Antibiotics-Basel最新文献

Antibiotic resistance is a growing public health challenge. Antimicrobial peptides (AMPs) effectively target microorganisms through non-specific mechanisms, limiting their ability to develop resistance. Therefore, the prediction and design of new AMPs is crucial. Recently, deep learning has spurred interest in computational approaches to peptide drug discovery. This study presents a novel deep learning framework for AMP classification, function prediction, and generation. We developed discoverAMP (dsAMP), a robust AMP predictor using CNN Attention BiLSTM and transfer learning, which outperforms existing classifiers. In addition, dsAMPGAN, a Generative Adversarial Network (GAN)-based model, generates new AMP candidates. Our results demonstrate the superior performance of dsAMP in terms of sensitivity, specificity, Matthew correlation coefficient, accuracy, precision, F1 score, and area under the ROC curve, achieving >95% classification accuracy with transfer learning on a small dataset. Furthermore, dsAMPGAN successfully synthesizes AMPs similar to natural ones, as confirmed by comparisons of physical and chemical properties. This model serves as a reliable tool for the identification of novel AMPs in clinical settings and supports the development of AMPs to effectively combat antibiotic resistance.

Antimicrobial stewardship is one of the cornerstones in the battle against antimicrobial resistance. Restrictive legislation aims to foster antimicrobial stewardship. Prophylactic prescription of antimicrobials is still a widespread practice in canine breeding management to prevent suspected infectious infertility. The aim of this study was to evaluate the efficacy of restrictive legislation in Germany (Veterinary Home Pharmacy Ordinance, TÄHAV) based on resistance profiles of common bacterial isolates from the vaginal tract by comparing the resistance situation before (time frame (TF1)) and after (TF2) its amendment. In total, results of 13,373 antimicrobial susceptibility tests of bacterial isolates of Escherichia coli (n = 5209), beta-hemolytic streptococci (n = 4010), and Staphylococcus (Staph.) intermedius group (n = 4154) derived from canine vaginal swabs were assessed. Antimicrobial susceptibility testing was performed on pure cultures using the broth microdilution method. Susceptibility to selected antimicrobials was evaluated. Susceptibility of Escherichia coli generally increased within TF2 with, however, a significant increase in the number of non-susceptible isolates to cefalexin (p < 0.0001). Beta-hemolytic streptococci exhibited good susceptibility to most antimicrobials. Susceptibility developed ambivalently within the Staphylococcus intermedius group. Despite an overall positive effect of increased susceptibility, an increase in non-susceptibility to single antimicrobials was detected, possibly indicating a need for refinement of the legislation.

Manuel Simões was included as a corresponding author in the original publication [...].

Objective: Multidrug-resistant, highly pathogenic Escherichia coli strains are the primary causative agents of intestinal and extraintestinal human diseases. The extensive utilization of antibiotics for farm animals has been identified as a contributing factor to the emergence and dissemination of E. coli strains that exhibit multidrug resistance and possess high pathogenic potential. Consequently, a significant research objective is to examine the genetic diversity of pathogenic E. coli strains and to identify those that may pose a threat to human health. Methods: In this study, we present the results of genome sequencing and analysis, as well as the physiological characterization of E. coli strain APEC 36, which was isolated from the liver of a broiler chicken with generalized colibacillosis. Results: We found that APEC 36 possess a number of mechanisms of antibiotic resistance, including antibiotic efflux, antibiotic inactivation, and antibiotic target alteration/replacement/protection. The most widely represented group among these mechanisms was that of antibiotic efflux. This finding is consistent with the strain's documented resistance to multiple antibiotics. APEC 36 has an extremely rare variant of the beta-lactamase CTX-M-169. Notwithstanding the multitude of systems for interfering with foreign DNA present in the strain, seven plasmids have been identified, three of which may possess novel replication origins. Additionally, qnrS1, which confers resistance to fluoroquinolones, was found to be encoded in the genome rather than in the plasmid. This suggests that the determinants of antibiotic resistance may be captured in the genome and stably transmitted from generation to generation. Conclusions: The APEC 36 strain has genes for toxins, adhesins, protectins, and an iron uptake system. The obtained set of genetic and physiological characteristics allowed us to assume that this strain has a high pathogenic potential for humans.

Background: The WHO Regional Office for Africa developed a Member States (MS)-endorsed regional strategy to fast-track the implementation of MS' national action plans (NAP) on Antimicrobial resistance (AMR). This study explored the perspectives of AMR's national focal points in MS on the implementation of the priority interventions of the regional strategy in their countries. Methods: An online survey consisting of ratings and discussions covering the implementation of the six priority interventions was conducted. Sums of the scores per priority intervention were obtained, and their percentage to the total possible scores were calculated to categorize the implementation as inadequate (0-25%), basic (26-50%), intermediate (51-75%), or advanced (76-100%). Results: Thirty-six of the forty-seven national AMR focal points responded to the survey between 12 November 2023 and 8 January 2024. The implementations were rated as 37-62% (basic-to-intermediate), with the multisectoral coordination and collaboration committee receiving the highest overall rating (62%, 421/684), while the promotion of sustainable investment for the NAP on AMR received the least overall rating (37%, 257/700). The focal points mainly recommended awareness campaigns, capacity building, and regulations and guidelines to improve the implementation of the AMR strategy. Conclusions: The survey revealed a need to enhance awareness campaigns, support the establishment and functioning of AMR evaluation and monitoring systems, and build the capacity of AMR staff with cost-benefit analysis and budgeting skills. It also showed the necessity to improve awareness and conduct education on AMR, streamline evidence generation through One Health Surveillance systems, integrate initiatives to reduce hospital-acquired infections in the antimicrobial stewardship programs, and enhance regulations and guidelines to optimize the use of antimicrobials.

Objective: An eucalyptus essential oil-based nanoemulsion was produced and evaluated for its antimicrobial properties against Streptococcus mutans and its cytotoxicity in the surface mucous cells of rabbits. Methods: The essential oil-based nanoemulsion was synthesized with two species of eucalyptus-Eucalyptus citriodora and Eucalyptus globulus-followed by physicochemical characterization and the determination of antimicrobial activity and cell viability. Subsequently, the mouthwash formulations (fluoride and fluoride-free) were functionalized with the nanoemulsion, and their in vitro antimicrobial actions were evaluated against S. mutans. Results: The nanoemulsion presented an average particle size of around 100 nm, a polydispersity index close to 0.3, a zeta potential between -19 and -30 mV, a pH close to 7, a spherical shape, and a cell viability above 50%. The antimicrobial activity analysis showed that the nanoemulsion was effective in the control of S. mutans. The mouthwashes functionalized with the nanoemulsion also presented bacteriostatic and bactericidal properties. Conclusions: The bio-based material produced with eucalyptus essential oil presented adequate physicochemical characteristics, with the potential to be used as an innovative material in preventive dentistry, contributing to the maintenance of oral and systemic health.

Background: Microplastic aging affects the dynamics of antibiotic resistance genes (ARGs) on microplastics, yet no review presents the effects of microplastic aging on the associated ARGs. Objectives: This review, therefore, aims to discuss the effects of different types of microplastic aging, as well as the other pollutants on or around microplastics and the chemicals leached from microplastics, on the associated ARGs. Results: It highlights that microplastic photoaging generally results in higher sorption of antibiotics and ARGs due to increased microplastic surface area and functional group changes. Photoaging produces reactive oxygen species, facilitating ARG transfer by increasing bacterial cell membrane permeability. Reactive oxygen species can interact with biofilms, suggesting combined effects of microplastic aging on ARGs. The effects of mechanical aging were deduced from studies showing larger microplastics anchoring more ARGs due to rough surfaces. Smaller microplastics from aging penetrate deeper and smaller places and transport ARGs to these places. High temperatures are likely to reduce biofilm mass and ARGs, but the variation of ARGs on microplastics subjected to thermal aging remains unknown due to limited studies. Biotic aging results in biofilm formation on microplastics, and biofilms, often with unique microbial structures, invariably enrich ARGs. Higher oxidative stress promotes ARG transfer in the biofilms due to higher cell membrane permeability. Other environmental pollutants, particularly heavy metals, antibacterial, chlorination by-products, and other functional genes, could increase microplastic-associated ARGs, as do microplastic additives like phthalates and bisphenols. Conclusions: This review provides insights into the environmental fate of co-existing microplastics and ARGs under the influences of aging. Further studies could examine the effects of mechanical and thermal MP aging on their interactions with ARGs.

Recently, the German Federal Institute for Medicines and Medical Products restricted the use of fosfomycin in transrectal biopsy of the prostate (TRBP). Accordingly, the need for other antibiotic agents for prophylaxis in TRBP is urgent since antibiotic prophylaxis is mandatory in accordance with these guidelines. After the restriction of the use of ciprofloxacin, and before the use of fosfomycin in Germany was falsely allowed, amoxicillin/clavulanic acid was evaluated as an alternative for antibiotic prophylaxis in TRBP. Regarding hospitalization for post-interventional infections, 359 patients at the Department of Urology of the University of Regensburg, at Caritas-St. Josef Medical Center as a single center, underwent TRBP between 2 July 2019 and 30 June 2020. Regarding antibiotic prophylaxis, the post-interventional hospitalization rate due to bacterial complications was relevant. Of the 359 patients, 10 (2.8%) had an infection requiring hospitalization post-TRBP. A total of 349 (97.2%) patients had no infection-related hospitalization. This corresponds to an incidence rate of only 2.8%. Referring to the previous infection rates under the now obsolete ciprofloxacin, amoxicillin/clavulanic acid can show a similar, if not tendentially even lower, risk of infection, and so this substance can be an alternative for antibiotic prophylaxis in TRBP. Another advantage is that, according to the WHO's AWaRe classification, amoxicillin/clavulanic acid is one of the so-called Access antibiotics. This study is limited as rectal swabs and urine cultures were not performed on every patient before TRBP.

Background: Antimicrobial consumption (AMC) data in Latin America are scarce and usually spread out across different sources used to make AMC calculations, making it difficult to both standardize and compare regions through similar time frames. The main objective was to analyze AMC trends in Social Security tertiary care hospitals in Costa Rica in the period spanning January 2017 to December 2021, using both the defined daily dose (DDD)/100 bed days and DDD/100 discharges. Methods: This is a retrospective observational study of antimicrobial consumption. Global consumption trends were calculated and expressed as DDD/100 bed days and DDD/100 discharges. Trends in antimicrobial consumption were analyzed using a simple linear regression model to determine potential differences in antimicrobial usage throughout the study's duration. Results: A statistically significant increase in the consumption expressed in DDD/100 discharges was observed in the following groups: carbapenems, 7.6% (trend: 64.68, p < 0.0001), trimethoprim-sulfamethoxazole: 12.6% (trend: 16.45, p < 0.0001), quinolones 9.4% (trend: 36.80, p = 0.02), vancomycin 2.0% (trend: 16.30, p = 0.03), echinocandins: 6.0% (trend: 15.17, p = 0.01) and azole antifungals: 12.10% (trend: 102.05, p < 0.0001). Additionally, a statistically significant increase of 10.30% in the consumption of azole antifungals expressed in DDD/100 bed days was observed (p = 0.0008). In contrast, a statistically significant decrease in consumption, expressed in DDD/100 discharges, was identified for cephalosporins -6.0% (p < 0.0001) and macrolides -16.5% (p < 0.0001). Macrolides also showed a downward trend in consumption, as expressed in DDD/100 bed days (-14.3%, p < 0.0001). According to World Health Organization (WHO) access, watch and reserve (AWaRe) classification trend analysis, only the reserve group showed a statistically significant upward change of 9.2% (p = 0.016). Conclusions: This five-year analysis demonstrated trends over time in overall antimicrobial consumption measured in DDD/100 bed days and DDD/100 discharge rates that correlate. In general, for all antimicrobials, after the implementation of antimicrobial stewardship programs (ASP), a downward trend is reported; in contrast, during the COVID-19 pandemic the AMC shows a general upward trend. The comparison between DDD/100 bed days and DDD/100 discharges allows for complementary comparisons to be made regarding antimicrobial exposure in a clinical setting.

Drug interactions are a significant and integral part of the concept of medication-related adverse events, whether referring to potential interactions or those currently observed in real-world conditions. The high global consumption of antibiotics and their pharmacokinetic and pharmacodynamic mechanisms make antibiotic-drug interactions a key element that requires continuous study due to their clinical relevance. In the present work, the current state of knowledge on antibiotic-drug interactions, which are less studied than other drug-drug interactions despite their frequent use in acute settings, has been consolidated and updated. The focus was on the interactions of the commonly used antibiotics in clinical practice, on the characteristics of the geriatric population susceptible to interactions, and on the impact of online drug interaction checkers. Additionally, strategies for optimizing the management of these interactions, including spacing out administrations, monitoring, or avoiding certain combinations, are suggested. Sustained research and careful monitoring are critical for improving antibiotic safety and efficacy, especially in susceptible populations, to enhance precision in managing antibiotic-drug interactions.