Candidiasis Research Articles

The stress-protectant molecule trehalose mediates fluconazole tolerance in Candida glabrata.

The incidence of non-albicans Candida infections has witnessed a substantial rise in recent decades. Candida glabrata (Nakaseomyces glabratus), an opportunistic human fungal pathogen, is accountable for both superficial mucosal and life-threatening bloodstream infections, particularly in immunocompromised individuals. Distinguished by its remarkable resilience to environmental stressors, C. glabrata exhibits intrinsic tolerance to azoles and a high propensity to swiftly develop azole resistance during treatment. The molecular mechanism for the high tolerance is not fully understood. In this work, we investigated the possible role of trehalose in this tolerance. We generated mutants in the C. glabrata TPS1, TPS2, and NTH1 genes, encoding trehalose 6-phosphate synthase (Tps1), trehalose 6-phosphate phosphatase (Tps2), and neutral trehalase (Nth1), respectively. As expected, the tps1∆ strain cannot grow on glucose. The tps2∆ strain demonstrated diminished trehalose accumulation and very high levels of trehalose 6-phosphate (T6P), the biosynthetic intermediate, in comparison to the wild-type (WT) strain. Whereas these higher T6P levels did not affect growth, the lower trehalose levels clearly resulted in lower environmental stress tolerance and a lower susceptibility to fluconazole. More interestingly, the tps2∆ strain completely lost tolerance to fluconazole, characterized by the absence of slow growth at supra-MIC concentrations of this drug. All these phenotypes are reversed in the nth1∆ strain, which accumulates high levels of trehalose. Our findings underscore the role of trehalose in enabling tolerance toward fluconazole in C. glabrata. We further show that the change in tolerance is a result of the effect that trehalose has on the sterol pattern in the cell.

Esophageal Candida Infection and Esophageal Cancer Risk in Patients With Achalasia

Patients with achalasia face a higher risk of developing esophageal cancer (EC), but the surveillance strategies for these patients remain controversial due to the long disease duration and the lack of identified risk factors. To investigate the prevalence of esophageal Candida infection among patients with achalasia and to assess the association of Candida infection with EC risk within this population. This retrospective cohort study included patients with achalasia diagnosed at or referred for treatment and monitoring to the Erasmus University Medical Center in Rotterdam, the Netherlands, between January 1, 1980, and May 31, 2024. Data analysis was conducted from August 1 to October 31, 2024. Esophageal Candida infection. The primary outcomes were the prevalence of esophageal Candida infection and its association with EC development among patients with achalasia. Associations were estimated using time-dependent Cox proportional hazards regression models with esophageal Candida infection as a time-varying covariate, adjusting for age at diagnosis and sex. This study included 234 patients with achalasia (median [IQR] age at diagnosis, 45 [32-63] years; 117 [50%] male), with a median follow-up time of 13 (4-22) years. Esophageal Candida infection was identified in 29 patients (12%), while EC was observed in 24 patients (10%). Esophageal cancer risk analysis was performed for 207 patients with 2 or more consecutive endoscopy follow-up visits (median [IQR] age at diagnosis, 43 [32-60] years; 104 [50%] male). The median (IQR) follow-up time for this subgroup was 16 (9-26) years. Among these patients, esophageal Candida infection was independently associated with an increased risk of EC (adjusted hazard ratio [AHR], 8.24 [95% CI, 2.97-22.89]). Additionally, age at diagnosis (AHR, 1.06 [95% CI, 1.03-1.10]) and male sex (AHR, 3.34 [95% CI, 1.08-10.36]) were independently associated with EC risk. This retrospective cohort study found that prior esophageal Candida infection, older age at diagnosis, and male sex were associated with increased risk of EC among patients with achalasia. These findings provide an important rationale for optimizing the monitoring of patients with achalasia.

The role of biotribocorrosion in the development and progression of clinical manifestations of pseudomembranous candidiasis

Objective. To establish the effect of biotribocorrosion on the development and chronic course of pseudomembranous candidiasis. Materials and methods. The study was conducted at the Department of Orthopedic Dentistry and Gnatology and at the Department of Propaedeutics of Orthopedic Dentistry of the Russian University of Medicine. The study involved 80 patients with pseudomembranous candidiasis using metal dentures and 40 patients with pseudomembranous candidiasis without metal-containing structures, who made up the control group. All participants in the study measured the difference in oral biopotentials, hydrogen index, and salivation rate. Results. In patients of the main group, the content of Fe, Cr, Ni, Ti, Si, K, Na in saliva was significantly increased (p < 0.05) compared with the control group. It was found that dissimilar metal alloys have different effects on the duration of use of dentures. In pseudomembranous candidiasis and the presence of metal-containing structures with signs of biotribocorrosion, a more pronounced electrochemical reaction of stainless steel coated with titanium nitride and uncoated significantly reduces the life of dentures (from 3 to 5 years), compared with CCC metal-ceramic prostheses (from 2 to 10 years) and Ni-Cr-Ni-Cr (from 5 to 8 years old). The greatest pH shift to the acidic side is observed with a combination of stainless steel and Ni-Cr prostheses (pH 5.5–6.0). In pseudomembranous candidiasis, patients using metal dentures have the highest potential differences between M-M. Conclusions. Due to tribocorrosion, corrosion products enter the oral fluid, under their influence, a decrease in pH occurs, provoking a weakening of the protective properties of saliva, a violation of metabolic processes and structural changes in the oral mucosa. Thus, there is a favorable environment for the growth of fungi of the genus Candida, inflammation of the oral mucosa occurs. Microbial flora and fungi that stimulate the development of the inflammatory process are localized in inflammatory areas.

Long-Term Safety and Efficacy of Bimekizumab in Axial Spondyloarthritis: 2-Year Results from Two Phase 3 Studies.

Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)‑17F in addition to IL-17A, previously demonstrated efficacy and was well tolerated to 1 year in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). Here, we report bimekizumab safety and efficacy to 2 years. Patients completing week 52 in the phase 3 studies BE MOBILE 1 (nr-axSpA; NCT03928704) and 2 (r‑axSpA; NCT03928743) were eligible for an ongoing open‑label extension (OLE; NCT04436640). All OLE patients received subcutaneous bimekizumab 160 mg every 4 weeks. Safety outcomes for patients who received ≥1 bimekizumab dose, and efficacy outcomes for all randomised patients, are reported to week 104. In the OLE (Weeks 52 - 104), 70.8% (367/518) of patients reported ≥1 treatment‑emergent adverse event (TEAE). Most frequent TEAEs (EAIR/100PY) were SARS-CoV-2 (COVID-19) infection (25.2), nasopharyngitis (11.0) and oral candidiasis (5.4). Fungal infection EAIR/100PY was 11.8 (majority Candida infections: 6.8; most mild/moderate, none serious/systemic). Inflammatory bowel disease and uveitis rates were low; no major adverse cardiovascular events or deaths occurred. TEAE incidence rate was generally similar across Weeks 0-52 and 52-104.At week 104, >50% of randomised patients (N = 586) achieved ASAS40; ∼60% achieved ASDAS low disease activity (<2.1) and >30% achieved ASDAS inactive disease (<1.3). Bimekizumab demonstrated sustained suppression of MRI inflammation at week 104, with >57% of patients achieving MRI remission. The safety profile of bimekizumab remained consistent with prior reports, with no new safety signals identified. 1-year efficacy was sustained to 2 years across patients with nr‑axSpA and r-axSpA.

The Effect of a Secondary Stressor on the Morphology and Membrane Structure of an Already Challenged Maternal and Foetal Red Blood Cell Population.

The red blood cell (RBC) membrane is unique and crucial for maintaining structural-functional relationships. Maternal smoking induces significant changes in the morphological, rheological, and functional parameters of both maternal and foetal RBCs, mainly due to the continuous generation of the free radicals. The major aim of this study was to follow the consequences of a secondary stressor, like fungal infection, on the already compromised RBC populations. The impact of Candida infection, a growing health concern, was investigated on four blood sample groups: mothers and their neonates originating from non-smoking versus smoking populations. Here, we searched for phenotypical and molecular markers that precisely reflected the effect of Candida infection on the RBC membrane; this included the level of hemolysis, appearance of morphological variants, formation of the lipid peroxidation marker 4-hydroxyl-nonenal, arrangement of the Band 3 molecules and activation of the Caspase 3. In most of the examined cases, the fungal infection increased the adverse symptoms induced by smoking, indicating a general stress response, likely due to an altered redox state of the cells. However, we were able to identify an atypical phenotype (clustered populations with shrinkage and membrane blebbing) in both the non-smoking and smoking populations, which might be a unique marker for Candida spp. infection.

Epidemiology of Vulvovaginal Candidiasis in Greece: A 2-Year Single-Centre Study.

The epidemiology of vulvovaginal candidiasis (VVC) in Greece remains poorly reported and outdated. We therefore conducted a 2-year retrospective survey to assess the epidemiological aspects of the infection among symptomatic Greek patients. High vaginal swab samples were collected from adult women with clinically suspected VVC attending a private diagnostic laboratory in Athens. VVC was confirmed through microscopic examination of a wet mount preparation revealing yeasts and Candida-positive culture. Species were identified by MALDI-ToF MS, and invitro susceptibility was determined according to the EUCAST-E.Def 7.4. Predisposing host factors were associated with the occurrence of the infection and isolated Candida spp. using Fisher's exact test, and epidemiological changes over time were analysed with the χ2 test for trend. Among 1300 women screened, 283 VVC episodes were recorded among 233 (18%) patients, whereof 11 (5%) had recurrent VVC (RVVC) and 19 (8%) had mixed Candida infections. Coinfection with other pathogens and recent prior use of antifungals were associated with RVVC. Candida albicans was the most prevalent pathogen (50%), followed by Candida parapsilosis sensu stricto (SS) (35%), Nakaseomyces glabratus (former Candida glabrata) (10%), Pichia kudriavzevii (former Candida krusei) (3%), Candida orthopsilosis (1.5%) and Clavispora lusitaniae (former Candida lusitaniae) (0.5%). Regarding the RVVC cases, 54% were attributed to C. albicans, 37% to N. glabratus and 9% to C. parapsilosis SS. Resistance to fluconazole was found in 4% of C. albicans and 23% of N. glabratus strains with cross-resistance to other azoles. Fluconazole-resistant isolates were recovered from 5 of 11 RVVC patients, whereof 4 of 5 had previous exposure to azoles. During the study period, an increase in N. glabratus VVC and fluconazole resistance was noted. VVC is common in our region, with C. albicans as the predominant species, followed by C. parapsilosis SS and N. glabratus. Fluconazole resistance is low in C. albicans but high in N. glabratus, emphasising the need for targeted antifungal strategies.

Synthesis, Characterization and Antimicrobial Activity of Mixed-Ligand Metal Complexes of 4,4'-Bipyridine and Aniline-2,5-Disulfonic Acid

In this study, we prepared mixed-ligand Co(II) complex{[Co(ADSA)(BP)]n.2H2O, 1}, Ni(II) complex {[Ni(ADSA)(BP)]n, 2}, and Zn(II) complex {[Zn(ADSA)(BP)(H2O)2]n.3H2O, 3} of 4,4'-bipyridine (BP) with aniline-2,5-disulfonic acid (H2ADSA). The 1-3 were characterized by elemental analysis, AAS, TGA, IR, UV-Vis, molar conductivity and magnetic susceptibility techniques. Furthermore, the microdilution method was used to explore the antibacterial and antifungal activities of the initial and the synthesized metal complexes against the following bacteria and yeast: Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis and Candida albicans. Antibacterial and antifungal activity results were compared with antibiotics (Vancomycin, Levofloxacin, Cefepime, Chloramphenicol, Fluconazole and Ketoconazole). Through the examination of the conducted studies, it was noted that the recently created compounds demonstrated efficacy in combating both bacterial and yeast infections.

Epidemiology of invasive candidiasis before and during the COVID-19 pandemic at a hospital in southeastern Brazil.

Invasive candidiasis is an important cause of nosocomial infection and recent studies have shown an increase in the number of cases during the coronavirus disease 2019 (COVID-19) pandemic. The present study aimed to evaluate the epidemiology and incidence of invasive candidiasis before and during the COVID-19 pandemic at a reference tertiary hospital in Brazil. A retrospective observational study was performed with 148 patients infected with Candida spp. The incidence of invasive candidiasis was 3.43 cases per 1000 admissions in the pre-pandemic period and 4.54 cases per 1000 admissions in the pandemic period, with a particularly high incidence in the intensive care unit. Compared to the pre-pandemic period, patients presented more frequently with immunosuppression (p = 0.01), sepsis (p = 0.03), and need for mechanical ventilation (p = 0.01) during the pandemic. The prevailing type of Candida spp. infection was candidemia, mostly by C. albicans. Invasive candidiasis was associated with high mortality; 52% of the infected patients died from this disease in the pre-pandemic period, while 62% died in the pandemic period. COVID-19, mechanical ventilation, and sepsis were significantly associated with mortality (p = 0.008, p < 0.001, and p < 0.001 respectively). A high incidence of Candida infection was observed at a tertiary general hospital in Brazil between 2018 and 2022. An increase in incidence of Candida infection during the COVID-19 pandemic was associated with a greater number of critical patients. Sepsis, mechanical ventilation, and COVID-19 were related to higher mortality in patients with invasive candidiasis.

The Role of Rotational Thromboelastometry in Early Detection of the Hemostatic Derangements in Neonates with Systemic Candida Infection.

Systemic Candida infection (SCI) is the third most common cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). While platelet involvement in fungal infections has been extensively studied, evaluation of the hemostatic mechanism in Candida infections, especially in neonates, has not been widely investigated. The aim of the current study was to evaluate the hemostatic profile of neonates with SCI through rotational thromboelastometry (ROTEM), a laboratory method that assesses the viscoelastic properties of blood. This is a single-centered prospective cohort study including a group of neonates with SCI (n = 21); the control group consisted of healthy neonates (n = 24). Demographics, clinical parameters, and laboratory data were recorded at the disease onset. Neonatal scores for the assessment of disease severity (Modified NEOMOD, nSOFA, and NeoBAT) were also calculated. ROTEM parameters of neonates with SCI were compared to those of healthy neonates. ROTEM parameters differed between neonates with SCI and healthy neonates, indicating a hypocoagulable profile of infected neonates. Specifically, neonates with SCI had significantly prolonged clotting time (CT) and clot formation time (CFT), as well as lower clot amplitude at 10 min (A10) and maximum clot firmness (MCF) when compared to healthy neonates (p values < 0.05), findings that remained consistent after adjusting for confounding factors such as gestational age, birth weight, and sex. In addition, a strong correlation was noted between ROTEM parameters and disease severity based on the modified NEOMOD, nSOFA, and NeoBAT scores. ROTEM parameters revealed a hypocoagulable profile in neonates during the early stages of SCI, which is also associated with disease severity. The results of this study highlight the need for monitoring of hemostatic status of this vulnerable group of patients and indicate that ROTEM analysis may have a role in the early detection of the hemostatic derangements associated with SCI in neonates, in order to ensure timely diagnosis and targeted therapeutic intervention.

Riboflavin- and Hypericin-Mediated Antimicrobial Photodynamic Therapy as Alternative Treatments for Oral Candidiasis: A Systematic Review.

Background: Oral candidiasis, predominantly caused by Candida albicans, presents significant challenges in treatment due to increasing antifungal resistance and biofilm formation. Antimicrobial photodynamic therapy (aPDT) using natural photosensitizers like riboflavin and hypericin offers a potential alternative to conventional antifungal therapies. Material and Methods: A systematic review was conducted to evaluate the efficacy of riboflavin- and hypericin-mediated aPDT in reducing Candida infections. The PRISMA framework guided the selection and analysis of 16 eligible studies published between 2014 and 2024. Data on light parameters, photosensitizer concentrations, and outcomes were extracted to assess antifungal effects. Results: Both riboflavin- and hypericin-mediated aPDT demonstrated significant antifungal activity, achieving substantial reductions in Candida biofilm and planktonic cell viability. Riboflavin activated by blue light and hypericin activated by yellow or orange light effectively targeted fluconazole-resistant Candida strains with minimal cytotoxicity to host tissues. However, complete biofilm eradication remained challenging, and variations in protocols highlighted the need for standardization. Conclusions: Riboflavin- and hypericin-mediated aPDT present promising, biocompatible alternatives for managing antifungal resistance in Candida infections. Further clinical trials and standardized protocols are essential to optimize outcomes and confirm efficacy in broader clinical settings.

Exploring the anti-biofilm and gene regulatory effects of anti-inflammatory drugs on Candida albicans.

Researchers have repurposed several existing anti-inflammatory drugs as potential antifungal agents in recent years. So, this study aimed to investigate the effects of anti-inflammatory drugs on the growth, biofilm formation, and expression of genes related to morphogenesis and pathogenesis in Candida albicans. The minimum inhibitory concentration (MIC) of anti-inflammatory drugs was assessed using the broth microdilution method. Biofilm formation in C. albicans was evaluated using XTT reduction assay following exposure to different concentrations of drugs. Additionally, the expression of adhesin-related genes (ALS1, ALS3), hyphal cell wall specific genes (EAP1, HWP1), secreted aspartyl proteinase (SAP4, SAP6), and morphogenesis pathway regulatory gene (EFG1) was analyzed using quantitative RT-PCR. Betamethasone and dexamethasone markedly inhibited C. albicans biofilm formation by up to 80% at a concentration of 2mg/mL. Moreover, the inhibition of C. albicans biofilm formation was significant at concentrations ranging from 0.6 to 10mg/mL for piroxicam and from 0.75 to 12mg/mL for diclofenac. The expression of key genes involved in biofilm formation including EFG1, HWP1, and ALS3 was all downregulated under hyphae-inducing conditions. Moreover, the expression proteinase genes of C. albicans were upregulated following exposure with corticosteroids. The data obtained provides valuable insights into the antifungal potential of anti-inflammatory drugs. Our novel findings indicate the downregulation of several Candida genes that are crucial for morphogenesis, pathogenesis, and biofilm formation. However, further research is necessary to fully elucidate the clinical applications and effectiveness of anti-inflammatory drugs as alternative or adjunctive therapies for Candida infections.

Antifungal susceptibility profile of Candida species and uncommon yeasts from drug abusers with oral candidiasis

In Iran, there is limited information regarding the species distribution and antifungal susceptibility profiles of yeast isolates from drug addicts suffering from oral candidiasis (OC). In this study, 104 yeast isolates, including 98 Candida species and 6 uncommon yeasts, were collected from 71 drug abusers with OC. The susceptibility profiles of Candida spp. and uncommon yeasts to amphotericin B (AMB), itraconazole (ITC), nystatin (NYC), fluconazole (FLC), and caspofungin (CAS) were evaluated using the CLSI broth microdilution method. The prevalence of OC in the sampled population was found to be 29%. The susceptibility profile of Candida spp. revealed remarkable sensitivity, with 100% and 99% of isolates susceptible to NYC and AMB, respectively. However, concerning levels of resistance or non-wild-type minimum inhibitory concentrations (MICs) were observed, with 13.2% of Candida isolates showing resistance to FLC, 13.2% to ITC, and 16.3% to CAS. Notably, 35.2% of patients showed mixed yeast species, while 5.1% of Candida isolates exhibited multidrug resistance. The analysis of the uncommon yeast species showed that the overall frequencies of the highest MICs were observed for CAS. Furthermore, within the six non-Candida species identified, Hanseniaspora opuntiae and one isolate of Pichia kluyveri exhibited resistance to FLC and ITC, respectively, while all non-Candida species were susceptible to AMB and NYC. Additionally, one isolate of Pichia kluyveri exhibited simultaneously high MICs to two drugs ITC and CAS. Furthermore, the Hanseniaspora opuntiae isolate showed high MICs to CAS and FLC. The findings from the present study suggest that AMB and NYC can be suitable choices for empiric treatment of both common Candida species and uncommon yeast infections in substance abuse patients.

A Cross-Sectional Study of the Maternal Health Factors: The Interplay Between Breastfeeding Patterns, Gut Microbiota, Anemia, and Cardiovascular Risk in Lactating Mothers.

Objective This cross-sectional study explored the interplay between breastfeeding patterns, gut microbiota composition, anemia, and cardiovascular risk in lactating mothers. The study examined how these factors contribute to postpartum maternal and infant health outcomes. Methods Forty-five lactating mothers, with a mean age of 32.73 years, participated in the study. Data on breastfeeding patterns, gut microbiota composition, anemia, and cardiovascular risk factors were collected. Microbial diversity was assessed, and associations with comorbidities and infections were explored. Statistical analyses, including chi-square and Kolmogorov-Smirnov tests, were performed to evaluate the relationships between these variables. Results Among the participants, 35.6% practiced exclusive breastfeeding, and 46.7% were classified as obese (BMI ≥30). Gut microbiota analysis revealed a prevalence of Escherichia coli (31.1%) and Lactobacillus (26.7%). Mothers with lower microbial diversity exhibited higher rates of infections (31.1% yeast infections and 26.7% UTIs) and comorbidities, including gestational diabetes (42.2%) and hypertension (13.3%). Cardiovascular risk was elevated among obese mothers, with 37.8% requiring cardiac medications. Anemia was prevalent, with 42.2% of mothers on folic acid supplements and 31.1% on iron supplements. Conclusion The study highlighted significant associations between obesity, gut microbiota diversity, and cardiovascular risk. Exclusive breastfeeding was linked to a higher prevalence of anemia treatment, suggesting potential nutritional challenges. Further research is necessary to develop interventions targeting maternal health during lactation.

Identification and determination of resistance to antimycotic factors in yeast clinical isolates during respiratory diseases

The prevalence of yeast infections has increased significantly over the past few decades, with resistance of isolated pathogens to antimicrobial agents becoming progressively more pressing. Commonly occurring pathogenic yeasts include genus Candida, with C. albicans species being the dominant in both superficial and invasive infectious processes. This report presents data on the identification and determination of antimycotic drug resistance for yeast isolates obtained from clinical material of a patient with chronic bronchitis and a patient with generalized fungal infection. As a result of genomic identification, the strain causing the generalized infection was identified as Candida utilis, confirming the literature data on its increasing prevalence, considered a rare pathogen of invasive processes, as a new dangerous pathogen. Antimycotic susceptibility testing revealed resistance of C. utilis strain to commonly used antifungal drugs such as ketoconazole, itraconazole and fluconazole, weak sensitivity to clotrimazole, nystatin and amphotericin B. The strain from a patient with chronic bronchitis was identified as C. africana, considered to be a C. albicans species. Excepting itraconazole, the strain showed varying sensitivity to the five antimycotic drugs used in the experiment. Both isolated yeast strains actively grew at elevated temperature, were able to form a capsule, hyphal sprouts and biofilms, features which distinguish potentially pathogenic Candida from saprotrophic strains. Combined antifungal therapy includes the use of probiotic preparations based on microorganisms that exhibit antagonism against fungi. The present work shows an effective inhibitory effect from secreted water-soluble metabolites of spore-forming bacteria Bacillus subtilis and Bacillus lichenformis, antiseptics “Octenisept” and “Chlorhexidine”, as well as rosemary and sandalwood oil extracts on growth activity of the studied pathogenic yeast strains and a typical control strain of C. albicans Y-583.

Risk of Candida and Overall Fungal Infections with IL-17 Inhibitors in the Treatment of Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis.

Risk of Candida and Overall Fungal Infections with IL-17 Inhibitors in the Treatment of Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis.

Novel Isoxazole-Based Antifungal Drug Candidates.

Microbiological communities have a significant impact on health and disease. Candida are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then Candida infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of Candida albicans-based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti-Candida potential. Two compounds, PUB14 and PUB17, displayed selective antifungal activity without negatively affecting beneficial microbiota, such as Lactobacillus sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of PUB14 and PUB17 against C. albicans, coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by Candida reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs.

Research upon Ag-Doped ZnO Nanoparticles Coated on Cotton Fabric for Antibacterial Boxer Briefs Underwear

Bacterial growth on textiles, particularly underwear products for both men and women, can result in serious health issues such as rashes, blisters, yeast infections, and even an increased risk of prostate cancer for men and cervical cancer for women. Additionally, it can cause unpleasant smells, stains, and discolorations in the fabric, reducing the product’s life cycles and environmental issues. This study aims to develop a fabric for underwear that can terminate bacteria and bring comfort to the wearer. The cotton fabric treated with Ag-doped ZnO nanoparticles (NPs) was investigated in this research. Tensile strength, morphology, structure, moisture content, and antibacterial properties based on the disc method and count plate against Staphylococcus aureus and Escherichia coli were examined. Both strains showed 99.9% antibacterial activity by cotton fabric treated with Ag-doped ZnO nanoparticles. The results demonstrate that the treated fabrics have excellent performance, making them ideal for use in underwear products and reducing health problems caused by bacteria.

Perspectives on the Use of Echinocandins in the Neonatal Intensive Care Unit.

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile.

Effect of Mn(II) and Co(II) on Anti-Candida Metabolite Production by Aspergillus sp. an Endophyte Isolated from Dizygostemon riparius (Plantaginaceae).

Background/Objectives: This study evaluates the effect of Mn(II) and Co(II) ions on the production of anti-Candida metabolites by the endophytic fungus Aspergillus sp., isolated from Dizygostemon riparius. The objective was to identify metal-induced secondary metabolites with antifungal potential against drug-resistant Candida species. Methods: Aspergillus sp. was cultivated in Czapek agar supplemented with MnCl₂ (400 µM) or CoCl₂ (200 µM). Metabolite profiles were analyzed using UHPLC-DAD and LC-ESI-HRMS, followed by structural elucidation via NMR. Antifungal and biofilm inhibition activities were tested against Candida albicans and Candida parapsilosis. Toxicity was assessed using Tenebrio molitor larvae. Results: Key metabolites, including pyrophen, penicillquei B, and fonsecinone B, demonstrated antifungal activity with MIC values of 4.37-280.61 µg/mL. Fonsecinone B exhibited superior biofilm inhibition, surpassing fluconazole in reducing biofilm biomass and viability. In vivo assays showed low toxicity, with survival rates above 80% at 2× MIC/kg. Conclusions: Mn(II) and Co(II) significantly modulated the production of antifungal metabolites in Aspergillus sp. Fonsecinone B emerged as a promising candidate for antifungal therapy due to its potent activity and low toxicity. These findings support further investigation into the therapeutic potential of metal-induced fungal metabolites for combating drug-resistant Candida infections.

Anidulafungin exposure and population pharmacokinetics in critically ill patients with invasive candidiasis.

Anidulafungin is recommended as a first-line treatment for invasive Candida infections in critically ill patients. Pharmacokinetic (PK) variability is large in critically ill patients, potentially compromising pharmacokinetic-pharmacodynamic (PKPD) target attainment under standard dosing. We aimed to assess anidulafungin exposure, PKPD target attainment, and population (pop)PK in critically ill patients. Adult ICU patients receiving standard anidulafungin dosing [200mg on day 1, then 100mg daily] were included (NCT04045366). We performed rich blood sampling on an early (day 2 ± 1) and/or late (day 5 ± 1) treatment day. Using total anidulafungin plasma concentrations, we developed a popPK model (NONMEM7.5) and conducted Monte Carlo simulations (n = 1,000 per virtual patient) to evaluate the impact of patient factors on PKPD target attainment (AUC24h target 83.5mg×h/L). Twenty patients contributed 188 anidulafungin concentrations. PKPD target attainment was 45% and 65% on early and late sampling days, respectively. A two-compartment popPK model with first-order elimination described the data. Anidulafungin clearance increased with bodyweight and central volume of distribution increased as serum albumin decreased. Both bodyweight and serum albumin had a clinically relevant impact on PKPD target attainment at day 1 (area under the ROC curve; AUROC 0.82 and 0.62, respectively), and bodyweight on PKPD target attainment at day 14 (AUROC 0.94). Standard anidulafungin dosing regimen fails to achieve adequate target attainment throughout the treatment period. Standard anidulafungin dosing is insufficient for achieving adequate exposure in critically ill patients. An interactive simulation tool is provided to aid dose-finding research and explore different dosing strategies and targets.