beta-Lactamases

β - 内酰胺酶
  • 文章类型: Letter
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  • 文章类型: Journal Article
    尿路感染的管理受到全球抗菌素耐药性(AMR)增加的挑战。在这项研究中,我们描述了在过去5年中从加纳最大的私营部门实验室分离出的尿路病原体的耐药性趋势.我们回顾了2017年至2021年MDS柳叶刀实验室的尿液培养阳性。确定了加纳标准治疗指南推荐的对口服和肠胃外抗菌药物具有耐药性的尿路病原体的比例。多重耐药菌株的比例,确定了产ESBL和碳青霉烯酶的表型。在接受培养的94,134份尿液样本中,20,010(22.1%)为培养阳性。肠杆菌是最常见的一组生物,大肠杆菌(70.6%)是最常见的分离株和肠球菌属。最常见的革兰氏阳性(1.3%)生物。在口服抗菌药物中,对环丙沙星(62.3%)和头孢呋辛(60.2%)的耐药率最高,对磷霉素的耐药率最低(1.9%).肠胃外抗菌药物中耐药性最小的是美罗培南(0.3%)。在克雷伯菌属中观察到最高的多药耐药水平。(68.6%)和大肠杆菌(64.0%)。克雷伯菌属的超广谱β-内酰胺酶(ESBL)阳性率最高。(58.6%)和大肠杆菌(50.0%)。可能需要审查加纳标准治疗指南,以反映尿路病原体对推荐的抗菌药物的耐药性增加。
    Management of urinary tract infections is challenged by increasing antimicrobial resistance (AMR) worldwide. In this study, we describe the trends in antimicrobial resistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. The proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and carbapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales was the most common group of organisms, E. coli (70.6%) being the most common isolate and Enterococcus spp. the most common gram-positive (1.3%) organisms. Among oral antimicrobials, the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2%) and the least resistance to fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem (0.3%). The highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). Extended-spectrum beta-lactamase (ESBL) positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recommended antimicrobials.
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  • 文章类型: Journal Article
    急性单纯性肾盂肾炎患者常表现为免疫功能受损,加重感染性疾病。最近对UTI的一些治疗建议进行了修订,部分原因是抗生素耐药菌的出现,如喹诺酮耐药大肠杆菌和产超广谱β-内酰胺酶(ESBL)的细菌,主要是大肠杆菌和肺炎克雷伯菌,不同国家或地区之间的出现和传播频率不同。抗菌素耐药性(AMR)的时代已经到来,应该重新考虑使用抗生素。几种新建立的抗微生物剂可用于治疗耐药细菌,如青霉素或头孢菌素与β-内酰胺酶抑制剂。新版的亚洲尿路感染和性传播感染协会(AAUS)急性单纯性肾盂肾炎指南包括基于抗生素耐药性变化趋势的抗生素使用新建议。
    Patients with acute uncomplicated pyelonephritis often show impaired immune function that aggravates infectious diseases. Some of the therapeutic recommendations for UTIs have been revised recently, partly because of the emergence of antibiotic resistant bacteria such as quinolone-resistant Escherichia coli and Extended spectrum beta-lactamase (ESBL) producing bacteria, mainly E. coli and Klebsiella pneumoniae, which vary from country to country or between regions in frequency of emergence and spread. An era of antimicrobial resistance (AMR) has arrived, where the use of antibiotics should be reconsidered. Several newly established antimicrobial agents are commercially available for the treatment of resistant bacteria, such as penicillins or cephalosporins with beta-lactamase inhibitors. This new edition of Asian Association of UTI & STI (AAUS) guideline for acute uncomplicated pyelonephritis includes new recommendations for antibiotic use based on changing trends in antibiotic resistance.
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  • 文章类型: Journal Article
    给β-内酰胺酶变体指定名称是不一致的,并且在已发表的文献中导致混淆。全基因组测序的普遍可用性导致新的β-内酰胺酶基因的数量呈指数增长。2021年11月,一个由β-内酰胺酶专家组成的国际小组几乎开会,就天然存在的β-内酰胺酶基因的命名方式达成共识。本文件正式确定了新型β-内酰胺酶的命名过程,随后发表。
    Assigning names to β-lactamase variants has been inconsistent and has led to confusion in the published literature. The common availability of whole genome sequencing has resulted in an exponential growth in the number of new β-lactamase genes. In November 2021 an international group of β-lactamase experts met virtually to develop a consensus for the way naturally-occurring β-lactamase genes should be named. This document formalizes the process for naming novel β-lactamases, followed by their subsequent publication.
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  • 文章类型: Consensus Development Conference
    背景:β-内酰胺抗生素(βLA)是重症监护病房(ICU)中最常用的抗生素。ICU患者表现出许多导致药代动力学(PK)和药效学(PD)特异性的病理生理特征,导致剂量不足的风险。法国药理学与治疗学学会(SFPT)和法国麻醉与重症监护医学学会(SFAR)已联手为ICU患者提供优化β-内酰胺治疗的指南。
    方法:由来自两个学会的18名专家组成的共识委员会的使命是制定这些指南。整个过程独立于任何行业资金进行。根据PICO模型制定的问题清单(人口,干预,比较,和结果)是由专家起草的。然后,两位书目专家根据PRISMA建议使用预定义的关键词分析了自2000年1月以来发表的文献。使用GRADE®方法评估从文献中鉴定的数据的质量。由于缺乏以死亡率为主要判断标准的有力研究,决定了,在起草建议之前,仅制定“可选”建议。
    结果:经过两轮评级和一次修订,SFPT-SFAR指南小组就21个可选建议和涵盖四个领域的护理概论算法达成了强有力的一致:(i)药代动力学变异性,(二)PK-PD关系,(iii)管理方式,和(iv)治疗药物监测(TDM)。关于ICU患者中βLA给药的最重要建议涉及(i)考虑该人群中PK变异性的许多来源;(ii)将100%给药间隔内致病菌最小抑制浓度(MIC)的4至8倍的游离血浆浓度定义为PK-PD目标,以最大程度地提高细菌学和临床反应;(iii)在最严重的患者中使用连续或长期给药βLA,在高MIC细菌的情况下和在下呼吸道感染的情况下提高临床治愈;和(iv)使用TDM提高PK-PD目标的实现。
    结论:专家强烈建议使用个性化给药,在危重患者中施用βLA时,连续或长时间输注和治疗药物监测。
    BACKGROUND: Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients.
    METHODS: A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only \"optional\" recommendations.
    RESULTS: After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement.
    CONCLUSIONS: The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients.
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  • 文章类型: Journal Article
    与内窥镜传播相关的产生碳青霉烯酶的肠杆菌科临床感染的爆发已得到充分证明。与这些感染相关的高发病率和死亡率强调需要重新评估内镜后处理方案。澳大利亚胃肠病学会成立了一个多学会委员会,以制定基于证据的共识声明,以预防和管理产生碳青霉烯酶的肠杆菌科的内窥镜传播。利用MEDLINE数据库进行文献检索。进一步的参考文献来自已出版的纸质参考书目。提出了九项声明。使用Delphi方法,这些声明最初由委员会成员以电子方式进行审查,随后在墨尔本举行的面对面会议上进行审查,澳大利亚。经过进一步讨论,增加了四个子报表,共13个报表。每个陈述都被评估了证据水平,建议等级和对建议的投票记录。对于要接受的声明,六名委员会成员中有五名不得不“完全接受”或“有保留地接受”。“所有13项声明都达成了共识。十一项陈述达到100%“完全接受。“两个陈述83%”完全接受“和17%”保留接受。“特别重要的是,自动柔性内窥镜再处理器被要求进行高水平的消毒,并且强制空气干燥柜的使用被要求用于内窥镜存储。这些基于证据的声明鼓励预防策略,旨在确保柔性内窥镜再处理的最高标准,从而优化患者安全。除了更广泛的已发布的内窥镜检查中的感染控制指南外,还必须考虑它们。
    Outbreaks of carbapenemase-producing Enterobacteriaceae clinical infections related to endoscopic transmission are well documented. The high morbidity and mortality associated with these infections emphasizes the need to reassess endoscopic reprocessing protocols. The Gastroenterological Society of Australia established a multi-society committee to formulate evidence-based consensus statements on the prevention and management of endoscopic transmission of carbapenemase-producing Enterobacteriaceae. A literature search was undertaken utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Nine statements were formulated. Using the Delphi methodology, the statements were initially reviewed electronically by the committee members and subsequently at a face-to-face meeting in Melbourne, Australia. After further discussion, four additional sub-statements were added resulting in a total of 13 statements. Each statement was assessed for level of evidence, recommendation grade and the voting on recommendation was recorded. For a statement to be accepted, five out of six committee members had to \"accept completely\" or \"accept with some reservation.\" All 13 statements achieved consensus agreement. Eleven statements achieved 100% \"accepted completely.\" Two statements were 83% \"accepted completely\" and 17% \"accepted with some reservation.\" Of particular significance, automated flexible endoscope reprocessors were mandated for high-level disinfection, and the use of forced-air drying cabinets was mandated for endoscope storage. These evidence-based statements encourage preventative strategies with the aim of ensuring the highest possible standards in flexible endoscope reprocessing thereby optimizing patient safety. They must be considered in addition to the broader published guidelines on infection control in endoscopy.
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  • 文章类型: Journal Article
    High-dose cefepime-tazobactam (1:1; WCK 4282), a novel antibacterial combination consisting of the β-lactamase inhibitor tazobactam and a fourth-generation cephalosporin, is under clinical development for the treatment of serious Gram-negative infections. A quality control (QC) study was performed to establish disk diffusion and MIC ranges for cefepime-tazobactam for multiple QC reference strains. The cefepime-tazobactam QC ranges for a fixed tazobactam MIC of 8 μg/ml and disk diffusion (30/20-μg disk) test methods were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing in January 2015 and January 2016. These QC ranges will be important for accurate in vitro activity evaluations of cefepime-tazobactam when tested against clinical Gram-negative bacteria during clinical studies and routine patient care.
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  • 文章类型: Letter
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