Pub Date : 2024-10-21DOI: 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}
Pub Date : 2024-10-21DOI: 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}
Pub Date : 2024-10-20DOI: 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.
{"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}
Pub Date : 2024-10-19DOI: 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}
Pub Date : 2024-10-19DOI: 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.
{"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}
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.
{"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}
Pub Date : 2024-10-18DOI: 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.
{"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}
Pub Date : 2024-10-18DOI: 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.
{"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}
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.
{"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}
Pub Date : 2024-10-18DOI: 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.
{"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}