Antibiotics-Basel最新文献

Recently, the high proportion of methicillin-resistant Staphylococcus aureus infections worldwide has highlighted the urgent need for novel antibiotics to combat this crisis. The recent progress in computational techniques for use in health and medicine, especially artificial intelligence (AI), has created new and potential approaches to combat antibiotic-resistant bacteria, such as repurposing existing drugs, optimizing current agents, and designing novel compounds. Halicin was previously used as a diabetic medication, acting as a c-Jun N-terminal protein kinase (JNK) inhibitor, and has recently demonstrated unexpected antibacterial activity. Although previous efforts have highlighted halicin's potential as a promising antibiotic, evidence regarding its effectiveness against clinical strains remains limited, with insufficient proof of its clinical applicability. In this study, we sought to investigate the antibacterial activity of halicin against MRSA clinical strains to validate its clinical applicability, and a C. elegans model infected by MRSA was employed to evaluate the in vivo effect of halicin against MRSA. Our findings revealed the antibacterial activity of halicin against methicillin-resistant S. aureus clinical strains with MICs ranging from 2 to 4 µg/mL. Our study is also the first work to evaluate the in vivo effect of halicin against S. aureus using a C. elegans model, supporting its further development as an antibiotic.

Objectives: In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly Prevotella intermedia, induce severe neutrophilic inflammation. In addition, we aimed to test the efficacy of macrolides, which has not been resolved in the neutrophilic inflammation induced by P. intermedia. Methods: NCl-H292 human airway epithelial cells were pre-incubated with clarithromycin for 2 h before incubation with P. intermedia supernatants. Then, C-X-C motif chemokine ligand 8 (CXCL8) transcription and interleukin (IL)-8 production were measured. To elucidate the signaling pathway, mitogen-activated protein kinase inhibitors were added to the cell culture, and the cells were subjected to Western blotting. Results:P. intermedia supernatants promoted CXCL8 transcription and IL-8 production, and the reactions were significantly suppressed by clarithromycin pretreatment. Only trametinib, the selective mitogen-activated extracellular signal-regulated kinase inhibitor, downregulated CXCL8 transcription and IL-8 production. Furthermore, Western blotting revealed that stimulation with P. intermedia supernatants specifically induces extracellular signal-regulated kinases (ERK) 1/2 phosphorylation, which is suppressed by clarithromycin pretreatment. Notably, the interference analysis revealed that ERK3 might be dispensable for IL-8 production under the stimulation of P. intermedia supernatants. Conclusions: Our results provide new insight into the mechanism underlying P. intermedia-induced production of IL-8 from human airway epithelial cells. Furthermore, macrolides might have therapeutic potential in regulating periodontal pathogen-induced neutrophilic inflammation in the lungs.

Antimicrobial resistance (AMR) is a concern in the dairy industry. Recent studies have indicated that bedding serves as a reservoir for antimicrobial-resistant bacteria and antimicrobial-resistance genes (ARGs), while silage has been proposed as another possible source. The impact of AMR in dairy farming can be significant, resulting in decreased productivity and economic losses for farmers. Several studies have highlighted the safety implications of AMR bacteria and genes in bedding and silage, emphasizing the need for further research on how housing, bedding, and silage management affect AMR in farm environments. Exposure to sub-lethal concentrations of antibiotics, such as those from contaminated bedding and silage, can prompt bacteria to develop resistance mechanisms. Thus, even if antimicrobial usage is diminished, ARGs may be maintained in the dairy farm environment. By implementing proactive measures to tackle AMR in dairy farming, we can take steps to preserve the health and productivity of dairy cattle while also protecting public health. This involves addressing the prudent use of antibiotics during production and promoting animal welfare, hygiene, and management practices in bedding and farm environments to minimize the risk of AMR development and spread. This narrative review compiles the growing research, positioning the contribution of bedding and silage to the prevalence and dissemination of AMR, which can elicit insights for researchers and policymakers.

Objectives: Campylobacter spp. remain a leading cause of bacterial gastroenteritis worldwide, with resistance to antibiotics posing significant challenges to treatment and public health. This study examines profiles in antimicrobial resistance (AMR) for Campylobacter isolates from human and animal sources over the past decade. Methods: We conducted a comprehensive review of resistance data from studies spanning ten years, analyzing profiles in resistance to key antibiotics, ciprofloxacin (CIP), tetracycline (TET), erythromycin (ERY), chloramphenicol (CHL), and gentamicin (GEN). Data were collated from various regions to assess global and regional patterns of resistance. Results: The analysis reveals a concerning trend of increasing resistance patterns, particularly to CIP and TET, across multiple regions. While resistance to CHL and GEN remains relatively low, the high prevalence of CIP resistance has significantly compromised treatment options for campylobacteriosis. Discrepancies in resistance patterns were observed between human and animal isolates, with variations across different continents and countries. Notably, resistance to ERY and CHL showed regional variability, reflecting potential differences in antimicrobial usage and management practices. Conclusions: The findings underscore the ongoing challenge of AMR in Campylobacter, highlighting the need for continued surveillance and research. The rising resistance prevalence, coupled with discrepancies in resistance patterns between human and animal isolates, emphasize the importance of a One Health approach to address AMR. Enhanced monitoring, novel treatment strategies, and global cooperation are crucial for mitigating the impact of resistance and ensuring the effective management of Campylobacter-related infections.

The discovery of antibiotics revolutionized modern medicine, effectively treating bacterial infections that were once fatal [...].

Background/objectives: The implementation of information quality value stream maps (IQ-VSMs) in food animal production systems can increase our understanding of the opportunities and challenges when using laboratory testing for antimicrobial resistance (AMR) to support antimicrobial stewardship (AMS). Our objectives were to (1) explore the implementation of information quality value stream mapping as a continuous improvement tool to inform decisions for bovine respiratory disease (BRD) management and AMS and (2) apply the information quality dimensions to identified Kaizen opportunities for the integration of laboratory data into BRD management systems to assess the appropriateness of BRD treatment plans in western Canadian feedlot production.

Methods: A 'Current State' IQ-VSM outlined the processes, available information, information processing steps, and control decisions contributing to BRD management and treatment in commercial western Canadian feedlots, recognizing that laboratory BRD pathogens and AMR data are typically not part of BRD management.

Results: The 'Future State' IQ-VSM incorporated Kaizen opportunities for improvement, including (i) the strategic collection of respiratory samples from representative samples of calves for laboratory analysis, regardless of clinical BRD status, (ii) compilation of laboratory data at the pen and feedlot levels, and (iii) analysis of pen- and feedlot-level laboratory data to inform the veterinarian's assessment of the appropriateness of current BRD treatment plans.

Conclusions: The IQ-VSMs provided a valuable framework to visualize the integration of BRD pathogen and AMR laboratory data to support AMS and address any potential future testing requirements.

Background/objectives: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno.

Methods: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ''Ruggi D'Aragona'' Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system.

Results: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems.

Conclusions: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.

(1) Background: The aim of this study was to evaluate the safety of intraoperative cell salvage (ICS) during reimplantation in the two-stage revision of septic hip arthroplasties. (2) Methods: As part of an internal quality control study, blood cultures were taken from the processed ICS blood during reimplantation and examined for possible bacterial load (study group). Due to a high rate of bacterial detection with uncertain clinical significance, consecutive ICS samples were also examined from patients undergoing aseptic revision hip arthroplasty (control group). Microbiological samples, patient and surgical characteristics and the follow-up data were analyzed retrospectively. (3) Results: 9 out of 12 (75%) patients in the study group and 5 out of 8 (63%) patients in the control group had positive ICS blood cultures. There was no significant difference between the groups (p = 0.642). The initial pathogens causing the periprosthetic joint infection (PJI) were not detected, but the bacterial spectrum resembled skin flora, with a high proportion of coagulase-negative staphylococci. No complications due to possible bloodstream-associated infections were observed. In summary, the detected pathogens were interpreted as contamination without clinical significance. (4) Conclusions: ICS in the context of reimplantation was considered a safe and recommendable procedure to optimize patient blood management.

Background/Objectives. The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen, causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit the growth or impair the survival of bacterial pathogens. Given their large structural and chemical diversity, as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against Gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin-resistant S. aureus (MRSA) and the multi-drug-resistant community-acquired strain USA300LAC. Methods. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Results/Conclusions. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 μg/mL), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane-associated mechanism of action.

Background: Streptococcus mutans is a leading causative agent of dental caries and exerts pathogenicity by forming biofilms. Dental caries continues to be a significant public health issue worldwide, affecting an estimated 2.5 billion people, showing a 14.6% increase over the past decade. Herein, the antibacterial potential of Chlorophyllin extracted from Spinacia oleracea was evaluated against biofilm-forming S. mutans via in vitro and in silico studies.

Methodology: The antimicrobial activity of chlorophyllin extract against S. mutans isolates was tested using the agar well diffusion method. Chlorophyllin extract was also tested against biofilm-forming isolates of S. mutans. Chlorophyllin was docked with the antigen I/II (AgI/II) protein of S. mutans to evaluate its antimicrobial mechanism. The chemical structure and canonical SMILES format of Chlorophyllin were obtained from PubChem. Additionally, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses of Chlorophyllin were performed using ADMETlab 2.0 to assess its pharmacokinetic properties.

Results: An agar well diffusion assay revealed that all S. mutans isolates were susceptible to Chlorophyllin extract and showed a variety of inhibition zones ranging from 32 to 41 mm. Chlorophyllin reduces the biofilm strength of four isolates from strong to moderate and six from strong to weak. The antibiofilm potential of Chlorophyllin was measured by a reduction in the number of functional groups observed in the Fourier Transform Infrared Spectrometer (FTIR) spectra of the extracellular polymeric substance (EPS) samples. Chlorophyllin showed binding with AgI/II proteins of S. mutans, which are involved in adherence to the tooth surface and initiating biofilm formation. The ADMET analysis revealed that the safety of Chlorophyllin exhibited favorable pharmacokinetic properties.

Conclusions: Chlorophyllin stands out as a promising antibacterial and antibiofilm agent against biofilm-forming S. mutans, and its safety profile highlights its potential suitability for further investigation as a therapeutic agent.