首页 > 最新文献

Antibiotics-Basel最新文献

英文 中文
Resilience of Loin Meat Microbiota and of Resistance Genes to a Chlortetracycline Treatment in Weaned Piglets. 断奶仔猪腰肉微生物群和抗性基因对金霉素治疗的恢复力
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-21 DOI: 10.3390/antibiotics13100997
Xavier C Monger, Linda Saucier, Alex-An Gilbert, Sophie Gosselin, Éric Pouliot, Sylvain Fournaise, Antony T Vincent

Objectives: This project studied the impact of a chlortetracycline treatment in weaning piglets on the taxonomy and antibiotic resistance gene (ARG) content of the microbiomes on carcasses and loins.

Methods: Two groups of piglets from two farrowing barns with either an average or a lower sanitary health status were used. Each group was divided in half: a control group and a treatment group receiving feed supplemented with 660 g of chlortetracycline per tonne for 21 days. The piglets then went through fattening and were sent to the abattoir when they reached the targeted slaughter weight.

Results: The microbiomes of the pig carcasses and loins were sampled, and DNA was extracted and sequenced with a whole-genome approach. The microbiomes of the carcasses differed depending on the farrowing barn source in both taxonomical composition and ARG content; however, the microbiomes on the loins were similar, regardless of the farrowing barn source and the treatment group.

Conclusions: While there were differences in the carcass microbiomes between treatments after processing by the abattoir, the loin microbiomes were consistent and unaffected by treatment with chlortetracycline or the sanitary status of the farrowing barn.

目标:本项目研究断奶仔猪金霉素治疗对胴体和腰部微生物组的分类和抗生素耐药基因(ARG)含量的影响:方法:使用两组来自卫生健康状况一般或较差的两个产仔舍的仔猪。每组分成两半:对照组和治疗组,治疗组在每吨饲料中添加 660 克金霉素,持续 21 天。仔猪随后进行育肥,达到目标屠宰重量后送往屠宰场:对猪胴体和猪腰的微生物组进行了采样,并采用全基因组方法提取了 DNA 并进行了测序。胴体的微生物组在分类组成和ARG含量方面因产仔舍来源而异;然而,无论产仔舍来源和处理组,猪腰的微生物组都是相似的:结论:屠宰场加工后,不同处理组的胴体微生物组存在差异,而里脊微生物组则一致,且不受金霉素处理或产仔舍卫生状况的影响。
{"title":"Resilience of Loin Meat Microbiota and of Resistance Genes to a Chlortetracycline Treatment in Weaned Piglets.","authors":"Xavier C Monger, Linda Saucier, Alex-An Gilbert, Sophie Gosselin, Éric Pouliot, Sylvain Fournaise, Antony T Vincent","doi":"10.3390/antibiotics13100997","DOIUrl":"https://doi.org/10.3390/antibiotics13100997","url":null,"abstract":"<p><strong>Objectives: </strong>This project studied the impact of a chlortetracycline treatment in weaning piglets on the taxonomy and antibiotic resistance gene (ARG) content of the microbiomes on carcasses and loins.</p><p><strong>Methods: </strong>Two groups of piglets from two farrowing barns with either an average or a lower sanitary health status were used. Each group was divided in half: a control group and a treatment group receiving feed supplemented with 660 g of chlortetracycline per tonne for 21 days. The piglets then went through fattening and were sent to the abattoir when they reached the targeted slaughter weight.</p><p><strong>Results: </strong>The microbiomes of the pig carcasses and loins were sampled, and DNA was extracted and sequenced with a whole-genome approach. The microbiomes of the carcasses differed depending on the farrowing barn source in both taxonomical composition and ARG content; however, the microbiomes on the loins were similar, regardless of the farrowing barn source and the treatment group.</p><p><strong>Conclusions: </strong>While there were differences in the carcass microbiomes between treatments after processing by the abattoir, the loin microbiomes were consistent and unaffected by treatment with chlortetracycline or the sanitary status of the farrowing barn.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Synergy of Machine Learning and Epidemiology in Addressing Carbapenem Resistance: A Comprehensive Review. 机器学习与流行病学在应对碳青霉烯类耐药性方面的协同作用:全面回顾。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-21 DOI: 10.3390/antibiotics13100996
Aikaterini Sakagianni, Christina Koufopoulou, Petros Koufopoulos, Georgios Feretzakis, Dimitris Kalles, Evgenia Paxinou, Pavlos Myrianthefs, Vassilios S Verykios

Background/objectives: Carbapenem resistance poses a significant threat to public health by undermining the efficacy of one of the last lines of antibiotic defense. Addressing this challenge requires innovative approaches that can enhance our understanding and ability to combat resistant pathogens. This review aims to explore the integration of machine learning (ML) and epidemiological approaches to understand, predict, and combat carbapenem-resistant pathogens. It examines how leveraging large datasets and advanced computational techniques can identify patterns, predict outbreaks, and inform targeted intervention strategies.

Methods: The review synthesizes current knowledge on the mechanisms of carbapenem resistance, highlights the strengths and limitations of traditional epidemiological methods, and evaluates the transformative potential of ML. Real-world applications and case studies are used to demonstrate the practical benefits of combining ML and epidemiology. Technical and ethical challenges, such as data quality, model interpretability, and biases, are also addressed, with recommendations provided for overcoming these obstacles.

Results: By integrating ML with epidemiological analysis, significant improvements can be made in predictive accuracy, identifying novel patterns in disease transmission, and designing effective public health interventions. Case studies illustrate the benefits of interdisciplinary collaboration in tackling carbapenem resistance, though challenges such as model interpretability and data biases must be managed.

Conclusions: The combination of ML and epidemiology holds great promise for enhancing our capacity to predict and prevent carbapenem-resistant infections. Future research should focus on overcoming technical and ethical challenges to fully realize the potential of these approaches. Interdisciplinary collaboration is key to developing sustainable strategies to combat antimicrobial resistance (AMR), ultimately improving patient outcomes and safeguarding public health.

背景/目的:碳青霉烯类耐药性破坏了抗生素最后一道防线的功效,对公共卫生构成了重大威胁。应对这一挑战需要创新的方法,这些方法可以增强我们对耐药病原体的了解和抗击耐药病原体的能力。本综述旨在探讨如何整合机器学习(ML)和流行病学方法,以了解、预测和抗击耐碳青霉烯类病原体。它探讨了如何利用大型数据集和先进的计算技术来识别模式、预测疫情爆发并为有针对性的干预策略提供信息:方法:综述了当前有关碳青霉烯耐药机制的知识,强调了传统流行病学方法的优势和局限性,并评估了 ML 的变革潜力。现实世界中的应用和案例研究用来证明将 ML 与流行病学相结合的实际好处。此外,还探讨了数据质量、模型可解释性和偏差等技术和伦理挑战,并提出了克服这些障碍的建议:结果:通过将 ML 与流行病学分析相结合,可以显著提高预测准确性、识别疾病传播的新模式以及设计有效的公共卫生干预措施。案例研究说明了跨学科合作在应对碳青霉烯类耐药性方面的益处,但必须应对诸如模型可解释性和数据偏差等挑战:结论:将 ML 与流行病学相结合,有望提高我们预测和预防耐碳青霉烯类感染的能力。未来的研究应侧重于克服技术和伦理挑战,以充分发挥这些方法的潜力。跨学科合作是制定可持续的抗菌药耐药性(AMR)防治策略的关键,最终将改善患者的治疗效果并保障公众健康。
{"title":"The Synergy of Machine Learning and Epidemiology in Addressing Carbapenem Resistance: A Comprehensive Review.","authors":"Aikaterini Sakagianni, Christina Koufopoulou, Petros Koufopoulos, Georgios Feretzakis, Dimitris Kalles, Evgenia Paxinou, Pavlos Myrianthefs, Vassilios S Verykios","doi":"10.3390/antibiotics13100996","DOIUrl":"https://doi.org/10.3390/antibiotics13100996","url":null,"abstract":"<p><strong>Background/objectives: </strong>Carbapenem resistance poses a significant threat to public health by undermining the efficacy of one of the last lines of antibiotic defense. Addressing this challenge requires innovative approaches that can enhance our understanding and ability to combat resistant pathogens. This review aims to explore the integration of machine learning (ML) and epidemiological approaches to understand, predict, and combat carbapenem-resistant pathogens. It examines how leveraging large datasets and advanced computational techniques can identify patterns, predict outbreaks, and inform targeted intervention strategies.</p><p><strong>Methods: </strong>The review synthesizes current knowledge on the mechanisms of carbapenem resistance, highlights the strengths and limitations of traditional epidemiological methods, and evaluates the transformative potential of ML. Real-world applications and case studies are used to demonstrate the practical benefits of combining ML and epidemiology. Technical and ethical challenges, such as data quality, model interpretability, and biases, are also addressed, with recommendations provided for overcoming these obstacles.</p><p><strong>Results: </strong>By integrating ML with epidemiological analysis, significant improvements can be made in predictive accuracy, identifying novel patterns in disease transmission, and designing effective public health interventions. Case studies illustrate the benefits of interdisciplinary collaboration in tackling carbapenem resistance, though challenges such as model interpretability and data biases must be managed.</p><p><strong>Conclusions: </strong>The combination of ML and epidemiology holds great promise for enhancing our capacity to predict and prevent carbapenem-resistant infections. Future research should focus on overcoming technical and ethical challenges to fully realize the potential of these approaches. Interdisciplinary collaboration is key to developing sustainable strategies to combat antimicrobial resistance (AMR), ultimately improving patient outcomes and safeguarding public health.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut Microbiota and New Microbiome-Targeted Drugs for Clostridioides difficile Infections. 肠道微生物群与治疗艰难梭菌感染的新型微生物靶向药物。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-20 DOI: 10.3390/antibiotics13100995
Ahran Lee, Jung Sik Yoo, Eun-Jeong Yoon

Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice.

艰难梭菌是抗生素相关性腹泻的主要致病菌,在临床环境中,艰难梭菌感染(CDI)可能导致危及生命的疾病。CDIs发病的大多数风险因素,即抗生素的使用、质子泵抑制剂的治疗、高龄和住院,都与肠道微生物群和相关代谢产物的菌群失调有关,因此,CDIs的治疗方案包括使肠道微生物群的组成正常化。在这篇综述中,首先介绍了 CDI 及其全球流行病学,回顾了与 CDI 相关的肠道微生物群特征及其代谢产物,并介绍了微生物群靶向治疗方案,美国食品药品管理局(U.S. FDA)最近批准将其作为一种新药,而不是一种医疗实践。
{"title":"Gut Microbiota and New Microbiome-Targeted Drugs for <i>Clostridioides difficile</i> Infections.","authors":"Ahran Lee, Jung Sik Yoo, Eun-Jeong Yoon","doi":"10.3390/antibiotics13100995","DOIUrl":"https://doi.org/10.3390/antibiotics13100995","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> is a major causative pathogen for antibiotic-associated diarrhea and <i>C. difficile</i> infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combinations of Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Extracts with Selected Antibiotics Against Antibiotic-Resistant Bacteria: Bioactivity and Phytochemistry. Terminalia bellirica (Gaertn.) Roxb.和 Terminalia chebula Retz.萃取物与部分抗生素的组合,可对抗耐抗生素细菌:生物活性和植物化学。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-19 DOI: 10.3390/antibiotics13100994
Gagan Tiwana, Ian Edwin Cock, Matthew James Cheesman

Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates the antibacterial activity of solvent extracts prepared using Terminalia bellirica and Terminalia chebula fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of T. bellirica and T. chebula showed substantial zones of inhibition (ZOIs) against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The activity against those bacteria was strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the T. bellirica methanolic extract showed noteworthy antibacterial activity against Escherichia coli and an extended spectrum β-lactamase (ESBL) E. coli strain (MIC values of 755 µg/mL for both). The aqueous T. bellirica and T. chebula extracts also inhibited Klebsiella pneumoniae growth (MIC values of 784 µg/mL and 556 µg/mL, respectively). The corresponding methanolic extracts also inhibited ESBL K. pneumoniae growth (MIC values of 755 µg/mL and 1509 µg/mL, respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Strong antagonism occurred when any of the extracts were mixed with polymyxin B. Liquid chromatography-mass spectroscopy (LC-MS) analysis of the extracts revealed several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities, suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study.

由于抗生素的过度使用和滥用,产生了抗菌素耐药性(AMR)。抗生素耐药性降低了标准治疗的效果,使某些感染难以控制,从而增加了发病率和死亡率。随着抗生素失去疗效,药用植物正引起越来越多的关注。本研究采用盘扩散法和肉汤微量稀释法评估了用贝母果和星云果制备的溶剂提取物对六种细菌病原体的抗菌活性。贝母果和星云果的水提取物和甲醇提取物对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA)显示出很大的抑制区(ZOIs)。对这些细菌的活性很强,最低抑菌浓度(MIC)从 94 µg/mL 到 392 µg/mL。此外,贝壳杉甲醇提取物对大肠杆菌和一种广谱β-内酰胺酶(ESBL)大肠杆菌菌株具有显著的抗菌活性(两者的 MIC 值均为 755 µg/mL)。水提取物 T. bellirica 和 T. chebula 也能抑制肺炎克雷伯氏菌的生长(MIC 值分别为 784 µg/mL 和 556 µg/mL)。相应的甲醇提取物也能抑制 ESBL 肺炎克雷伯菌的生长(MIC 值分别为 755 µg/mL 和 1509 µg/mL)。当提取物与参考抗生素结合使用时,可观察到 18 种相加作用。当任何一种提取物与多粘菌素 B 混合时,都会产生强烈的拮抗作用。提取物的液相色谱-质谱(LC-MS)分析发现了几种有趣的黄酮类化合物和单宁酸,包括 6-galloyl-glucose、1,2,6-trigalloyl-β-D-glucopyranose、6-O-[(2E)-3-苯基-2-丙烯酰基]-1-O-(3,4,5-三羟基苯甲酰基)-β-D-吡喃葡萄糖、没食子酸丙酯、没食子酸甲酯、桑吉宁 H4、金缕梅单宁、焦没食子醇、没食子酸、鞣花酸、诃子酸和诃子苷 II。在盐水虾试验中,所有提取物均无毒性。这种无毒性以及它们的抗菌活性表明,这些植物物种可能是很有希望的抗菌化合物来源,值得进一步研究。
{"title":"Combinations of <i>Terminalia bellirica</i> (Gaertn.) Roxb. and <i>Terminalia chebula</i> Retz. Extracts with Selected Antibiotics Against Antibiotic-Resistant Bacteria: Bioactivity and Phytochemistry.","authors":"Gagan Tiwana, Ian Edwin Cock, Matthew James Cheesman","doi":"10.3390/antibiotics13100994","DOIUrl":"https://doi.org/10.3390/antibiotics13100994","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates the antibacterial activity of solvent extracts prepared using <i>Terminalia bellirica</i> and <i>Terminalia chebula</i> fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of <i>T. bellirica</i> and <i>T. chebula</i> showed substantial zones of inhibition (ZOIs) against <i>Staphylococcus aureus</i> and methicillin-resistant <i>S. aureus</i> (MRSA). The activity against those bacteria was strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the <i>T. bellirica</i> methanolic extract showed noteworthy antibacterial activity against <i>Escherichia coli</i> and an extended spectrum β-lactamase (ESBL) <i>E. coli</i> strain (MIC values of 755 µg/mL for both). The aqueous <i>T. bellirica</i> and <i>T. chebula</i> extracts also inhibited <i>Klebsiella pneumoniae</i> growth (MIC values of 784 µg/mL and 556 µg/mL, respectively). The corresponding methanolic extracts also inhibited ESBL <i>K. pneumoniae</i> growth (MIC values of 755 µg/mL and 1509 µg/mL, respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Strong antagonism occurred when any of the extracts were mixed with polymyxin B. Liquid chromatography-mass spectroscopy (LC-MS) analysis of the extracts revealed several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities, suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetics of Vancomycin in Healthy Korean Volunteers and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients with Normal Renal Function. 万古霉素在韩国健康志愿者体内的药代动力学以及蒙特卡罗模拟探索肾功能正常患者的最佳剂量方案。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-19 DOI: 10.3390/antibiotics13100993
Yong Kyun Kim, Doee Kim, Gaeun Kang, Dae Young Zang, Dong-Hwan Lee

Background/Objectives: To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the concentration-time curve (AUC) in adult patients with normal renal function. Methods: We conducted a prospective clinical study, analysing PK samples from 12 healthy participants using noncompartmental analysis and non-linear mixed-effects modelling. The population PK parameters derived were employed in Monte Carlo simulations to evaluate the adequacy of the current dosing regimen and to formulate dosing recommendations. Results: The PK profiles were optimally described by a two-compartment model, with body weight and age as significant covariates affecting total clearance. The simulations indicated that to achieve a therapeutic target-defined as an AUC at steady-state over 24 h of 400-600 mg·h/L-daily doses ranging from 60 to 70 mg/kg are necessary in adults with normal renal function. Conclusions: This study underscores the need to actively adjust dosage and administration based on a vancomycin PK model that adequately reflects the demographic characteristics of patients to meet both safety and efficacy standards.

背景/目的:迄今为止,尚未对健康的韩国成年人进行万古霉素的群体药代动力学(PK)研究。本研究旨在调查万古霉素在健康志愿者中的 PK 特性,并根据肾功能正常的成人患者的浓度-时间曲线下面积(AUC)确定最佳给药方案。研究方法我们进行了一项前瞻性临床研究,利用非室分析和非线性混合效应模型分析了 12 名健康参与者的 PK 样本。得出的群体 PK 参数被用于蒙特卡罗模拟,以评估当前给药方案的适当性并制定给药建议。结果:两室模型对 PK 曲线进行了最佳描述,体重和年龄是影响总清除率的重要协变量。模拟结果表明,对于肾功能正常的成人,要达到治疗目标,即 24 小时内稳态时的 AUC 为 400-600 毫克-小时/升,则每日剂量为 60-70 毫克/千克。结论:本研究强调了根据万古霉素 PK 模型积极调整剂量和给药的必要性,该模型能充分反映患者的人口统计学特征,从而同时满足安全性和有效性标准。
{"title":"Pharmacokinetics of Vancomycin in Healthy Korean Volunteers and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients with Normal Renal Function.","authors":"Yong Kyun Kim, Doee Kim, Gaeun Kang, Dae Young Zang, Dong-Hwan Lee","doi":"10.3390/antibiotics13100993","DOIUrl":"https://doi.org/10.3390/antibiotics13100993","url":null,"abstract":"<p><p><b>Background/Objectives</b>: To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the concentration-time curve (AUC) in adult patients with normal renal function. <b>Methods</b>: We conducted a prospective clinical study, analysing PK samples from 12 healthy participants using noncompartmental analysis and non-linear mixed-effects modelling. The population PK parameters derived were employed in Monte Carlo simulations to evaluate the adequacy of the current dosing regimen and to formulate dosing recommendations. <b>Results</b>: The PK profiles were optimally described by a two-compartment model, with body weight and age as significant covariates affecting total clearance. The simulations indicated that to achieve a therapeutic target-defined as an AUC at steady-state over 24 h of 400-600 mg·h/L-daily doses ranging from 60 to 70 mg/kg are necessary in adults with normal renal function. <b>Conclusions</b>: This study underscores the need to actively adjust dosage and administration based on a vancomycin PK model that adequately reflects the demographic characteristics of patients to meet both safety and efficacy standards.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isatin Bis-Imidathiazole Hybrids Identified as FtsZ Inhibitors with On-Target Activity Against Staphylococcus aureus. Isatin Bis-Imidathiazole Hybrids 被鉴定为 FtsZ 抑制剂,对金黄色葡萄球菌具有靶向活性。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-19 DOI: 10.3390/antibiotics13100992
Rita Morigi, Daniele Esposito, Matteo Calvaresi, Tainah Dorina Marforio, Giovanna Angela Gentilomi, Francesca Bonvicini, Alessandra Locatelli

In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop a new class of heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- and community-acquired infections. A remarkable inhibitory activity against Staphylococcus aureus was demonstrated for a subset of compounds (range: 13.8-90.1 µM) in the absence of toxicity towards epithelial cells and human red blood cells. The best performing derivative was further investigated to measure its anti-biofilm potential and its effectiveness against methicillin-resistant Staphylococcus aureus strains. A structure-activity relationship study of the synthesized molecules led to the recognition of some important structural requirements for the observed antibacterial activity. Molecular docking followed by molecular dynamics (MD) simulations identified the binding site of the active compound FtsZ, a key protein in bacterial cell division, and the mechanism of action, i.e., the inhibition of its polymerization. The overall results may pave the way for a further rational development of isatin hybrids as FtsZ inhibitors, with a broader spectrum of activity against human pathogens and higher potency.

本研究设计并合成了一系列异汀双咪唑杂环化合物,以开发一类新的杂环化合物,提高其对医院和社区感染病原体的抗菌活性。部分化合物对金黄色葡萄球菌具有明显的抑制活性(范围:13.8-90.1 µM),且对上皮细胞和人类红细胞无毒性。我们进一步研究了性能最佳的衍生物,以衡量其抗生物膜的潜力及其对耐甲氧西林金黄色葡萄球菌菌株的有效性。通过对合成的分子进行结构-活性关系研究,我们认识到了观察到的抗菌活性所需的一些重要结构要求。通过分子对接和分子动力学(MD)模拟,确定了活性化合物 FtsZ(细菌细胞分裂中的一种关键蛋白)的结合位点和作用机制,即抑制其聚合。总体结果可能为进一步合理开发作为 FtsZ 抑制剂的isatin 杂交化合物铺平了道路,这种化合物对人类病原体的活性谱更广,效力更高。
{"title":"Isatin Bis-Imidathiazole Hybrids Identified as FtsZ Inhibitors with On-Target Activity Against <i>Staphylococcus aureus</i>.","authors":"Rita Morigi, Daniele Esposito, Matteo Calvaresi, Tainah Dorina Marforio, Giovanna Angela Gentilomi, Francesca Bonvicini, Alessandra Locatelli","doi":"10.3390/antibiotics13100992","DOIUrl":"https://doi.org/10.3390/antibiotics13100992","url":null,"abstract":"<p><p>In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop a new class of heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- and community-acquired infections. A remarkable inhibitory activity against <i>Staphylococcus aureus</i> was demonstrated for a subset of compounds (range: 13.8-90.1 µM) in the absence of toxicity towards epithelial cells and human red blood cells. The best performing derivative was further investigated to measure its anti-biofilm potential and its effectiveness against methicillin-resistant <i>Staphylococcus aureus</i> strains. A structure-activity relationship study of the synthesized molecules led to the recognition of some important structural requirements for the observed antibacterial activity. Molecular docking followed by molecular dynamics (MD) simulations identified the binding site of the active compound FtsZ, a key protein in bacterial cell division, and the mechanism of action, i.e., the inhibition of its polymerization. The overall results may pave the way for a further rational development of isatin hybrids as FtsZ inhibitors, with a broader spectrum of activity against human pathogens and higher potency.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived Streptomyces sp. Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived Streptomyces sp.
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.3390/antibiotics13100989
Shengbin Jin, David F Bruhn, Cynthia T Childs, Erica Burkman, Yovany Moreno, Angela A Salim, Zeinab G Khalil, Robert J Capon

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm Dirofilaria immitis microfilaria and/or the gastrointestinal parasite Haemonchus contortus L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of Streptomyces sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (1-10), together with the known actinopyrones A (11) and C (12). Structures for 1-12 were assigned on the basis of detailed spectroscopic and chemical analysis, with preliminary structure activity relationship analysis revealing selected γ-pyrones >50-fold and >13-fold more potent than isomeric α-pyrones against D. immitis mf motility (e.g., EC50 0.05 μM for 1; EC50 2.7 μM for 5) and H. contortus L1-L3 larvae development (e.g., EC50 0.58 μM for 1; EC50 8.2 μM for 5), respectively.

在澳大利亚公民科学活动 "土壤促进科学"(Soil for Science)的支持下,对收集的×19 个土壤样本进行了调查,结果发现了×559 个化学去复制微生物分离物,其中×54 个对心丝虫(Dirofilaria immitis)微丝蚴和/或胃肠道寄生虫(Haemonchus contortus)L1-L3 幼虫具有显著的驱虫活性。通过化学(GNPS 和 UPLC-DAD)和培养(MATRIX)分析,对链霉菌 S4S-00196A10 进行了详细的化学研究,发现了新的抗蠕虫多酮类化合物鹅膏并吡喃酮 A-J(1-10),以及已知的放线菌酮 A(11)和 C(12)。根据详细的光谱和化学分析,确定了 1-12 的结构,初步的结构活性关系分析表明,所选的γ-吡喃酮类化合物对稻瘟病虫的作用比同分异构体α-吡喃酮类化合物强 50 倍和 13 倍以上(例如:EC50 0.05 μMf,EC50 0.05 μMf,EC50 0.05 μMf,EC50 0.05 μMf)、例如,1 的 EC50 为 0.05 μM;5 的 EC50 为 2.7 μM)和 H. contortus L1-L3 幼虫的发育(例如,1 的 EC50 为 0.58 μM;5 的 EC50 为 8.2 μM)。
{"title":"Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived <i>Streptomyces</i> sp.","authors":"Shengbin Jin, David F Bruhn, Cynthia T Childs, Erica Burkman, Yovany Moreno, Angela A Salim, Zeinab G Khalil, Robert J Capon","doi":"10.3390/antibiotics13100989","DOIUrl":"https://doi.org/10.3390/antibiotics13100989","url":null,"abstract":"<p><p>An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm <i>Dirofilaria immitis</i> microfilaria and/or the gastrointestinal parasite <i>Haemonchus contortus</i> L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of <i>Streptomyces</i> sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (<b>1</b>-<b>10</b>), together with the known actinopyrones A (<b>11</b>) and C (<b>12</b>). Structures for <b>1</b>-<b>12</b> were assigned on the basis of detailed spectroscopic and chemical analysis, with preliminary structure activity relationship analysis revealing selected γ-pyrones >50-fold and >13-fold more potent than isomeric α-pyrones against <i>D. immitis</i> mf motility (e.g., EC<sub>50</sub> 0.05 μM for <b>1</b>; EC<sub>50</sub> 2.7 μM for <b>5</b>) and <i>H. contortus</i> L1-L3 larvae development (e.g., EC<sub>50</sub> 0.58 μM for <b>1</b>; EC<sub>50</sub> 8.2 μM for <b>5</b>), respectively.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Boosting Expression of a Specifically Targeted Antimicrobial Peptide K in Pichia pastoris by Employing a 2A Self-Cleaving Peptide-Based Expression System. 利用基于 2A 自裂解肽的表达系统促进特定靶向抗菌肽 K 在 Pichia pastoris 中的表达。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.3390/antibiotics13100986
Yunhui Zhu, Yuwen Li, Yuxin Fang, Mingyang Hu, Lu Zhao, Mingrui Sui, Na Dong

Background/Objectives: The current epidemic of drug-resistance bacterial strains is one of the most urgent threats to human health. Antimicrobial peptides (AMPs) are known for their good activity against multidrug resistance bacteria. Specifically targeted AMPs (STAMPs) are a fraction of AMPs that target specific bacteria and maintain the balance of the healthy microbiota of a host. We reported a STAMP Peptide K (former name: peptide 13) for E. coli. The aim of this study was to effectively produce peptide K using methylotrophic yeast Pichia pastoris. Methods: Three inserts (sequence of peptide K (K), two copies of peptide K fused with 2A sequence (KTK), and two copies of peptide K fused with 2A and an extra α mating factor (KTAK)) were designed to investigate the effect of the number of repeats and the trafficking of peptide on the yield. Results: The yield from KTK was the highest-more than two-fold higher compared with K-implying the role of the 2A sequence in heterologous peptide expression apart from the co-translation. Then, the fermentation condition for KTK was optimized. The optimized yield of KTK was 6.67 mg/mL, suggesting the efficiency of the expression system. Selectivity, antibacterial activity, biocompatibility, and the stability of the fermentation product were equivalent to the chemically synthesized peptide. The actional mechanism of the fermentation product included membrane permeabilization and ROS induction. Conclusions: Together, our work provided a new perspective to augment the yield of the antimicrobial peptide in the microbial system, building a technological foundation for their large-scale production and expanding the market application of AMPs.

背景/目标:目前,耐药性细菌菌株的流行是人类健康面临的最紧迫威胁之一。众所周知,抗菌肽(AMPs)对多重耐药细菌具有良好的活性。特异性靶向抗菌肽(STAMPs)是抗菌肽中的一部分,可针对特定细菌,维持宿主健康微生物群的平衡。我们报道了一种针对大肠杆菌的 STAMP 肽 K(原名:肽 13)。本研究的目的是利用养甲基酵母 Pichia pastoris 有效地生产肽 K。方法:设计了三个插入物(多肽 K 的序列(K)、两个多肽 K 与 2A 序列融合的拷贝(KTK)、两个多肽 K 与 2A 和一个额外的 α 交配因子融合的拷贝(KTAK)),以研究重复次数和多肽的贩运对产量的影响。结果KTK的产量最高,比K高出两倍多,这表明2A序列在异源多肽表达中的作用除了共转化之外。随后,对 KTK 的发酵条件进行了优化。优化后的 KTK 产量为 6.67 mg/mL,表明该表达系统的效率很高。发酵产物的选择性、抗菌活性、生物相容性和稳定性与化学合成多肽相当。发酵产物的作用机制包括膜通透性和 ROS 诱导。结论:总之,我们的工作为提高微生物系统中抗菌肽的产量提供了一个新的视角,为大规模生产抗菌肽奠定了技术基础,并扩大了 AMPs 的市场应用。
{"title":"Boosting Expression of a Specifically Targeted Antimicrobial Peptide K in <i>Pichia pastoris</i> by Employing a 2A Self-Cleaving Peptide-Based Expression System.","authors":"Yunhui Zhu, Yuwen Li, Yuxin Fang, Mingyang Hu, Lu Zhao, Mingrui Sui, Na Dong","doi":"10.3390/antibiotics13100986","DOIUrl":"https://doi.org/10.3390/antibiotics13100986","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The current epidemic of drug-resistance bacterial strains is one of the most urgent threats to human health. Antimicrobial peptides (AMPs) are known for their good activity against multidrug resistance bacteria. Specifically targeted AMPs (STAMPs) are a fraction of AMPs that target specific bacteria and maintain the balance of the healthy microbiota of a host. We reported a STAMP Peptide K (former name: peptide 13) for E. coli. The aim of this study was to effectively produce peptide K using methylotrophic yeast <i>Pichia pastoris</i>. <b>Methods:</b> Three inserts (sequence of peptide K (K), two copies of peptide K fused with 2A sequence (KTK), and two copies of peptide K fused with 2A and an extra α mating factor (KTAK)) were designed to investigate the effect of the number of repeats and the trafficking of peptide on the yield. <b>Results:</b> The yield from KTK was the highest-more than two-fold higher compared with K-implying the role of the 2A sequence in heterologous peptide expression apart from the co-translation. Then, the fermentation condition for KTK was optimized. The optimized yield of KTK was 6.67 mg/mL, suggesting the efficiency of the expression system. Selectivity, antibacterial activity, biocompatibility, and the stability of the fermentation product were equivalent to the chemically synthesized peptide. The actional mechanism of the fermentation product included membrane permeabilization and ROS induction. <b>Conclusions:</b> Together, our work provided a new perspective to augment the yield of the antimicrobial peptide in the microbial system, building a technological foundation for their large-scale production and expanding the market application of AMPs.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ceftazidime-Avibactam Versus Polymyxin-Based Combination Therapies: A Study on 30-Day Mortality in Carbapenem-Resistant Enterobacterales Bloodstream Infections in an OXA-48-Endemic Region. 头孢他啶-阿维巴坦与多粘菌素联合疗法的比较:一项关于 OXA-48 流行地区耐碳纳芬肠杆菌血流感染 30 天死亡率的研究。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.3390/antibiotics13100990
Rıdvan Dumlu, Meyha Şahin, Okan Derin, Özlem Gül, Sedef Başgönül, Rehile Zengin, Çiğdem Arabacı, Funda Şimşek, Serap Gençer, Ayşe Sesin Kocagöz, Ali Mert

Background: Ceftazidime-avibactam (CAZ-AVI) is recommended as first-line treatment for Oxacillinase-48 (OXA-48) β-Lactamase-producing carbapenem-resistant Enterobacterales (CRE) infections, while polymyxin-based combination therapies (PBCTs) are used as a last resort when CAZ-AVI is unavailable. Research comparing the effectiveness of CAZ-AVI and PBCT in CRE blood stream infections (CRE-BSIs) is limited, mostly focusing on Klebsiella pneumoniae carbapenemase (KPC)-producing isolates. In Turkey, OXA-48 is endemic and OXA-48-Like is common. Therefore, our study aimed to compare the impact of these treatments on 30-day mortality in patients with CRE-BSIs in endemic regions. Methods: Retrospective data from January 2019 to May 2023 were collected from four tertiary healthcare centers in Istanbul. Demographic, clinical, and outcome data of ICU patients treated with CAZ-AVI monotherapy or PBCT for CRE-BSIs were analyzed. The effect on 30-day survival was evaluated using Cox regression analysis post propensity score matching (PSM). Results: Out of 151 patients, 44.4% (n: 67) received CAZ-AVI and 55.6% (n: 84) received PBCT. All-cause mortality rates were 20% (n: 13) with CAZ-AVI and 36.9% (n: 31) with PBCT. Cox regression analysis post PSM indicated CAZ-AVI monotherapy significantly reduced the mortality risk compared to PBCT (HR: 0.16, 95%CI: 0.07-0.37, p < 0.001), while age increased the risk (HR: 1.02 per year, 95% CI 1.0-1.04, p: 0.01). Conclusions: In OXA-48-predominant areas, CAZ-AVI demonstrated significantly lower mortality in patients with CRE-BSIs compared to PBCT. The results were attributed to the pharmacokinetic and pharmacodynamic disadvantages of polymyxins compared to CAZ-AVI, and the impact of age-related physical conditions. Therefore, CAZ-AVI should be the preferred treatment for CRE-BSIs in OXA-48-endemic regions.

背景:头孢唑肟-阿维巴坦(CAZ-AVI)被推荐为治疗产氧西林酶-48(OXA-48)β-内酰胺酶耐碳青霉烯类肠杆菌(CRE)感染的一线疗法,而多粘菌素类联合疗法(PBCT)则是在无法使用 CAZ-AVI 时的最后手段。比较 CAZ-AVI 和 PBCT 对 CRE 血流感染(CRE-BSI)疗效的研究非常有限,主要集中在产碳青霉烯酶(KPC)的肺炎克雷伯菌分离株上。在土耳其,OXA-48 是地方病,OXA-48-Like 也很常见。因此,我们的研究旨在比较这些治疗方法对流行地区 CRE-BSIs 患者 30 天死亡率的影响。研究方法从伊斯坦布尔的四家三级医疗保健中心收集了 2019 年 1 月至 2023 年 5 月的回顾性数据。分析了使用 CAZ-AVI 单药或 PBCT 治疗 CRE-BSIs 的 ICU 患者的人口统计学、临床和结果数据。采用倾向评分匹配 (PSM) 后的 Cox 回归分析评估了对 30 天生存率的影响。结果在151名患者中,44.4%(67人)接受了CAZ-AVI治疗,55.6%(84人)接受了PBCT治疗。CAZ-AVI 的全因死亡率为 20%(13 人),PBCT 为 36.9%(31 人)。PSM 后的 Cox 回归分析表明,与 PBCT 相比,CAZ-AVI 单药治疗可显著降低死亡风险(HR:0.16,95%CI:0.07-0.37,p < 0.001),而年龄会增加风险(HR:每年 1.02,95% CI 1.0-1.04,p:0.01)。结论在以 OXA-48 为主的地区,与 PBCT 相比,CAZ-AVI 可显著降低 CRE-BSIs 患者的死亡率。这一结果归因于多粘菌素与 CAZ-AVI 相比在药代动力学和药效学上的劣势,以及与年龄相关的身体状况的影响。因此,在 OXA-48 流行地区,CAZ-AVI 应作为治疗 CRE-BSIs 的首选药物。
{"title":"Ceftazidime-Avibactam Versus Polymyxin-Based Combination Therapies: A Study on 30-Day Mortality in Carbapenem-Resistant Enterobacterales Bloodstream Infections in an OXA-48-Endemic Region.","authors":"Rıdvan Dumlu, Meyha Şahin, Okan Derin, Özlem Gül, Sedef Başgönül, Rehile Zengin, Çiğdem Arabacı, Funda Şimşek, Serap Gençer, Ayşe Sesin Kocagöz, Ali Mert","doi":"10.3390/antibiotics13100990","DOIUrl":"https://doi.org/10.3390/antibiotics13100990","url":null,"abstract":"<p><p><b>Background</b>: Ceftazidime-avibactam (CAZ-AVI) is recommended as first-line treatment for Oxacillinase-48 (OXA-48) β-Lactamase-producing carbapenem-resistant Enterobacterales (CRE) infections, while polymyxin-based combination therapies (PBCTs) are used as a last resort when CAZ-AVI is unavailable. Research comparing the effectiveness of CAZ-AVI and PBCT in CRE blood stream infections (CRE-BSIs) is limited, mostly focusing on <i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing isolates. In Turkey, OXA-48 is endemic and OXA-48-Like is common. Therefore, our study aimed to compare the impact of these treatments on 30-day mortality in patients with CRE-BSIs in endemic regions. <b>Methods</b>: Retrospective data from January 2019 to May 2023 were collected from four tertiary healthcare centers in Istanbul. Demographic, clinical, and outcome data of ICU patients treated with CAZ-AVI monotherapy or PBCT for CRE-BSIs were analyzed. The effect on 30-day survival was evaluated using Cox regression analysis post propensity score matching (PSM). <b>Results</b>: Out of 151 patients, 44.4% (<i>n</i>: 67) received CAZ-AVI and 55.6% (<i>n</i>: 84) received PBCT. All-cause mortality rates were 20% (<i>n</i>: 13) with CAZ-AVI and 36.9% (<i>n</i>: 31) with PBCT. Cox regression analysis post PSM indicated CAZ-AVI monotherapy significantly reduced the mortality risk compared to PBCT (HR: 0.16, 95%CI: 0.07-0.37, <i>p</i> < 0.001), while age increased the risk (HR: 1.02 per year, 95% CI 1.0-1.04, <i>p</i>: 0.01). <b>Conclusions</b>: In OXA-48-predominant areas, CAZ-AVI demonstrated significantly lower mortality in patients with CRE-BSIs compared to PBCT. The results were attributed to the pharmacokinetic and pharmacodynamic disadvantages of polymyxins compared to CAZ-AVI, and the impact of age-related physical conditions. Therefore, CAZ-AVI should be the preferred treatment for CRE-BSIs in OXA-48-endemic regions.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antibiotic Prophylaxis and Treatment for Cardiac Device Infections. 心脏设备感染的抗生素预防和治疗。
IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.3390/antibiotics13100991
Claudio Pandozi, Andrea Matteucci, Carlo Pignalberi, Luca Sgarra, Michela Bonanni, Marco Valerio Mariani, Vincenzo Mirco La Fazia, Lorenzo Nesti, Stefania Angela Di Fusco, Federico Nardi, Furio Colivicchi

Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing the risk of infection. The role of antibiotic prophylaxis in infection prevention is crucial, including the emerging use of antibiotic-supported tools and other local antibiotic delivery systems, which may reduce the risk of infection at the device implant site. In this contemporary review, we provide an overview of the prophylactic treatment and different antibiotic regimens for the treatment of CDIs, emphasizing early diagnosis, appropriate choice of antibiotics, and individualized treatment.

心脏装置感染(CDIs)是植入装置患者的一种严重并发症,会导致发病率上升、住院时间延长和医疗费用增加。要有效控制这些感染,需要结合适当的抗生素治疗和旨在降低感染风险的预防策略。抗生素预防在感染预防中的作用至关重要,包括新出现的抗生素支持工具和其他局部抗生素给药系统,它们可以降低器械植入部位的感染风险。在这篇当代综述中,我们概述了治疗 CDI 的预防性治疗和不同的抗生素方案,强调了早期诊断、抗生素的适当选择和个体化治疗。
{"title":"Antibiotic Prophylaxis and Treatment for Cardiac Device Infections.","authors":"Claudio Pandozi, Andrea Matteucci, Carlo Pignalberi, Luca Sgarra, Michela Bonanni, Marco Valerio Mariani, Vincenzo Mirco La Fazia, Lorenzo Nesti, Stefania Angela Di Fusco, Federico Nardi, Furio Colivicchi","doi":"10.3390/antibiotics13100991","DOIUrl":"https://doi.org/10.3390/antibiotics13100991","url":null,"abstract":"<p><p>Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing the risk of infection. The role of antibiotic prophylaxis in infection prevention is crucial, including the emerging use of antibiotic-supported tools and other local antibiotic delivery systems, which may reduce the risk of infection at the device implant site. In this contemporary review, we provide an overview of the prophylactic treatment and different antibiotic regimens for the treatment of CDIs, emphasizing early diagnosis, appropriate choice of antibiotics, and individualized treatment.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Antibiotics-Basel
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1