Antibiotics-Basel最新文献

Background: The rapid rise in antimicrobial resistance has become one of the 10 most pressing health problems worldwide in recent years. Antibiotic stewardship offers hope in the fight against antibiotic resistance, but it is currently still falling short of expectations. A better understanding of the dynamics of the interaction between antibiotic consumption and the emergence and spread of resistance is urgently needed. Methods: We discuss a simple dynamic model based on a differential equation to describe the increase in the proportion of a pathogen's antimicrobial resistance to an antibiotic as a function of the time-dependent consumption of that antibiotic. Furthermore, we investigate the association of heterogeneity in the consumption of antibiotics with the rate of resistant pathogens. Data basis is the hospital information system and the patient data-management system of a German hospital, restricted to the intensive care unit. To quantify heterogeneity, we discuss and compare different entropy measures. Results: For some pathogen-antibiotic pairs, the consumption-dependent dynamic model for the growth in the proportion of antimicrobial resistance provides acceptable predictions, while for others, the model is less suitable. Cross-resistance and complex interactions with other pathogens and antibiotics may be responsible for this, suggesting that the observed dynamic behavior should be complementary, described using heterogeneity models. Time courses of Shannon entropy, the Antibiotic Heterogeneity Index, and the negative Gini Index correlate positively with the time series of the resistance rate. Thus, an increase in heterogeneity correlates with a decreasing resistance rate. However, a time-delayed cross-correlation of a differential entropy measure with resistance share suggests a functional dependence that can be utilized for antibiotic stewardship. Conclusions: Evidence is provided that the amount of consumption of certain antibiotics drives the corresponding proportions of pathogens' resistance to these antibiotics; however, the model predictions of these univariable models are generally not sufficiently good, pointing to a more complex interaction dynamics. Therefore, we switch to the level of structural features and show that the degree of constantly mixing of the shares of antibiotic consumption has a control function regarding the incidence of resistance. Controlling differential consumption heterogeneity, therefore, appears to be a feasible operational basis for antibiotic stewardship. Experimental studies are demanded to identify functional dependencies; however, the integration of clinical expertise with model-based prediction appears to be a feasible antibiotic stewardship strategy.

Background/objectives: The integration of silver nanoparticles (AgNPs) into plastic materials has emerged as a promising strategy to provide biomedical and dental devices with an active antimicrobial barrier. In this review, we aimed to synthesize the scientific evidence published between 2013 and 2024 regarding the therapeutic efficacy, biocompatibility, and safety of AgNP-functionalized plastics by following the 2020 PRISMA guidelines.

Methods: Searches were conducted in PubMed, Scopus, Web of Science, SciELO, and ScienceDirect. A total of 634 records were identified, of which 21 studies met the inclusion criteria after full-text evaluation.

Results: Plastics containing AgNPs show a significant reduction in microbial load (Escherichia coli, Stafilococcus aureus, and Candida albicans) and exhibit controlled release of Ag⁺ ions, with generally low cytotoxicity levels. The most frequent applications included catheters, dental prostheses, dressings, and orthodontic resins. However, methodological heterogeneity and the scarcity of clinical trials limit the extrapolation of findings.

Conclusions: AgNPs confer relevant therapeutic advantages to polymers, but long-term clinical studies are needed to confirm their safety and effectiveness.

Background/Objectives: Postbiotics derived from lactic acid bacteria are emerging as promising antimicrobial agents due to their antibacterial, antibiofilm, and immunomodulatory properties. Among their metabolites, lactic acid (LA) is thought to play a major role in antimicrobial activity. This study investigated the proteomic response of Pseudomonas aeruginosa and Staphylococcus aureus to Lacticaseibacillus rhamnosus cell-free supernatant (CFS) and compared it with that elicited by LA alone. Methods: Overnight bacterial cultures were exposed to sub-MIC LA or CFS (1:10 for P. aeruginosa and 1:8 for S. aureus; ~12.5-15.6 mM LA) for 6 h at 37 °C. Intracellular proteins were harvested and subsequently quantified and purified to be analysed by HPLC-MS/MS, for quantitative label-free proteomics. Results: Proteomic analysis revealed clear separation of treated samples from controls, with largely overlapping responses to CFS and LA. Hallmark acid-stress adaptations were observed, including urease-mediated pH buffering, confirming that part of the response was driven by mild organic acid. In P. aeruginosa, treatments suppressed virulence pathways (phenazines, T3SS), while shifting metabolism toward lactate utilisation and reinforcing the outer membrane (lipid A, polyamine). In S. aureus, decreased abundance of the SaeRS-regulated immune-evasion factor Sbi, together with changes in envelope, ROS and translation-related proteins, suggested a bacteriostatic-like state. S. aureus differences between CFS and LA were more pronounced; CFS uniquely increased cell-wall defences, oxidative stress (SodA, SodM) and chaperone expression (GroS, GrpE), suggesting stress beyond acidification alone. Conclusions: These findings shed light on the molecular mechanisms underlying bacterial adaptation to CFS and highlight their potential as a novel antimicrobial approach.

Background/Objectives: Antimicrobial resistance (AMR) threatens global public health. This systematic review and meta-analysis, as part of the "ENVIRE" project (interventions to control the dynamics of antimicrobial resistance from chickens through the environment), assesses the prevalence of phenotypic and genotypic resistance, including extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases, carbapenemases, colistin, and fluoroquinolone resistance, in broiler chickens and their environment. Methods: The analysis covers the years 2002-2022, focusing on Escherichia (E.) coli, Klebsiella spp., Enterobacter spp., and Citrobacter spp. in fecal, meat, environmental, and other-than-feces samples from observational studies published in PubMed and Web of Science. Quality assessment was performed using the Alberta Heritage Foundation criteria. Results: Data from 170 studies, conducted in Europe, North Africa, and North America, were included. The most frequently studied resistance was to beta-lactam, with focus on ESBL-producing and AmpC beta-lactamase isolates. The pooled prevalence of ESBL-resistant E. coli observed in meat samples at 41% and in fecal samples at 38% demonstrated significant heterogeneity between the studies. The negative binomial regression analysis of prevalence data revealed significantly higher ESBL-producing E. coli rates in European meat samples compared to North African samples. Conclusions: This systematic review revealed substantial variation in prevalence and emphasizes the need for standardized surveillance systems and robust study designs.

Antimicrobial resistance (AMR) has become a major health crisis worldwide, and it is expected to surpass cancer as one of the leading causes of death by 2050. Conventional antibiotics are struggling to keep pace with the rapidly evolving resistance trends, underscoring the urgent need for novel antimicrobial therapeutic strategies. Antimicrobial peptides (AMPs) function through diverse, often membrane-disrupting mechanisms that can address the latest challenges to resistance. However, the identification, prediction, and optimization of novel AMPs can be impeded by several issues, including extensive sequence spaces, context-dependent activity, and the higher costs associated with wet laboratory screenings. Recent developments in artificial intelligence (AI) have enabled large-scale mining of genomes, metagenomes, and quantitative species-resolved activity prediction, i.e., MIC, and de novo AMPs designed with integrated stability and toxicity filters. The current review has synthesized and highlighted progress across different discriminative models, such as classical machine learning and deep learning models and transformer embeddings, alongside graphs and geometric encoders, structure-guided and multi-modal hybrid learning approaches, closed-loop generative methods, and large language models (LLMs) predicted frameworks. This review compares models' benchmark performances, highlighting AI-predicted novel hybrid approaches for designing AMPs, validated by in vitro and in vivo methods against clinical and resistant pathogens to increase overall experimental hit rates. Based on observations, multimodal paradigm strategies are proposed, focusing on identification, prediction, and characterization, followed by design frameworks, linking active-learning lab cycles, mechanistic interpretability, curated data resources, and uncertainty estimation. Therefore, for reproducible benchmarks and interoperable data, collaborative computational and wet lab experimental validations must be required to accelerate AI-driven novel AMP discovery to combat multidrug-resistant Gram-negative pathogens.

Background: Asymptomatic bacteriuria (ASB) is frequently overtreated in emergency departments (EDs), contributing to antimicrobial resistance without improving clinical outcomes. The rapid pace of clinical decision-making and high patient turnover in the ED further predispose clinicians to unnecessary antibiotic prescribing. Methods: A quasi-experimental study was conducted in the ED of a tertiary hospital in Barcelona, Spain, from January 2024 to September 2025. The intervention included targeted education for ED staff and daily audit-feedback on antibiotic prescriptions for suspected ASB. The outcomes were the following variables, compared between study periods: cases of ASB with unnecessary antibiotic treatment per month, antimicrobial consumption, urine culture (UC) requests, 30-day return visits to the ED for urinary tract infection, and 30-day all-cause mortality for safety assessment. Results: A total of 93 patients with suspected ASB in the pre-intervention period and 102 patients in the intervention period were included. The median cases of ASB with unnecessary antibiotic treatment per month decrease from 19 (IQR 16-26) in the pre-intervention period to 9 (IQR 9-13) in the intervention period (p = 0.018). Antimicrobial consumption declined: meropenem and imipenem decreased from 5.5 to 3.0 DDD/1000 admissions, ertapenem from 5.6 to 3.1, and ceftriaxone from 35.0 to 24.1. UC requests fell by 16.1%. Clinical safety outcomes did not differ significantly between periods: 30-day return visit to the ED for UTI with the same isolate dropped from 8.6% to 1.9% (p = 0.076), overall UTI return visits to the ED dropped from 11.8% to 5.9% (p = 0.225), and 30-day mortality remained stable (8.6% vs. 4.9%, p = 0.455). Conclusions: These findings support the use of combined educational and audit-feedback strategies as effective and safe Antimicrobial Stewardship interventions in high-intensity clinical environments such as the ED, as they reduce inappropriate antibiotic use and unnecessary UC requests without compromising patient safety.

Background: Surface contamination in healthcare environments plays a key role in the persistence and transmission of microorganisms. Long-lasting antimicrobial coatings based on copper-polymer complexes offer a promising passive strategy to minimize environmental contamination and healthcare-associated infections. Methods: This study evaluated a copper-alloy polymeric tape through physicochemical, in vitro, and hospital-based assessments. Structural analyses (XRD, Raman, SEM, EDX) were used to characterize the material, while antimicrobial efficacy was determined against Gram-positive and Gram-negative bacteria following ISO 22196:2011. A randomized 19-week clinical study was conducted in the Emergency and Urgent Unit of the University Hospital of Brasília to quantify microbial loads on high-touch surfaces covered with the copper-alloy tape or a non-antimicrobial control. Results: Structural characterization techniques validated the integrity and heterogeneous distribution of copper within the polymeric matrix. All tested bacterial strains exhibited complete growth inhibition on the copper-alloy tape, with final counts consistently below the detection threshold (<1.00 log10 CFU/mL). Human keratinocytes analyzed by SEM showed preserved morphology. In hospital conditions, treated surfaces maintained significantly lower microbial loads than controls over 19 weeks. The number of yeast-positive samples was small compared to the total number of samples collected during the study, but Candida parapsilosis was the most frequently identified species. Conclusions: These findings support its use as a sustainable intervention to reduce environmental contamination and infection risks in healthcare settings.

Background/Objectives: Respiratory tract infections (RTIs) remain a leading cause of morbidity worldwide and are frequently associated with the emergence of multidrug-resistant pathogens. In this context, natural compounds represent a valuable source of novel antimicrobial and immunomodulatory agents. The present study aimed to evaluate the antibacterial, anti-inflammatory, and antioxidant activities of Protegol, a natural food supplement enriched in bioactive phytochemicals including hydroalcoholic extracts of propolis and hedge mustard (Sisymbrium officinale (L.) Scop.) aerial parts, together with honey, against clinically relevant bacterial strains and in cellular models of inflammation and oxidative stress. Furthermore, the ability of the multi-herbal formulation to alter the permeability of the bacterial cell wall was assessed. Methods: The antibacterial properties of Protegol were evaluated by determining its minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) against a panel of Gram-positive and Gram-negative bacteria, using the broth microdilution method. Cell wall permeability was investigated through the propidium iodide (PI) uptake assay. The anti-inflammatory potential was investigated in LPS-stimulated RAW 264.7 macrophages by measuring nitric oxide (NO) production with the Griess assay. The antioxidant activity was evaluated in BALB/3T3 fibroblasts exposed to hydrogen peroxide, using the DCFH-DA assay. Results: Protegol exhibited a broad-spectrum antibacterial effect, with MIC values ranging from 1.5 to 6.2 mg/mL and MBC values between 3.1 and 12.4 mg/mL. The strongest activity was observed against Staphylococcus aureus and Streptococcus pyogenes, including clinical isolates, while moderate efficacy was detected against resistant Klebsiella pneumoniae strains. PI uptake assays confirmed a dose-dependent disruption of bacterial membrane integrity, supporting a direct effect of Protegol on cell wall permeability. In macrophages, Protegol significantly and dose-dependently reduced NO release, lowering production to 44% at the highest concentration tested. In BALB/3T3 cells, Protegol markedly decreased ROS accumulation to 24% at the same concentration. Conclusions: Overall, the findings support the potential of Protegol as a natural adjuvant to the conventional therapies for respiratory tract health by counteracting bacterial pathogens, reducing inflammation, and mitigating oxidative stress, thereby supporting host defense mechanisms in the context of respiratory tract infections.

Background: Artichoke, a medicinal plant with various therapeutic uses, is widely cultivated in many of the world's geographical areas. The aim of this study was to establish the antimicrobial profile by means of comparative evaluation of the phytochemical constituents, antioxidant, anti-lipid peroxidation, and antimicrobial activities of the basal and cauline leaves, as well as the following by-products: stems, bracts, and inflorescences, from Cynara scolymus L. cultivated in the Republic of Moldova. Methods: Qualitative and quantitative characterization of the main phenolic compounds from ethanolic extracts was carried out by the HPLC-UV-MS method. The in vitro antioxidant activity was evaluated using DPPH˙, ABTS˙⁺, FRAP, and NO˙ scavenging methods. The lipid-lowering effect was established with a malonic dialdehyde complex and thiobarbituric acid. Antimicrobial properties were screened using the diffusion method. Results: The HPLC UV-MS analysis highlighted that the green aerial parts of C. scolymus are characterized by the presence of five phenolic acids (kaempferol, gentisic, chlorogenic, p-coumaric, ferulic, and caffeic) and four flavonoid heterosides and aglycones (isoquercitrin, quercitrin, luteolin, and apigenin). Correlation between total polyphenolic content and antioxidant activity was found to be statistically significant (p < 0.01). The extracts of C. scolymus's aerial parts exhibited significant antibacterial and antifungal activities (p < 0.05) against all tested microorganisms, while no inhibitory effect for inflorescences was observed. Conclusions: Artichoke leaves and by-products may be considered important and promising sources of bioactive compounds for herbal medicinal products, functional foods, and nutraceuticals, due to their antimicrobial properties. This study makes an original contribution to the specialized literature by the detailed characterization of the antimicrobial profile of the extracts obtained from artichoke cultivated in the Republic of Moldova, a species introduced for the first time on the territory of this country. The obtained results highlight the medicinal potential and economic value of the Moldovan artichoke, with particular emphasis on its by-products: stems, bracts, and inflorescences, which less explored so far, as sources of bioactive compounds. Our analyses indicate that the leaves and by-products of the plant represent promising resources for the development of phytopharmaceutical preparations, functional foods, and nutraceuticals, offering new directions for the integral and sustainable valorization of this species acclimatized in Moldova.

Background: Milk is a highly nutritious food, but its composition makes it an ideal medium for microbial growth, particularly for bacteria like Staphylococcus aureus (S. aureus). In Ecuador, raw milk consumption is culturally rooted, and contamination risks are heightened, especially in informal markets. Staphylococcus aureus, a Gram-positive, coagulase-positive bacterium, commonly colonizes mucous membranes and can cause a range of infections due to its production of thermostable toxins. Its impact extends to bovine mastitis, severely affecting dairy production. Of particular concern is the emergence of methicillin-resistant S. aureus (MRSA) strains, associated with the acquisition of the mecA gene located on the "staphylococcal chromosomal cassette mec" (SCCmec) element and identification of a mecA homologue, mecC, further complicates detection and monitoring efforts. Objectives: This study evaluated the prevalence of S. aureus and MRSA strains in raw milk from Ecuadorian provinces Pichincha and Manabí. Methods: A total of 633 samples were collected and analyzed via real-time PCR (qPCR) and bacterial isolation methods, complemented by endpoint PCR assays for mecA and mecC genes detection. Results: A high prevalence of S. aureus (84%) was observed, with significant differences between regions. MRSA was detected in 23% of all samples, with mecA being more prevalent than mecC among isolates. Sequencing of 16S rDNA confirmed the identity of isolates, while phylogenetic analysis of mecA and mecC genes validated their presence. The findings suggest that suboptimal hygiene practices and varied biosecurity protocols, especially among small and medium dairy producers, may contribute to the persistence of resistant strains. Conclusions: This study highlights the presence of S. aureus and MRSA in raw milk, underscoring the need for strengthened surveillance, improved hygiene practices, the use of molecular diagnostic tools, and proper heat treatments to reduce the public health risks associated with contaminated milk and its derivatives.