Candidiasis Research Articles

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.

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.

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].

A-273 Rapid, Portable Invasive Fungal Infection Diagnostic and Candida Antimicrobial Susceptibility Testing

Abstract Background Traumatic wounds are associated with a higher risk of invasive fungal infections (IFI), which lead to a significant increase in amputation or death. Actionable treatment decisions are hampered because true infections can be difficult to differentiate from external wound contaminates, and tissue biopsy and quantification of fungal load is required to determine if treatment is necessary, which currently takes several days. GeneCapture is developing the CAPTURE 60-minute, portable infection identification platform to detect infectious levels of common fungi including the genera Aspergillus, Fusarium, and Scedosporium, the family Herpotrichiellaceae, and the order Mucorales. The company is also pursuing rapid identification and antimicrobial susceptibility testing for Candida species from multiple infection types. Methods This study seeks to determine the Limit of Detection (LoD), sensitivity and specificity of the CAPTURE ID assay for fungal pathogens. Since tissue biopsy samples must be used to assess the presence of IFI in wounds, GeneCapture has developed a manual process for the crude homogenization of muscle tissue to allow this matrix to be used as the starting sample for the ID assay. Mock samples were tested for inclusivity and exclusivity on a series of IFI ID panels against multiple strains of the included fungi, against fungi not yet specifically detected on the panel, and against bacteria that commonly infect wounds. While the LoD for yeasts may be determined in CFU/mL, there is no similar, easy-to-define metric for molds. GeneCapture has developed a quantitative PCR method to detect the single copy beta-tubulin gene to roughly correlate fungal dry mass and nuclei number to assay signal for molds cultured in Potato Dextrose Broth. Determining beta-tubulin copy numbers for extracts from mock samples then allowed detection of the progression of IFI over the course of infection. Lastly, antimicrobial susceptibility testing (AST) was performed on two species of Candida to validate utilizing GeneCapture’s rapid phenotypic AST method for fungal infections. Results To date, the CAPTURE ID panel has been tested against 27 included or excluded strains of fungi or bacteria with 97% sensitivity and 100% specificity. The current LoD for mold organisms varies from approximately 1,000 nuclei for Aspergillus species, to 100,000 nuclei for Fusarium species. Additional work to understand this range is underway. Lastly, we have correctly determined the susceptibility of Candida species using our novel approach within 4-6 hours. Conclusions GeneCapture’s ID and AST technology offer a unique solution to address the increasing prevalence of fungal infections. Our platform can identify the most common fungal components in a wound within 60 minutes of receiving a tissue biopsy sample. Candida infections occur across multiple matrices and rapidly identifying the species of Candida and then determining its phenotypic susceptibility profile will have a large impact on treating these difficult pathogens.

Health of Saudi Women in the Post-Pandemic Era: Candidiasis Incidence and Post COVID-19 and COVID-19-Vaccination.

Candidiasis, commonly known as yeast infection, affects people worldwide due to the overgrowth of Candida species. Of several types, genital candidiasis, particularly vulvovaginal candidiasis (VVC), primarily caused by C. albicans is frequently observed in females of reproductive age. Candidiasis has also become a serious issue in the post-pandemic era, as it occurs as a secondary infection in COVID-19 patients during or after the course of viral illness. Therefore, this study investigated the incidence of C. albicans infections in women of reproductive age, and its relationship with the incidence of COVID-19 and vaccination in Saudi Arabia. Additionally, this study aimed to determine the awareness of women on candidiasis and its subsequent impact on the occurrence of infection. A survey-based quantitative study was conducted in which primary data were collected from participants using a self-reported questionnaire. A total of 200 women aged 18-45 were selected through random sampling. Apart from their sociodemographic characteristics, the history of COVID-19 incidence, COVID-19 vaccination, and candidiasis occurrences among respondents were recorded. Their level of awareness and knowledge of candidiasis, along with their perceptions of strategies for mitigating the risk of incidence, were also evaluated. The collected data were analysed using different statistical tools. The findings of this study revealed a positive correlation between candidiasis, viral infection, and vaccination, regardless of the type and dosage of vaccine administered. Furthermore, both COVID-19 incidence and vaccination had a positive and significant impact on the occurrence of candidiasis among Saudi women. Despite certain limitations, this study has theoretical and managerial implications for improved management of candidiasis in the post-COVID era.

Efficacy and Tolerance of a Polymeric Surfactant Technology-Based Cleanser for Clinically Diagnosed Sensitive Skin.

Cleansing is an important hygiene activity, necessary to prevent bacterial, fungal, yeast, and viral infection. However, in the presence of skin disease, cleansing can take on a new challenge: removing the sebum, sweat, externally applied substances, environmental debris, and organisms from the face without damaging the skin barrier. Since cleansers cannot easily distinguish between sebum and the intercellular lipids required to maintain skin integrity, unique cleansing technologies are necessary to provide mild cleansing for the many manifestations of sensitive skin. This 4-week clinical study aimed to evaluate the appropriateness of a cosmetic facial foaming gel cleanser with a polymeric surfactant technology in a diverse sensitive skin population. 85 subjects with sensitive skin due to eczema/atopic dermatitis, rosacea, acne, or cosmetic intolerance syndrome were evaluated via investigator grading, self-assessment questionnaire, noninvasive measurements, and digital photography. The foaming gel cleanser was well tolerated showing no significant increases in investigator-graded irritation endpoints. Sensitive skin subjects saw considerable reduction (P&lt;0.05) in stinging, itching, burning, tightness, and overall sensitivity at 2 and 4 weeks. Improvements in smoothness, softness, clarity, radiance, and overall skin appearance, were observed by both the investigator and patients (P&lt;0.05) at 2 and 4 weeks. The polymeric surfactant technology-based foaming gel cleanser provided a rich, foaming lather that felt gentle and left skin feeling comfortable. J Drugs Dermatol. 2024;23(10):889-893. doi:10.36849/JDD.8510.

A Chart Review for Epidemiology and Outcome of Fungal Bloodstream Infections Among Neonates in a Tertiary Care Hospital at North India

Background and Aims The risk of fungal bloodstream infection (BSI) and accompanying mortality in neonates varies widely in between centres depending on the region, the population characteristics and the risk factors. Methods This chart review of neonatal cases with fungal BSI admitted in a tertiary care teaching hospital in North India aimed to comprehensively investigate the epidemiology, profile of fungal species (and their susceptibility to various antifungal agents), risk factors, clinical profile and outcomes in these neonates. The study spanned over a one-year period, from September 2022 to August 2023, included all symptomatic neonates with positive blood cultures for fungal pathogen. Results Over one year, 24 out of 1,174 neonates at risk were diagnosed with fungal BSI, with a cumulative risk of 2.0 per 100 neonates. A peak in cases occurred in February. Candida pelliculosa was the predominant species (75% of isolates), while Candida albicans constituted 4.2%. Most isolates were sensitive to fluconazole, except for some fluconazole-resistant Candida pelliculosa (5.5%) and Candida tropicalis (25.0%), which remained susceptible to amphotericin-B and voriconazole. Around 60% of neonates were preterm, 40% had very low birth weight and 37% were small for gestational age. Nearly all had received prior broad-spectrum antibiotics, with 92% receiving prolonged courses over five days. Respiratory support, including intubation and mechanical ventilation, was used in 83% before onset of fungal sepsis. Intriguingly, all neonates had some invasive device in place for more than seven days. Mortality rate of 25% was observed, with preterm birth and gastrointestinal anomalies contributing to adverse outcomes. Conclusions This study confirms the ongoing shift in trend from albicans to non-albicans Candida infections in our region as well. A seasonal peak of fungal sepsis noted in the month of February hinted at potential seasonal variation or lapses in infection control practices during colder months. The analysis of trends in fungal BSI might hold a significance within neonatal intensive care units (NICUs) for the prompt detection of outbreaks. Simultaneously, understanding and analysing risk factors associated with fungal BSI are essential for targeted prevention.

Wild-type MIC distributions and epidemiological cutoff values for 5-flucytosine and Candida species as determined by EUCAST broth microdilution.

EUCAST has established clinical breakpoints and epidemiological cutoff values (ECOFFs) for Candida spp. However, limited data are available for 5-flucytosine (5-FC). We assessed the in vitro susceptibility of 5-FC against a large collection of clinical Candida species using EUCAST methodology and determined the associated ECOFFs. A total of 5622 Candida isolates were collected from patients across the Netherlands between 2008 and 2024. 5-FC MICs were determined using the EUCAST microbroth dilution reference method. Furthermore, MICs were extracted from the EUCAST website. The MICs from this study and those extracted were used to determine ECOFFs and local ECOFFs (L-ECOFFs). 5-FC exhibited potent in vitro activity against C. albicans, N. glabratus and C. parapsilosis, while decreased susceptibility was observed for C. tropicalis, Pichia species, K. marxianus, Y. lipolytica, and C. auris. The ECOFFs (mg/L) and the percentages of WT isolates for 5-FC were: C. albicans: 0.5 (97.2%), N. glabratus: 0.5 (96.6%), C. parapsilosis: 0.5 (99.5%) and P. kudriavzevii: 8 (99.4%). The L-ECOFF (mg/L) and the percentages of WT isolates for 5-FC were: C. dubliniensis: 0.25 (96.8%), C. tropicalis: 0.25 (67.2%), K. marxianus: 0.25 (48.0%), C. lusitaniae: 0.25 (86.5%), M. guillermondii: 0.125 (95.9%) and P. norvegiensis: 8 (94.2%). 5-FC remains a valuable drug to manage difficult-to-treat invasive Candida infections. In vitro susceptibility cannot be predicted based on species identification for most Candida species, but requires MIC-testing. ECOFFs will help to interpret the MICs to support treatment decisions.

The Influence of Invasive Candida Infections on Prognosis and Analysis of Their Risk Factors After Liver Transplantation

PurposeThis study aimed to investigate the incidence, timing, risk factors, and impacts of invasive Candida infections (ICIs) within 3 months after liver transplantation (LT) on LT recipients’ prognosis. MethodsPatients undergoing LT from January 2015 to December 2022 in a tertiary university hospital were investigated the incidence, onset, and risk factors of ICIs and the effects of ICIs on the outcome of LT recipients using statistical methods. FindingsThe mean age of involved 389 LT recipients was 47.3 ± 10.5 years, with 322 (82.8%) being men. The incidence of ICIs was 3.3% (13/389), and the median time between LT and onset of ICIs was 5.0 days. The univariate analysis of predictors of ICIs identified that massive blood loss, prolonged duration of central line and urethral catheter, and prophylactic antifungal therapy were related to post-LT ICI risk. Multivariate logistic regression analysis adjusted for men and age identified that intraoperative blood loss ≥5000 mL (odds ratio [OR] = 7.005, 95% CI: 2.084–23.542, P = 0.002) and central line duration >14 days (OR = 5.270, 95% CI: 1.556–17.854, P = 0.008) were independently associated with the development of post-LT ICIs. Post-LT prophylactic antifungal therapy >3 days reduced ICIs (OR = 0.103, 95% CI: 0.021–0.501, P = 0.005). Regarding clinical outcomes, patients with ICIs were more likely to stay in the intensive care unit for 7 days or longer compared with those without ICIs (OR = 6.910, 95% CI: 1.737−27.493, P = 0.006). ICIs had no impact on hospitalization stay and 1-month all-cause mortality after LT. ImplicationsICIs are frequent and occur early after LT. Predictors of post-LT ICIs were massive intraoperative blood loss and prolonged duration of the central line. However, post-LT prophylactic antifungal therapy reduced ICIs. Patients with ICIs stayed longer in the intensive care unit than those without ICIs.

Assessing 1-year sodium-glucose co-transporter-2 inhibitor tolerance in older adults.

Evidence concerning tolerability of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older adults is limited due to under-representation in clinical trials. Our study aimed to determine the extent to which SGLT2 inhibitor intolerance increases with age and explore additional factors associated with intolerance. This retrospective observational study included patients in the Veterans Health Administration who initiated an SGLT2 inhibitor between 1 January 2013 and 31 December 2021. One-year discontinuation served as a proxy for intolerance. Relative risk (RR) for 1-year discontinuation was contrasted across age groups using log-binomial regression to adjust for confounding. Of 232 495 patients who initiated an SGLT2 inhibitor, 60 582 (26.1%) discontinued within one year. A difference was observed across age groups, <65, 65-74, 75-84 and ≥85years, where 25.8%, 25.3%, 28.5% and 34.9% of patients discontinued, respectively (P < .001). After adjustment for confounding factors, patients 75-84 and ≥85years were at 8% (RR = 1.08; 95% CI: 1.05, 1.10) and 21% increased risk (RR = 1.21; 95% CI: 1.15, 1.26) for discontinuation, respectively, relative to patients <65years. Additional risk factors were identified: female (RR = 1.41; 95% CI: 1.37, 1.45), estimated glomerular filtration rate stage 4 (RR = 1.49; 95% CI: 1.39, 1.60), underweight (RR = 1.15; 95% CI: 1.03, 1.29), urinary tract infection history (RR = 1.25; 95% CI: 1.21, 1.30) and yeast infection history (RR = 1.39; 95% CI: 1.27, 1.51). No clinically meaningful differences in SGLT2 inhibitor intolerance were observed in patients up to 84years. Our findings support having closer follow-up when initiating in patients 85years and older.