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BackgroundCoccidioidomycosis, an emerging fungal disease in the western USA, exhibits seasonal patterns that are poorly understood, including periods of strong cyclicity, aseasonal intervals, and variation in seasonal timing that have been minimally characterized, and unexplained as to their causal factors. Coccidioidomycosis incidence has increased markedly in recent years, and our limited understanding of intra- and inter-annual seasonality has hindered the identification of important drivers of disease transmission, including climate conditions. In this study, we aim to characterize coccidioidomycosis seasonality in endemic regions of California and to estimate the relationship between drought conditions and coccidioidomycosis seasonal periodicity and timing.MethodsWe analysed data on all reported incident cases of coccidioidomycosis in California from 2000 to 2021 to characterize seasonal patterns in incidence, and conducted wavelet analyses to assess the dominant periodicity, power, and timing of incidence for 17 counties with consistently high incidence rates. We assessed associations between seasonality parameters and measures of drought in California using a distributed lag nonlinear modelling framework.FindingsAll counties exhibited annual cyclicity in incidence (i.e., a dominant wavelet periodicity of 12 months), but there was considerable heterogeneity in seasonal strength and timing across regions and years. On average, 12-month periodicity was most pronounced in the Southern San Joaquin Valley and Central Coast. Further, the annual seasonal cycles in the Southern San Joaquin Valley and the Southern Inland regions occurred earlier than those in coastal and northern counties, yet the timing of annual cycles became more aligned among counties by the end of the study period. Drought conditions were associated with a strong attenuation of the annual seasonal cycle, and seasonal peaks became more pronounced in the 1-2 years after a drought ended.InterpretationWe conclude that drought conditions do not increase the risk of coccidioidomycosis onset uniformly across the year, but instead promote increased risk concentrated within a specific calendar period (September to December). The findings have important implications for public health preparedness, and for how future shifts in seasonal climate patterns and extreme events may impact spatial and temporal coccidioidomycosis risk.FundingNational Institutes of Health.

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background and Objectives: Knowledge about the current spectrum of dermatomycoses is important for diagnosis and therapy. Patients and Methods: A retrospective, monocentric analysis of mucocutaneous fungal infections diagnosed at a large European academic dermatology department in Munich was conducted; 87,229 samples from 48,916 patients from January 1, 2011, to August 30, 2020, were included. Results: Fungi were detected in 11,513 samples from 48,916 (23.54%), and 36 different species were identified. Candida (C.) albicans was the most common pathogen (5,055 detections; 43.91% of all positive samples), followed by Trichophyton (T.) rubrum (3,076 detections; 26.72% of all positive samples) and Candida parapsilosis (923 detections; 8.02% of all positive samples). Rare pathogens such as Trichophyton raubitschekii were also detected. Coinfections with multiple species were detected in 44 cases. Conclusions: Even though C. albicans, T. rubrum, and C. parapsilosis were confirmed as the most common pathogens, rare pathogens should also be considered in clinical practice. The predominant spectrum of fungi differed from that reported in other countries. Furthermore, a difference in the pathogen spectrum could be observed depending on the age group and body site. [ABSTRACT FROM AUTHOR]

Background: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. Methods: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve. Results: Participants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. Conclusion: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment. [ABSTRACT FROM AUTHOR]

Fungal infections (FIs) are spreading globally, raising a significant public health concern. However, its documentation remains sparse in Africa, particularly in Rwanda. This report provides a comprehensive review of FIs in Rwanda based on a systematic review of reports published between 1972 and 2022. The findings reveal a rich diversity of fungal pathogens, including Blastomyces, Candida, Cryptococcus, Histoplasma, Microsporum, Pneumocystis, Rhinosporidium, and Trichophyton caused human infections. Candida infections predominantly affect the vagina mucosa, while Histoplasma duboisi was linked to disseminated infections. Other pathogens, such as Blastomyces dermatitidis and Rhinosporidium seeberi, were associated with cerebellar and nasal mucosa infections, respectively. The widespread observation of soilborne fungi affecting bean crops highlights the pathogens' threat to agricultural productivity, food security, and socioeconomic stability, as well as potential health impacts on humans, animals, and the environment. Of particular importance is that there is no information about FIs among animals in the country. Moreover, the analysis underscores significant limitations in the detection, reporting, and healthcare services related to FIs in the country, indicating gaps in diagnostic capacity and surveillance systems. This is underscored by the predominant use of traditional diagnostic techniques, including culture, cytology, and histopathology in the absence of integrating more sensitive and specific molecular tools in investigating FIs. Developing the diagnostic capacities and national surveillance systems are urgently needed to improve the health of crops, animals, and humans, as well as food security and socioeconomic stability in Rwanda. Also, it is important to indicate severe gaps in the evidence to inform policymaking, guide strategic planning, and improve healthcare and public health services, underscoring the urgent need to build national capacity in fungal diagnosis, surveillance, and research. Raising awareness among the public, scientific community, healthcare providers, and policymakers remains crucial. Furthermore, this report reveals the threats of FIs on public health and food insecurity in Rwanda. A multisectoral one health strategy is essential in research and intervention to determine and reduce the health and safety impacts of fungal pathogens on humans, animals, and the environment. [ABSTRACT FROM AUTHOR]

Fungal infections represent a growing public health problem, mainly stemming from two phenomena. Firstly, certain diseases (e.g., AIDS and COVID-19) have emerged that weaken the immune system, leaving patients susceptible to opportunistic pathogens. Secondly, an increasing number of pathogenic fungi are developing multi-drug resistance. Consequently, there is a need for new antifungal drugs with novel therapeutic targets, such as type I and II DNA topoisomerase enzymes of fungal organisms. This contribution summarizes the available information in the literature on the biology, topology, structural characteristics, and genes of topoisomerase (Topo) I and II enzymes in humans, two other mammals, and 29 fungi (including Basidiomycetes and Ascomycetes). The evidence of these enzymes as alternative targets for antifungal therapy is presented, as is a broad spectrum of Topo I and II inhibitors. Research has revealed the genes responsible for encoding the Topo I and II enzymes of fungal organisms and the amino acid residues and nucleotide residues at the active sites of the enzymes that are involved in the binding mode of topoisomerase inhibitors. Such residues are highly conserved. According to molecular docking studies, antifungal Topo I and II inhibitors have good affinity for the active site of the respective enzymes. The evidence presented in the current review supports the proposal of the suitability of Topo I and II enzymes as molecular targets for new antifungal drugs, which may be used in the future in combined therapies for the treatment of infections caused by fungal organisms. [ABSTRACT FROM AUTHOR]

Objective: Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms, including coordinated innate and adaptive immune responses, to neutralize invading fungi effectively. Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections. Methods: The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans -infected mice and healthy control mice using single-cell transcriptomics, fluorescence quantitative PCR, and Western blotting. We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration, pathway enrichment, and differentiation during Candida albicans infection. Results: Our findings indicate that infiltration of CD4 + naive cells, regulatory T (Treg) cells, and Microtubules-associated (MT)-associated cells increased after infection, along with impaired T cell activity. Notably, CD4+T cells and plasma cells were enhanced after infection, suggesting that antibody production is dependent on T cells. In addition, we screened 6 hub genes, transcription factor forkhead box protein 3(Foxp3), cytotoxic T-lymphocyte associated protein 4 (CTLA4), Interleukin 2 Receptor Subunit Beta (Il2rb), Cd28, C-C Motif Chemokine Ligand 5 (Ccl5), and Cd27 for alterations associated with CD4+T cell differentiation. Conclusions: These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rise of drug resistance has led to attempts to the development of new herbal medicines. This study aimed to develop two types of nanocarriers containing Zingiber officinale essential oil. The oil's components were identified using GC-MS analysis. Alginate and chitosan nanoparticles containing Z. officinale essential oil were prepared using the ionic gelation method. Particle size, zeta potential, and successful loading of the essential oil in the nanoparticles were investigated using DLS, Zetasizer, and ATR-FTIR analysis, respectively. Chitosan nanoparticles exhibited a significantly smaller particle size (102 ± 9 nm) and more positive zeta potential (12 ± 2 mV) compared to alginate counterparts (188 ± 7 nm, −19 ± 1.2 mV). ATR-FTIR analysis confirmed the successful encapsulation in both types of nanoparticles. Notably, chitosan nanoparticles with IC50 values of 82 and 67 µg/mL against MCF-7 and MDA-MB-231, respectively, displayed superior potency compared to non-formulated essential oil and alginate nanoparticles. Likewise, the antibacterial efficacy of chitosan nanoparticles with IC50 values of 661 and 462 µg/mL against Escherichia coli and Staphylococcus aureus, respectively, showed a significant potency compared to two other samples. Furthermore, chitosan nanoparticles demonstrated antifungal activity against Candida krusei (MIC 4.25 µg/mL) and Candida parapsilosis (MIC 8.5 µg/mL) while showing no significant antifungal activity against Aspergillus flavus (MIC > 1200). Considering their high potency and straightforward preparation, chitosan nanoparticles loaded with Z. officinale essential oil warrant further investigation in vivo. [ABSTRACT FROM AUTHOR]

The drug delivery through the eye has been challenging due to the complex physiology of the eye. The ocular region is commonly considered the most advantageous site for the topical application of medicines for management of eye disorders. The effectiveness of this approach is commonly impeded by the strong protective mechanisms of eye, leading to restricted access of the drugs. Ocular fungal infections are commonly reported as one of the predominant eye illnesses caused by various fungal species like Fusarium species, Candida glabrata, Aspergillus flavus, and Aspergillus fumigatus. Liposomes are biocompatible lipid nanocarriers which have emerged as innovative therapeutic technologies in ophthalmology to overcome ocular obstacles, provide targeted drug delivery along with enhancement of drug's safety margin. This review elucidates about causes of ocular fungal infection, fungal evasion by host immune system, pharmacological profile of drug used for treatment of ocular fungal infections, and challenges of existing formulations in management of ocular infections. This article focused upon the current advancements in domain of topical applications of liposomes of ophthalmic medicines in management of ocular fungal infection. [ABSTRACT FROM AUTHOR]

Introduction: Advances in diagnostic technologies, particularly Point-of-Care Diagnostics (POCDs), have revolutionized clinical practice by providing rapid, user-friendly, and affordable testing at or near the patient's location. POCDs have been increasingly introduced in medical mycology and hold promise to improve patient outcomes in a variety of important human fungal diseases. Areas covered: This review focuses on validated POCDs, particularly lateral flow assays (LFAs), for various fungal diseases. Additionally, we discuss emerging innovative techniques such as body fluid analysis, imaging methods, loop-mediated isothermal amplification (LAMP), microfluidic systems, clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics, and the emerging role of artificial intelligence. Expert opinion: Compact and user-friendly POCDs have been increasingly introduced in medical mycology, and some of these tests (e.g. Cryptococcus and Histoplasma antigen LFAs) have become mainstream diagnostics, while others, such as LFA in invasive aspergillosis show promise to become part of our routine diagnostic armamentarium. POCDs offer immense benefits such as timely and accurate diagnostic results, reduced patient discomfort, and lower healthcare costs and might contribute to antifungal stewardship. Integrated fluidics combined with microtechnology having multiplex capabilities will be pivotal in medical mycology. [ABSTRACT FROM AUTHOR]

Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris , its control, patient outcomes, and lessons learned. The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris ; 27 (87.1%) were colonized with C auris , while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks. • Candida auris can cause protracted outbreaks in healthcare settings. • A multidisciplinary response is successful at controlling outbreaks. • Admission screening of high-risk patients may have a role in preventing outbreaks. [ABSTRACT FROM AUTHOR]

Disparities in social determinants of health (SDOH) play a significant role in causing health inequities globally. The physical environment, including housing and workplace environment, can increase the prevalence and spread of fungal infections. A number of professions are associated with increased fungal infection risk and are associated with low pay, which may be linked to crowded and sub-optimal living conditions, exposure to fungal organisms, lack of access to quality health care, and risk for fungal infection. Those involved and displaced from areas of armed conflict have an increased risk of invasive fungal infections. Lastly, a number of fungal plant pathogens already threaten food security, which will become more problematic with global climate change. Taken together, disparities in SDOH are associated with increased risk for contracting fungal infections. More emphasis needs to be placed on systematic approaches to better understand the impact and reducing the health inequities associated with these disparities.

Introduction: Aspergillosis is a fungal infection commonly found in human lungs and takes several forms. Chronic pulmonary aspergillosis (CPA) commonly affects individuals with underlying disease, most usually lung tuberculosis (TB). Aspergillosis can cause the formation of a fungus ball in the lung cavity and can also manifest in the tracheobronchial area, although this is rarely seen in immunocompetent patients. Case: A 23-year-old woman came with persistent cough, hemoptysis, and shortness of breath for 4 months. The patient also had a significant weight loss and a history of lung TB 3 years ago. She had completed her lung TB medication. Physical examination showed increased respiratory rate and rhonchi on the left lung. GeneXpert showed no Mycobacterium tuberculosis (MTB) detected. The chest X-ray showed a cavity on the left superior lobe of the lung. Bronchoscopy showed multiple plaques along the trachea, carina, and left main bronchus. A chest computed tomography (CT) scan with contrast enhancement was performed, and a fungus ball was found inside the cavity in the left upper lobe of the lung. The patient was given intravenous fluconazole as therapy and continued with oral fluconazole when discharged. A second bronchoscopy was performed, and improvement was shown. Conclusion: Early detection and treatment should be applied to CPA patients since some studies showed poor prognosis and low five-year survival rates.

Abstract Background The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. Methods The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score’s receiver operating characteristic curve. Results Participants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. Conclusion We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma­-caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%–12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%–14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%–15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

A 59-year-old immunocompetent male who initially presented with symptoms of stroke was found to have an incidental rim-enhancing lesion on magnetic resonance imaging (MRI) of the brain. This discovery led to a lumbar puncture to analyze the cerebrospinal fluid, resulting in the diagnosis of cryptococcoma. The patient was subsequently managed with liposomal amphotericin B, followed by consolidation and maintenance therapy with fluconazole. The patient achieved a positive outcome, demonstrating the effectiveness of early diagnosis and targeted treatment. The rarity of cryptococcoma in immunocompetent individuals makes this case particularly unusual and noteworthy. It underscores the need for more extensive research to enable prompt diagnosis and effective management.

Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. Methods: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. Findings: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292–5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274–5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117–5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262–5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553–6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822–18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073–0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558–5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay. [ABSTRACT FROM AUTHOR]

Background: Miconazole nitrate, a BCS class II drug which is used for treatment of fungal infections. To minimize the disadvantages of sticky creams and ointments and their tendency to rub off, an intelligent dosage regimen needs to be designed as a film-forming spray formulation. The aim of this investigation was to develop a film-forming spray formulation containing 0.5% Miconazole nitrate for the treatment of fungal infections on the skin. Materials and Methods: The Miconazole nitrate film-forming spray formulation was prepared using different concentrations of Eudragit RL-100, Ethylcellulose, Camphor and Menthol crystals (Eutectic mixture), Polyethene glycol 400 and Ethanol by simple solvent dissolving method using a statistical tool, 23 full factorial design to optimize the film forming spray formulation. The film-forming spray underwent thorough testing to evaluate its formulation characteristics, including pH, viscosity, evaporation time, density, drug release and container-related factors such as spray angle, spray diameter and amount of spray solutions released per actuation at valve assembly. To carry out an antifungal activity test on an optimized spray formulation and compare it with a commercially available cream. Results and Discussion: From the study, the ethyl cellulose concentration has a greater influence on the viscosity and density, 45 cps and 0.8472 g/mL of the spray formulation respectively. Eudragit RL-100 and the eutectic mixture have a higher impact on the drug release 92.44% at 8 hr in pH 6.8 phosphate buffer. Conclusion: The topical treatment of fungal infections proved to be suitable for the Miconazole nitrate film-forming spray formulation. Longer, continuous medication administration is facilitated by the skin's longer retention period. The medication exhibits good antifungal effectiveness in preventing fungal infections, according to antifungal investigations. The Miconazole nitrate film-forming spray is a considerably better alternative to current dosage forms for treating topical fungal infections, as evidenced by its good stability, simplicity of administration and action. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L‐AMB). Objectives: Because excess potassium (K) leakage occurs during renal tubular injury caused by L‐AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L‐AMB than hypokalaemia identified from a one‐point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated. Methods: A ≥ 10% decrease in K concentration from the reference concentration within a 7‐day timeframe was evaluated. The hypokalaemia index, which combines the duration of K concentration lower than the reference and a marked low K concentration, was calculated from the area over the concentration curve. Results: Eighty‐six patients were included in the study. The incidences of AKI and decrease in K concentration were 36.0% and 63.9%, respectively. Of patients who developed both adverse events, a decrease in K concentration occurred first in 22 of 26 patients, followed by AKI 7 days later. Hypokalaemia did not increase AKI risk whereas a decrease in K concentration was an independent risk factor for AKI. The hypokalaemia index in patients with AKI was significantly higher than those without AKI (5.35 vs. 2.50 points, p = 0.002), and ≥3.45 points was a significant predictor for AKI. Conclusion: A ≥ 10% decrease in the K concentration was a significant factor for AKI in patients receiving L‐AMB therapy. In such patients, dose reduction or alternative antifungals could be considered based on the hypokalaemia index. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage (BAL) is a widely used diagnostic procedure in pulmonology, yet its utility across diverse pulmonary conditions warrants further evaluation. Methods: This prospective study involved 47 patients suspected of having pulmonary diseases, where conventional diagnostics were inconclusive. BAL was performed to diagnose infections, interstitial lung diseases (ILDs), and malignancies, with subsequent analysis for sensitivity, specificity, and diagnostic yield. Results: BAL identified tuberculosis in 15 cases (31.9%), bacterial pneumonia in 10 (21.3%), fungal infections in 2 (4.3%), ILDs in 5 (10.6%), and malignancies in 6 (12.8%). The procedure demonstrated high diagnostic accuracy with sensitivity and specificity rates notably high across conditions: tuberculosis (88.2%, 97.0%; p<0.001), bacterial pneumonia (76.9%, 98.5%; p<0.001), fungal infections (66.7%, 99.0%; p=0.005), ILDs (83.3%, 96.7%; p=0.001), and malignancies (85.7%, 97.5%; p<0.001). Conclusion: The study highlights BAL's substantial diagnostic value in pulmonary diseases, reinforcing its role in enhancing diagnostic accuracy and informing therapeutic strategies. BAL emerges as an indispensable tool in the early detection and management of complex lung diseases. [ABSTRACT FROM AUTHOR]

Fungi cause diseases in a variety of marine animal hosts. The need for new antifungal agents arises from the rising prevalence of invasive fungal infections (IFI) and the ineffectiveness, severe side effects, and high mortality of the current antifungal agents. The present study aims to assess Caulerpa scalpelliformis seaweed extract's antifungal efficacy against human fungal infections. Using methanol solvents, the antifungal activity of marine macroalgae C.scalpelliformis was assessed against Candida albicans, Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Cryptococcus neoformans. C. scalpelliformis showed strong fungal activity against A. fumigatus, A. niger, and A. flavus compared to C. albicans and C. neoformans, similar to the positive control drug Amphotericin B in the current study.This is the first report from Tuticorin's Periyathalai coast. These results point to the use of green seaweed, C. scalpelliformis methanol extract as a natural antibiotic in conjunction with synthetic antibiotics, which has paved the way for the development of new anti-aspergillus, anti-cryptococcal, and anti-candidal compounds. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a life-saving technique used in critical care medicine for patients with severe respiratory or cardiac failure. This review examines the treatment and prophylaxis of fungal infections in ECMO patients, proposing specific regimens based on available data for different antifungals (azoles, echinocandins, amphotericin B/liposomal amphotericin B) and invasive fungal infections. Currently, isavuconazole and posaconazole have the most supported data, while modified dosages of isavuconazole are recommended in ECMO. Echinocandins are preferred for invasive candidiasis. However, choosing echinocandins is challenging due to limited and varied data on concentration loss in the ECMO circuit. Caution is likewise advised when using liposomal amphotericin B due to uncertain concentrations and potential ECMO dysfunction based on scarce data. We further conclude with the importance of further research on the impact of ECMO on antifungal drug concentrations to optimize dosing regimens in critically ill patients. [ABSTRACT FROM AUTHOR]

Inflatable penile prosthesis (IPP) surgery is an effective treatment for erectile dysfunction (ED), but infections pose a significant threat to its success. Current guidelines lack antifungal recommendations, despite rising fungal infection rates post-IPP surgery. This review examines epidemiology, risk factors (including diabetes mellitus, immunosuppression, and obesity), and pathogenesis, highlighting the role of biofilm formation in device contamination. Clinical manifestations vary from acute to delayed, with fungal biofilms presenting challenges in diagnosis. Prophylactic strategies, including broad-spectrum antibiotics and antifungals, are crucial, with evidence suggesting a 92% reduction in infections. With fungal infections showing lower salvage rates, management involves culture-guided treatment, irrigation, and oral antibiotics. Future research aims to understand biofilm mechanisms and develop biomaterials to reduce infection rates. Implementing antifungal therapy, along with standard practices like the no-touch technique and antibiotic dips, is crucial in preventing IPP infections. [ABSTRACT FROM AUTHOR]

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p < 0.001). Candida spp. showed higher rate in non-COVID-19 (74.2 % vs. 66.8 %; p = 0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4 % vs. 19.1 %; p < 0.001). IPA was diagnosed in 703 patients and 11.2 % (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9–3.1), p < 0.001]. B-cell malignancies – specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia – showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50 % and 72 %. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients. COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted. [ABSTRACT FROM AUTHOR]

Purpose of Review: The aim of this review is to examine healthcare-associated fungal outbreaks (HAFO) in children. Our primary objective is to dissect epidemiology and etiology aspects to contribute to the investigation, prevention, and control of HAFO in pediatric settings. Recent Findings: Latest studies have highlighted an increase in fungal infections among hospitalized children. These studies have revealed the involvement of environmental sources and cross-transmission through healthcare workers in the development of outbreaks. The diagnosis of fungal infections poses challenges, as does outbreak control due to non-routine surveillance and resistance of fungi to disinfectants and therapeutic drugs. Summary: Recognition of risk factors, etiologic agents, diagnostic methods, and types of transmission that facilitate fungal infections in children is crucial to understand the importance of prompt outbreak investigation and control. Addressing research gaps in disinfection technologies and exploring the potential application of artificial intelligence on outbreak anticipation could aid in mitigating the impact of HAFO on pediatric populations. [ABSTRACT FROM AUTHOR]

Background:Candida species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to evaluate invasive candidiasis (IC) risk factors in critically ill patients undergoing surgery. Patients and Methods: We retrospectively reviewed the medical records of 583 patients who underwent emergency surgery for complicated intra-abdominal infections between January 2016 and December 2021. Patients were divided into two groups according to the presence or absence of IC during their hospital stay. IC was defined as culture-proven candidemia and intra-abdominal candidiasis. Results: This study included 373 patients for the final analysis, of whom 320 were discharged without IC (IC absent group) and 53 presented with IC (IC present group) during their hospital stay. The IC present group showed a higher in-hospital mortality rate (35.8 vs. 8.8%; p < 0.001), with 66.0% of the patients diagnosed within 10 days, whereas only 6.5% were diagnosed beyond 20 days after admission. Stomach (odds ratio [OR], 4.188; 95% confidence interval [CI], 1.204–14.561; p = 0.024) and duodenum (OR, 7.595; 95% CI, 1.934–29.832; p = 0.004) as infection origin, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR, 1.097; 95% CI, 1.044–1.152; p < 0.001), and lower initial systolic blood pressure (OR, 0.983; 95% CI, 0.968–0.997; p = 0.018) were risk factors of IC after emergency gastrointestinal surgery. Conclusions: Patients who had stomach and duodenum as infection origin, higher APACHE II scores, and lower initial systolic blood pressure had a higher risk of developing IC during their hospital stay after emergency gastrointestinal surgery. Prophylactic antifungal agents can be carefully considered for critically ill patients with these features. [ABSTRACT FROM AUTHOR]

Summary: Background: Coccidioidomycosis, an emerging fungal disease in the western USA, exhibits seasonal patterns that are poorly understood, including periods of strong cyclicity, aseasonal intervals, and variation in seasonal timing that have been minimally characterized, and unexplained as to their causal factors. Coccidioidomycosis incidence has increased markedly in recent years, and our limited understanding of intra- and inter-annual seasonality has hindered the identification of important drivers of disease transmission, including climate conditions. In this study, we aim to characterize coccidioidomycosis seasonality in endemic regions of California and to estimate the relationship between drought conditions and coccidioidomycosis seasonal periodicity and timing. Methods: We analysed data on all reported incident cases of coccidioidomycosis in California from 2000 to 2021 to characterize seasonal patterns in incidence, and conducted wavelet analyses to assess the dominant periodicity, power, and timing of incidence for 17 counties with consistently high incidence rates. We assessed associations between seasonality parameters and measures of drought in California using a distributed lag nonlinear modelling framework. Findings: All counties exhibited annual cyclicity in incidence (i.e., a dominant wavelet periodicity of 12 months), but there was considerable heterogeneity in seasonal strength and timing across regions and years. On average, 12-month periodicity was most pronounced in the Southern San Joaquin Valley and Central Coast. Further, the annual seasonal cycles in the Southern San Joaquin Valley and the Southern Inland regions occurred earlier than those in coastal and northern counties, yet the timing of annual cycles became more aligned among counties by the end of the study period. Drought conditions were associated with a strong attenuation of the annual seasonal cycle, and seasonal peaks became more pronounced in the 1–2 years after a drought ended. Interpretation: We conclude that drought conditions do not increase the risk of coccidioidomycosis onset uniformly across the year, but instead promote increased risk concentrated within a specific calendar period (September to December). The findings have important implications for public health preparedness, and for how future shifts in seasonal climate patterns and extreme events may impact spatial and temporal coccidioidomycosis risk. Funding: National Institutes of Health.

ABSTRACT Invasive fungal infections (IFIs) caused by pathogenic fungi pose a significant public health concern, particularly for immunocompromised individuals. Mortality rates for IFIs remain high, and currently available treatment options are limited. Existing antifungal agents often suffer from limited clinical efficacy, poor fungicidal activity within the host, potential toxicity, and increasing ineffectiveness due to emerging resistance, especially against triazole drugs, the current mainstay of antifungal treatment. A recent study has identified MBX-7591, a small molecule with promising antifungal activity against Aspergillus fumigatus and other pathogenic fungi, including strains resistant to triazoles (C. Gutierrez-Perez, C. Puerner, J. T. Jones, S. Vellanki, E. M. Vesely, et al., mBio e01166-24, 2024, https://doi.org/10.1128/mbio.01166-24). This novel compound appears to inhibit stearoyl-CoA 9-desaturase, a key enzyme involved in fungal fatty acid biosynthesis. By disrupting the conversion of saturated fatty acids to oleic acid, MBX-7591 offers a unique mechanism of action, potentially reducing the risk of resistance development. Here, we now discuss the implications of these groundbreaking findings for overcoming antifungal drug resistance.

Background: In the Balkans, rising concerns about invasive fungal infections over the past decade stem from various factors. Primarily, there has been a notable uptick in immunocompromised individuals, including those with chronic illnesses like immunological and hematological diseases. Thus, it is essential to assess the region's laboratory capabilities and the availability of antifungals. This evaluation is vital for gauging the preparedness to diagnose and treat fungal infections effectively, thus minimizing their public health impact. Methods: Data were collected via an online questionnaire targeting healthcare professionals specializing in relevant fields across diverse healthcare settings in Balkan countries. The survey covered various aspects, including diagnostic methods, imaging techniques, and available antifungal armamentarium. Results: Responses were obtained from 50 institutions across the Balkans. While conventional diagnostic methods like microscopy (96 %) and culture (100 %) diagnostics were widely available, access to newer diagnostic tools such as molecular assays (61 %) were limited, often relying on outsourced services. Imaging modalities like ultrasound (100 %) and CT scans (93 %) were universally accessible. A variety of antifungal drugs were available, including amphotericin B formulations (80 %), echinocandins (79 %), and triazoles (100 %). However, access to newer agents like posaconazole (62 %) and isavuconazole (45 %) was inconsistent. Therapeutic drug monitoring (53 %) services were also limited. Conclusion: The study underscores the need for equitable access to diagnostic facilities and antifungal treatments across healthcare settings in the Balkan geographic region. Improving access to molecular diagnostic tools and essential antifungal drugs, as well as implementing therapeutic drug monitoring, would optimize the management of fungal infections in the region.

This article discusses the co-morbidity of COVID-19 and fungal infections. It highlights the significant role that fungal infections play in the prognosis of COVID-19 patients, with candidemia and mucormycosis being particularly prevalent. The article emphasizes the need for improved antifungal therapies, early detection strategies, and preventive measures to reduce fungal transmission. It also calls for multidisciplinary collaboration and research to better understand the pathogenesis of fungal co-infections in COVID-19 patients. [Extracted from the article]

This article discusses a rare case of pheohyphomycosis caused by Exophiala jeanselmei, a type of opportunistic fungal infection. The patient, a 44-year-old woman with lupus nephritis and chronic renal failure, presented with reddish globular lumps on her right leg. The diagnosis was confirmed through skin biopsy and culture, and the patient was treated with antifungal agents. However, the lesion did not improve and the patient eventually died of a disseminated infection. The article emphasizes the importance of accurate and timely diagnosis in order to prevent inappropriate treatment. [Extracted from the article]

Background: Candida species, commonly present in the human body, can result in severe infections. Non-albicans Candida (NAC) species, with increasing antifungal resistance, pose a growing concern. Aims and Objectives: This study aims to evaluate candidiasis prevalence and antifungal susceptibility in isolated Candida species among suspected patients at tertiary care hospitals in Butwal, emphasizing early identification and appropriate treatment to avoid unnecessary use of toxic antifungal drugs. Materials and Methods: In a descriptive study on 303 patients with clinical symptoms of Candida infections, specimens underwent direct microscopic examination and culture on Sabouraud dextrose agar. Species identification involved phenotypic methods such as chromogenic character on CHROMagar Candida media, germ tube examination, and microscopic characteristics. Subsequently, isolated species were tested for antifungal susceptibility using the disc diffusion method. Results: Among the 303 samples tested, 80 (26.4%) were positive for candidal infection. NAC species were the most commonly isolated, with Candida albicans and Candida krusei being the most virulent. The isolates exhibited the highest sensitivity to fluconazole (77.5%) followed by itraconazole (75%), whereas amphotericin B showed the lowest effectiveness with 63.75% resistance. Conclusion: The rising prevalence of NAC species, particularly their growing resistance to Amphotericin B, has become a significant concern, as these species are frequently detected in various clinical samples. These findings underscore the importance of diligent monitoring and judicious selection of antifungal agents to ensure effective treatment strategies.

Coccidioidomycosis is a fungal infection endemic to the southwestern United States and Central/South America, and its range is expanding with the warming climate. People with HIV/AIDS are at increased risk of developing disseminated infection, and furthermore are at risk for developing immune reconstitution inflammatory syndrome (IRIS) if they are initiating or re-initiating anti-retroviral therapy (ART). There have been few cases of coccidioidomycosis-related IRIS reported in the literature, and there is no clear guidance on treatment. We present a case of paradoxical IRIS in a patient with AIDS who clinically improved after initiating corticosteroids.

Using next-generation sequencing (NGS), we developed and validated a whole-genome sequencing (WGS)-based clinical test for fungal species identification on clinical isolates. The identification is mainly based on the fungal ribosomal internal transcribed spacer (ITS) region as the primary marker, and additional marker and genomic analysis applied for species within the Mucorales family (using the 28S rRNA gene) and Aspergillus genus (using the beta-tubulin gene and k-mer tree-based phylogenetic clustering). The validation study involving 74 unique fungal isolates (22 yeasts, 51 molds, and 1 mushroom-forming fungus) showed high accuracy, with 100% (74/74) concordance on the genus-level identifications and 89.2% (66/74) concordance on the species level. The 8 discrepant results were due to either the limitation of conventional morphology-based methodology or taxonomic changes. After one year of implementation in our clinical laboratory, this fungal NGS test was utilized in 29 cases; the majority of them were transplant and cancer patients. We demonstrated the utility of this test by detailing five case studies, in which accurate fungal species identification led to correct diagnosis, treatment adjustment or was ruled out for hospital acquired infection. This study provides a model for validation and implementation of WGS for fungal identification in a complex health system that serves a large immunocompromised patient population.

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.

Introduction: Invasive candidiasis is a global public health problem as it poses a significant threat in hospital-settings. The aim of this study was to evaluate C14R, an analog derived from peptide BP100, as a potential antimicrobial peptide against the prevalent opportunistic yeast Candida albicans and the emergent multidrug-resistant yeast Candida auris. Methods: Antifungal susceptibility testing of C14R against 99 C. albicans and 105 C. auris clinical isolates from Colombia, was determined by broth microdilution. Fluconazole was used as a control antifungal. The synergy between C14R and fluconazole was assessed in resistant isolates. Assays against fungal biofilm and growth curves were also carried out. Morphological alterations of yeast cell surface were evaluated by scanning electron microscopy. A permeability assay verified the pore-forming ability of C14R. Results: C. albicans and C. auris isolates had a geometric mean MIC against C14R of 4.42 µg/ml and 5.34 µg/ml, respectively. Notably, none of the isolates of any species exhibited growth at the highest evaluated peptide concentration (200 µg/ml). Synergistic effects were observed when combining the peptide and fluconazole. C14R affects biofilm and growth of C. albicans and C. auris. Cell membrane disruptions were observed in both species after treatment with the peptide. It was confirmed that C14R form pores in C. albicans' membrane. Discussion: C14R has a potent antifungal activity against a large set of clinical isolates of both C. albicans and C. auris, showing its capacity to disrupt Candida membranes. This antifungal activity remains consistent across isolates regardless of their clinical source. Furthermore, the absence of correlation between MICs to C14R and resistance to fluconazole indicates the peptide's potential effectiveness against fluconazole-resistant strains. Our results suggest the potential of C14R, a pore-forming peptide, as a treatment option for fungal infections, such as invasive candidiasis, including fluconazole and amphotericin B -resistant strains. [ABSTRACT FROM AUTHOR]

In recent years, the incidence of fungal infections in humans has increased dramatically, accompanied by an expansion in the number of species implicated as etiological agents, especially environmental fungi never involved before in human infection. Among fungal pathogens, Candida species are the most common opportunistic fungi that can cause local and systemic infections, especially in immunocompromised individuals. Candida albicans (C. albicans) is the most common causative agent of mucosal and healthcare-associated systemic infections. However, during recent decades, there has been a worrying increase in the number of emerging multi-drug-resistant non-albicans Candida (NAC) species, i.e., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris, and C. ciferrii. In particular, Candida ciferrii, also known as Stephanoascus ciferrii or Trichomonascus ciferrii, is a heterothallic ascomycete yeast-like fungus that has received attention in recent decades as a cause of local and systemic fungal diseases. Today, the new definition of the S. ciferrii complex, which consists of S. ciferrii, Candida allociferrii, and Candida mucifera, was proposed after sequencing the 18S rRNA gene. Currently, the S. ciferrii complex is mostly associated with non-severe ear and eye infections, although a few cases of severe candidemia have been reported in immunocompromised individuals. Low susceptibility to currently available antifungal drugs is a rising concern, especially in NAC species. In this regard, a high rate of resistance to azoles and more recently also to echinocandins has emerged in the S. ciferrii complex. This review focuses on epidemiological, biological, and clinical aspects of the S. ciferrii complex, including its pathogenicity and drug resistance. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 (HSP90) is a critical target for anticancer and anti-fungal-infection therapies due to its central role as a molecular chaperone involved in protein folding and activation. In this study, we developed in vitro Förster Resonance Energy Transfer (FRET) assays to characterize the binding of C. albicans HSP90 to its co-chaperone Sba1, as well as that of the homologous human HSP90α to p23. The assay for human HSP90α binding to p23 enables selectivity assessment for compounds aimed to inhibit the binding of C. albicans HSP90 to Sba1 without affecting the physiological activity of human HSP90α. The combination of the two assays is important for antifungal drug development, while the assay for human HSP90α can potentially be used on its own for anticancer drug discovery. Since ATP binding of HSP90 is a prerequisite for HSP90-Sba1/p23 binding, ATP-competitive inhibitors can be identified with the assays. The specificity of binding of fusion protein constructs—HSP90-mNeonGreen (donor) and Sba1-mScarlet-I (acceptor)—to each other in our assay was confirmed via competitive inhibition by both non-labeled Sba1 and known ATP-competitive inhibitors. We utilized the developed assays to characterize the stability of both HSP90–Sba1 and HSP90α–p23 affinity complexes quantitatively. Kd values were determined and assessed for their precision and accuracy using the 95.5% confidence level. For HSP90-Sba1, the precision confidence interval (PCI) was found to be 70–120 (100 ± 20) nM while the accuracy confidence interval (ACI) was 100–130 nM. For HSP90α-p23, PCI was 180–260 (220 ± 40) nM and ACI was 200–270 nM. The developed assays were used to screen a nucleoside-mimetics library of 320 compounds for inhibitory activity against both C. albicans HSP90-Sba1 and human HSP90α-p23 binding. No novel active compounds were identified. Overall, the developed assays exhibited low data variability and robust signal separation, achieving Z factors > 0.5. [ABSTRACT FROM AUTHOR]