Search Results (221)

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a health related threat world-wide. Biosynthesized gold nanoparticles (AuNPs) using plant extracts have been reported to exhibit certain biological activity. This study aimed to biosynthesize AuNPs using an aqueous extract of Eruca sativa leaves and to evaluate their biocompatibility, antimicrobial activity, and antioxidant properties. Methods: AuNPs were biosynthesized using an aqueous extract of Eruca sativa leaves. Their biocompatibility was evaluated through hemolytic activity and assessments of hepatic and renal functions in rats. AuNPs were biologically evaluated as antimicrobial and antioxidant agents. Results: The AuNPs exhibited particle sizes of 27.78 nm (XRD) and 69.41 nm (AFM). Hemolysis assays on red blood cells revealed negligible hemolytic activity (<1%). Hepatic enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were studied. ALT, AST, and ALP levels showed no significant changes compared to the negative control. However, LDH levels were elevated at higher concentration (52.8 µg/mL), while the lower concentration (26.4 µg/mL) appeared to be safer. Renal biomarkers, urea and creatinine, showed no significant changes at either concentration, indicating minimal nephrotoxicity. The antimicrobial activity of AuNPs, plant extract, and gold salt was tested against five microorganisms: two Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and a fungal strain (Candida albicans). The AuNPs exhibited minimum inhibition concentrations (MICs) of 13.2 µg/mL against S. aureus and S. pneumoniae, 26.4 µg/mL against E. coli and C. albicans, and 39.6 µg/mL against P. aeruginosa, suggesting selectivity towards Gram-positive bacteria. Furthermore, the AuNPs demonstrated strong antioxidant activity, surpassing that of vitamin C. Conclusions: The biosynthesized AuNPs exhibited promising biocompatibility, selective antimicrobial properties, and potent antioxidant activity, supporting their potential application in combating the AMR. Full article

Introduction/objectives: Peritonitis resulting from Candida spp. is common among critically ill patients and has been associated with adverse clinical outcomes. This study aimed to determine the effects of isolates of Candida species in patients with peritonitis on in-hospital mortality, general hospital stay, and intensive care unit (ICU) stays. Methods: This retrospective cohort study was conducted in two highly complex hospitals in Bogotá, Colombia, specifically by reference to patients who were hospitalized in the ICU between 2016 and 2022 with a clinical and microbiological diagnosis of peritonitis. For the analysis conducted for this research, two groups were established: patients with isolates of Candida spp. in the peritoneum and patients who had at least one bacterial microorganism in the culture. Multivariate logistic regression models and counting models featuring different mortality outcomes, different lengths of stay in the ICU, and different lengths of stay in the hospital were generated to evaluate the effect of the presence of Candida spp. and to account for potentially confounding variables. Results: A total of 373 patients, including 83 with Candida spp. and 290 with a bacterial etiology, were identified. Among the former group of patients, the most frequently identified species were C. albicans (50, 60.2%), C. tropicalis (18, 21.7%), and C. glabrata (7, 8.4%), whereas among the latter group, E. coli (186, 48.5%), K. pneumoniae (110, 29.8%), and E. faecalis (63, 16.9%) were most frequent. The 30-day mortality rate among patients with peritonitis and Candida isolates was 36.1%, and the corresponding rate among patients in the bacterial peritonitis group was 31.4% (p = 0.071). After adjustments were made to account for covariates, no significant differences were observed in mortality at 30 days (OR 0.75, 95% CI 0.20–1.18), length of hospital stay (iRR 1.11, 95% CI 0.90–1.40), or length of stay in the ICU (iRR 1.11, 95% CI 0.39) with respect to patients with peritonitis without fungal isolates. The Simplified Acute Physiology Score (SAPS2) (OR 1.04, 95% CI 1.03–1.06), World Society of Emergency Surgery (WSES) score (OR 1.11, (1.03–1.19), previous use of antifungals (OR 2.33, 1.21–4.52), and connective tissue disease (OR 3.71, 95% CI 1.30–10.99) were associated with 30-day mortality. Conclusions: The isolation of Candida species in peritoneal fluid from critically ill patients with peritonitis was not significantly associated with in-hospital mortality, length of hospital stay, or length of ICU stay after adjustments were made to account for other variables. Full article

Respiratory syncytial virus (RSV) represents one of the main respiratory infections found among immunocompromised patients. Objective: The study analyzes the incidence of RSV infection in different populations of immunocompromised patients as organ transplant recipients (lung, other solid organs, hematopoietic stem cells) and oncologic patients (solid organ malignancy and hematological malignancy) compared to a group of non-immunocompromised patients. We also assessed the prevalence of viral, bacterial, and mycotic coinfection. Moreover, we aimed at evaluating the efficacy of ribavirin treatment in terms of mortality reduction. Methods: We conducted a retrospective analysis on a total of 466 transplant patients undergoing bronchoscopy with bronchoalveolar lavage for suspected viral disease or surveillance between 2016 and 2023, compared to 460 controls. Results: The incidence of RSV was significantly higher in immunocompromised patients, particularly in those with lung and bone marrow transplants. Among RSV+ patients, a higher prevalence of viral (influenza virus), bacterial (S. pneumoniae, M. pneumoniae, Nocardia spp.), and fungal (Aspergillus spp.) coinfections were observed. The efficacy of ribavirin in reducing mortality did not show significant differences compared to supportive therapy alone. Conclusions: The results of our exploratory study suggest that immunocompromised patients are particularly vulnerable to RSV infection and coinfections. Our hypothesis-generating data warrant the need for future studies aimed at exploring preventive and therapeutic strategies for RSV infection in these high-risk patient groups. Full article

Pneumocystis pneumonia (PCP) is a serious fungal infection affecting immunocompromised hosts. Decompensated cirrhosis leads to cirrhosis-associated immune dysfunction (CAID), a form of impaired cellular immunity that may predispose patients to opportunistic infections such as PCP. We conducted a retrospective review of 727 patients with proven or probable PCP from 2017 to 2025. Of these, 33 had decompensated cirrhosis. These patients were stratified into two groups: Cirrhosis Only (n = 16) and Cirrhosis with Additional Immunocompromising Conditions (n = 17). Among the patients with cirrhosis, the overall mortality was 48%, with the 90-day mortality reaching 57.6% (95% CI: 39.2–74.5%). Compared with those without cirrhosis, the patients with cirrhosis had a higher risk of mortality (OR: 4.08, 95% CI: 2.01–8.30, p < 0.001), increased intensive care unit (ICU) admission (87% vs. 42%, p < 0.001), and greater need for renal replacement therapy (54.6% vs. 7.5%, p < 0.001). These findings suggest that decompensated cirrhosis alone may represent a sufficient and underrecognized risk factor for PCP, with a high associated mortality. Given the preventable nature of this infection, future studies are needed to assess the incidence, define the risk, and investigate the role of prophylaxis in this vulnerable population. Full article

Conventional diagnostic methods (CDMs) for lower respiratory infections (LRIs) have limitations in detecting causative pathogens. This study evaluates the utility of shotgun metagenomic sequencing (SMS) as a complementary diagnostic tool using bronchoalveolar lavage (BAL) fluid. Sixteen BAL fluid samples from pneumonia patients with positive CDM results—including bacterial/fungal cultures; PCR for Mycobacterium tuberculosis or cytomegalovirus; and the BioFire^® FilmArray^® Pneumonia Panel (BioFire Diagnostics LLC, Salt Lake City, UT, USA)—underwent 10 Gb SMS on the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Reads were aligned to the NCBI RefSeq database; with fungal identification further supported by internal transcribed spacer (ITS) analysis. Antibiotic resistance genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database. Microbial reads accounted for 0.00002–0.04971% per sample. SMS detected corresponding bacteria in 63% of cases, increasing to 69% when subdominant taxa were included. Fungal reads were low; however, Candida species were identified in four samples via ITS. No viral reads were detected. ARGs meeting perfect match criteria were found in two cases. This is the first real-world study comparing SMS with CDMs, including semiquantitative PCR, in BAL fluid for LRI. SMS shows promise as a supplementary diagnostic method, with further research needed to optimize its performance and cost-effectiveness. Full article

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes. Full article

Specific monosaccharide residue, β-D-galactofuranose (Galf) featuring a five-membered ring structure, is found in the glycans of fungi and bacteria, but is normally absent in healthy mammals and humans. In this study, synthetic oligosaccharides mimicking bacterial and fungal glycans were investigated by SERS (Surface-Enhanced Raman Scattering) techniques for the first time to distinguish between different types of glycan chains. SERS spectra of oligosaccharides related to fungal α-(1→2)-mannan, β-(1→3)-glucan, β-(1→6)-glucan, galactomannan of Aspergillus, galactan I of Klebsiella pneumoniae, and diheteroglycan of Enterococcus faecalis were measured. To analyze the spectra, a number of machine learning methods were used that complemented each other: principal component analysis (PCA), confidence interval estimation (CIE), and logistic regression with L1 regularization. Each of the methods has shown own effectiveness in analyzing spectra. Namely, PCA allows the visualization of the divergence of spectra in the principal component space, CIE visualizes the degree of overlap of spectra through confidence interval analysis, and logistic regression allows researchers to build a model for determining the belonging of the analyte to a given class of carbohydrate structures. Additionally, the methods complement each other, allowing the determination of important features representing the main differences in the spectra containing and not containing Galf residue. The developed mathematical models enabled the reliable identification of Galf residues within glycan compositions. Given the high sensitivity of SERS, this spectroscopic technique serves as a promising basis for developing diagnostic test systems aimed at detecting biomarkers of fungal and bacterial infections. Full article

In recent years, the incidence of acute and chronic inflammatory diseases has increased significantly worldwide, intensifying the search for new therapeutic agents, especially anti-inflammatory drugs. Therefore, the aim of this work was to synthesize, biologically assess, and explore the structure–activity relationships of new compounds containing the cyclohex-1-ene-1-carboxylic acid moiety. Six new derivatives, 2a–2f, were synthesized through the reaction of amidrazones 1a–1f with 3,4,5,6-tetrahydrophthalic anhydride. Their toxicity was evaluated in cultures of human peripheral blood mononuclear cells (PBMCs). Additionally, their antiproliferative properties and effects on the synthesis of TNF-α, IL-6, IL-10, and IL-1β were assessed in mitogen-stimulated PBMCs. The antimicrobial activity of derivatives 2a–2f was determined by measuring the minimal inhibitory concentration (MIC) values against five bacterial strains—Staphylococcus aureus, Mycobacterium smegmatis, Escherichia coli, Yersinia enterocolitica, and Klebsiella pneumoniae—and the fungal strain Candida albicans. All compounds demonstrated antiproliferative activity, with derivatives 2a, 2d, and 2f at a concentration of 100 µg/mL being more effective than ibuprofen. Compound 2f strongly inhibited the secretion of TNF-α by approximately 66–81% at all studied doses (10, 50, and 100 µg/mL). Derivative 2b significantly reduced the release of cytokines, including TNF-α, IL-6, and IL-10, at a high dose (by approximately 92–99%). Compound 2c exhibited bacteriostatic activity against S. aureus and M. smegmatis, while derivative 2b selectively inhibited the growth of Y. enterocolitica (MIC = 64 µg/mL). Some structure–activity relationships were established for the studied compounds. Full article

A commercially available loop-mediated isothermal amplification assay (LAMP) for the detection of Pneumocystis jirovecii (P. jirovecii) has been evaluated for the diagnosis of Pneumocystis pneumonia (PcP) in critically ill patients. Altogether, 109 lower respiratory tract specimens from 95 patients with a positive P. jirovecii test in routine diagnostics were collected from five distinct university hospitals in Germany. All samples were tested with a qPCR and eazyplex^® LAMP assay. qPCR was set as the gold standard and was evaluated beforehand with samples from 100 patients categorized to have proven, probable, and possible PcP according to the EORTC/MSGERC guidelines. The sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the LAMP were assessed. Sensitivity was 68%, specificity was 86%, and PPV and NPV were 99% and 16%, respectively. All patients with proven PcP were positive in the LAMP. There was a weak correlation between the time to positivity and the fungal load (squared Pearson correlation coefficient (r²) = 0.5653). A positive result in the LAMP indicates a PcP. Because of the low sensitivity, negative results do not rule out an infection and should be clarified with further molecular methods. The LAMP should be used in patients in whom a PcP is expected, not for screening only. Full article

Background and Objectives: Secondary pulmonary fungal infections in coronavirus disease 2019 (COVID-19) remain underexplored despite emerging reports linking them to heightened morbidity. Comorbidities, steroid use, and prolonged hospital stays can predispose patients to opportunistic fungi. This study aimed to evaluate the impact of fungal coinfection on inflammatory markers, disease severity, antifungal resistance profiles, and outcomes in hospitalized COVID-19 patients. Methods: This retrospective observational study enrolled 280 adults (≥18 years) with real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 admitted to a tertiary care center (January 2023–December 2024). Patients were divided into a COVID-19-only group (n = 216) and a COVID–fungal group (n = 64) based on bronchoalveolar lavage, sputum, and/or blood culture positivity for fungal pathogens. Inflammatory markers (C-reactive protein (CRP), procalcitonin, the neutrophil-to-lymphocyte ratio, and the systemic immune inflammation index) and severity scores (Acute Physiology and Chronic Health Evaluation II, CURB-65 score, and the National Early Warning Score) were measured. We assessed antifungal susceptibilities and recorded ICU admissions, ventilation, hospital length of stay, and mortality. Results: Aspergillus fumigatus (31.3%), Candida albicans (28.1%), Cryptococcus neoformans (7.8%), Pneumocystis jirovecii (6.3%), and Mucorales (6.3%) dominated; Candida glabrata, Candida tropicalis, and mixed infections were also noted. Multidrug-resistant (MDR) isolates or resistance to triazoles occurred in 25.0% of cultures. The COVID-19–fungal group showed significantly higher CRP (85.7 vs. 71.6 mg/L, p < 0.001), procalcitonin (2.4 vs. 1.3 ng/mL, p < 0.001), and APACHE II scores (18.6 vs. 14.8, p < 0.001). intensive-care unit admissions (39.1% vs. 19.9%, p = 0.004) and mechanical ventilation (26.6% vs. 10.2%, p = 0.01) were more frequent with fungal coinfection. Mortality trended at a higher rate (15.6% vs. 7.4%, p = 0.06). Conclusions: Pulmonary fungal coinfections intensify the inflammatory milieu, elevate severity scores, and lead to more frequent ICU-level interventions in COVID-19 patients. Early identification, guided by culture-based and molecular diagnostics, alongside prompt antifungal therapy, could mitigate adverse outcomes. These findings underscore the critical need for proactive fungal surveillance and rigorous stewardship in managing severe COVID-19 pneumonia. Full article

Extracts from 58 species of corticioid fungi (phylum Basidiomycota), mainly belonging to the orders Hymenochaetales, Polyporales and Russulales, were tested for their inhibitory activity against five species of bacteria: Corynebacterium striatum, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Twenty-four of the species we analyzed in this study were tested for antibacterial activity for the first time. The fruiting bodies of the fungi were collected from dead wood in the forests of north-eastern Poland, and macerated in methanol. Dried extracts were redissolved in dimethyl sulfoxide and applied to broth cultures of the bacteria, which were then inoculated on agar plates. Noblesia crocea demonstrated moderate inhibitory activity against all five tested bacteria; Amylocorticium subincarnatum, Laxitextum bicolor, Peniophora laeta, P. rufomarginata, Phanerochaete sordida, and Xylobolus frustulatus inhibited four bacterial species. The extracts from 14 fungal species tested were moderately active against only two bacteria, P. aeruginosa and C. striatum; 17 species were active against C. striatum only. The full inhibition was observed with concentrations of extract 25 or 50 mg/mL. Full article

The dynamic development of various branches of medicine and pharmacy, along with the emergence of new preventive and alternative therapies for various diseases, creates opportunities for new solutions utilizing carriers of active substances. Their therapeutic effect may occur through direct contact with skin lesions or indirectly, where medicinal substances penetrate the capillary network in the deeper layers of the skin and reach the bloodstream. The aim of the research was to obtain carriers with a matrix consisting of two renewable-source polymers (chitosan and ethylcellulose) and a core material derived from Ginkgo biloba green leaf extract (GBE). The obtained ethylcellulose microcapsules with encapsulated chitosan nanoparticles with extract {Et[Ch(GB)NP]} were characterized with respect to size, shape, surface morphology (SEM microscopy), and active substance release kinetics (UV-VIS and mathematical release models). The kinetics of active substance release were analyzed using UV-VIS spectroscopy and mathematical release models. The released active components were assessed microbiologically for activity against six bacterial strains and two fungal strains, as well as chromatographically using HPLC-ESI-QTOF-MS/MS fingerprinting. The microcapsules with a dual polymer layer exhibited a slow release of the core material, which demonstrated microbiological activity. The strongest antimicrobial effects were observed against Klebsiella pneumoniae and Salmonella enteritidis, with a minimum inhibitory concentration (MIC) of 410 µg/mL. The release of the core material from the double-layer polymer structures was more efficient in a physiological saline environment, with the best fit for the extract release kinetics following a zero-order model (regression coefficient R² = 0.9939). The obtained microcapsules with a dual polymer layer show great potential for therapeutic applications in the medical industry. Their controlled release properties and antibacterial effectiveness make them a promising carrier for active substances in modern therapies. Full article

Twelve marine-derived fungal strains were evaluated for their ability to synthesize silver nanoparticles (AgNPs). Mycogenic AgNPs were preliminarily characterized using different techniques, and their antimicrobial activities were assessed. Penicillium citrinum IBCLP11 and Aspergillus niger IBCLP20 were selected for AgNPs’ synthesis optimization by varying parameters such as AgNO₃ concentration, biomass, agitation, temperature, and pH. AgNP_IBCLP11 and AgNP_IBCLP20 were able to inhibit the growth of Pseudomonas aeruginosa IPT322, Staphylococcus aureus IPT246, and Klebsiella pneumoniae IPT412 at concentrations of 25 μg/mL or higher. Aspergillus niger IPT295 and Aspergillus parasiticus IPT729 were the most sensitive to AgNP_IBCLP20. Further studies are needed to fully elucidate the effects of all parameters influencing mycogenic AgNPs synthesis. However, it is evident that maintaining optimal conditions, such as temperature and pH during agitation, is crucial for preventing undesirable reactions and ensuring nanoparticle stability. Full article

Background/Objectives: This study aims to gain insights into the antimicrobial and antiherpetic activity of hyperforin-rich Hypericum perforatum L. (HP) extract using nanostructured lipid carriers (NLCs) as delivery platforms. Methods: Two established NLC specimens, comprising glyceryl behenate and almond oil or borage oil, and their extract-loaded counterparts (HP-NLCs) were utilized. Their minimal bactericidal/fungicidal concentrations (MBC; MFC) were investigated against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 10145, Klebsiella pneumoniae ATCC 10031, and Candida albicans ATCC 10231. The anti-herpesvirus (HSV-1) potential was evaluated concerning antiviral and virucidal activity and impact on viral adsorption. Results: The borage oil-based extract-loaded nanodispersion (HP-NLC2) exhibited pronounced microbicidal activity against S. aureus (MBC 6.3 mg/mL), K. pneumoniae (MBC 97.7 µg/mL), and C. albicans (MFC < 48.8 µg/mL), unlike the almond oil-containing sample (HP-NLC1), which showed only weak inhibition of the fungal growth. HP-NLC2 was found to be less cytotoxic and to suppress HSV-1 replication slightly more than HP-NLC1, but generally, the effects were weak. Neither the empty lipid nanoparticles nor the HP extract-loaded carriers expressed activity against E. coli, P. aeruginosa, the HSV-1 extracellular virions, or viral adhesion. Conclusions: It could be concluded that both HP-NLC samples revealed only minor antiherpetic potential of the hyperforin-rich extract, but HP-NLC2 demonstrated significant antibacterial and antimycotic activity. Therefore, the latter was featured as a more convenient HP-carrier system for nano-designed dermal pharmaceutical formulations. Such a thorough investigation of hyperforin-determined anti-HSV-1 effects and antibacterial and antimycotic properties, being the first of its kind, contributes to the fundamental knowledge of HP and reveals new perspectives for the utilization, limitations, and therapeutic designation of its non-polar components. Full article