Candidiasis Research Articles

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 >18 years with a left ventricular ejection fraction of >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 > 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 > 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.

A case report of severe drug-induced immune hemolytic anemia caused by piperacillin

Piperacillin is a beta-lactamase inhibitor frequently used in the treatment of urinary tract infections. It is a broad-spectrum antibiotic with strong antibacterial action against Pseudomonas aeruginosa and Enterobacter, especially extended-spectrum beta-lactamase-producing Enterobacteria and Enterococcus. Side effects of piperacillin include allergic reactions, rashes such as urticaria, leukopenia, interstitial nephritis, asthma attacks, serological reactions, candida infection, and bleeding with more severe reactions resulting in anaphylactic shock. Anemia and hemolytic anemia are rare adverse reactions to piperacillin, with an incidence of 0.01–0.10%. We report herein the case of a severe postoperative immune hemolytic reaction to piperacillin. Fortunately, we quickly recognized and identified the drug reaction caused by piperacillin, immediately stopped the use of piperacillin, and performed a blood transfusion. The patient recovered and was subsequently discharged from the hospital.

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.

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.

Biological Potential of Asphodelus microcarpus Extracts: α-Glucosidase and Antibiofilm Activities In Vitro

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC50 value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management.

Increased risk of adverse events among patients with vs. without systemic autoimmune rheumatic disease prescribed sodium-glucose cotransporter 2 inhibitors: a retrospective cohort study.

Systemic autoimmune rheumatic disease (SARD) patients have been excluded from sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials given putative risks, but this risk magnitude is unknown. We aimed to quantify SGLT2i adverse event risks among patients with vs. without SARD. METHODS: In a retrospective cohort study, patients with SARD at Mass General Brigham, a multihospital system in Boston, Massachusetts, prescribed SGLT2i were age-, self-reported race-, and sex-matched to patients prescribed the same SGLT2i between 1/1/2016 and 12/10/2021. Cumulative incidence and Cox models, overall and sex-stratified, estimated patient-reported adverse event risks from prescription date, censoring for discontinuation, death, or study end (12/12/2022). Four hundred sixty-eight SARD and 420 matched non-SARD patients were compared: mean age 64years (SD 11.3), 61% female, and 70% White. SARD patients had shorter SGLT2i use duration (8.4 vs. 12.7months; p < 0.0001) and time to adverse event (0.59 vs. 0.85years; p 0.04). Yeast infections (9.8% vs. 6.2%; p 0.047) and muscular symptoms (3.4% vs. 1.0%, p 0.01) were more prevalent among those with SARD. Adjusting for baseline demographics, adverse event risk was higher (MV HR 1.68;95% CI 1.28, 2.21), in patients with vs. without SARD. Risk was higher in women than men overall and in women with SARD vs. without (adjusted HR 1.86; 95% CI 1.36, 2.54). Patients with vs. without SARD had 68% higher adverse event risk with SGLT2i use. Women with vs. without SARD had > 85% higher adverse event risks, although most were not serious. Trials of safety and efficacy of SGLT2i among SARD patients are warranted. Key Points •To our knowledge, this is the first study to compare adverse events associated with SGLT2i utilization in patients with vs. without SARD, despite RCT exclusion and documented SGLT2i use in the population. •In our comparison of 468 patients with SARD and 420 patients without, we identified a greater than 65% increase in risk of adverse event outcomes among patients with SARD. •Furthermore, we found that this risk disproportionately affected female patients, with a 4.4-fold increased risk among women with SARD compared to men without.

Candidemia in Pediatric-Clinic: Frequency of Occurrence, Candida Species, Antifungal Susceptibilities, and Effects on Mortality (2020-2024).

Objective: Invasive candidiasis is defined as an important infection that increases the duration of patients' hospital stay, costs, mortality and morbidity. In this study, we aimed to investigate the frequency of candidiasis in blood cultures of pediatric hematology patients, Candida species, antifungal susceptibilities, and their effects on mortality. Materials and Methods: Patients with Candida growth in their blood cultures at follow-up in the pediatric hematology clinic of our hospital between 2020 and 2024 were included in the study. Age, gender, primary diseases and risk levels, subtypes and antifungal susceptibilities of Candida grown in blood cultures, the presence of neutropenia in patients, the antifungals used for prophylaxis and treatment, the duration of infection, other bacteria grown additionally during the fungal infection period, the local infection source and the patients' discharge status were obtained from medical records. These constituted the study data. Results: Blood cultures were requested for 594 patients from the Pediatric hematology Clinic, and Candida was grown in only 37 (6.7%) of them. A total of 43.2% of them were the Candida parapsilosis complex, 29.7% were Candida albicans and 8.1% were the Candida haemulonii complex. Antifungal susceptibilities were over 90% for anidulafungin, micafungin, caspofungin, posaconazole, itraconazole and amphotericin B, followed by 86.7% for fluconazole and 84.4% for voriconazole. The mean age of the patient group was 6.8 years, 50.5% of whom were female and 40.5% of whom were male. The Candida infections developed on the 12.1th day of the neutropenia process on average. The mean invasive Candida infection period was 7 days. A total of 18.9% had a second bacterial infection and 13.5% had a local infection. A total of 51.4% had a single antifungal, 18.9% had two antifungals and 2.1% had more than two antifungals. A total of 35.1% of the patients with invasive candidiasis died. The primary diagnosis of the disease, Patient risk level, and the female gender were important factors affetting mortality. Conclusions: In a pediatric hematology clinic, the non-albicans group in invasive candidiasis infections was notable, with the C. parapsilosis complex occurring most frequently. There was still a high sensitivity to echinocandin antifungals and a decreased sensitivity to triazoles. It was found that the factor of the clinical diagnosis, being in the high-risk group and being female had significant effects on the survival rate of patients with candidiasis infections.

Clotrimazole-induced shifts in vaginal bacteriome and lipid metabolism: insights into recovery mechanisms in vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant proportion of women worldwide, with recurrent episodes leading to detrimental effects on quality of life. While treatment with clotrimazole is common, the specific alterations it evokes in the vaginal bacteriome and metabolome were previously underexplored. In this prospective study, we enrolled reproductive-age women diagnosed with single VVC and conducted comprehensive analyses of vaginal fungi, bacteriome, and metabolome before and after local clotrimazole treatment. We observed a significant reduction in Candida albicans and notable improvements in vaginal cleanliness. Advanced sequencing revealed substantial shifts in the vaginal bacteriome, with an increase in Lactobacillus-dominant communities post-treatment. Our findings identified 17 differentially abundant bacterial species, including notable decreases in pathogenic anaerobes such as Gardnerella vaginalis, Dialister micraerophilus, and Aerococcus christensenii, suggesting a restoration of a healthier microbial balance. Furthermore, metabolomic analysis revealed significant changes in 230 metabolites, particularly within lipid metabolism pathways, with marked downregulation of lipid-related compounds linked to inflammation. Correlation studies indicated a strong interplay between lipid metabolites and specific bacterial species, emphasizing the influence of clotrimazole treatment on microbial and metabolic interactions. Importantly, predictive models using microbiota and metabolite signatures demonstrated high accuracy in distinguishing pre- and post-treatment states. This research highlights clotrimazole's dual role in effectively clearing Candida infection and promoting a healthier vaginal microenvironment, paving the way for novel microbial and metabolomic-based diagnostic approaches to enhance VVC management and understand its underlying mechanisms.

Rapid Molecular Diagnostics in Vulvovaginal Candidosis.

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. 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. 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. Molecular diagnostics offer a significant improvement in VVC management, though traditional methods remain valuable in resource-limited settings.

Case Report: Invasive candidiasis of the head and neck in a five-month-old infant: A case study

Invasive sino-orbital fungal infection is an uncommon, yet severe condition that predominantly affects individuals with compromised immune systems. In this study, we report the case of a 5-month-old immunocompetent infant who exhibited persistent dacryocystitis despite receiving broad-spectrum antibiotics. Subsequently, the patient developed ethmoiditis, orbital subperiosteal abscess, and ulceration of the hard palate. Mycological and histological samples were indicative of Candida infections. The patient underwent sinus surgery and surgical debridement, along with antifungal therapy. The treatment was successful, and the follow-up was uneventful for up to 6 months. To our knowledge, this is the first reported case of invasive sino-orbital candidiasis in an immunocompetent infant with dacryocystitis as the entry point. This study explores the clinical features, management approaches, and outcomes of this potentially fatal disease.

Double Trouble: The Perilous Intersection of Amoebic Colitis and Candida Infection Leading to Colonic Perforation

Double Trouble: The Perilous Intersection of Amoebic Colitis and Candida Infection Leading to Colonic Perforation

Invasive fungal disease in patients with cancer in a tertiary care pediatric hospital

Abstract Background In the last two decades, the raise in invasive fungal diseases (IFD) has been associated with increased morbidity and mortality in immunosuppressed hosts. Its incidence varies between 2 to 21% and depends on the host´s underlying disease, the intensity of immunosuppressive treatment and the presence of comorbidities. The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of IFD in patients with hematology-oncology disease. Methods Retrospective, descriptive study. Patients under 18 years of age with acute leukemias, lymphomas and solid tumors with a diagnosis of proven IFD (according to EORTC-MSG 2019 criteria) were included during the period from January 2020 to November 2023 in a tertiary care pediatric hospital. Results During the study period, 304 patients were under follow-up. 14 episodes of proven IFD were identified in 13 patients.The median age was 120 months. Male sex predominated (69.2%). The recognized factors associated were neutropenia (69.2%), use of corticosteroids in the last 3 months (61.5%) and use of previous antibiotics (92.3%). The most common underlying disease was Acute Lymphoblastic Leukemia (ALL) in 11 cases (78.5%), of which 3 were in relapse. The 21.4% of the episodes occurred in solid tumors (1 osteosarcoma of the tibia, 1 abdominal germ cell tumor, 1 neuroblastoma). Patients receiving primary prophylaxis for filamentous fungi were 3/14 (21.4%), according to the European Conference on Infections in Leukemia (ECIL-8). All received voriconazole. The fungal isolates identified were: 1 Rhizopus spp. (eye biopsy, paranasal sinuses) 1 Penicillum spp. (lung biopsy), 1 Exserohilum rostratum (skin biopsy), 1 Trichophyton asahii (blood cultures), 1 Purpuracillum lilacinus (skin biopsy), 1 Aspergillus fumigatus (Bronchoalveolar lavage, BAL),: 3 Candida parapsilosis (blood cultures), 1 Candida tropicalis (blood cultures), 1 Candida spp (blood cultures), 1 Malassezia (BAL). The patients with invasive molds infections were six, all of them with pathological chest tomography. Galactomannans (GM) were positive in 66% (4/6). BAL with positive GM was performed in 2 of them. The primary focus were: cutaneous (3/6), pulmonary (2/6) and orbital-rhinosinusal (1/6). Regarding IFD due to yeast fungi: all Candida infections were associated with central venous catheters fungemia. Malassezia infection presented with pulmonary involvement. Fungal co-infection was observed in 1 patient with documentation of Aspergillus fumigatus in BAL and Candida tropicalis in blood and urine cultures. Empirical antifungal therapy was liposomal amphotericin in 76.9 % of the patients. Two patients died (15.4%) at 30 days of follow-up. Conclusion Early diagnosis and timely antifungal therapy represent the main strategies to increase the survival of patients with IFD. Antifungal prophylaxis is postulated as an effective prevention measure and its indication should be defined according to the patient’s characteristics and the incidence of IFD at the treating center. We consider that patients with suspected IFD and clinical focus should undergo the corresponding tissue biopsy for culture, histological evaluation, and molecular biology, to direct the appropriate treatment. Candida species represent the most frequent isolates, however, Aspergillus and Rhizopus infections are associated with higher morbidity and mortality.

The first prevalence and antifungal susceptibility profile of Candida infections in Palestine, 2022

BackgroundCandida spp. are the most common cause of opportunistic fungal infections and are associated with a high mortality rate worldwide. In Palestine, the prevalence of Candida spp. infections remains elusive.MethodsWe performed our study at two hospitals in Palestine (Istishari Arab Hospital, and Najah National University Hospital). All patients diagnosed with candidiasis during the year 2022 have participated in the study. The prevalence of Candida spp., their distribution, and the activity of selected antifungals against Candida pathogens were assessed. In combination with phenotypic properties, Candida isolates were identified and tested for antifungal susceptibility using the colorimetric VITEK-2 Compact system.ResultsOur results showed that the prevalence of Candida spp. among infected samples was 11.6%. A total of eleven different Candida spp. were identified. Among these isolates, C. albicans (46.54%) was the most frequent, followed by C. glabrata (16.14%), C. tropicalis (13.83%), C. parapsilosis (4.82%), C. krusei (3.56%), C. dubliniensis (2.09%), C. ciferrii (1.67%), C. lusitaniae (0.83%), C. guilliermondii (0.62%), C. kefyer (0.41%) and C. spherica (0.20%). Among C. albicans, all isolates were 100% susceptible to fluconazole and micafungin. The susceptibility rates to Amphotericin B and flucytosine were 95% and 99%, respectively. The susceptibility rates of non-albicans Candida spp. (NAC) to fluconazole, voriconazole, amphotericine B, caspofungin, flucytosine and micafungin were 70%, 99%, 97%, ,72%, 92% and 100%, respectively. The incidence of Candida infections was higher in the intensive care unit and surgery department as compared to other hospital departments.ConclusionsFour pathogens are responsible for the most invasive infections: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. A notable characteristic of this study was the high frequency of NAC species which were often more resistant to antifungal agents. A quick and accurate system like Vitek 2 compact was suggested for the careful species identification of clinical isolates of Candida. We suggest that continued surveillance of species distribution and susceptibility to antifungals will enhance future burden estimates and assist in evaluating preventative measures’ effectiveness.

The development of single-domain VHH nanobodies that target the Candida albicans cell surface.

Candida albicans causes life-threatening invasive infections that are hard to diagnose and treat, with drug resistance leading to treatment failure. The goal of this study was to develop VHH (single variable domain on a heavy chain) nanobodies to detect drug-resistant infections. Llamas were immunized with a mixture of heat killed and fixed C. albicans cells of different morphologies. Llama lymphocyte RNA was used to generate phage display libraries that were tested for binding to C. albicans cells or cell wall fractions, and single antibody domains were isolated. The libraries were panned against echinocandin-resistant C. albicans isolates and counter-selected against echinocandin-susceptible isolates with the aim of isolating binding domains specific for antigens on drug-resistant cells. Thirty diverse VHH nanobodies were selected, and binding characteristics were assessed via dose-response ELISA. Binding was tested against a variety of C. albicans isolates and other Candida species, indicating that the VHHs were specific for C. albicans. The VHH nanobodies were sorted into four distinct groups based on their binding patterns. Two of the groups bound preferentially to the yeast cell poles and hyphae, respectively. Nanobody binding to C. albicans deletion mutants was tested by fluorescence microscopy and ELISA to identify the antigen targets. VHH19 nanobody, belonging to the largest group, recognized the Als4 adhesin. VHH14 antibody in the hyphae-specific group recognized Als3. None of the isolated VHH nanobodies was selective for drug-resistant clinical isolates. Our data indicate that this approach can generate valuable single-domain antibodies specific to C. albicans proteins.IMPORTANCEThe human fungal pathogen Candida albicans causes a range of diseases from superficial mucosal infections such as oral and vaginal thrush to life-threatening, systemic infections. Accurate and rapid diagnosis of these infections remains challenging, and currently, there are no rapid ways to diagnose drug-resistant infections without performing drug susceptibility testing from blood culture, which can take several days. In this proof-of-concept study, we have generated a diverse set of single domain VHH antibodies (nanobodies) from llamas that recognize and bind specifically to C. albicans cell surface. The nanobodies were classified into four groups based on their binding patterns, for example, cell poles or hyphae. Specific nanobodies were verified as recognizing the important adhesin Als4 or the hyphae associated invasin Als3, respectively. The data validate the approach that small VHH antibody domains hold future promise for diagnostic applications and as probes to study the fungal cell surface.

Characterization of Candida species isolated from clinical specimens: insights into virulence traits, antifungal resistance and molecular profiles

BackgroundCandida species have emerged as a significant cause of opportunistic infections. Alongside the expression of various virulence factors, the rise of antifungal resistance among Candida species presents a considerable clinical challenge.AimThis study aimed to identify different Candida species isolated from clinical specimens, evaluate their antifungal sensitivity patterns, identify key genes regulating virulence mechanisms using multiplex PCR and to assess any correlation between their virulence profiles and antifungal resistance patterns.MethodA total of 100 Candida spp. was isolated from 630 different clinical specimens and identified to the species level. Their antifungal susceptibility was phenotypically evaluated in accordance with CLSI guidelines using the Vitek-2 Compact System. Virulence markers, including biofilm formation capacity, protease production, melanin production, coagulase production and hemolysin production, were also phenotypically detected. The genetic determinants for biofilm formation and extracellular hydrolytic enzymes were assessed using a multiplex PCR assay.ResultsThe prevalence of Candida spp. was 15.9%, with C. albicans (48%) and C. glabrata (16%) being the most common. C. albicans showed the highest virulence, with strong biofilm formation, and high proteinase and melanin production. Multiplex PCR revealed Hlp in 22.0%, Hwp in 80.0%, Als in 56.0%, and Sap genes in 56.0% of isolates. Virulence genes were more common in C. albicans than in non-albicans Candida (NAC). Resistance patterns significantly correlated with virulence profiles, with notable associations between flucytosine resistance and the presence of Hlp and Hwp genes.ConclusionThe significant correlation between virulent markers such as germination, coagulase, hemolysin production and resistance patterns among different Candida isolates is crucial for predicting the severity and outcomes of Candida infections. This understanding aids in guiding tailored treatment strategies.

Antifungal properties of abnormal cannabinoid derivatives: Disruption of biofilm formation and gene expression in Candida species

Abnormal cannabinoids (including comp 3) are a class of synthetic lipid compounds with non-psychoactive properties and regioisomer configurations, but distinct from traditional cannabinoids since they do not interact with the established CB1 and CB2 receptors. Previous research showed the cardioprotective and anti-inflammatory potentials of comp 3 and more recently its antimicrobial effect on methicillin-resistant Staphylococcus aureus (MRSA). Given the escalating challenges posed by Candida infections and the rise of antifungal drug resistance, the exploration of novel therapeutic avenues is crucial. This study aimed to assess the anti-Candida properties of newly synthesized AbnCBD derivatives. AbnCBD derivatives were synthesized by acid catalysis-induced coupling and further derivatized. We evaluated the potential of the AbnCBD derivatives to inhibit the growth stages of various Candida species. By in vitro colorimetric assays and in vivo mice experiments, we have shown that AbnCBD derivatives induce differential inhibition of Candida growth. The AbnCBD derivatives, especially comp 3, comp 10, and comp 9 significantly reduced the growth of C. albicans, including FLC-resistant strains, and of C. tropicalis and C. parapsilosis but not of C auris compared to their controls (FLC and 0.5 % DMSO). Comp 3 also disrupted C. albicans biofilm formation and eradicated mature biofilms. Notably, other derivatives of AbnCBD disrupted the biofilm formation and maturation of C. albicans but did not affect yeast growth. In a murine model of VVC, comp 3 demonstrated significant fungal clearance and reduced C. albicans burden compared to vehicle and FLC controls. These findings highlight the potential of AbnCBDs as promising antifungal agents against Candida infections.

MICROBIOLOGICAL CHARACTERISTICS OF THE ORAL MUCOSAIN PATIENTS WITH LICHEN PLANUS ERYTHEMATOSUS

Lichen planus is a multifactorial disease that involves immune, neuroendocrine, microbiological, and other metabolic processes associated with skin and mucosal damage. The microflora of the oral cavity in CPL SOPR was studied by E. S. Leontieva etal., 2014, the microbiocenosis of various biotopes of the oral cavity in patients with CPL SOPR was studied. The study involved 95 patients with CPL SOPR, who underwent hygienic, periodontal and microbiological research methods. The results of the degree of bacterial contamination indicate a more pronounced colonization of foci of CPL lesion by representatives of the coccoid flora: Streptococcus salivares and Streptococcus mutans, but there is no correlation between them. Isolated Streptococcus Sanguis colonies were observed in 55% of patients. In addition, fungi of the genus Candida albicans were detected in 50%, the average level of adhesion of Candida albicans strains in patients with CPL was 16.78±1.64%. The frequency of detection of fungi of the genus Candida albicans in foci of CPL lesion correlates (r=0.79) with the activity of the disease course. The significance of Candida albicans contamination is determined not so much by the degree of contamination of the lesion foci, but by such pathogenic properties of Candida albicansas the level of adhesion and the activity of germination tubes formation [1,2,3,6,11,2,3,6,11]. Authors Chuikin S. V., Akmalova G. M., Chernysheva N. D., 2014, analyzed the qualitative and quantitative microbiocenosis of the oral cavity in patients with CPL. The study included 145 patients with CPL aged 21 to 76 years, of whom 5% were men and 95% were women. The predominant form of CPL was erosive-ulcerative form (33.1%), the lowest frequency was observed in 2% of patients with bullous form. The results of the study showed that dysbiotic changes were observed with a predominance of candida infection and were found in 57.2% of the examined patients, which are observed more often in erosive-ulcerative and bullous forms of CPL. The results of the study showed that all the examined patients had microbiocenosis disorders of varying severity from dysbiotic shift to IYgrade IY dysbiosis and high sensitivity to bacteriophages was revealed. It should be noted that high sensitivity of pathogenic and opportunistic microorganisms sown in дисбактериозахoral dysbiosis was detected to цефалоспориногоcephalosporin antibiotics (100%), oxacillin (79%), gentamicin (76%), lincomycin (73%). [5,7,9,12]. A number of foreign authors Villa (TG, Sá ncheznchez-Pérez rez Á, Sieiro C., 2021) believe that microbial infection triggers an autoimmune response. Withdysbiosisof the intestinal microbiota , there is a violationof the integrity of the intestinal barrier, followed by an increase in intestinal permeability, and the penetration микроорганизмof microorganisms and their toxinов into the circulatory system. Current knowledge about this disease requires the inclusion of this disease in the list of autoimmune diseases, since the progression of CPL involves colonization of locally affected areas by bacteria, fungi or viruses that occur after damage to the oral mucosa and skin. The process of healing the disease should include eliminating microbial dysbiosis and restoring the normal microbiota of the oral mucosa, skin, and intestines. [4,6,8,10,13,14].