Antibiotics-Basel最新文献

Background: Wastewater is a major source of Antibiotic-Resistant Bacteria (ARB) and a hotspot for the exchange of Antibiotic-Resistant Genes (ARGs). The occurrence of Carbapenem-Resistant Bacteria (CRB) in wastewater samples is a major public health concern. Objectives: This study aimed to analyze Antibiotic resistance in bacteria from wastewater sources in Pakistan. Methods: We analyzed 32 bacterial isolates, including 18 Escherichia coli, 4 Klebsiella pneumoniae, and 10 other bacterial isolates using phenotypic antibiotic susceptibility assay and whole-genome sequencing. This study identified the ARGs, plasmid replicons, and integron genes cassettes in the sequenced isolates. One representative isolate was further sequenced using Illumina and Oxford nanopore sequencing technologies. Results: Our findings revealed high resistance to clinically important antibiotics: 91% of isolates were resistant to cefotaxime, 75% to ciprofloxacin, and 62.5% to imipenem, while 31% showed non-susceptibility to gentamicin. All E. coli isolates were resistant to cephalosporins, with 72% also resistant to carbapenems. Sequence analysis showed a diverse resistome, including carbapenamases (blaNDM-5, blaOXA-181), ESBLs (blaCTX-M-15, blaTEM), and AmpC-type β-lactamases (blaCMY). Key point mutations noticed in the isolates were pmrB_Y358N (colistin) and ftsI_N337NYRIN, ftsI_I336IKYRI (carbapenem). The E. coli isolates had 11 different STs, with ST410 predominating (28%). Notably, the E. coli phylogroup A isolate 45EC1, (ST10886) is reported for the first time from wastewater, carrying blaNDM-5, blaCMY-16, and pmrB_Y358N with class 1 integron gene cassette of dfrA12-aadA2-qacEΔ1 on a plasmid-borne contig. Other carbapenamase, blaNDM-1 and blaOXA-72, were detected in K. pneumoniae 22EB1 and Acinetobacter baumannii 51AC1, respectively. The integrons with the gene cassettes encoding antibiotic resistance, and the transport and bacterial mobilization protein, were identified in the sequenced isolates. Ten plasmid replicons were identified, with IncFIB prevalent in 53% of isolates. Combined Illumina and Oxford nanopore sequencing revealed blaNDM-5 on an IncFIA/IncFIC plasmid and is identical to those reported in the USA, Myanmar, and Tanzania. Conclusions: These findings highlight the environmental prevalence of high-risk and WHO-priority pathogens with clinically important ARGs, underscoring the need for a One Health approach to mitigate ARB isolates.

The presence of antibiotic-resistant Escherichia coli in food is a serious and persistent problem worldwide. In this study, 68 E. coli strains isolated from Thai food samples were characterized. Based on antibiotic susceptibility assays, 31 of these isolates (45.59%) showed multiple antibiotic resistance (MAR) index values > 0.2, indicating high exposure to antibiotics. Among these, strain CM24E showed the highest resistance (it was resistant to ten antibiotics, including colistin and imipenem). Based on genome sequencing, we identified four isolates (namely, CF25E, EF37E, NM10E1, and SF50E) with novel Achtman-scheme multi-locus sequence types (STs) (ST14859, ST14866, ST14753, and ST14869, respectively). Clermont phylogrouping was used to subtype the 68 researched isolates into five Clermont types, mainly A (51.47%) and B1 (41.18%). The bla_EC gene was found only in Clermont type A, while the bla_EC-13 gene was predominant in Clermont type B1. A correlation between genotypes and phenotypes was found only in Clermont type B1, which showed a strong positive correlation between the presence of an afa operon and yersiniabactin-producing gene clusters with the colistin resistance phenotype. Strain SM47E1, of Clermont type B2, carried the highest number of predicted virulence genes. In summary, this study demonstrates the pressing problems posed by the prevalence and potential transmission of antimicrobial resistance and virulence genes in the food matrix.

Background/Objectives: The rose myrtle Rhodomyrtus tomentosa is a medicinal plant used in traditional Asian medicine. The active compound in R. tomentosa leaf extracts is rhodomyrtone, a chiral acylphloroglucinol. Rhodomyrtone exhibits an impressive breadth of activities, including antibacterial, antiviral, antiplasmodial, immunomodulatory, and anticancer properties. Its antibacterial properties have been extensively studied. Methods: We performed a comprehensive literature review on rhodomyrtone and summarized the current knowledge about this promising acylphloroglucinol antibiotic and its diverse functions in this review. Results: Rhodomyrtone shows nano to micromolar activities against a broad range of Gram-positive pathogens, including multidrug-resistant clinical isolates, and possesses a unique mechanism of action. It increases membrane fluidity and creates hyperfluid domains that attract membrane proteins prior to forming large membrane vesicles, effectively acting as a membrane protein trap. This mechanism affects a multitude of cellular processes, including cell division and cell wall synthesis. Additionally, rhodomyrtone reduces the expression of inflammatory cytokines, such as TNF-α, IL-17A, IL1β, and IL8. Generally showing low toxicity against mammalian cells, rhodomyrtone does inhibit the proliferation of cancer cell lines, such as epidermal carcinoma cells. The primary mechanism behind this activity appears to be the downregulation of adhesion kinases and growth factors. Furthermore, rhodomyrtone has shown antioxidant activity and displays cognitive effects, such as decreasing depressive symptoms in mice. Conclusions: Rhodomyrtone shows great promise as therapeutic agent, mostly for antibacterial but also for diverse other applications. Yet, bottlenecks such as resistance development and a better understanding of mammalian cell toxictiy demand careful assessment.

Background: Extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing Enterobacterales and Acinetobacter spp. pose significant challenges as nosocomial pathogens, demonstrating resistance against various antimicrobials. Their presence in food suggests that hospital kitchens could serve as antibiotic resistance reservoirs leading to patients' infection.

Objectives: The aim of this study was to assess the prevalence and characteristics of β-lactam-resistant strains of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter spp. isolated from the kitchen environment and from the staff of two Greek hospitals.

Methods: Strains were recovered after selective isolation with β-lactams and were identified with MALDI-TOF MS. Antimicrobial susceptibility and presence of common β-lactamase genes were evaluated. Protein profiles were examined to analyze potential relationships of the strain with those from hospital patients. E. coli strains were further categorized into phylogenetic groups.

Results: The overall prevalence in the kitchen environment was 4.5%, 1.5%, and 15.0% for E. coli, K. pneumoniae, and Acinetobacter spp., respectively, whereas the prevalence of Acinetobacter spp. in human skin was 4.0%. Almost all strains were multidrug-resistant. All E. coli strains were ESBL producers and belonged to phylogroups A and B1. All K. pneumoniae and seven Acinetobacter strains were carbapenemase-producers. A protein profile analysis showed relatedness between chicken and kitchen environment strains, as well as between kitchen environment and patient strains originated either from the same or from different hospitals.

Conclusions: The results suggest that hospital kitchens may act as important pathogen hotspots contributing to the circulation of resistant strains in the hospital environment.

Background/objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations.

Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany).

Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed.

Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes.

Background: Beef burgers are perishable meat products, and to extend their shelf life, EU Regulation 1129/11 permits the use of certain additives. Objectives: However, given the concerns of health-conscious consumers and the potential toxicity of synthetic substances, this study aimed to explore the use of fennel waste extracts as natural preservatives. Methods: This study characterized the bioactive compounds (phenolic content), the antioxidant activity (ABTS⁺ and DPPH assay), and the antimicrobial properties (against Salmonella enterica serotype Enteritidis, Escherichia coli, Staphylococcus aureus, Bacillus cereusi, and Pseudomonas aeruginosa) of different fennel waste extracts (LF, liquid fraction; SF, solid fraction and PF, pellet fraction). Additionally, the potential use of the best fennel extract was evaluated for its impact on beef burger shelf life (up to 18 days at 4 ± 1 °C) in terms of microbiological profile, pH, and activity water (a_w). Results: The PF extract, which was rich in flavones, hydroxybenzoic, and hydroxycinnamic acids, demonstrated the highest antioxidant and antimicrobial activities. Microbiological analyses on beef burgers with PF identified this extract as a potential antimicrobial substance. The a_w and pH values did not appear to be affected. Conclusions: In conclusion, fennel extracts could be proposed as natural compounds exploitable in beef burgers to preserve their quality and extend their shelf-life.

Periprosthetic joint infections are still a challenge in orthopedics and traumatology. Nowadays, genomics comes to the aid of diagnosis and treatment, in addition to traditional methods. Recently, a key role of the intestinal microbiota has been postulated, and great efforts are aimed at discovering its interconnection, which shows to be at different levels. Firstly, the gut microbiome influences the immune system through the gut-associated lymphoid tissue (GALT). A balanced microbiome promotes a strong immune response, which is essential to prevent all local and systemic infections, including PJI. Thus, a dysbiosis, i.e., the disruption of this system, leads to an imbalance between the various strains of microorganisms co-existing in the gut microbiome, which can result in a weakened immune system, increasing susceptibility to infections, including PJI. Additionally, the dysbiosis can result in the production of pro-inflammatory mediators that enter the systemic circulation, creating a state of chronic inflammation that can compromise the immune system's ability to fend off infections. Furthermore, the microbiome maintains the integrity of the gut barrier, preventing the translocation of harmful bacteria and endotoxins into the bloodstream; dysbiosis can compromise this protective "wall". In addition, the gut microbiome may harbor antibiotic-resistance genes; during antibiotic treatment for other infections or prophylaxis, these genes may be transferred to pathogenic bacteria, making the treatment of PJI more difficult. In this complex landscape, next-generation sequencing (NGS) technology can play a key role; indeed, it has revolutionized the study of the microbiome, allowing for detailed and comprehensive analysis of microbial communities. It offers insights into the functional potential and metabolic capabilities of the microbiome, studies the collective genome of the microbiome directly from environmental samples sequencing DNA without isolating individual organisms, analyzes the RNA transcripts to understand gene expression and functional activity of the microbiome, analyzes the RNA transcripts to understand gene expression and functional activity of the microbiome, investigates the metabolites produced by the microbiome and studies the entire set of proteins produced by the microbiome. NGS technology, the study of the micromyoma and its implications in the field of orthopedic trauma are innovative topics on which few publications are yet to be found in the international scientific literature. The costs are still high, the focus of research is maximum, and it will certainly change our approach to infections. Our study is an up-to-date review of the hot topic application of NGS in the study and investigation of periprosthetic infections and the microbiome.

Background: The oral cavity is an important but often overlooked reservoir for Staphylococcus aureus. The effective control and prevention of S. aureus colonization and infection in the oral and maxillofacial regions are crucial for public health. Fluoride is widely used in dental care for its remineralization and antibacterial properties. However, its effectiveness against S. aureus has not been thoroughly investigated. Objectives: This study aimed to evaluate the potential of combining sodium fluoride (NaF) with compounds to enhance its antibacterial and antibiofilm effects against S. aureus. Method: We found that a urea derivative significantly enhances the efficacy of fluoride by promoting the retention of fluoride ions within the cells. The synergistic antibacterial and antibiofilm effects of BPU with NaF were confirmed through various assays, including checkerboard assays, time-kill assays, and growth curve analysis. These findings were further supported by additional methods, including transmission electron microscopy (TEM), in silico simulations, and gene overexpression studies. Results: These findings suggest that targeting fluoride ion membrane exporters could enhance antibacterial efficacy. When combined with fluoride, 1,3-Bis [3,5-bis(trifluoromethyl)phenyl]urea (BPU) showed increased effectiveness in inhibiting S. aureus growth and reducing established biofilms. Conclusions: This novel combination represents a promising therapeutic strategy for treating biofilm-associated S. aureus infections, offering a new strategy in oral healthcare. To fully evaluate the clinical potential of this synergistic therapy, further in vivo studies are essential.

Bacteria have evolved and continue to change in response to environmental stressors including antibiotics. Antibiotic resistance and the ability to form biofilms are inextricably linked, requiring the continuous search for alternative compounds to antibiotics that affect biofilm formation. One of the latest drug classes is boron-containing compounds. Over the last several decades, boron has emerged as a prominent element in the field of medicinal chemistry, which has led to an increasing number of boron-containing compounds being considered as potential drugs. The focus of this review is on the developments in boron-containing organic compounds (BOCs) as antimicrobial/anti-biofilm probes and agents.

This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% fT_>MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m² was 8 g. The median age was 74 years (interquartile range (IQR) 57-82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% fT_>MIC occurred in 86% of the patients and decreased to 45% when a target of 100% fT_>4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion.