UTIs

UTI
  • 文章类型: Journal Article
    背景:近年来,抗生素耐药性已成为细菌感染如尿路感染(UTI)的全球健康问题.泌尿致病性大肠杆菌是引起简单和复杂UTI的最常见生物。金黄色葡萄球菌和铜绿假单胞菌经常与复杂的UTI相关。斯里兰卡拥有大量的药用植物资源,用于治疗阿育吠陀和传统医学中的UTI。
    方法:采用琼脂井扩散法和肉汤微量稀释法,测定10种药用植物甲醇提取物对铜绿假单胞菌ATCC27853、金黄色葡萄球菌ATCC25923、大肠杆菌ATCC25922及其从阳性培养板中提取的UTI阳性菌株的抗菌活性。作为初步的毒性试验,使用盐水虾死亡率测定(BSLA)来测定其细胞毒性。
    结果:余甘草的甲醇果实提取物对大肠杆菌ATCC25922和大肠杆菌UTI阳性菌株均表现出最高的抗菌活性。白花芽孢杆菌根提取物对金黄色葡萄球菌ATCC25923表现出最高的活性,而T.chebula果实提取物对金黄色葡萄球菌UTI阳性菌株表现出最高的活性。T.involucrata根提取物对铜绿假单胞菌ATCC27853显示出最高的活性,而Z.officinale根茎提取物对铜绿假单胞菌UTI阳性菌株显示出最高的活性。此外,该植物混合物对铜绿假单胞菌ATCC27853显示出最显著的抗菌作用。然而,C.melo的甲醇种子提取物对所选生物体没有任何抗微生物作用。所有植物材料,包括植物混合物,根据BSLA显示细胞毒性。
    结论:所有的甲醇提取物,包括余甘草果实,O.tenuiflorum整株植物,T.Chebula水果,Z.铁皮根茎,T.Terrestris根,T.intenucrata根,A.lanata全厂。白花蛇芽孢杆菌根和镰状芽孢杆菌根显示出对选定菌株的抗微生物作用,但C.melo种子提取物除外。本研究的结果显然支持这些植物在治疗UTI中的传统和阿育吠陀使用。这为为治疗UTI的新的基于植物的治疗产品开发铺平了道路。然而,药物剂量测定需要进一步的毒性研究.
    BACKGROUND: In recent years, antibiotic resistance has emerged as a global health concern in bacterial infections such as urinary tract infections (UTIs). Uropathogenic Escherichia coli is the most frequent organism responsible for both simple and complex UTIs. Staphylococcus aureus and Pseudomonas aeruginosa are frequently associated with complicated UTIs. Sri Lanka has significant resources of medicinal plants used to cure UTIs in Ayurvedic and traditional medicine.
    METHODS: Agar well diffusion and broth microdilution methods were used to determine the antibacterial activity of the methanolic extract of ten medicinal plants against P. aeruginosa ATCC27853, S.aureus ATCC25923, E.coli ATCC25922 and their UTI positive strains extracted from positive culture plates. As a preliminary toxicity assay, the Brine Shrimp Lethality Assay (BSLA) was used to determine its cytotoxicity.
    RESULTS: The methanolic fruits extract of P. emblica demonstrated the highest antibacterial activity against both E. coli ATCC25922 and E. coli UTI-positive strains. B. diffusa roots extract exhibited the highest activity against S. aureus ATCC25923, while T. chebula fruits extract showed the highest activity against the S. aureus UTI-positive strain. T. involucrata roots extract displayed the highest activity against P. aeruginosa ATCC27853, and Z. officinale rhizomes extract showed the highest activity against the P. aeruginosa UTI-positive strain. Moreover, the plant mixture showed the most substantial antibacterial effect against P. aeruginosa ATCC27853. However, the methanolic seed extract of C. melo did not exhibit any antimicrobial effects against the selected organisms. All plant material, including the plant mixture, showed cytotoxicity according to the BSLA.
    CONCLUSIONS: All the methanolic extracts including P. emblica fruits, O. tenuiflorum whole plant, T. chebula fruits, Z. officinale rhizome, T. terrestris roots, T. involucrata roots, A. lanata whole plant. B. diffusa roots and A. falcatus roots showed antimicrobial effects against selected strains except C. melo seed extract. The results of the present study evidently supports the traditional and ayurvedic use of these plants for the treatment of UTIs. This paves the way for another praise for new plant-based therapeutic product development for the treatment of UTIs. However, further toxicity studies are needed for medicinal dose determination.
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  • 文章类型: Journal Article
    细菌耐药性的出现,尤其是在与尿路感染(UTI)相关的药物中,已经开始了令人兴奋的努力,开发生物相容性纳米粒子来应对他们的威胁。设计简单,便宜,生物相容性和有效的纳米材料作为杀菌剂似乎是一个明智的应对这一问题。这里,采用溶剂热法一锅法制备纤维素胶(羧甲基纤维素,CMC)磁性复合材料,以制备具有成本效益的,高效,和用于银NP的植物基稳定的生物相容性支持物。使用一品红植物提取物高效地进行AgNP的绿色稳定化。各种表征方法,包括FT-IR,XRD,SEM,EDS,TEM,用VSM和VSM研究了Fe3O4@CMC/AgNPs的组成和性能。复合材料显示良好的完整性和单分散性,平均直径<300nm,表明其生物相关应用的潜力。提出的材料的CMC功能促进了AgNP的稳定,导致它们的单分散性和增强的性能。制造的复合材料被用作抗菌剂,用于去除UTIs剂,收集了200例急性冠脉综合征住院患者,显示出有希望的结果。这项研究表明,AgNPs的浓度与复合材料的抗菌性能有直接关系。
    The emergence of antimicrobial resistance in bacteria, especially in agents associated with urinary tract infections (UTIs), has initiated an exciting effort to develop biocompatible nanoparticles to confront their threat. Designing simple, cheap, biocompatible, and efficient nanomaterials as bactericidal agents seems to be a judicious response to this problem. Here, a solvothermal method was hired for the one-pot preparation of the cellulose gum (carboxymethyl cellulose, CMC) magnetic composite to prepare a cost-effective, efficient, and biocompatible support for the plant-based stabilization of the silver NPs. The green stabilization of the Ag NPs is performed using Euphorbia plant extract with high efficiency. Various characterization methods, including FT-IR, XRD, SEM, EDS, TEM, and VSM were used to study the composition and properties of Fe3O4@CMC/AgNPs. The composite shows well integrity and monodispersity with a mean diameter of <300 nm, indicating its potential for bio-related application. The CMC functionalities of the proposed material facilitated the stabilization of the Ag NPs, resulting in their monodispersity and enhanced performance. The manufactured composite was used as an antibacterial agent for the removal of UTIs agents, collected from 200 hospitalized patients with acute coronary syndrome, which showed promising results. This study showed that the concentration of the Ag NPs has a direct relationship with the antibacterial properties of the composite.
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  • 文章类型: Journal Article
    目的:水负荷与几种感染的关系尚不清楚。由于潜在的混杂因素,观察性研究很难进行明确的调查。在这项研究中,我们采用孟德尔随机化(MR)分析来评估基因预测的全身水质量(BWM)与几种感染之间的关联.
    方法:使用与BWM相关的418个SNP,在英国生物库的331,315个欧洲人中预测了BWM水平。对于结果,我们使用了英国生物银行和FinnGen联盟的全基因组关联数据,包括败血症,肺炎,肠道感染,尿路感染(UTI)和皮肤和软组织感染(STTI)。进行了逆方差加权MR分析以及一系列敏感性分析。
    结果:BWM的遗传预测与脓毒症风险增加相关(OR1.34;95%CI1.19至1.51;P=1.57×10-6),肺炎(OR:1.17;95%CI1.08至1.29;P=3.53×10-4),尿路感染(OR:1.26;95%CI1.16至1.37;P=6.29×10-8),和SSTIs(OR:1.57;95%CI1.25至1.96;P=7.35×10-5)。在脓毒症和肺炎亚组分析中,在细菌感染中观察到BWM与感染之间的关系,而在病毒感染中未观察到。证据表明,BWM对病毒性肠道感染有影响(OR:0.86;95%CI0.75至0.99;P=0.03)。有有限的证据表明BWM水平和细菌肠道感染之间的关联,和妊娠期泌尿生殖道感染(GUI)。此外,MR分析支持了几种水肿性疾病的BWM风险。然而,多变量MR分析表明,BWM与脓毒症,肺炎,考虑到这些性状时,UTI和STTI不受影响。
    结论:在这项研究中,系统研究了BWM与传染病的因果关系。需要进一步的前瞻性研究来验证这些发现。
    OBJECTIVE: The association of water loading with several infections remains unclear. Observational studies are hard to investigate definitively due to potential confounders. In this study, we employed Mendelian randomization (MR) analysis to assess the association between genetically predicted whole body water mass (BWM) and several infections.
    METHODS: BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted.
    RESULTS: Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10- 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10- 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10- 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10- 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits.
    CONCLUSIONS: In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.
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  • 文章类型: Journal Article
    尿路感染(UTI)是一种普遍的健康挑战,其特征在于泌尿系统中微生物的入侵和繁殖。不断探索新的治疗干预措施势在必行。研究的进展为彻底改变UTI的管理和改善受这些感染影响的个体的整体健康结果提供了希望。
    这篇综述旨在概述尿路感染的现有治疗方法,强调他们的优势和局限性。此外,我们探索并分析了临床开发中的最新治疗方式。最后,该评论提供了一幅图景,这些疗法对UTIs治疗的未来前景的潜在影响,讨论进一步研究可能的进步和挑战。
    从基础基础科学研究中收集了对UTI发病机理的理解,为探索新的治疗干预措施奠定基础。证据的主要来源主要来自在小鼠模型上进行的动物研究。然而,缺乏临床试验妨碍了人类获得强有力的证据。尿路病原体的异质性和毒力带来的挑战增加了额外的复杂性,构成了科学家和临床医生在寻求有效解决方案时积极应对的障碍。
    UNASSIGNED: Urinary tract infections (UTIs) are a prevalent health challenge characterized by the invasion and multiplication of microorganisms in the urinary system. The continuous exploration of novel therapeutic interventions is imperative. Advances in research offer hope for revolutionizing the management of UTIs and improving the overall health outcomes for individuals affected by these infections.
    UNASSIGNED: This review aimed to provide an overview of existing treatments for UTIs, highlighting their strengths and limitations. Moreover, we explored and analyzed the latest therapeutic modalities under clinical development. Finally, the review offered a picture into the potential implications of these therapies on the future landscape of UTIs treatment, discussing possible advancements and challenges for further research.
    UNASSIGNED: Comprehensions into the pathogenesis of UTIs have been gleaned from foundational basic science studies, laying the groundwork for the exploration of novel therapeutic interventions. The primary source of evidence originates predominantly from animal studies conducted on murine models. Nevertheless, the lack of clinical trials interferes the acquisition of robust evidence in humans. The challenges presented by the heterogeneity and virulence of uropathogens add an additional layer of complexity, posing an obstacle that scientists and clinicians are actively grappling with in their pursuit of effective solutions.
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  • 文章类型: Journal Article
    背景:尿路感染,一种流行的全球传染病,临床问题在HIV阳性个体中没有得到很好的研究。尿路感染已经成为一个全球性的耐药问题,但是TigrayHIV患者中引起UTI的细菌的患病率和抗生素敏感性模式,埃塞俄比亚,知之甚少。这项研究旨在确定UTI引起的细菌的患病率,他们的抗生素敏感性模式,以及在提格雷的Mekelle总医院和Ayder综合专科医院就诊ART诊所的HIV患者的相关危险因素,埃塞俄比亚北部。
    方法:从在Mekelle总医院和Ayder综合专科医院的ART诊所就诊的HIV患者中收集清洁捕获中游尿液样本(10-15mL)。基于使用半胱氨酸-乳糖电解质缺陷(CLED)琼脂的标准微生物方案分析样品。通过继代培养到Mac-Conkey中获得细菌分离株的纯菌落,甘露醇盐琼脂和血琼脂平板。然后使用宏观,微观,生物化学,和革兰氏染色方法。使用生化试验如三糖铁琼脂鉴定革兰氏阴性菌,西蒙的柠檬酸琼脂,赖氨酸铁琼脂,尿素,运动性试验,和吲哚测试,而革兰氏阳性分离株是使用过氧化氢酶和凝固酶试验鉴定的。使用Kirby-Bauer圆盘扩散技术分析细菌分离株的抗菌敏感性模式。使用SPSS版本25.0分析数据。
    结果:在224例患者中,其中28人(12.5%)感染了引起UTI的细菌。大肠杆菌是优势细菌(16(57%)),其次是肺炎克雷伯菌(4(14%)),和金黄色葡萄球菌(3(11%))。在所有细菌分离物中,其中22例(78.6%)出现多药耐药。发现所有革兰氏阳性(100%)和75%的革兰氏阴性细菌分离株对两种或多种药物具有抗性。有UTI病史的患者,与CD4计数<200细胞/mm3,更可能有显著的菌尿。与男性患者相比,女性患者受UTIs致病细菌的影响更大.超过93%的引起UTI的细菌分离株对呋喃妥因敏感,头孢曲松,环丙沙星,和庆大霉素;而它们对氨苄青霉素具有高度抗性(96%),复方新诺明(82%)和四环素(71%)。
    结论:大多数细菌分离株对氨苄青霉素具有高度耐药性,复方新诺明,还有四环素.女性患者受引起UTI的细菌影响更大。在HIV患者中,UTI的患病率最高(12.5%)需要特别注意,以便更好地管理和监测。以前的UTI病史和免疫抑制是UTI的预测因子,强调需要采取涉及分子研究的干预措施,以识别耐药细菌基因并促进患者免疫重建。
    BACKGROUND: Urinary tract infections, a prevalent global infectious disease, are clinical issues not well studied in HIV-positive individuals. UTIs have become a global drug resistance issue, but the prevalence and antibiotic susceptibility patterns of UTI-causing bacteria among HIV patients in Tigray, Ethiopia, are poorly understood. This study aims to identify the prevalence of UTI-causing bacteria, their antibiotic susceptibility patterns, and associated risk factors in HIV patients attending ART clinics at Mekelle General Hospital and Ayder Comprehensive Specialized Hospital in Tigray, Northern Ethiopia.
    METHODS: Clean-catch midstream urine samples (10-15 mL) were collected from HIV patients who are attending ART clinics at Mekelle General Hospital and Ayder Comprehensive Specialized Hospital. Samples were analyzed based on standard microbiological protocols using cysteine-lactose electrolyte deficient (CLED) agar. Pure colonies of bacterial isolates were obtained by sub-culturing into Mac-Conkey, Manitol Salt agar and blood agar plates. The bacterial isolates were then identified using macroscopic, microscopic, biochemical, and Gram staining methods. Gram-negative bacteria were identified using biochemical tests like triple sugar iron agar, Simon\'s citrate agar, lysine iron agar, urea, motility test, and indol test, whereas Gram-positive isolates were identified using catalase and coagulase tests. The Kirby-Bauer disk diffusion technique was used to analyze the antimicrobial susceptibility pattern of bacterial isolates. Data was analyzed using SPSS version 25.0.
    RESULTS: Among the 224 patients, 28 (12.5%) of them had been infected by UTIs-causing bacteria. E. coli was the dominant bacterium (16 (57%)) followed by K. pneumoniae (4 (14%)), and S. aureus (3 (11%)). Of the total bacterial isolates, 22 (78.6%) of them developed multi-drug resistance. All Gram-positive (100%) and 75% of Gram-negative bacterial isolates were found to be resistant to two or more drugs. Patients with a history of UTIs, and with CD4 count < 200 cells/ mm3, were more likely to have significant bacteriuria. Compared to male patients, female patients were more affected by the UTIs-causing bacteria. More than 93% of the UTIs-causing bacterial isolates were susceptible to nitrofurantoin, ceftriaxone, ciprofloxacin, and gentamycin; whereas they are highly resistant to ampicillin (96%), cotrimoxazole (82%) and tetracycline (71%).
    CONCLUSIONS: Most of the bacterial isolates were highly resistant to ampicillin, cotrimoxazole, and tetracycline. Female patients were more affected by the UTIs causing bacteria. The highest prevalence (12.5%) of UTIs in HIV patients needs special attention for better management and monitoring. Previous UTI history and immune suppression are predictors of UTIs, highlighting the need for intervention measures involving molecular studies to identify resistant bacteria genes and promote patient immune reconstitution.
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  • 文章类型: Journal Article
    大肠杆菌是一种多样化的病原体,在人类中引起一系列疾病,从自限性腹泻到尿路感染(UTI)。尿路致病性大肠杆菌(UPEC)是尿路感染中最常见的尿路病原体,高收入国家的常见病,每年产生数十亿美元的治疗费用。尽管大肠杆菌很容易在临床实验室中生长和鉴定,病原体的基因分型更加复杂,但对降低疾病发病率至关重要。这些目标可以通过大肠杆菌分离株的全基因组测序来实现,但是这种方法相对较慢,通常需要在实验室中培养病原体。从临床样本中快速、低成本地直接对大肠杆菌进行基因分型,包括但不限于尿液,我们开发并验证了多重扩增子测序测定,叫做ColiSeq.该测定法由设计用于大肠杆菌物种确认的靶标组成,高分辨率基因分型,和混合反卷积。为了证明它的效用,我们对从弗拉格斯塔夫的医院系统收集的230份临床尿液样本进行了ColiSeq分析筛选,亚利桑那,美国。检测限分析证明了ColiSeq在〜2基因组当量(GEs)/mL的浓度下鉴定大肠杆菌和在1×105GEs/mL的浓度下产生高分辨率基因分型的能力。这项研究的结果表明,ColiSeq可能是一种有价值的方法来了解UPEC菌株的来源并指导感染缓解工作。随着基于序列的诊断在临床实验室中被接受,ColiSeq等工作流程将提供可操作的信息,以改善患者的预后。重要泌尿系感染(UTI),主要由大肠杆菌引起,在美国和其他高收入国家造成巨大的医疗保健负担。从临床样本中早期发现大肠杆菌,包括尿液,对靶向治疗和预防进一步的患者并发症很重要。此外,了解大肠杆菌暴露的来源将有助于未来的缓解努力。在这项研究中,我们开发了,tested,并验证了扩增子测序测定法,该测定法专注于直接检测尿液中的大肠杆菌。所得到的序列数据被证明提供病原体的菌株水平分辨率。不仅证实了大肠杆菌的存在,可以集中治疗努力,还提供来源归因和联系人追踪所需的数据。这种测定法将产生廉价的,快速,和可由公共卫生机构部署的可重复数据进行跟踪,诊断,并有可能减轻由大肠杆菌引起的未来UTI。
    Escherichia coli is a diverse pathogen, causing a range of disease in humans, from self-limiting diarrhea to urinary tract infections (UTIs). Uropathogenic E. coli (UPEC) is the most frequently observed uropathogen in UTIs, a common disease in high-income countries, incurring billions of dollars yearly in treatment costs. Although E. coli is easily grown and identified in the clinical laboratory, genotyping the pathogen is more complicated, yet critical for reducing the incidence of disease. These goals can be achieved through whole-genome sequencing of E. coli isolates, but this approach is relatively slow and typically requires culturing the pathogen in the laboratory. To genotype E. coli rapidly and inexpensively directly from clinical samples, including but not limited to urine, we developed and validated a multiplex amplicon sequencing assay, called ColiSeq. The assay consists of targets designed for E. coli species confirmation, high resolution genotyping, and mixture deconvolution. To demonstrate its utility, we screened the ColiSeq assay against 230 clinical urine samples collected from a hospital system in Flagstaff, Arizona, USA. A limit of detection analysis demonstrated the ability of ColiSeq to identify E. coli at a concentration of ~2 genomic equivalent (GEs)/mL and to generate high-resolution genotyping at a concentration of 1 × 105 GEs/mL. The results of this study suggest that ColiSeq could be a valuable method to understand the source of UPEC strains and guide infection mitigation efforts. As sequence-based diagnostics become accepted in the clinical laboratory, workflows such as ColiSeq will provide actionable information to improve patient outcomes.IMPORTANCEUrinary tract infections (UTIs), caused primarily by Escherichia coli, create an enormous health care burden in the United States and other high-income countries. The early detection of E. coli from clinical samples, including urine, is important to target therapy and prevent further patient complications. Additionally, understanding the source of E. coli exposure will help with future mitigation efforts. In this study, we developed, tested, and validated an amplicon sequencing assay focused on direct detection of E. coli from urine. The resulting sequence data were demonstrated to provide strain level resolution of the pathogen, not only confirming the presence of E. coli, which can focus treatment efforts, but also providing data needed for source attribution and contact tracing. This assay will generate inexpensive, rapid, and reproducible data that can be deployed by public health agencies to track, diagnose, and potentially mitigate future UTIs caused by E. coli.
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  • 文章类型: Journal Article
    D-甘露糖被广泛用作细菌性尿路感染的非抗生素治疗。此应用程序基于与1型细菌菌毛结合的充分研究的机制,因此,阻止细菌粘附到尿路上皮细胞。为了在载体系统中实现D-甘露糖,糖在膀胱环境中的作用机制也是相关的,需要研究。在这里,描述了使用介孔二氧化硅纳米颗粒(MSN)的两种不同的甘露糖基化策略。通过MSN与各自生物体相互作用的共聚焦显微镜成像研究了不同化学接头对细菌粘附和膀胱细胞反应的影响。评估细胞毒性和Toll样受体4(TLR4)和小窝蛋白-1(CAV-1)的表达,在存在或不存在细菌脂多糖(LPS)模拟感染的情况下,使用人膀胱癌细胞系T24进行评价。Further,随着时间的推移,检查由于甘露糖基化材料引起的转录因子NF-κB的定位。结果表明,甘露糖基化修饰了细菌对纳米材料的粘附,并显着影响膀胱细胞中的TLR4,caveolin-1和NF-κB。这些元素是尿路感染期间炎症级联/病原体反应的必要成分。这些发现表明甘露糖基化是设计用于靶向生物医学应用的混合纳米载体的通用工具。
    D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.
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  • 文章类型: Randomized Controlled Trial
    目的:尿路感染(UTI)是人类非常常见的感染,和大肠杆菌(E.大肠杆菌)是导致UTI的最常见病原体。该细菌中β-内酰胺酶的产生导致其对许多抗生素的抗性。这项研究在双盲临床试验中比较了隔日三剂量阿米卡星与同期每日剂量的美罗培南,以治疗大肠杆菌的UTI。
    方法:当前的双盲临床试验比较了隔日三剂阿米卡星与同期每日剂量美罗培南治疗大肠杆菌尿路感染的效果。将患者分为两组:干预(以48小时为间隔,每天一次接受单剂量阿米卡星,持续一周,三个剂量)和对照(接受美罗培南1/TDS一周)。
    结果:大肠杆菌感染频率为61例(非ESBL21例,ESBL阳性40例),其他感染频率为52例(46%)。在ESBL大肠杆菌感染的患者中,环丙沙星(21;70%)表现出最高的抗生素耐药性,和呋喃妥因(33;91.7%)显示出最高的敏感性。对照组和干预组之间的基线变量没有显着差异(p>0.05)。在第24h和第1周,阿米卡星组和美罗培南组之间的体征和症状频率没有显着差异。在随访的第二周,两组均未出现临床症状或体征。
    结论:这项研究的结果表明,用阿米卡星治疗,1克q48h,一周(三次剂量)具有与美罗培南相同的结果,1gq8h,一周(21剂)。结果对于ESBL阳性和ESBL阴性的UTI的治疗是相同的。阿米卡星可以每48小时使用一次治疗尿路感染,费用较低,可以在门诊进行。
    背景:本研究于2018-02-13日在伊朗临床试验注册中心(IRCT)注册,ID号为IRCT20170417033483N2。
    OBJECTIVE: Urinary tract infections (UTIs) are very common infections in humans, and Escherichia coli (E. coli) is the commonest pathogen leading to UTIs. The generation of beta-lactamase enzymes in this bacterium results in its resistance against many antibiotics. This study compares three doses of amikacin on alternate days with a daily dose of meropenem in the same period for the treatment of UTIs with E. coli in a double-blind clinical trial.
    METHODS: The current double-blind clinical trial compares three doses of amikacin on alternate days with a daily dose of meropenem in the same period for the treatment of UTIs with E. coli. The patients were assigned to two groups: Intervention (receiving a single dose of amikacin once a day at 48-h intervals for a week, three doses) and control (receiving meropenem for 1/TDS for a week).
    RESULTS: The E. coli infection frequency was 61 (21 cases of non-ESBL and 40 cases of ESBL-positive infections) and the frequency of the other infections was 52 (46%). In the patients with ESBL E. coli infection, ciprofloxacin (21; 70%) showed the highest antibiotic resistance, and nitrofurantoin (33; 91.7%) showed the highest sensitivity. The baseline variables between the control and intervention groups indicated no significant difference (p > 0.05). The frequency of signs and symptoms showed no significant difference between the amikacin and meropenem groups in the first 24 h and the first week. In the second week of follow-up, no clinical signs or symptoms were observed in the two groups.
    CONCLUSIONS: The results of this study showed that treatment with amikacin, 1 g q48h, for one week (three doses) has the same result as meropenem, 1 g q8h, for one week (21 doses). The results are the same for the treatment of UTIs with ESBL positive and ESBL negative. Amikacin can be used once every 48 h to treat UTIs, is less expensive and can be administered on an outpatient basis.
    BACKGROUND: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20170417033483N2 on the date 2018-02-13.
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  • 文章类型: Journal Article
    尿路感染(UTI)是女性人群中常见的病理,在过去十年中越来越难以治疗。考虑到抗生素耐药性的增加-一个严重的全球公共卫生问题。进行了为期六个月的横断面回顾性研究,以报告有关最佳治疗所必需的尿路病原体的耐药率和易感性的最新信息。共筛查了5487名患者,其中524例(9.54%)为符合纳入标准的女性患者.大肠杆菌是最常见的病原体,占290例(55.34%),其次是肠球菌。82(15.64%)。大肠埃希菌对阿莫西林-克拉维酸的耐药性最高(R=33.1%),其次是甲氧苄啶-磺胺甲恶唑(R=32.41%)和左氧氟沙星(R=32.06%)。对磷霉素的敏感率最高(S=96.55%),其次是亚胺培南(S=93.1%)。肠球菌属。对左氧氟沙星的耐药性最高(R=50.0%),其次是青霉素(R=39.02%)。对磷霉素的敏感性最高(S=90.24%),利奈唑胺(S=89.02%),和呋喃妥因(S=86.58%)。第二常见的革兰氏阴性尿路病原体是克雷伯菌属。,对阿莫西林-克拉维酸的耐药性最高(R=35.89%),其次是左氧氟沙星(R=25.64)和甲氧苄啶-磺胺甲恶唑(R=24.35%)。最常见的相关病理是前一年的UTI发作,其次是糖尿病和慢性肾病。抗生素耐药性对于所有治疗UTI的临床医生来说都是一个严重的问题。抗生素耐药率的最新知识是阻止其进化的主要必要条件。总的来说,观察到氨基青霉素的耐药率最高,氟喹诺酮类药物,和甲氧苄啶-磺胺甲恶唑.观察到对磷霉素的最佳敏感率,呋喃妥因,和碳青霉烯类.我们的报告旨在指导临床医生在被迫凭经验开抗生素时。
    Urinary tract infections (UTIs) represent a frequent pathology among the female population that has become more and more difficult to treat in the past decade, considering the increase in antibiotic resistance-a serious global public health problem. A cross-sectional retrospective study was conducted for six months to report an update regarding the rates of resistance and susceptibility of uropathogens necessary for optimal treatment. A total of 5487 patients were screened, of which 524 (9.54%) were female patients who met the criteria for inclusion in the study. Escherichia coli was the most common pathogen, representing 290 cases (55.34%), followed by Enterococcus spp. 82 (15.64%). Escherichia coli presented the highest resistance to amoxicillin-clavulanic acid (R = 33.1%), followed by trimethoprim-sulfamethoxazole (R = 32.41%) and levofloxacin (R = 32.06%). The highest sensitivity rates were observed for fosfomycin (S = 96.55%), followed by imipenem (S = 93.1%). Enterococcus spp. showed the highest resistance to levofloxacin (R = 50.0%), followed by penicillin (R = 39.02%). The highest sensitivity was observed for fosfomycin (S = 90.24%), linezolid (S = 89.02%), and nitrofurantoin (S = 86.58%). The second most frequent Gram-negative uropathogen was represented by Klebsiella spp., which had the highest resistance to amoxicillin-clavulanic acid (R = 35.89%), followed by levofloxacin (R = 25.64) and trimethoprim-suflamethoxazole (R = 24.35%). The most frequently associated pathology was an episode of UTI in the previous year, followed by diabetes and chronic kidney disease. Antibiotic resistance is a serious problem for all clinicians who treat UTIs. An up-to-date knowledge of antibiotic resistance rates is a major necessity to stop its evolution. Overall, the highest resistance rates were observed for aminopenicillins, fluoroquinolones, and trimethoprim-sulfamethoxazole. The best susceptibility rates were observed for fosfomycin, nitrofurantoin, and carbapenems. Our report aims to guide clinicians whenever they are forced to prescribe antibiotics empirically.
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  • 文章类型: Journal Article
    多重耐药(MDR)革兰氏阴性病原菌对抗β-内酰胺类抗生素最常见的主要耐药机制之一,如青霉素,头孢菌素和碳青霉烯类是β-内酰胺酶的产生。由于AmpCβ-内酰胺酶的合成,尿路致病性大肠杆菌大多产生多药耐药性,因此需要新的抗生素和抑制剂来治疗不断发展的感染。本研究采用基于分子对接的虚拟筛选技术,针对大肠杆菌AmpCβ-内酰胺酶,使用分子动力学模拟与靶蛋白设计新化合物和结合模式分析的连接片段。已针对大肠杆菌的AmpCβ-内酰胺酶蛋白筛选了由9388片段组成的FCH组通用片段文库,并且还使用AmpCβ-内酰胺酶蛋白筛选了用于治疗尿路感染(UTI)的抗生素和抗感染药。在9388个片段中,选择339个候选片段并与对AmpC靶蛋白具有最大结合亲和力的头孢吡肟抗生素连接。还进行了相互作用的计算分析以及分子动力学(MD)模拟,以从对接研究中识别最有前途的配体-口袋复合物,以了解其热力学性质并验证对接结果。总的来说,连接复合物(LC)与AmpCβ-内酰胺酶表现出良好的结合相互作用。有趣的是,与头孢吡肟抗生素相比,我们基于片段的LC保持相对稳定.此外,S12片段连接的复合物在50ns期间保持最稳定,具有显著数量的相互作用,表明其在针对MDR大肠杆菌感染的新型前导发现中是有希望的候选物。
    One of the most common primary resistance mechanism of multi-drug resistant (MDR) Gram negative pathogenic bacteria to combat β-lactam antibiotics, such as penicillins, cephalosporins and carbapenems is the generation of β- lactamases. The uropathogenic E. coli is mostly getting multi-drug resistance due to the synthesis of AmpC β-lactamases and therefore new antibiotics and inhibitors are needed to treat the evolving infections. The current study was designed for targetting AmpC β-lactamase of E. coli using molecular docking based virtual screening, linking fragments for designing novel compounds and binding mode analysis using molecular dynamic simulation with target protein. The FCH group all-purpose fragment library consisting of 9388 fragments has been screened against AmpC β-lactamase protein of E. coli and the antibiotics and anti-infectives used in treatment of Urinary tract Infections (UTIs) were also screened with AmpC β-lactamase protein. Among the 9388 fragments, 339 fragment candidates were selected and linked with cefepime antibiotic having maximum binding affinity for AmpC target protein. Computational analysis of interactions as well as molecular dynamics (MD) simulations were also conducted for identifying the most promising ligand-pocket complexes from docking investigations to comprehend their thermodynamic properties and verify the docking outcomes as well. Overall, the linked complexes (LCs) showed good binding interactions with AmpC β-lactamase. Interestingly, our fragment-based LCs remained relatively stable in comparison with cefepime antibiotic. Moreover, S12 fragment linked complex remained the most stable during 50 ns with remarkable number of interactions indicating it as promising candidate in novel lead discovery against MDR E. coli infections.
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