Search Results (10,052)

Bacteremia is a life-threatening condition contributing significantly to sepsis-related mortality worldwide. With delayed appropriate antibiotic therapy, mortality increases by 20% regardless of antimicrobial resistance. This study evaluated the perceived clinical utility of Artificial Intelligence (AI)-powered Clinical Decision Support Systems (CDSSs) (OneChoice and OneChoice Fusion) among specialist physicians managing bacteremia cases. A cross-sectional survey was conducted with 65 unique specialist physicians from multiple medical specialties who were presented with clinical vignettes describing patients with bacteremia and 90 corresponding AI-CDSS recommendations. Participants assessed the perceived helpfulness of AI decision-making, the impact of AI recommendations on their own clinical judgment, and the concordance between AI recommendations and their own clinical judgment, as well as the validity of changing therapy based on CDSS recommendations. The study encompassed a diverse range of bacterial pathogens, with Escherichia coli representing 38.7% of the isolates and 30% being extended-spectrum β-lactamase (ESBL) producers. Findings show that 97.8% [(95% CI: 92.2–99.7%)] of physicians reported that AI facilitated decision-making and substantial concordance (87.8% [95% CI: 79.2–93.7%; Cohen’s κ = 0.76]) between AI recommendations and physicians’ therapeutic recommendations. Stratification by pathogen revealed the highest concordance for Escherichia coli bacteremia (96.6%, 28/29 cases). Implementation analysis revealed a meaningful clinical impact, with 68.9% [(95% CI: 58.3–78.2%)] of cases resulting in AI-guided treatment modifications. These findings indicate that AI-powered CDSSs effectively bridge critical gaps in infectious disease expertise and antimicrobial stewardship, providing clinicians with evidence-based therapeutic recommendations that can be integrated into routine practice to optimize antibiotic selection, particularly in settings with limited access to infectious disease specialists. For optimal clinical integration, we recommend that clinicians utilize AI-CDSS recommendations as an adjunct to clinical judgment rather than a replacement, particularly in complex cases involving immunocompromised hosts or polymicrobial infections. Future research should prioritize prospective clinical trials that evaluate direct patient outcomes to establish evidence of broader clinical effectiveness and applicability across diverse healthcare settings. Full article

The domesticated silkworm, Bombyx mori, is a highly valued biodiversity and economic asset, acclaimed for its silk production, besides making important contributions to various scientific disciplines. However, the sericulture industry faces ongoing threats from bacterial and viral infections, which severely impact silkworm health and silk yield. This review provides a comprehensive overview of the innate immune response of B. mori against bacterial and viral pathogens, emphasizing the fundamental molecular and cellular defense mechanisms. We explore the humoral and cellular immune response using antimicrobial peptides (AMPs), pattern recognition receptors (PRRs) like peptidoglycan recognition protein (PGRP), and glucan recognition protein (GRP), which activate canonical signaling pathways. The review further highlights the molecular mechanisms underlying the silkworm’s defense against viruses, incorporating RNA interference (RNAi), apoptosis, and distinct signaling pathways such as Toll and Imd, JAK/STAT, and STING. We also discussed the viral suppression strategies and modulation of host metabolism during infection. Furthermore, the review explores the recent use of CRISPR-Cas gene editing to enhance disease resistance, presenting a promising avenue for mitigating pathogen-induced losses in sericulture. By elucidating these mechanisms, the work provides a synthesis that is critical in terms of developing particular interventions and developing more resistant silkworm strains to ensure that the industry of sericulture becomes viable and productive. Full article

The production of β-lactamases is the main mechanism underlying carbapenem resistance. This study combined in silico and in vitro approaches to identify potential polyphenols as carbapenemase inhibitors. Molecular docking, molecular dynamics, and ADMET prediction were performed to assess the binding affinity, stability, and safety of quercetin, kaempferol, caffeic acid, and 3,4-dihydroxybenzoic acid against KPC-2, NDM-1, and OXA-48 carbapenemases. In vitro antibacterial assays and checkerboard analyses were conducted against Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa to assess antibacterial and synergistic effects. Then, the inhibition of the β-lactam hydrolytic activity was confirmed. In silico results showed that quercetin, kaempferol, and caffeic acid exhibited strong binding affinity and consistent stability towards the targets. Therefore, quercetin and kaempferol showed the strongest affinities (−8.0 kcal/mol) and stable interactions with key catalytic residues. ADMET profiles indicated good pharmacokinetic behavior and low acute toxicity. In vitro assays revealed that the polyphenols exhibited MIC values ranging from 12.5 to 25 mg/L and MBC values of 25–50 mg/L. Combined with cefotaxime, they enhanced bacterial susceptibility and inhibited β-lactam hydrolysis, with quercetin achieving complete inhibition at 200 mg/L. These findings highlight the potential of the four polyphenols as natural β-lactamase inhibitors. Further enzyme kinetics and in vivo studies are needed to confirm their therapeutic relevance. Full article

Klebsiella pneumoniae (K. pneumoniae) is a major nosocomial pathogen with increasing antibiotic resistance. Treatment failures and high mortality rates in sepsis caused by K. pneumoniae are associated with difficulties in choosing an adequate antibacterial therapy in the presence of resistance to all available antibiotics, based on the results of susceptibility tests. This study aimed to identify “weak points” in the metabolism of K. pneumoniae, to be able to use these features in the future. Ten nosocomial K. pneumoniae strains were incubated with fourteen broad-spectrum antibiotics representing major drug classes. Aromatic metabolites were analyzed using gas chromatography–mass spectrometry after 24 h exposure. Phenyllactic acid (PhLA), comprising 86% of detected phenylcarboxylic acids, served as the metabolic activity marker. Antibiotics demonstrated multidirectional effects on aromatic compound metabolism. Doxycycline, nitrofurantoin, rifampicin, and tigecycline significantly suppressed metabolic activity, confirmed by decreased PhLA levels. Conversely, meropenem, cephalosporins (ceftriaxone, cefepime, cefotaxime, and ceftazidime), ciprofloxacin, and amikacin stimulated PhLA production, suggesting that bacterial metabolic activity was maintained despite the presence of antibiotics. PhLA is a promising biomarker for quantifying K. pneumoniae’s metabolic response to antibiotics. This potentially introduces a novel approach for future investigations into resistance mechanisms and has the potential to increase the effectiveness of therapies for multidrug-resistant K. pneumoniae infections by providing an additional analytical tool to traditional susceptibility testing methodologies. Full article

Silver and gold nanoparticles (NPs) have gained considerable attention in recent years due to their wide-ranging applications in medicine, agriculture, industry, and other fields where they may interact with the environment. Green synthesis of NPs supports sustainability by reducing chemical waste and energy use while improving their biocompatibility through plant phytochemicals. Accordingly, it is important to assess the effects of metal NPs on microorganisms, which play vital roles in ecosystems and biogeochemical cycles. This study aimed to investigate microbial growth dynamics in the presence of green-synthesized silver and gold NPs (using an aqueous extract of Mentha × piperita leaves) and to evaluate potential mechanisms of their interaction. Microorganisms were cultivated in 96-well microtiter plates, and growth curves were analyzed alongside bacterial enumeration on Petri plates. Silver NPs affected the growth of Brevundimonas vesicularis USM1, Pseudarthrobacter oxydans USM2, and Pseudomonas putida USM4, although these strains exhibited partial resistance. In contrast, gold NPs did not inhibit the growth of the tested strains. The ability of Brevundimonas vesicularis USM1 to precipitate metal NPs highlights its potential for sustainable bioremediation applications. The findings contribute to a better understanding of the environmental impact and sustainability aspects of silver and gold NPs in microbial systems. Full article

Acinetobacter baumanni (A. baumannii) is a well-known pathogen associated with antimicrobial-resistant infections. It is a major cause of nosocomial infections and is frequently associated with polymicrobial and antibiotic-resistant infections. This study investigates the frequency of A. baumannii infections, its antimicrobial resistance profile and the main co-pathogens isolated in respiratory samples at the San Giovanni di Dio e Ruggi d’Aragona Hospital in 2015–2019 (pre-COVID-19 pandemic) and 2020–2023 (during/post-COVID-19 pandemic). Bacterial identification and antibiotic susceptibility testing were performed using the VITEK^® 2 system (2015–2019), while identification was carried out with MALDI-TOF MS starting from 2020. A total of 1679 strains were isolated between 2015 and 2019, and 1186 between 2020 and 2023, with significantly higher frequencies in males 61–80 and females 71–80. A. baumannii was isolated predominantly from respiratory specimens, derived predominantly in intensive care units (ICUs). The antimicrobial resistance rates of A. baumannii were above 90% for gentamicin, trimethoprim/sulfamethoxazole, imipenem and ciprofloxacin, while colistin resistance was less than 1% (0.95%) in pre-pandemic and alarmingly increased during/post pandemic period (6.1%). A. baumannii was most frequently associated with Klebsiella pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa in respiratory tract infections. A. baumannii represents a serious global health threat due to its extensive antimicrobial resistance, highlighting the need for continuous surveillance, detailed strain characterization, and development of new antimicrobial agents. Full article

The use of electronic cigarettes has increased in the U.S. with menthol and mint flavors showing notably higher sales. While research on the bacterial microbiome of traditional tobacco products is growing, particularly regarding menthol and nicotine effects, data regarding potential microbial contaminants within electronic liquids (e-liquids) remain limited. Additionally, the potential antibacterial properties of e-liquids remain sparse. To address these gaps, we evaluated the prevalence of viable bacteria in e-liquids; characterized their antimicrobial susceptibility patterns; and tested the antibacterial activity of the e-liquids. Two e-liquid flavors (menthol and non-menthol) across three different nicotine concentrations (0, 6 and 12 mg/mL) were tested using culture-based methods and Sanger sequencing. Antimicrobial susceptibility testing and e-liquid antibacterial activity assays were performed using the Kirby Bauer disc diffusion method. The majority of the isolates (63.15%) were identified as Pseudomonas aeruginosa and Bacillus spp. (B. pumilus, B. megaterium and B. cereus). Notably, P. aeruginosa and P. fluorescens isolates exhibited multidrug resistance against penicillin, tetracyclines, and phenicols. The e-liquids also demonstrated antimicrobial activity, inhibiting the growth of B. cereus, P. aeruginosa, and Staphylococcus aureus, with greater inhibition of P. aeruginosa growth at higher (12 mg/mL) compared to lower (0 mg/mL) nicotine concentrations across the menthol-flavored samples. These findings offer preliminary evidence of viable, multidrug-resistant bacteria and antibacterial properties in e-liquids, underscoring potential public health concerns regarding user exposure risks and microbial interactions, and emphasizing the need for continued surveillance of microbial safety in electronic cigarette products. Full article

Background/Objectives: Biofilm-associated infections pose a major clinical challenge since bacteria within biofilms exhibit highly antibiotic tolerance. Pseudomonas aeruginosa forms persistent biofilms that cause chronic infections in vulnerable patients, including those with cystic fibrosis, burns, or medical implants. Such biofilm-associated chronic infections require prolonged treatments that promote antimicrobial resistance. To address this, recent strategies focus on enhancing biofilm dispersion. Methods: Thirty-six N-arylimino-1,2,3-dithiazoles were screened for their biofilm dispersal activity using a crystal violet assay. Their cytotoxicity was assessed on A549 and HaCat eukaryotic cells. Moreover, their influence on bacterial growth and virulence was investigated. Lastly, fluorescence anisotropy was used to measure membrane fluidity to obtain the first insights on the mechanism of action of these chemicals. Results: Our results showed that quinazoline-derivatives of imino-1,2,3-dithiazoles display biofilm dispersion activity. These compounds do not increase virulence through pyocyanin production, do not modify the growth kinetics of P. aeruginosa, and do not show cytotoxicity towards eucaryotic cells. Conclusions: These findings highlight the potential use of N-arylimino-1,2,3-dithiazole-derived compounds as safe and effective dispersal agents of P. aeruginosa biofilms. Full article

The occurrence of antibiotic residues in the environment is of concern not only because of their contribution to the spread of bacterial resistance, but also due to their possible toxicity to non-target organisms. In this study, the aquatic environmental toxicity of ciprofloxacin (CIP) and sulfamethoxazole (SMX) was assessed in the following model organisms: Daphnia magna and Artemia salina (embryonic and immobilisation test with a 10-d follow-up), Phaeodactylum tricornutum (algal growth inhibition test), and Spirodela polyrhiza (duckweed growth inhibition test). Results showed that among the two saltwater organisms, A. salina was insensitive to both antibiotics, whilst P. tricornutum responded only to SMX with an EC₅₀ of 2.7 mg L⁻¹. In freshwater species, D. magna embryos were more sensitive than juveniles to SMX (EC₅₀ 53.8 and 439.2 mg L⁻¹, respectively), whereas the opposite trend was observed for CIP (EC₅₀ 95.9 and 15 mg L⁻¹, respectively). S. polyrhiza confirmed the remarkable sensitivity of aquatic plants to fluoroquinolones, with EC₅₀ values between 0.28 and 0.34 mg L⁻¹ depending on the endpoint considered. Notably, this species was also more sensitive to SMX than expected, with EC₅₀ values between 1.5 and 2.5 mg L⁻¹, which are an order of magnitude lower than those typically obtained with Lemna spp. exposed to sulphonamides. Considering the high environmental input of these antibiotics from both human and veterinary treatments, adverse effects on aquatic plants cannot be excluded, potentially leading to ecosystem-level consequences. Full article

Background: The escalating burden of antimicrobial resistance (AMR) poses a critical threat to public health in Pakistan, with rates of high antibiotic consumption and limited standardized surveillance on AMR rates. Our study aimed to carry out a multicentric surveillance of AMR to generate regional antibiograms for Northern Punjab, Pakistan, to guide empirical antimicrobial therapy and stewardship efforts. Methods: A laboratory-based, retrospective cross-sectional study was conducted over a six-month period across three tertiary care hospitals. Socio-demographic, clinical, and microbiological data (including specimen type and antibiotic prescription rates) were collected from N = 485 patients with confirmed bacterial infections. Antimicrobial susceptibility testing was performed based on Clinical Laboratory Standards Institute (CLSI) recommendations. Statistical analyses were carried out using SPSS v.22.0. Results: In our study setting, Gram-positive bacteria were common causes (60.0%) of infections, with Staphylococcus aureus (12.2%) and Streptococcus pneumoniae (10.3%) being the most relevant. Among Gram-negative bacteria (40.0%), Escherichia coli (14.0%) and Pseudomonas aeruginosa (5.8%) were shown to be important pathogens. Overall, 25.0% of S. aureus isolates were methicillin-resistant (MRSA), while ~30% of E. coli showed resistance to third-generation cephalosporins (3GCs). Enterobacterales species had highly variable susceptibility rates (40–70%) for fluoroquinolones. Meropenem and vancomycin/linezolid retained high efficacy (>90%) against most Gram-negative and Gram-positive isolates, respectively. In all healthcare settings studied, ceftriaxone was the most frequently prescribed antibiotic. Conclusions: High levels of resistance against first-line antibiotics were noted in our setting of Northern Punjab, Pakistan, underscoring the critical need for robust antimicrobial stewardship programs, tailored to local institutional contexts, capabilities, and needs. The regional antibiogram developed based on our data may provide vital evidence for informing local empirical treatment guidelines, which need to be continuously updated. Full article

Over the past two decades, the meat industry has faced increasing pressure to prevent foodborne outbreaks and reduce economic losses associated with delayed detection of spoilage. This demand has accelerated the development of on-site, real-time sensing tools capable of identifying early signs of contamination. Electrospun nanofiber (NF) platforms have emerged as particularly promising due to their large surface area, tunable porosity, and versatile chemistry, which make them ideal scaffolds for immobilizing enzymes, antibodies, or aptamers while preserving bioactivity under field conditions. These NFs have been integrated into optical, electrochemical, and resistive devices, each enhancing response time and sensitivity for key targets ranging from volatile organic compounds indicating early decay to specific bacterial markers and antibiotic residues. In practical applications, NF matrices enhance signal generation (SERS hotspots), facilitate analyte diffusion through three-dimensional networks, and stabilize delicate biorecognition elements for repeated use. This review summarizes major NF fabrication strategies, representative sensor designs for meat quality monitoring, and performance considerations relevant to industrial deployment, including reproducibility, shelf life, and regulatory compliance. The integration of such platforms with data networks and Internet of Things (IoT) nodes offers a path toward continuous, automated surveillance throughout processing and cold-chain logistics. By addressing current technical and regulatory challenges, NF-based biosensors have the potential to significantly reduce waste and safeguard public health through early detection of contamination before it escalates into costly recalls. Full article

Background: The COVID-19 pandemic profoundly affected healthcare delivery and antibiotic prescribing, raising concerns about increasing antimicrobial resistance. This study investigated seven-year trends in bacterial resistance, underlying resistance mechanisms, and antibiotic consumption in COVID-19 and non-COVID-19 units at a tertiary hospital in Slovakia. Methods: A retrospective cohort analysis (2018–2024) was conducted using clinical isolates of Klebsiella sp., Acinetobacter sp., and P. aeruginosa. Data on hospitalizations, resistance profiles, resistance mechanisms, and standardized antibiotic use were compared between COVID-19 and non-COVID-19 departments. Results: Hospitalizations markedly decreased in COVID-19 units, while pathogen occurrence—particularly of Acinetobacter sp.—was substantially higher compared with non-COVID-19 units. Resistance in Klebsiella sp. shifted from extended-spectrum beta-lactamase production to carbapenemase production. Acinetobacter sp. remained highly resistant, although some declines were observed in ceftazidime and gentamicin resistance. P. aeruginosa showed a gradual reduction in resistance, notably to piperacillin/tazobactam and imipenem. Antibiotic consumption was consistently higher in COVID-19 units, particularly for broad-spectrum beta-lactams and carbapenems, whereas fluoroquinolone use decreased over time. Clinically effective treatment options were considerably fewer in COVID-19 units, often limited to colistin. Conclusions: COVID-19 units experienced greater pathogen burden, higher broad-spectrum antibiotic exposure, and increased prevalence of critical resistance mechanisms. Tailored antimicrobial stewardship and infection prevention, and control are essential to reduce selective pressure and preserve last-line antibiotics. Full article

Melia azedarach L. (Meliaceae) exhibits potential as a source of bioactive antibacterial compounds. In this study, the effect of solvent polarity on ultrasound-assisted extraction of M. azedarach leaves and twigs was evaluated in relation to their phytochemical composition and antibacterial activity against both non-resistant and multidrug-resistant bacteria. The results showed that solvent polarity significantly affected the extraction yield, with methanol and water producing yields above 10%. The methanol extracts of twigs and leaves exhibited the strongest antibacterial activity, showing greater potency against Escherichia coli than Bacillus subtilis. Consistent with these findings, the methanol extracts inhibited the growth of multidrug-resistant enteropathogenic E. coli K1-1, resulting in inhibition zone diameters of 10.93 mm (leaf) and 7.73 mm (twig). Furthermore, the methanol extract contained the highest levels of phenolic, flavonoid, and hydroxyl-rich compounds, which were associated with its antibacterial properties. In silico analysis further revealed that isofucosterol, meliasenin, and melianone exhibited strong predicted binding affinities to key antibacterial proteins, particularly those involved in multidrug-resistant bacterial mechanisms. Full article

β-blockers are among the most widely prescribed cardiovascular drugs and are increasingly recognised as emerging pollutants due to their persistence, continuous release into aquatic environments, and potential toxicological effects on aquatic organisms. Their removal in conventional wastewater treatment plants is often inefficient, highlighting the need for biological remediation strategies. This study aimed to identify bacterial strains with the highest potential for the biotransformation of β-blockers. Therefore, we isolated and characterised bacterial strains capable of transforming two commonly used β-blockers—propranolol and metoprolol. The strains BB2 and BB3, which were able to transform propranolol and metoprolol, respectively, were identified as Raoultella terrigena and Stenotrophomonas terrae, respectively. BB2 showed broad metabolic versatility, utilising a wide range of carbon sources, whereas BB3 exhibited limited substrate utilisation. Antibiotic resistance profiling further distinguished the strains, with BB2 resistant across multiple antibiotic classes and BB3 largely sensitive. Co-metabolic assays demonstrated that supplementation with specific carbon and nitrogen sources markedly enhanced β-blocker removal, increasing propranolol biotransformation from 5% to 50% and metoprolol from 4% to 36%. These findings demonstrate the bioremediation potential of newly isolated strains and emphasise the importance of aligning microbial metabolic traits with nutrient conditions to improve pharmaceutical removal in wastewater treatment systems. Full article

Caffeoylquinic acids (CQAs), a class of phenolic acid metabolites widely distributed in plants, encompass 15 positional isomers from mono- to tetra-esters, with 5-O-caffeoylquinic acid (5-CQA) as the predominant form. The biosynthesis of 5-CQA from phenylalanine proceeds through five primary pathways, which are finely regulated by environmental, hormonal, and transcription factors from families such as MYB, WRKY, and bHLH. These regulators control 5-CQA synthesis by binding specifically to the promoter regions of key structural genes, including PAL, 4CL and HCT/HQT. Subsequently, 5-CQA serves as a central precursor for the biosynthesis of other CQAs. In terms of bioactivity, CQAs possess remarkable pharmacological activities, encompassing antioxidant, antimicrobial, anti-diabetic, anti-inflammatory and anti-tumor properties. For instance, anti-inflammatory effects are demonstrated by the ability of 5-CQA to reduce key pro-inflammatory cytokines (e.g., TNF-α and IL-1β) and downregulate the TLR4/NF-κB pathway. The synergistic action of 5-CQA with ultraviolet-A reduced succinate-coenzyme Q reductase activity by approximately 72%, highlighting its potential to disrupt bacterial metabolism and combat antibiotic resistance. Furthermore, 3,4,5-triCQA exhibits potent anti-influenza virus activity, potentially through a mechanism distinct from existing neuraminidase inhibitors. Beyond medicine, CQAs show promise in light industry. They serve as antibiotic alternatives in livestock feed to enhance gut health, extend food shelf life through their antioxidant activity, and function as active ingredients in UV-protective skincare formulations. CQAs also enhance plant stress tolerance to cold, arsenic, and pests by mechanisms such as scavenging reactive oxygen species and inhibiting pest mobility. While this review consolidates progress in the biosynthesis and bioactivity of CQAs specifically with caffeoyl substituents, future efforts should leverage modern biotechnological tools and interdisciplinary approaches to bridge critical knowledge gaps in their biosynthesis, transport, and clinical translation. Full article