGA) was castoff to consider the decomposition of the complexes and Schiff base ligand. Herein, the calf thymus DNA (CT DNA) binding Goldfeather#12#kinships of complexes have been examined by UV–visible spectroscopy. All complexes interact with DNA through an intercalating way. In a series of dilution experiments with Kanamycin and Fluconazole as standards, the ligand and its metallic complexes (1-4) demonstrated antimicrobial activity against a variety of bacterial and fungal species, including Gram-positive (Staphylococcus aureus, Pseudomonas aeruginosa) and Gram-negative (Escherichia coli, Bacillus Subtilis, Salmonella Typhi), as well as fungal infections, as well as fungal infections, as well as fungal infections, as well as fungal infections, yeast infections, and yeast infections. The preliminary in vitro antimicrobial screening revealed that the newly synthesised Schiff base inhibits bacterial and fungal growth significantly, compared to standard drugs. Additionally in silico studies of molecular docking were also done for Schiff base ligand and its multiplexes in the active site of DNA Gyrase enzyme (PDB code:6TCK), demonstrating strong hydrogen bonding interactions of drug targets and can be used as antibacterial drugs angainst pathogens. The performance of complexes closely matched the reactivity order seen in in-vitro studies. Overall, the complexes are intriguing candidates for antimicrobial development. We intend to use these compounds in a therapeutic context. Synthesized substances were determined to be non-toxic after undergoing ADME/T analysis to assess their drug-likeness.

Development of Novel Women's Friendly Antifungal Microemulsion Loaded Gel for Vulvovaginal Infections

Aim: The research was carried out to develop the microemulsion-loaded gel of curcu-min, alkylpolyglucoside, and tea tree oil to treat vulvovaginal candidiasis infection. Methods: Screening of oils, surfactants, and co-surfactants was done based on solubility studies and the construction of pseudo-ternary phase diagrams with curcumin. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex-vivo studies were carried out using Franz diffusion cells. The antifungal activity of microemulsion-loaded hydrogel was evaluated using the cup plate method using Candida albicans ATCC 10231 in glucose yeast agar medium. Results: The selected micro-emulsion consisted of curcumin 35μg/mL, IPM+TTO (1:1) 0.1 mL, Milcoside 100 + Acconon MC 8-2 EP NF 0.6-0.3 mL, phosphate buffer pH 4 160 mL showed maximum thermodynamic stability and exhibited lowest particle size and highest intensity. The viscosity of microemulsion-loaded gel was 11.2 pa.s. The surface tension of the microemulsion was measured by tensiometer and was found to be 26.07 mN/m. Antimicrobial susceptibility test-ing assay was done according to NCCLs assay protocol, and the EC50 value of our formulation was found to be 0.4465 μg/mL. In-vitro drug release and ex-vivo permeation studies showed 67.9% release in 420 minutes and 83.02% release in 360 minutes, respectively. An in-vitro irrita-tion study concluded that there was no redness or irritation on goat mucosa. Conclusion: The texture analysis test showed adhesiveness at -172.46 g s at - 4.60 adhesive force, and the peak load was 13.40 g. The microemulsion-loaded gel formulation can be a promis-ing alternative to the marketed formulations available for vaginal yeast infections.

In-vitro Interactions between Fluconazole and Diphenyl Diselenide against Various Candida Species

Background: In the immunocompromised population, Candida species are the most aetiologic agents causing severe nosocomial fungal infections. Candida species, irrespective of being commensals in the human microbiome, are the fourth most prevalent source of potentially fatal yeast infections. Monotherapy is frequently employed to treat invasive fungal infections, but sometimes, patients do not favor the monotherapy treatment regime. It may be because of the reduced susceptibility of the pathogen toward traditional antimycotic drugs. Antimycotic drug combination therapy could be a better choice in such specific circumstances. In our study, we evaluated the interactions of fluconazole with diphenyl diselenide. Methods: The antimycotic susceptibilities of Candida species for fluconazole and diphenyl diselenide were determined by broth microdilution assay, and the in-vitro interactions of fluconazole with diphenyl diselenide were studied by using disc diffusion assay and chequerboard assay. The nature of the interactions was assessed by calculating the fractional inhibitory concentration index (FICI). The interactions were also analyzed by the response surface approach. Results: The minimum inhibitory concentrations (MICs) for fluconazole and diphenyl diselenide as determined by the broth microdilution assay against Candida species were 4 μg/ml-512 μg/ml and 1 μg/ml-32 μg/ml, respectively. The FICI values varied from 0.375 to 2. Conclusion: Our finding demonstrated that there is no antagonism interaction between fluconazole and diphenyl diselenide in Candida species. Thus, this innovative combination should be explored in the future.

The Use of Candida Scoring as a Predictor for Candida Infection in Patients Admitted in the Intensive Care Units of a Tertiary Medical Center

The Use of Candida Scoring as a Predictor for Candida Infection in Patients Admitted in the Intensive Care Units of a Tertiary Medical Center

Brodalumab: Six-Year US Pharmacovigilance Report.

Brodalumab is a human interleukin-17 receptorA antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the USA, brodalumab has a boxed warning regarding suicidal ideation and behavior and is only available under a Risk Evaluation and Mitigation Strategy, but no causal association has been established. To assess long-term safety of brodalumab, we summarize pharmacovigilance data from 6years of real-world clinical practice. Crude adverse event (AE) reporting rates per 100 patients were calculated for common AEs and AEs of special interest reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017 through August 14, 2023. Brodalumab exposure was estimated as time from the first to last prescription-dispensing authorization dates. Adverse events were defined by Medical Dictionary for Regulatory Activities v26.0 Preferred Terms and standardized MedDRA queries. Data were collected from 5138 US patients (estimated exposure of 6900 patient-years). Over 6years, 13 cases of adjudicated major adverse cardiovascular events were reported (0.25 events/100 patients). The rate of serious infections was 2.20 events/100 patients. Since the 5-year report, there was one new case of Candida infection and a serious fungal infection of the elbow. Among 57 reported malignancies affecting 49 patients, 4 were deemed possibly related to brodalumab. One new case of indeterminate inflammatory bowel disease unrelated to brodalumab was reported. No new suicide attempts were reported in year6, and there were no completed suicides throughout 6years. Pharmacovigilance data throughout 6years are consistent with the safety profile of brodalumab established in clinical trials and previous US pharmacovigilance reports, with no completed suicides and a low fungal infection rate.

ScRNA-Seq Analysis of Tongue Tissues in Chronic Hyperplastic Candidiasis.

Chronic hyperplastic candidiasis (CHC) is a rare but severe subtype of oral candidiasis distinguished by its potential malignant transformation and suboptimal response to antifungal therapies. However, the cells and mechanisms that play key roles in this process remain unclear. Therefore, we performed the first single-cell RNA sequencing (scRNA-seq) analysis of CHC-affected tongue tissues to reveal the microenvironmental changes and immunological etiology of CHC. First, the features of CHC lesions manifesting as thickening and hardening nodular lesions, including their pathological and microbiological characteristics, were elucidated. Then, a comprehensive cellular atlas and distinct immune landscape in CHC compared with healthy tissues were characterized using scRNA-seq, highlighting significant modifications in the cell number and functionality of fibroblasts and T/NK cells. Importantly, the central role of fibroblasts in cell-cell interactions in CHC was hinted, and possible ligand-receptor pairs mainly associated with inflammation and carcinogenesis were identified. Moreover, it was revealed that significant functional activation of fibroblasts, related to the activation of the epithelial-mesenchymal transition pathways and increased expression of collagen I, matrix metalloproteinase 1 (MMP1), and MMP2, could be a hallmark of CHC, correlating with CHC's clinical characteristics of tongue hardening and intense inflammation. Notably, there is sequencing evidence of the recruitment of CD8+Tex cells and activation of PD-1 and TIGIT immune checkpoint pathways. Moreover, cDC_LAMP3 cells exhibited high CD274 expression, suggesting immune exhaustion and an increased susceptibility to carcinogenesis. This pioneering study provides valuable insights into CHC pathogenesis and immune responses, enhancing our understanding of potential therapeutic strategies.

MRI differentiation of CNS fungal infections: correlating imaging features with microbiological and histopathological findings.

The study aims to evaluate the magnetic resonance (MR) features of central nervous system (CNS) fungal infections and determine the associations between these findings and the type of fungus. Our main objective was to assess whether imaging can serve as a predictor for identifying the specific group of fungi responsible for the infection using microbiology and histopathology as a benchmark. A retrospective analysis was done on 50 patients with proven CNS fungal infections. Fungal type was determined and grouped according to microbial classifications into four subtypes: hyalohyphomycetes, mucorales, yeasts and dematiaceous molds. MR findings were compared with histopathology/microbiology and associations between fungal groups were sought. A total of 37 males and 13 females with a mean age of 39.3 years were included in the study. Aspergillus spp. infection (48%) was the most common. Most patients (54%) had an underlying risk factor for the infection. Pseudo-tumoral mass-like behavior was observed with Aspergillus, and the presence of meningitis was associated with yeast infections (p < 0.001). Of the 19 abscesses, 9 (47.3%) showed a dual rim sign on susceptibility-weighted imaging (SWI), and 10 (52.6%) showed intracavitary dot-like foci of dropouts on SWI. Both findings were statistically significant with dematiaceous molds (p = 0.04 and p = 0.009, respectively). Although radiological characteristics are non-specific and can overlap with each type of fungi, our study shows that certain MR features can help radiologists point towards the causative type. More specifically, dot-like foci of susceptibility point towards abscesses caused by dematiaceous molds possibly owing to melanin pigment and metal chelation properties.

The Neosartorya (Aspergillus) fischeri antifungal protein NFAP2 has low potential to trigger resistance development in Candida albicans in vitro.

Due to the increase in the number of drug-resistant Candida albicans strains, new antifungal compounds with limited potential for the development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted by Neosartorya (Aspergillus) fischeri, is a promising candidate. We investigated the ability of C. albicans to develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC). C. albicans adapted to only 1× minimum inhibitory concentration (MIC) of NFAP2, which can be considered tolerance rather than resistance, compared with 32× MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-tolerant strains and in several genes in FLC-resistant strains. Tolerance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-tolerant strains did not change to FLC, amphotericin B, micafungin, and terbinafine. These strains did not show altered susceptibility to AFPs from Penicillium chrysogenum, except one which had less susceptibility to Penicillium chrysogenum antifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs from P. chrysogenum. NFAP2-tolerant and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of tolerance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Tolerance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.IMPORTANCEDue to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunistic Candida species. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment of Candida infection. Data on the development of resistance to antifungal proteins in Candida albicans are lacking. In this study, we provide evidence that NFAP2 has a low potential to trigger resistance in C. albicans in vitro, and the developed tolerance to NFAP2 is not associated with severe phenotypic changes compared with development of resistance to generic fluconazole. These results suggest the slow emergence of NFAP2-resistant Candida strains, and NFAP2 can reliably be used long-term in the clinic.

Recommendations for Research to Develop a Patient-Centered Clinical Follow-Up Protocol for Oral Epithelial Dysplasia.

Oral epithelial dysplasia (OED) is the primary histological marker for assessing the progression of oral potentially malignant disorders (OPMDs) to cancer. Despite challenges in grading and low inter-pathologist reproducibility, OED severity remains the key predictor of malignant transformation. However, globally accepted guidelines for OED monitoring are lacking, despite calls for individualized management based on host and lesion characteristics. The proposed research protocol involves acquiring high-quality intraoral images, assessing oral hygiene and periodontal status, eliminating chronic mechanical irritation and Candida infections, and applying adjunctive diagnostic methods like toluidine blue staining, optical evaluation, and brush cytology. Tailored follow-up regimens based on individual risk assessments are emphasized, with frequent monitoring for high-grade dysplasia or patients at higher risk of progression. Therefore, effective OED management should consider the patient's immune status, dietary habits, and oral microbiota, aiming to develop personalized treatment strategies that optimize patient-centered care.

Bimekizumab Efficacy and Safety in Patients With Psoriatic Arthritis Who Had Skin and Nail Psoriasis at Baseline: Up to 2-year Results From Two Phase 3 Studies

Introduction: Bimekizumab (BKZ), a humanized anti-IL17F anti-IL17A antibody has demonstrated efficacy and tolerability to 1 year in patients with psoriatic arthritis (PsA) and psoriasis.1 Nail psoriasis is associated with increased PsA risk, more severe disease and decreased quality of life, in patients with psoriasis.2,3 Here, efficacy and safety of BKZ treatment are reported to 2 years in patients with PsA, skin involvement and nail psoriasis in two phase 3 trials. Methods: BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi‑IR) assessed subcutaneous BKZ 160 mg Q4W in patients with PsA. Placebo (PBO) patients switched to BKZ (PBO/BKZ) at Wk16. BE OPTIMAL included a reference arm (adalimumab [ADA] 40 mg Q2W); ADA patients switched to BKZ at Wk52 (ADA/BKZ). BE OPTIMAL Wk52 and BE COMPLETE Wk16 completers could enter BE VITAL (open-label extension; NCT04009499), where all patients received BKZ. Post-hoc data reported for patients with baseline skin involvement (≥3% body surface area) and nail psoriasis (modified Nail Psoriasis Severity Index &gt;0). Efficacy reported to Wk104 of BE OPTIMAL/Wk100 of BE COMPLETE. Missing data imputed using non‑responder, multiple or worst-category imputation. Safety data are reported for all patients treated with BKZ. Results: Of 263/852 (30.9%) bDMARD-naïve and 159/400 (39.8%) TNFi-IR patients with baseline skin and nail psoriasis, 230 (87.5%) and 136 (85.5%) patients completed Wk104/Wk100. Efficacy responses at Wk52 on BKZ were sustained to Wk104/Wk100 across joint, skin, nail, physical function and composite outcomes. ADA/BKZ cohort showed sustained responses after switch. For bDMARD-naïve and TNFi-IR patients on BKZ, the exposure-adjusted incidence rates per 100 patient-years (EAIR/100 PY) for ≥1 treatment-emergent adverse event (TEAE) were 154.9 and 78.8, respectively; and for serious TEAEs, 6.6 and 5.2 respectively. None of the reported Candida infections were serious or systemic; all 3 deaths were deemed unrelated to treatment. Conclusions: BKZ treatment demonstrated sustained clinical efficacy to 2 years in patients with PsA, skin involvement and nail psoriasis, regardless of prior TNFi treatment. BKZ was well tolerated; consistent safety profile to previous reports.1

Kushen Gel combined with antifungal drugs for the treatment of vulvovaginal candidiasis: A systematic review and meta-analysis of randomized controlled trials

Ethnopharmacological relevanceVulvovaginal candidiasis (VVC) represents the most prevalent form of candidal infections, imposing a significant societal burden. Kushen gel, a chinese patent medicine, has demonstrated favorable outcomes in the treatment of VVC. In clinical practice, Kushen gel is often used in conjunction with antifungal drugs. However, the clinical evidence supporting the combined use of Kushen gel with antifungal drugs for the treatment of VVC is currently limited. Aim of the studyThis study aimed to evaluate the effectiveness and safety of Kushen gel combined with antifungal drugs in the treatment of vulvovaginal candidiasis (VVC). Materials and methodsDatabases namely CNKI, Wanfang Database, VIP Database, CBM, PubMed, Cochrane Library, and Embase were searched from their inception to January 2024. Randomized controlled trials (RCTs) applying Kushen gel combined with antifungal drugs for the treatment of VVC were included. Methodological quality assessment was performed using the Cochrane risk of bias assessment tool (RoB 1.0). A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were total efficacy rate, recurrence rate, secondary outcomes included adverse events and time to clinical symptom resolution. ResultsA Meta-analysis of 42 RCTs, encompassing a total of 4259 VVC patients was conducted. The results indicated that compared to antifungal drugs alone, Kushen gel combined with antifungal drugs increased the effectiveness (RR = 1.20, 95%CI [1.17, 1.23], P < 0.00001) and reduced the recurrence rate (RR = 0.21, 95%CI [0.13, 0.34], P < 0.00001), with no significant difference in safety (RR = 0.56, 95%CI [0.30, 1.03], P = 0.11). ConclusionsBased on the available results, it appears that the combination of Kushen gel with antifungal drugs may increase the effectiveness and reduce the recurrence rate. However, due to the poor methodological quality of the included studies, more high-quality evidence from large-sample and well-designed research is needed in the future.

Abstract 4134772: Optimizing Heart Failure with Preserved Ejection Fraction Management: Quality Review of SGTL2 Inhibitor Use

Heart failure with preserved ejection fraction (HFpEF) remains a diagnostic challenge despite a 50% incidence of HF admissions. H2FPEF tool is a validated scoring system that estimates HFpEF probability with a sensitivity of 69% and positive predictive value of 85%. Despite clinical research interest and therapeutic advances in HFpEF, implementation of therapies remain inconsistent. Currently ACC/AHA guidelines classify sodium-glucose cotransporter 2 inhibitors (SGLT2i) use a 2A recommendation with benefits for reducing hospital admissions. We assess the utilization of current guidelines. An observational retrospective analysis was performed of patients &gt;18 years with a left ventricular ejection fraction of &gt;50% seen in cardiology clinic with an ICD.10 code of diastolic heart failure from January 2022 to 2024 at a large tertiary hospital. Electronic records were reviewed for patient demographics, documentation of heart failure diagnosis, medication list and echocardiogram parameters. Primary outcome was HF related hospitalization. The study screened 79 patients, 51% females and 49% males. 20.2% of the patients were on SGLT2i, a quarter of which were female. Of those on SGLT2i, 56% were on diuretics, 81% had H2FpEF score &gt; 5, 56% had diabetes, and 19% had a HF hospitalization. SGLT2i was stopped in 1 patient due to cost. Of the (63) 79.8% of patients not on SGLT2I, 65% were on diuretics, 90% had H2FPEF score &gt; 5, 23% had diabetes and 32% had a HF hospitalization. 43% were males, with an average age of 71 for males and 62 for females. Ten patients had documented reasons for not being on SGLT2i including CKD, dialysis, yeast infection and denied insurance coverage. Unadjusted effect measures for HF hospitalization (HR 0.59, RRR 40.9%, OR 0.496; p 0.134). As guidelines are readily investigated and updated by expert consensus groups, evaluating practice patterns is key. Unlike other cardiac medications, SGLT2is are primarily initiated by cardiologists and recognizing barriers can identify generalizability of current guidelines. Our data looked at both objective and clinical endpoints for HFPEF diagnosis. Interestingly, women were less often started on SGLT2i and coverage was not a frequent cause for not using SGLT2i. Our quality metric analysis shows a potential protective effect of HF readmission with SGLT2i use in a highly symptomatic cohort, and suggests future directives need to focus on broadening educational reach among cardiologists.

Association of multilocus sequence typing, MSH2 gene mutations, and antifungal resistance in Candida glabrata: implications for clinical outcomes in Chinese hospitals

BackgroundCandida glabrata is the second most common cause of invasive candidiasis worldwide. In this study, we determined the clinical characteristics and drug sensitivity of C. glabrata isolates and investigated the associations between MSH2 gene mutations, sequence types (ST), and drug resistance.MethodsA total of 154 C. glabrata isolates were collected from patients being treated in three hospitals in China. The antifungal sensitivity of the strains was assessed using the broth microdilution method. Multilocus sequence typing (MLST) was also performed, followed by MSH2 sequencing. The clinical features and outcomes of C. glabrata infection were analysed for a total of 49 strains, which were collected from patients with invasive Candida infection at Longhua Hospital.ResultsAll 154 isolates were found to be susceptible to amphotericin, 5-fluorocytosine, anidulafungin, caspofungin, and micafungin, whereas 11.7% were fluconazole-resistant, 18.8% were itraconazole non-wild type, and 35.7% were voriconazole non-wild type. ST7 (62.34%) was the most common ST genotype, followed by ST10 (16.88%) and ST15 (7.79%). The total azole resistance rates for all isolates, ST7, ST10, and other STs were 36.4, 42.7, 34.6, and 18.8%, respectively. The ST7 and ST10 isolates were characterised by a higher drug resistance rate than the other minor ST isolates. Moreover, 59.09% of isolates had one or more MSH2 non-synonymous mutations, with V239L being the most commonly detected mutation. The frequency of MSH2 mutations was significantly higher in azole-resistant isolates than in other isolates, whereas P6L or L87P mutations were associated with the highest azole resistance rates of up to 87.5% and 80%, respectively. Our results indicated that ST7 and ST15 are independent predictors of mortality caused by C. glabrata infection and revealed a higher 30-day mortality in patients infected with these strains than in those infected with other ST isolates.ConclusionsOur findings revealed the relationships between MLST, MSH2 gene mutations, and drug resistance in the common pathogenic fungus C. glabrata, and thereby enabled us to identify strains that are associated with higher rates of mortality. These findings will contribute to enhancing our understanding of the pathogenesis of C. glabrata infection.

Evaluation of biofilm formation and antimicrobial susceptibility (drug resistance) of Candida albicans isolates.

Candida albicans comprises over 80% of isolates from all forms of human candidiasis. Biofilm formation enhances their capacity to withstand therapeutic treatments. In addition to providing protection, biofilm formation by C. albicans enhances its pathogenicity. Understanding the fundamental mechanisms underlying biofilm formation is crucial to advance our understanding and treatment of invasive Candida infections. An initial screening of 57 Candida spp. isolates using CHROMagar Candida (CHROMagar) media revealed that 46 were C. albicans. Of these, 12 isolates (33.3%) had the capacity to form biofilms. These 12 isolates were subjected to multiple biochemical and physiological tests, as well as 18S rRNA sequencing, to confirm the presence of C. albicans. Upon analysis of their sensitivity to conventional antifungal agents, the isolates showed varying resistance to terbinafine (91.6%), voriconazole (50%), and fluconazole (42%). Among these, only CD50 showed resistance to all antifungal agents. Isolate CD50 also showed the presence of major biofilm-specific genes such as ALS3, EFG1, and BCR1, as confirmed by PCR. Exposure of CD50 to gentamicin-miconazole, a commonly prescribed drug combination to treat skin infections, resulted in elevated levels of gene expression, with ALS3 showing the highest fold increase. These observations highlight the necessity of understanding the proteins involved in biofilm formation and designing ligands with potential antifungal efficacy.

Inhibition of Virulence Associated Traits by β-Sitosterol Isolated from Hibiscus rosa-sinensis Flowers Against Candida albicans: Mechanistic Insight and Molecular Docking Studies.

The emerging drug resistance and lack of safer and more potent antifungal agents make Candida infections another hot topic in the healthcare system. At the same time, the potential of plant products in developing novel antifungal drugs is also in the limelight. Considering these facts, we have investigated the different extracts of the flowers of Hibiscus rosa-sinensis of the Malvaceae family for their antifungal efficacy against five different pathogenic Candida strains. Among the various extracts, the chloroform extract showed the maximum zone of inhibition (26.6 ± 0.5mm) against the Candida albicans strain. Furthermore, the chloroform fraction was isolated, and a sterol compound was identified as β-sitosterol. Mechanistic studies were conducted to understand the mechanism of action, and the results showed that β-sitosterol has significant antifungal activity and is capable of interrupting biofilm formation and acts by inhibiting ergosterol biosynthesis in Candida albicans cells. Microscopic and molecular docking studies confirmed these findings. Overall, the study validates the antifungal efficacy of Candida albicans due to the presence of β-sitosterol which can act as an effective constituent for antifungal drug development individually or in combination.

Mycotic Necrotizing Fasciitis of the Face: A Case Report and Review of Literature

Necrotizing fasciitis is a rare but potentially serious and fatal infection. It is a dermo-hypodermitis with necrosis of the superficial fascia, typically caused by Streptococcus pyogenes. However, rare cases of fungal necrotizing fasciitis have been reported. We report the case of a 65-year-old type II diabetic patient who developed necrotizing cellulitis of the right hemiface with homolateral orbito-palpebral extension. The initial management was based on drainage of purulent collections with resection of necrotic tissues associated with parenteral antibiotherapy without clinical improvement. Bacteriological sampling revealed the presence of yeast. The mycological examination was positive for Candida albicans resistant to fluconazole. Antifungal treatment with intravenous amphotericin B was initiated with good clinical progression and complete remission after 1 month. The aim of this paper is to highlight the importance of promptly considering this diagnosis and extending the initial assessment of necrotic skin lesions to include mycological examination to detect severe forms of cutaneous candidiasis.

N -butanol fraction of Terminalia catappa possesses anti-Candida albicans properties and in vivo action on Tenebrio molitor alternative infection model

Current treatment of Candida infections is threatened by antifungal drug resistance. Thus, medicinal plants have been studied to identify new and highly effective antifungal substances with low toxicity. Here, we showed that the tannin-rich n-butanol fraction of Terminalia catappa (FBuOH) possesses antifungal and antibiofilm properties and protects Tenebrio molitor larvae against Candida albicans infection. FBuOH showed antifungal activity against Candida spp. vaginal isolates (MIC values ranged from 7 to 500 μg/mL). Moreover, a combination of FBuOH with fluconazole (FICI ≤0.5) showed considerably increased anti-yeast, anti-biofilm activity and significantly improved the survival rate (up to 100 %) of T. molitor larvae against C. albicans infection. Furthermore, FBuOH acted synergistically with fluconazole by reducing C. albicans membrane ergosterol content. These results could also explain the synergistic activity between FBuOH and fluconazole, indicating that FBuOH exerted its effects on C. albicans membrane integrity, increasing its permeability. Our findings provide insights into the antifungal activity and low cytotoxicity of FBuOH, showing its potential use as a new antimycotic.

Menthol as an effective inhibitor of quorum sensing and biofilm formation in Candida albicans and Candida glabrata by targeting the transcriptional repressor TUP1.

Menthol, a natural quorum sensing molecule, is derived from the Mentha species. Combating pathogenicity by inactivating quorum sensing is an emerging approach. Therefore, our objective was to investigate anti-quorum sensing and anti-biofilm potentials of menthol in Candida albicans and Candida glabrata. The antifungal properties of menthol were evaluated using a broth microdilution assay and a time-kill assay, and its effects on quorum sensing-mediated virulence factors, cellular reactive oxygen species (ROS), and biofilm formation were tested by evaluating TUP1 expression levels in both C. albicans and C. glabrata. Quorum sensing-mediated virulence factors and biofilm formation were inhibited by menthol in both C. albicans and C. glabrata. Furthermore, coinciding with elevated ROS levels, mRNAs of the quorum sensing-related gene TUP1 were upregulated in both C. albicans and C. glabrata. This study highlights the anti-quorum sensing potential of menthol through the inhibition of quorum sensing-mediated virulence factors, ROS generation, and biofilm development by targeting TUP1, which could have potential in the treatment of Candida infections.

Genomic Assessment of Resistance of Invasive Fungal Infections in Immunocompromised Patients

Introduction: Invasive fungal infections (IFIs) are emerging and significantly increased in immunocompromised populations. These infections are the most commonly acquired by inhalation of spores and can be transmitted by percutaneous inoculation in cutaneous and subcutaneous infections. Candida and Aspergillus species remain the most common cause of invasive fungal infections including neutropenia, hematological malignancies, bone marrow transplantation, parenteral nutrition prolonged treatment with corticosteroids, chemotherapy, HIV infection, invasive medical procedures, and the newer immune suppressive agents. Materials and Methods: An observational study was carried out at SRM MCH&amp;RC, Tamil Nadu, India, in January 2020. Invasive fungal infections were identified in conventional methods (KOH, Gram staining, culture, sugar assimilation, sugar fermentation, LPCB). Antifungal susceptibility testing was done as per standard guidelines; the resistant species were subjected to molecular testing to identify the gene. Results: Clinical samples are collected from the various departments (blood, pus, tissues, BAL, pleural fluid, and other body fluids). Out of 110 clinical samples, 16 samples were positive for yeast infections and five were positive for moulds. Eighty-nine samples were negative for fungal infection. Among yeast isolates, Candida tropicalis (37%) was the most common in the study population, followed by C albicans (25%), C krusei (19%), C.glabrata (13%), and C.parapsilosis (6%). Among the filamentous fungi, all the isolates were present in the same prevalence. Some of the Candida spp. were found to be resistant to amphotericin B (2), fluconazole (2), and itraconazole (1). All moulds were found to be sensitive to the tested antifungals by microbroth dilution methods. Among the resistant Candida, spp.ERG11 gene was found to be common. Conclusion: We observed that the early detection of etiological agents by microscopy and culture and prompt initiation of antifungal therapy can aid in the reduction of morbidity and mortality among immunocompromised patients.