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The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review. 利福昔明-α临床相关微生物耐药的发展潜力:叙述性回顾。
IF 9.6 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-11-16 DOI: 10.1128/cmr.00039-23
Herbert L DuPont

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although in vitro testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler's diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant Enterococcus in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between in vitro resistance and rifaximin-α efficacy.

利福昔明-α是一种肠道靶向抗生素,适用于多种胃肠道和肝脏疾病。其多方面的作用机制超越了直接的抗菌作用,包括改变细菌毒力,对宿主上皮细胞的细胞保护作用,改善受损的肠通透性,以及通过激活妊娠X受体减少促炎细胞因子的表达。利福昔明-α几乎不被吸收,具有较低的全身药物水平,有助于其良好的安全性。虽然在结肠中存在高浓度的药物,但低水溶性导致结肠药物生物利用度低,从而保护肠道微生物群。利福昔明-α似乎在富含胆汁的小肠中更活跃。其重要的生物效应主要是在亚抑制浓度。尽管对利福昔明接受者的临床分离株进行的体外测试在一些研究中发现了利福昔明耐药菌株,但出现利福昔明-α耐药的风险似乎低于许多其他抗生素。利福昔明-α多年来一直用于旅行者腹泻,在致病病原体的耐药水平没有明显增加。此外,利福昔明-α在长期和反复使用慢性胃肠道疾病后仍保持其疗效。微生物对利福昔明-α的耐药风险可能低于其他药物的耐药风险有很多原因,包括在水结肠中的肠道生物利用度低,利福昔明-α的作用机制不需要药物的抑制浓度,以及利福昔明-α耐药性在细菌物种之间交叉传播的风险低。据报道,在利福昔明维持治疗的肝病患者中出现万古霉素耐药肠球菌需要积极研究。需要进一步的研究来评估体外耐药性与利福昔明-α疗效之间可能的相关性。
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引用次数: 0
2023 Acknowledgment of CMR Reviewers. 2023 感谢 CMR 评审员。
IF 36.8 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 DOI: 10.1128/cmr.00138-23
Graeme Forrest
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引用次数: 0
Virulence attributes of successful methicillin-resistant Staphylococcus aureus lineages. 成功耐甲氧西林金黄色葡萄球菌谱系的毒力特性。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-11-20 DOI: 10.1128/cmr.00148-22
Jhih-Hang Jiang, David R Cameron, Cara Nethercott, Marta Aires-de-Sousa, Anton Y Peleg

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of severe and often fatal infections. MRSA epidemics have occurred in waves, whereby a previously successful lineage has been replaced by a more fit and better adapted lineage. Selection pressures in both hospital and community settings are not uniform across the globe, which has resulted in geographically distinct epidemiology. This review focuses on the mechanisms that trigger the establishment and maintenance of current, dominant MRSA lineages across the globe. While the important role of antibiotic resistance will be mentioned throughout, factors which influence the capacity of S. aureus to colonize and cause disease within a host will be the primary focus of this review. We show that while MRSA possesses a diverse arsenal of toxins including alpha-toxin, the success of a lineage involves more than just producing toxins that damage the host. Success is often attributed to the acquisition or loss of genetic elements involved in colonization and niche adaptation such as the arginine catabolic mobile element, as well as the activity of regulatory systems, and shift metabolism accordingly (e.g., the accessory genome regulator, agr). Understanding exactly how specific MRSA clones cause prolonged epidemics may reveal targets for therapies, whereby both core (e.g., the alpha toxin) and acquired virulence factors (e.g., the Panton-Valentine leukocidin) may be nullified using anti-virulence strategies.

耐甲氧西林金黄色葡萄球菌(MRSA)是导致严重且经常致命感染的主要原因。耐甲氧西林金黄色葡萄球菌的流行是一波又一波地发生的,在这种情况下,以前成功的谱系被更适合和更好适应的谱系所取代。医院和社区环境中的选择压力在全球范围内并不统一,这导致了地理上不同的流行病学。这篇综述的重点是在全球范围内引发当前MRSA主流谱系的建立和维持的机制。虽然抗生素耐药性的重要作用将贯穿始终,但影响金黄色葡萄球菌在宿主内定植和致病能力的因素将是本综述的主要重点。我们表明,虽然MRSA拥有包括α毒素在内的多种毒素,但一个谱系的成功不仅仅涉及产生损害宿主的毒素。成功通常归因于与定植和生态位适应有关的遗传元件的获得或丢失,例如精氨酸分解代谢移动元件,以及调节系统的活性,并相应地转移代谢(例如,辅助基因组调节因子,agr)。准确了解特定的MRSA克隆如何引起长期流行可能会揭示治疗的靶点,因此核心(例如α毒素)和获得性毒力因子(例如潘通-瓦伦丁杀白细胞素)都可以通过抗毒策略无效。
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引用次数: 0
Biofilm antimicrobial susceptibility testing: where are we and where could we be going? 生物膜抗菌药物敏感性测试:我们在哪里,我们可以去哪里?
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-10-09 DOI: 10.1128/cmr.00024-23
Tom Coenye

Our knowledge about the fundamental aspects of biofilm biology, including the mechanisms behind the reduced antimicrobial susceptibility of biofilms, has increased drastically over the last decades. However, this knowledge has so far not been translated into major changes in clinical practice. While the biofilm concept is increasingly on the radar of clinical microbiologists, physicians, and healthcare professionals in general, the standardized tools to study biofilms in the clinical microbiology laboratory are still lacking; one area in which this is particularly obvious is that of antimicrobial susceptibility testing (AST). It is generally accepted that the biofilm lifestyle has a tremendous impact on antibiotic susceptibility, yet AST is typically still carried out with planktonic cells. On top of that, the microenvironment at the site of infection is an important driver for microbial physiology and hence susceptibility; but this is poorly reflected in current AST methods. The goal of this review is to provide an overview of the state of the art concerning biofilm AST and highlight the knowledge gaps in this area. Subsequently, potential ways to improve biofilm-based AST will be discussed. Finally, bottlenecks currently preventing the use of biofilm AST in clinical practice, as well as the steps needed to get past these bottlenecks, will be discussed.

摘要在过去的几十年里,我们对生物膜生物学的基本方面,包括生物膜抗菌敏感性降低背后的机制的了解急剧增加。然而,到目前为止,这些知识还没有转化为临床实践的重大变化。尽管生物膜的概念越来越受到临床微生物学家、医生和医疗保健专业人员的关注,但临床微生物学实验室中研究生物膜的标准化工具仍然缺乏;其中一个特别明显的领域是抗微生物药敏试验(AST)。人们普遍认为,生物膜的生活方式对抗生素的易感性有巨大影响,但AST通常仍在浮游细胞中进行。除此之外,感染部位的微环境是微生物生理学和易感性的重要驱动因素;但这在当前的AST方法中反映得很差。本综述的目的是概述生物膜AST的技术现状,并强调该领域的知识差距。随后,将讨论改进基于生物膜的AST的潜在方法。最后,将讨论目前阻碍生物膜AST在临床实践中使用的瓶颈,以及克服这些瓶颈所需的步骤。
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引用次数: 0
Klebsiella pneumoniae carbapenemase variants: the new threat to global public health. 肺炎克雷伯菌碳青霉烯酶变体:对全球公共健康的新威胁。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-11-08 DOI: 10.1128/cmr.00008-23
Li Ding, Siquan Shen, Jing Chen, Zhen Tian, Qingyu Shi, Renru Han, Yan Guo, Fupin Hu

Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild blaKPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 blaKPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting blaKPC variants, treatment options, and future perspectives of blaKPC variants worldwide to alert this new great public health threat.

SUMMARYKlebsiella pneumoniae碳青霉烯酶(KPC)变体是指与野生blaKPC型相比氨基酸序列的取代、插入或缺失,它降低了头孢他啶-阿维巴坦(CZA)的效用,头孢他啶是治疗碳青霉烯耐药性肠杆菌感染的先锋抗菌剂。到目前为止,全球已报告了150多种blaKPC变体,其中大多数新变体是在过去3年中发现的,这需要公众警惕。KPC变体蛋白通过改变KPC结构来增强对头孢他啶的亲和力,并削弱对阿维巴坦的亲和力,从而介导细菌对CZA的耐药性。目前,仍然没有指导方针或专家共识来就KPC变异株引起的感染的诊断和治疗提出建议。此外,美罗培南-沃博巴坦、亚胺培南-雷巴坦和其他新的β-内酰胺酶抑制剂组合对KPC变体的讨论很少。这篇综述旨在讨论世界范围内blaKPC变异株的临床特征、危险因素、流行病学特征、抗菌药物敏感性、检测方法、治疗选择和未来前景,以提醒人们注意这一新的巨大公共卫生威胁。
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引用次数: 0
Changes in fungal taxonomy: mycological rationale and clinical implications. 真菌分类学的变化:真菌学原理和临床意义。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-11-06 DOI: 10.1128/cmr.00099-22
Andrew M Borman, Elizabeth M Johnson

Numerous fungal species of medical importance have been recently subjected to and will likely continue to undergo nomenclatural changes as a result of the application of molecular approaches to fungal classification together with abandonment of dual nomenclature. Here, we summarize those changes affecting key groups of fungi of medical importance, explaining the mycological (taxonomic) rationale that underpinned the changes and the clinical relevance/importance (where such exists) of the key nomenclatural revisions. Potential mechanisms to mitigate unnecessary taxonomic instability are suggested, together with approaches to raise awareness of important changes to minimize potential clinical confusion.

SUMMARY由于分子方法在真菌分类中的应用以及双重命名法的放弃,许多具有医学重要性的真菌物种最近受到并可能继续经历命名法的变化。在这里,我们总结了影响具有医学重要性的关键真菌群的变化,解释了支撑这些变化的真菌学(分类学)原理,以及关键命名修订的临床相关性/重要性(如果存在)。提出了减轻不必要的分类学不稳定性的潜在机制,以及提高对重要变化的认识以最大限度地减少潜在临床混乱的方法。
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引用次数: 0
MicroRNAs in infectious diseases: potential diagnostic biomarkers and therapeutic targets. 传染病中的微小RNA:潜在的诊断生物标志物和治疗靶点。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-11-01 DOI: 10.1128/cmr.00015-23
Muneyoshi Kimura, Sagar Kothari, Wajiha Gohir, Jose F Camargo, Shahid Husain

MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. They have been implicated in the pathogenesis of cancer and neurological, cardiovascular, and autoimmune diseases. Several recent studies have suggested that miRNAs are key players in regulating the differentiation, maturation, and activation of immune cells, thereby influencing the host immune response to infection. The resultant upregulation or downregulation of miRNAs from infection influences the protein expression of genes responsible for the immune response and can determine the risk of disease progression. Recently, miRNAs have been explored as diagnostic biomarkers and therapeutic targets in various infectious diseases. This review summarizes our current understanding of the role of miRNAs during viral, fungal, bacterial, and parasitic infections from a clinical perspective, including critical functional mechanisms and implications for their potential use as biomarkers and therapeutic targets.

SUMMARYMicroRNAs(miRNAs)是一种保守的、短的、非编码的RNA,在基因表达的转录后调控中起着至关重要的作用。它们与癌症、神经、心血管和自身免疫性疾病的发病机制有关。最近的几项研究表明,miRNA是调节免疫细胞分化、成熟和激活的关键参与者,从而影响宿主对感染的免疫反应。感染引起的miRNA的上调或下调影响负责免疫反应的基因的蛋白质表达,并可决定疾病进展的风险。最近,miRNA已被探索作为各种传染病的诊断生物标志物和治疗靶点。这篇综述从临床角度总结了我们目前对miRNA在病毒、真菌、细菌和寄生虫感染中的作用的理解,包括其关键的功能机制及其作为生物标志物和治疗靶点的潜在用途。
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引用次数: 0
2023 Acknowledgment of CMR Reviewers. 2023 感谢 CMR 评审员。
IF 36.8 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 DOI: 10.1128/cmr.00138-23
Graeme Forrest
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引用次数: 0
Diagnosis and management of cryptococcal meningitis in HIV-infected adults. 成人hiv感染者隐球菌性脑膜炎的诊断和治疗。
IF 36.8 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-20 Epub Date: 2023-11-28 DOI: 10.1128/cmr.00156-22
Thomas C McHale, David R Boulware, John Kasibante, Kenneth Ssebambulidde, Caleb P Skipper, Mahsa Abassi

Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.

隐球菌性脑膜炎是全球发病率和死亡率的主要原因,特别是在晚期艾滋病患者中。在与晚期艾滋病毒疾病相关的所有死亡中,有近20%是由隐球菌性脑膜炎造成的,疾病负担主要由资源有限国家的人们承担。诊断方面的重大进展带来了低成本、易于使用的抗原检测,具有非常高的灵敏度和特异性。这些检测提高了诊断的准确性,对于减少隐球菌病负担的筛查运动至关重要。在过去的5年里,一些高质量的、多地点的临床试验已经导致了治疗方法的创新,从而简化了方案,使其具有更好的耐受性,并且减少了对药物不良反应的密集监测和管理。一项试验发现,较短的7天脱氧胆酸两性霉素B疗程与较长的14天疗程一样有效,氟胞嘧啶是降低疾病急性期死亡率的重要配套药物。单剂量脂质体两性霉素B也被发现与7天脱氧胆酸两性霉素B疗程一样有效。这些发现使得更简单、更安全的治疗方案成为可能,也减轻了医疗保健系统的负担。这篇综述提供了一个详细的讨论最新的证据指导临床管理和特殊情况下,使隐球菌脑膜炎独特的难以治疗。
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引用次数: 0
Wastewater-based surveillance as a tool for public health action: SARS-CoV-2 and beyond 将废水监测作为公共卫生行动的工具:SARS-CoV-2 及其后
IF 36.8 1区 医学 Q1 MICROBIOLOGY Pub Date : 2023-12-14 DOI: 10.1128/cmr.00103-22
Michael D. ParkinsBonita E. LeeNicole AcostaMaria BautistaCasey R. J. HubertSteve E. HrudeyKevin FrankowskiXiao-Li Pang1Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada2Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada3O’Brien Institute of Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada4Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada5Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, Alberta, Canada6Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada7Advancing Canadian Water Assets, University of Calgary, Calgary, Alberta, Canada8Provincial Health Laboratory, Alberta Health Services, Calgary, Alberta, Canada, Graeme N. Forrest
Clinical Microbiology Reviews, Ahead of Print.
临床微生物学评论》,印刷版前。
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引用次数: 0
期刊
Clinical Microbiology Reviews
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