Antibiotics-Basel最新文献

Background/Objectives: The global emergence of carbapenem resistance is a major public health concern. Campylobacter jejuni and Campylobacter coli, key zoonotic agents causing human campylobacteriosis, are mainly isolated from poultry, their primary host. Their increasing resistance in animals and humans highlights the risk of gene transfer. This study investigates the molecular mechanisms of carbapenem resistance in 287 avian Campylobacter spp. isolates from Tunisia within a One Health approach. Methods: Antibiotic susceptibility of 287 carbapenem-resistant isolates, including 147 C. jejuni and 140 C. coli, was determined according to CLSI. All isolates were screened by PCR for genes encoding the most reported carbapenemases, including VIM, IMP, NDM and OXA-48. Eleven multidrug-resistant (MDR)/carbapenem-resistant C. coli isolates were selected to determine their clonal lineage by Multilocus sequence typing (MLST). Results: All isolates were susceptible to imipenem, but resistance to meropenem and ertapenem were observed in 60.71% and 35.71% of C. coli isolates, respectively, versus 13.6% in C. jejuni for each antibiotic. The bla_VIM, bla_NDM and bla_OXA-48 genes were detected in 15, 8, and 19 of the 20 C. jejuni isolates, respectively. However, for C. coli, 53, 12, and 15 isolates harbored bla_VIM, bla_NDM and bla_OXA-48 genes, respectively. The eleven (MDR)/carbapenem-resistant C. coli isolates belonged to a unique ST sequence type ST13450. Conclusions: We report for the first time the emergence of bla_VIM, bla_NDM, and bla_OXA-48 genes in Campylobacter spp. isolates of poultry origin highlighting possible horizontal transfer of these genes to pathogenic Gram-negative bacteria of the poultry's microbiota.

Background/objectives: Studies evaluating the longitudinal impact (beyond a decade) of antibiotic stewardship programs (ASPs) on the volume/quality of antibiotic prescriptions, as well as the impact on antibiotic resistance, are lacking. Since 2008, the ASP at Singapore General Hospital has implemented various strategies in the following phases: (1) initiation, (2) expansion, (3) optimisation, and (4) innovation. In this study, we aim to evaluate the volume/quality of antibiotic prescribing and susceptibility trends of clinically significant Gram-negative bacilli (GNBs), along with the evolution of ASP strategies over time. Methods: We conducted a single-centre, retrospective observational study from 2011 to 2024. Antibiotic consumption, appropriateness, and susceptibility trends of six GNBs to seven commonly used antibiotics were analysed using the Kendall tau test to identify potential monotonic trends based on aggregated rather than patient-level data. Results: We demonstrated sustained improvement in appropriateness of seven broad-spectrum IV antibiotics, accompanied by significant reductions in IV ciprofloxacin, cefepime, and ertapenem use (p < 0.05). Hospital-wide susceptibility of six GNBs to all evaluated antibiotics improved significantly (p < 0.05), except for E. coli's susceptibility to ertapenem and Enterobacterales's susceptibility to ciprofloxacin. Conclusions: With an evolving, multi-pronged stewardship approach, antibiotic prescribing and GNB susceptibility to most antibiotics have improved. In a rapidly evolving healthcare landscape, ASPs must remain agile, continually refining priorities and employing innovative strategies.

Background: Antimicrobial resistance (AMR) is one of the most significant global health threats of the 21st century, endangering healthcare systems worldwide as a silent pandemic. Despite the globally recognized role of pharmacists as antimicrobial stewards, their involvement remains limited in antimicrobial stewardship (AMS) endeavors in Pakistan.

Methods: By utilizing the Straussian grounded theory methodology, this study aimed to develop a pharmacist-centered novel AMS approach for healthcare in Pakistan in order to enhance the engagement of pharmacists in AMS and reduce the burden of AMR in Pakistan. Through 13 semi-structured in-depth interviews with pharmacists and AMS experts, this study explored the facilitators and obstacles faced by pharmacists in Pakistan pertaining to their participation in AMS.

Results: The findings highlighted the underutilization of pharmacists in AMS owing to persistent policy, institutional, and resource-level barriers. Several facilitators were also identified, including institutional ownership and pharmacist-prescriber-patient (3P) communication. The evidence generated informed the development of the pharmacist-centered novel AMS approach, which recommends extending AMS policy support to pharmacists, improving One Health interdisciplinary collaborations, promoting pharmacist-led behavior change campaigns, granting prescribing rights to pharmacists for minor ailments, and advancing AMS trainings and education.

Conclusions: Formally integrating pharmacists into AMS efforts is the need of the hour to contain the consequences of AMR in Pakistan.

Urinary tract infections, as one of the most common infectious diseases, contribute substantially to the global healthcare burden, particularly due to the rising prevalence of resistant bacterial strains such as Klebsiella pneumoniae. Background/Objectives: The aim was to investigate the prevalence of urinary tract infection pathogens among hospitalized patients at Saint Apostol Luka Hospital in Doboj during the period 2021-2023. Methods: This retrospective cross-sectional study was conducted at Saint Apostol Luka Hospital, Doboj, Republic of Srpska, Bosnia and Herzegovina. Data from the Department of Microbiology were analyzed for the period 2021-2023, including patients with positive urine cultures (≥10³ CFU/mL) of a single uropathogen. Bacterial identification and susceptibility testing were performed according to EUCAST standards, and statistical analysis was carried out using SPSS v24. Results: Escherichia coli was the most frequent isolate (29.2%), followed by Klebsiella spp. (24.2%) and Enterococcus spp. (19.8%). A significant rise in K. pneumoniae prevalence and resistance to multiple antibiotics-including β-lactams, carbapenems, aminoglycosides, and colistin-was observed during the study period. Conclusions: This study revealed that E. coli and Klebsiella spp. were the leading uropathogens, with notable differences in distribution by sex, age, and hospital department. A marked rise in multidrug resistance, particularly among K. pneumoniae, was observed across the study period. These findings underscore the urgent need for continuous surveillance and stronger antimicrobial stewardship to curb resistance trends.

Antimicrobial resistance remains one of the most urgent challenges in modern medicine, demanding innovative research tools for understanding and combating bacterial adaptation. Microfluidic technologies enable precise control over experimental conditions, single-cell resolution, and high-throughput analysis, offering unique advantages over traditional microbiological methods. This review summarizes recent (2020-2025) developments in the application of microfluidics to antibiotic resistance research, emphasizing approaches used in fundamental studies rather than diagnostic implementations. The discussed technologies are grouped according to their primary research focus: (i) microfluidic cultivation and screening of antibiotic-producing microorganisms; (ii) tools for antibiotic screening and mechanistic studies, and (iii) models for studying microbial stress responses and resistance development. Collectively, these approaches provide unprecedented insight into antibiotic action, resistance evolution, and microbial physiology. Continued development and integration of microfluidics with complementary analytical tools will further accelerate the discovery of novel antimicrobials and rational design of combination therapies, ultimately bridging the gap between fundamental microbiology and translational applications in antimicrobial resistance research.

Background/Objectives: The inappropriate use of veterinary medicines in feed for food-producing animals can compromise food safety. Intensive animal production is associated with the inappropriate use of antibiotics in feed, at subtherapeutic concentrations, to promote animal growth. It is therefore crucial to develop an effective multi-detection method to ensure that this feed complies with the requirements of European Commission Regulations. This control is essential to ensure consumer protection, as adequate supervision contributes to reducing antimicrobial resistance, a growing concern worldwide. Methods: A literature search was conducted using scientific databases, namely PubMed, ScienceDirect, Scopus and Google Scholar, as well as European Union Regulations. Results: It was observed that the most used standard solution solvents are methanol, acetonitrile, ultrapure water, or mixtures of these solvents. For extraction, the most frequently used solvents include trichloroacetic acid combined with McIlvaine buffer or with acetonitrile, and acetonitrile or methanol combined with formic acid or with ethylenediaminetetraacetic acid disodium (Na₂EDTA). For extraction and purification of the analyte, several steps were verified, such as solid-phase extraction (SPE), dispersive solid-phase extraction (d-SPE), liquid-liquid extraction (LLE), Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS), protein precipitation through freezing and dilution prior to analysis. Liquid chromatography coupled with mass spectrometry is the preferred choice, especially for multiple detection methods. Conclusions: Based on this data, the foundation is established for the development of an appropriate method for the simultaneous extraction of multiple classes of antibiotics, which is applicable to feed different food-production animals.

Background/Objectives: Clostridioides difficile is an anaerobic Gram-positive bacterium and a leading cause of healthcare-associated diarrhea. In this study, C. difficile strains isolated from human patients with diarrhea and companion dogs in South Korea were compared to reveal the potential transmission between different hosts. Methods: A total of 304 C. difficile strains were isolated, including 217 human isolates and 87 dog isolates. The strains were characterized for antimicrobial susceptibility and genotypic features, including antimicrobial resistant genes and toxin genes. In addition, comparative genomic analyses were performed to investigate their genetic relatedness. Results: Although antimicrobial susceptibility test revealed no significant difference in overall resistance, human isolates had higher resistance to moxifloxacin and cefotetan, while dog isolates showed slightly higher resistance to clindamycin and ampicillin. Resistance to vancomycin (3.7%), rifampin (8.3%), and chloramphenicol (0.9%) was observed only in human isolates. Toxin genes (tcdA and tcdB) were found in 57.1% of human isolates and 43.7% of dog isolates, while binary toxin genes (cdtA and cdtB) were detected only in isolates from humans. Multilocus sequence typing (MLST) analysis identified 34 sequence types (STs) in human isolates and 16 in dog isolates. Among them, 15 STs were detected in the isolates from both origins; notably, ST203 and ST42 were the predominant taxa that were equally derived from humans and dogs. Although tcdA and tcdB have not been previously reported in ST203, they were detected in 7 out of 34 ST203 isolates. The whole genomes of 36 representative isolates belonging to ST42 and ST203 were classified according to the STs of the source origin. Conclusions: These results indicate that similar C. difficile strain populations are present in both humans and companion dogs, which is compatible with interspecies dissemination or circulation of shared strain populations, and may also reflect host adaptation.

Background/objectives: Drug efflux pumps represent a significant challenge that contributes to the development of antibiotic resistance in bacteria. This research aimed to evaluate the flavonoids apigenin, chrysin, glycitein, and hesperetin for their potential to inhibit efflux pumps in drug-resistant Escherichia coli.

Method: The antibacterial activity of the flavonoids was assessed using minimum inhibitory concentration (MIC) and modulation assays. Dye accumulation and efflux assays were performed to evaluate effects on efflux pump function, while membrane permeability and biofilm formation assays were also conducted. Molecular docking was used to examine interactions between the flavonoids and the AcrB efflux transporter.

Results: Although the flavonoids showed limited intrinsic antibacterial activity, they enhanced the effectiveness of erythromycin, ciprofloxacin, and clarithromycin against drug-resistant E. coli. Apigenin and hesperetin significantly increased dye accumulation and reduced dye efflux, indicating interference with substrate translocation through efflux pumps. All compounds exhibited no effect on inner membrane permeability, while apigenin, chrysin, and glycitein inhibited biofilm formation. Docking results showed that apigenin and chrysin bind favorably within the distal binding pocket of AcrB, forming hydrophobic and π-π interactions with key aromatic residues such as Phe610 and Phe628, with binding affinities of -8.8 to -8.9 kcal/mol.

Conclusions: The results suggest that apigenin and chrysin have promising efflux-pump inhibitory potential in drug-resistant E. coli, supporting their possible role as adjuvants to improve antibiotic efficacy.

Background: The efficiency of vermicomposting in reducing antibiotic resistance genes (ARGs) in dairy manure may be compromised by co-pollutants like arsenic (As) and microplastics. Specifically, plasmids serving as carriers and vectors of ARGs were largely distributed in this process. However, the impact of As and microplastics on plasmids carrying ARGs during vermicomposting is largely unknown. Methods: This study utilized a controlled experimental design and applied plasmid metagenomics to investigate the individual and combined effects of As and polyethylene terephthalate (PET) microplastics on plasmid-mediated ARG dynamics during vermicomposting. Results: We found that vermicomposting alone mainly enriched non-mobilizable plasmids, while PET microplastics selectively promoted conjugative and mobilizable plasmids, whereas As significantly increased all plasmid types. Moreover, both PET or As alone and combined exposure (PET and As) increased total ARG abundance, with their combination inducing synergistic ARG enrichment despite unchanged total plasmid abundance. Furthermore, co-occurrence network analysis combined with ARGs/plasmid ratio assessments demonstrated that As influences ARGs through co-selective pressure by enriching ARGs co-localized with As resistance genes (e.g., the ars operon) on plasmids while simultaneously promoting horizontal gene transfer (HGT) via activation of oxidative stress and SOS response pathways. In contrast, PET primarily facilitates ARG dissemination through a "metabolism-resistance" coupling strategy by enriching colonizing bacteria with PET-degrading capacity. Their co-exposure formed As-enrichment hotspots on PET microplastic surfaces, functioning as a "super-mixer" that selectively screened for superbugs carrying potent resistance mechanisms (e.g., bla_OXA-50 and mdtB/mdtE). Conclusions: This study provides the first plasmidome-level evidence of synergistic ARG propagation by As and PET microplastics during vermicomposting, highlighting mobile genetic elements' critical role in co-pollutant risk assessments.

Background/Objectives Plant lectins have emerged as potential antifungal molecules, where the carbohydrate recognition domain (CRD) is possibly the main mode of action of these proteins. Previously, we saw that the lectin extracted from the seeds of Dioclea violacea (DVL) has anti-candida activity against Candida krusei cells by acting to inhibit ergosterol biosynthesis, cell wall deformation, and deregulation of the redox system. Methods We have now confirmed this anti-candida activity by proteomic analysis, with the expression of proteins that show us how C. krusei cells respond to this treatment. Results A total of 395 proteins were identified: 142 proteins exclusively found in untreated C. krusei cells and 245 proteins exclusive to DVL-treated cells. Eight proteins were detected in both conditions. Six displayed positive accumulation (fold change > 1.5), one exhibited negative accumulation (fold change < 0.5). We observed the expression of proteins related to cell wall remodeling; alteration of energy metabolism, suggesting a metabolic adaptation to stress; oxidative stress was responded to through the expression of proteins with antioxidant action, in addition to identifying multidrug transport proteins that are often involved in the process of antifungal resistance and sterol transport to the membrane. Conclusions Our results show the complexity of adaptive responses of C. krusei cells to treatment with DVL, elucidating new mechanisms of resistance and paving the way for the development of more effective and innovative antifungal therapies.