synergy

协同作用
  • 文章类型: Journal Article
    微塑料(MP)和药品和个人护理产品(PPCPs)在水生环境中无处不在。藻类在水生环境中起着重要作用。因此,研究藻类对MPs和PPCPs联合暴露的反应具有重要意义。这里,我们综述了MPs和PPCPs对藻类的影响。首先,总结了MPs和PPCPs对藻类的个体作用。第二,系统分析了MPs和PPCPs对藻类的联合作用。(1)拮抗作用:①当MPs太大而不能进入藻类细胞时,PPCPs在MPs上的吸附导致MPs和PPCPs与藻类的接触减少;②PPCPs和MPs对同一生物靶标具有相反的作用;③MPs增加藻类中代谢酶的活性,从而促进PPCP降解。(2)协同作用:①当MP小到可以进入藻类细胞时,PPCPs在MPs上的吸附促进了PPCPs的进入;②当MPs带负电荷时,MPs对带正电的PPCPs的吸附降低了静电斥力,增加藻类与MPs之间的相互作用;③MPs与PPCPs之间的互补作用方式对同一生物靶标表现出联合作用。第三,使用随机森林模型评估影响综合效应的因素的相对重要性,按以下顺序降低:PPCP类型>藻类>MP大小>MP浓度>MP类型>暴露时间。最后,提出了MP和PPCP共同作用的未来方向,这将有助于更好地了解国会议员和PPCPs的环境命运和风险。
    Microplastics (MPs) and pharmaceuticals and personal care products (PPCPs) are ubiquitous in aquatic environments. Algae play an important role in aquatic environments. Thus, it is important to study the response of algae to combined exposure of MPs and PPCPs. Here, we review the effects of MPs and PPCPs on algae. First, the individual effects of MPs and PPCPs on algae were summarized. Second, the combined effects of MPs and PPCPs on algae were systematically analyzed. (1) Antagonism: ① when the MPs are too large to enter the algal cells, the adsorption of PPCPs onto MPs results in decreased the contact of MPs and PPCPs with algae; ② PPCPs and MPs have opposing actions on the same biological target; ③ MPs increase the activity of metabolic enzymes in algae, thus promoting the PPCP degradation. (2) Synergy: ① when the MPs are small enough to enter algal cells, the adsorption of PPCPs on MPs promotes the entry of PPCPs; ② when MPs are negatively charged, the adsorption of positively charged PPCPs by MPs decreases the electrostatic repulsion, increasing the interaction between algae and MPs; ③ complementary modes of action between MPs and PPCPs show combined effects on the same biological target. Third, the relative importance of the factors that impact the combined effects are evaluated using the random forest model decreased in the following order: PPCP types > algal species > MP size > MP concentration > MP types > exposure time. Finally, future directions for the combined effects of MPs and PPCPs are proposed, which will facilitate a better understanding of the environmental fate and risks of both MPs and PPCPs.
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  • 文章类型: Journal Article
    多重耐药性细菌的增加显着降低了抗生素药库的有效性,并随后夸大了治疗失败的程度。植物成分是抗性改性车辆的特殊替代品。这些植物似乎是发现新型抗菌化合物的深井。这是由于植物的许多诱人的特性,它们很容易获得且便宜,来自植物的提取物或化学物质通常具有显著的抗感染作用,它们很少引起严重的不良影响。植物化学物质的大量选择提供了非常独特的化学结构,可以提供抗菌活性的新机制,并在细菌细胞内部为我们提供不同的靶标。它们可以直接影响细菌或与致病性的关键事件一起起作用,以这种方式降低细菌产生抗性的能力。丰富的植物成分证明了对多药耐药细菌的各种作用机制。总的来说,这篇全面的综述将提供有关植物成分作为细菌感染替代疗法的潜力的见解,特别是由多药耐药菌株引起的。通过考察这一领域的研究现状,该综述将阐明开发新的抗微生物疗法的潜在未来方向。
    The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies.
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  • 文章类型: Journal Article
    免疫疗法,特别是免疫检查点抑制剂(ICIs),无疑是肺癌研究的重大突破之一。患者的生存和预后都得到了改善,尽管由于肿瘤细胞的各种免疫逃逸机制,许多患者对免疫疗法没有反应。最近的临床前和临床证据表明,立体定向放射治疗(SBRT),也被称为立体定向消融放射治疗,具有突出的免疫启动作用,可以引发针对特定肿瘤抗原的抗肿瘤免疫并破坏远处的肿瘤细胞,从而达到难以捉摸的横断效果,与由此产生的免疫活性肿瘤环境也更有利于ICI。一些具有里程碑意义的试验已经证明了SBRT加免疫疗法对转移性非小细胞肺癌的生存益处。而PEMBRO-RT等其他研究进一步表明,在免疫治疗中加入SBRT可以将目前的适应症扩大到那些历史上对ICIs反应不佳的患者.在本次审查中,首先简要概述了驱动SBRT和免疫治疗协同作用的生物学机制;然后,总结了目前来自临床试验的理解,并对免疫治疗和SBRT协同作用在肺癌治疗中不断演变的作用提供了新的见解.最后,突出了新的发现途径。本综述的创新之处在于将非ICI免疫治疗纳入讨论,对SBRT+免疫治疗协同作用的发展现状和未来趋势进行了较为全面的展望。
    Immunotherapy, particularly immune checkpoint inhibitors (ICIs), is undoubtedly one of the major breakthroughs in lung cancer research. Patient survival and prognosis have all been improved as a result, although numerous patients do not respond to immunotherapy due to various immune escape mechanisms of the tumor cells. Recent preclinical and clinical evidence has shown that stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy, has a prominent immune priming effect that could elicit antitumor immunity against specific tumor antigens and destroy distant tumor cells, thereby achieving the elusive abscopal effect, with the resulting immuno‑active tumor environment also being more conducive to ICIs. Some landmark trials have already demonstrated the survival benefit of the dynamic duo of SBRT plus immunotherapy in metastatic non‑small‑cell lung cancer, while others such as PEMBRO‑RT further suggest that the addition of SBRT to immunotherapy could expand the current indication to those who have historically responded poorly to ICIs. In the present review, the biological mechanisms that drive the synergistic effect of SBRT and immunotherapy were first briefly outlined; then, the current understanding from clinical trials was summarized and new insight into the evolving role of immunotherapy and SBRT synergy in lung cancer treatment was provided. Finally, novel avenues for discovery were highlighted. The innovation of the present review lies in the inclusion of non‑ICI immunotherapy in the discussion, which provides a more comprehensive view on the current development and future trend of SBRT + immunotherapy synergy.
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  • 文章类型: Journal Article
    这篇综述针对空气污染控制领域的研究人员,旨在了解挥发性有机化合物(VOC)去除的最新进展。实施等离子体催化技术以去除挥发性有机化合物(VOC)导致降解产率和矿化速率显着提高,副产物形成少。等离子体-催化组合可以以两种不同的方式使用:(I)催化剂位于等离子体放电的下游,被称为“后等离子体催化配置”(PPC),和(II)催化剂位于等离子体区并直接暴露于放电,称为“在等离子体催化配置中”(IPC)。将这两种技术结合起来,尤其是对VOCs的消除近年来引起了许多研究者的兴趣。术语“协同作用”在他们的作品中被广泛报道,并与等离子体催化组合的积极作用有关。这篇综述论文研究了新发表的关于催化的论文的最新水平,光催化,非热等离子体,以及它们的组合用于VOC去除应用。重点是了解在等离子体和催化之间相互作用的不同协同源,并将其分为两个主要部分:等离子体放电对催化剂的影响和催化剂对等离子体放电的影响。这种方法具有应用于工业过程或室内环境的空气净化系统的潜力。
    This review is aimed at researchers in air pollution control seeking to understand the latest advancements in volatile organic compound (VOC) removal. Implementing of plasma-catalysis technology for the removal of volatile organic compounds (VOCs) led to a significant boost in terms of degradation yield and mineralization rate with low by-product formation. The plasma-catalysis combination can be used in two distinct ways: (I) the catalyst is positioned downstream of the plasma discharge, known as the \"post plasma catalysis configuration\" (PPC), and (II) the catalyst is located in the plasma zone and exposed directly to the discharge, called \"in plasma catalysis configuration\" (IPC). Coupling these two technologies, especially for VOCs elimination has attracted the interest of many researchers in recent years. The term \"synergy\" is widely reported in their works and associated with the positive effect of the plasma catalysis combination. This review paper investigates the state of the art of newly published papers about catalysis, photocatalysis, non-thermal plasma, and their combination for VOC removal application. The focus is on understanding different synergy sources operating mutually between plasma and catalysis discussed and classified into two main parts: the effect of the plasma discharge on the catalyst and the effect of the catalyst on plasma discharge. This approach has the potential for application in air purification systems for industrial processes or indoor environments.
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  • 文章类型: Journal Article
    背景:尽管有一些证据支持协同概念,通常已知的假设是,由于累加或协同作用,一种制剂中几种草药的组合可以具有更好的功效,但尚未明确研究。
    目的:该研究旨在揭示宿主细胞对植物杂交制剂(BHP)干预的原位分子相互作用,并证明在临床实践中实施BHP的益处。
    结果:本前瞻性文献综述提供了红景天(北极根)与其他植物的BHP的最新临床和网络药理学研究的结果,包括Withaniasomnifera(L.)Dunal(ashwagandha),(山茶(L.)昆兹(绿茶),刺五加球菌(Rupr。和马克西姆。)马克西姆。(eleuthero),五味子(Turcz。)Baill。(schisandra),Leuzeacarthamoides(威尔德。)DC。,咖啡因,蛹虫草,银杏L.(银杏),actaearacemosaL.(黑升麻),藏红花(藏红花),和L-肌肽.
    结论:来自BHP网络药理学研究的最重要发现是支持BHP成分协同相互作用的证据,揭示了新的BHP特有的意想不到的新药理活性。一些研究表明,与单药相比,BHP具有更好的疗效。同时,一些先验设计的组合可能会失败,推测是由于参与生物对干预的细胞和整体反应的分子网络内分子靶标之间的拮抗相互作用和串扰。网络药理学研究有助于预测旨在发现新适应症和不可预测的不良事件的研究结果。
    BACKGROUND: Despite some evidence supporting the synergy concept, the commonly known assumption that combinations of several herbs in one formulation can have better efficacy due to additive or synergistic effects has yet to be unambiguously and explicitly studied.
    OBJECTIVE: The study aimed to reveal the molecular interactions in situ of host cells in response to botanical hybrid preparations (BHP) intervention and justify the benefits of implementing BHP in clinical practice.
    RESULTS: This prospective literature review provides the results of recent clinical and network pharmacology studies of BHP of Rhodiola rosea L. (Arctic root) with other plants, including Withania somnifera (L.) Dunal (ashwagandha), (Camellia sinensis (L.) Kuntze (green tea), Eleutherococcus senticosus (Rupr. and Maxim.) Maxim. (eleuthero), Schisandra chinensis (Turcz.) Baill. (schisandra), Leuzea carthamoides (Willd.) DC., caffeine, Cordyceps militaris L., Ginkgo biloba L.(ginkgo), Actaea racemosa L. (black cohosh), Crocus sativus L. (saffron), and L-carnosine.
    CONCLUSIONS: The most important finding from network pharmacology studies of BHP was the evidence supporting the synergistic interaction of BHP ingredients, revealing unexpected new pharmacological activities unique and specific to the new BHP. Some studies show the superior efficacy of BHP compared to mono-drugs. At the same time, some a priori-designed combinations can fail, presumably due to antagonistic interactions and crosstalk between molecular targets within the molecular networks involved in the cellular and overall response of organisms to the intervention. Network pharmacology studies help predict the results of studies aimed at discovering new indications and unpredicted adverse events.
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  • 文章类型: Systematic Review
    化疗耐药是癌症治疗中的一个挑战,限制化疗的有效性。蘑菇提取物已显示出作为癌症治疗方法的潜力,提供了一个可能的解决方案来克服化学抗性。本系统综述旨在探讨蘑菇提取物在增强肿瘤细胞化疗和逆转化疗耐药中的作用。我们搜查了PubMed,WebofScience和Scopus数据库,遵循PRISMA准则,并在PROSPERO注册。提取物通过抑制癌细胞的增殖起作用,以及增强化疗的效果。它们的作用机制包括调节抗凋亡蛋白,抑制JAK2/STAT3通路,抑制ERK1/2通路,调节微小RNA和调节P-糖蛋白。这些结果突出了蘑菇提取物调节多种机制以提高化疗疗效的潜力。这项工作揭示了使用蘑菇提取物作为化疗的辅助手段来对抗化疗耐药性。虽然研究有限,蘑菇及其生物活性化合物的多样性为更有效地治疗癌症的创新策略显示了有希望的结果。进行进一步的研究以更好地了解蘑菇提取物的治疗潜力,以提高化疗在癌细胞中的疗效至关重要。
    Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of Science and Scopus databases, following the PRISMA guidelines, and registered on PROSPERO. The extracts acted by inhibiting the proliferation of cancer cells, as well as enhancing the effect of chemotherapy. The mechanisms by which they acted included regulating anti-apoptotic proteins, inhibiting the JAK2/STAT3 pathway, inhibiting the ERK1/2 pathway, modulating microRNAs and regulating p-glycoprotein. These results highlight the potential of mushroom extracts to modulate multiple mechanisms in order to improve the efficacy of chemotherapy. This work sheds light on the use of mushroom extracts as an aid to chemotherapy to combat chemoresistance. Although studies are limited, the diversity of mushrooms and their bioactive compounds show promising results for innovative strategies to treat cancer more effectively. It is crucial to carry out further studies to better understand the therapeutic potential of mushroom extracts to improve the efficacy of chemotherapy in cancer cells.
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  • 文章类型: Journal Article
    磨损(侵蚀/磨损)和腐蚀在几个工业装置中协同作用,其中腐蚀性流体与固相一起循环,导致相互损坏。高熵合金(HEAs)是有前途的材料,可用于这种类型的环境,因为它们具有出色的化学性能,电化学和机械性能。虽然目前有几篇关于腐蚀的评论文章,机械性能,HEAs的发展,微观结构,和HEA涂层,不可否认,缺乏针对散装HEA的摩擦学行为和摩擦腐蚀的全面而严格的审查。这项工作旨在收集,总结,并批判性地回顾HEA在过去20年中处理磨损的主要成就和进展,腐蚀,和耐磨性。它突出了可以影响HEAs性能的最重要方面,包括基础合金元素的变化,温度的影响,热处理,和磨损测试参数(负载,速度,持续时间,距离)。此外,运行机制,以及显微组织与耐磨性之间的关系,将描述微观结构和耐腐蚀性之间的关系。最后,将回顾文献中报道的有关HEAs摩擦腐蚀的文章。这项研究的结果有望指导潜在的研究人员,并为他们提供HEAs在耐腐蚀性方面的当前趋势的总和,耐磨性和两者的协同作用,希望帮助他们做出正确的决定来设计和开发新的HEAs或改进现有HEAs的研究。
    Wear (erosion/abrasion) and corrosion act in synergy in several industrial installations where corrosive fluids circulate together with a solid phase causing mutual damage. High entropy alloys (HEAs) are promising materials to be used in that type of environments because of their outstanding chemical, electrochemical and mechanical properties. While several review articles are currently available on corrosion, mechanical properties, development of HEAs, microstructure, and HEA coatings, there is an undeniable lack of a comprehensive and critical review focusing on the tribological behaviour and tribocorrosion of bulk HEAs. This work aims to collect, summarise, and critically review the major accomplishments and progresses of HEAs over the last 20 years dealing with wear, corrosion, and wear-corrosion resistance. It highlights the most significant aspects that can influence the performance of HEAs including the change of the base alloying elements, the influence of the temperature, heat treatment, and wear test parameters (load, velocity, duration, distance). Furthermore, operating mechanisms, together with the relationship between microstructure and wear resistance, and between microstructure and corrosion resistance will be described. Finally, the articles that have been reported in the literature dealing with tribocorrosion of HEAs will be reviewed. The results of this study are expected to guide potential researchers and provide them with the sum of current trends in HEAs in terms of corrosion resistance, wear resistance and the synergy of both, in the hope of helping them to make the right decision to design and develop new HEAs or improve the research on the existing ones.
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  • 文章类型: Review
    耐甲氧西林金黄色葡萄球菌(MRSA)菌血症可以是持续性和难治性的;然而,治疗的最佳方法尚未确定。尽管磷霉素(FOM)已被证明在体外与抗MRSA药物具有协同作用,FOM联合治疗的临床经验有限.因此,我们介绍了持续性MRSA菌血症的病例,这些病例在添加FOM后得到改善.在病例1中,尽管施用了万古霉素(VCM)和达托霉素(DAP),但患有人工血管移植物感染的48岁男性仍出现了持续的MRSA菌血症。第46天,第一次血培养阳性后,我们将FOM添加到DAP中。血液培养在第53天变为阴性。在病例2中,一名85岁的女性出现了与起搏器相关的MRSA菌血症。她接受了VCM治疗,其次是DAP和DAP加利福平。然而,菌血症持续了32天,因为难以立即移除起搏器.将FOM添加到DAP后,血培养在第38天变为阴性.在病例3中,一名57岁的妇女在食管癌全食管切除术后由于肺动脉瓣心内膜炎和肺动脉血栓形成而出现了持续性MRSA菌血症。尽管用DAP治疗,菌血症仍持续50天,其次是VCM,VCM加米诺环素,DAP加利奈唑胺(LZD),和VCM加LZD。由于手术并发症,她得到了保守的管理。在第51天向VCM添加FOM后,血液培养物在第58天变为阴性。FOM联合治疗可有效消除细菌,并可作为难治性MRSA菌血症的挽救治疗。
    Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia can be persistent and refractory; however, the optimal approach for its treatment has not been determined. Although fosfomycin (FOM) has been shown to have synergistic effects with anti-MRSA agents in vitro, clinical experience with FOM combination therapy is limited. Thus, we present cases of persistent MRSA bacteremia that improved with the addition of FOM. In case 1, a 48-year-old man with prosthetic vascular graft infection developed persistent MRSA bacteremia despite vancomycin (VCM) and daptomycin (DAP) administration. On day 46, after the first positive blood culture, we added FOM to DAP. The blood culture became negative on day 53. In case 2, an 85-year-old woman presented with pacemaker-related MRSA bacteremia. She was treated with VCM, followed by DAP and DAP plus rifampicin. However, the bacteremia persisted for 32 days because of difficulties in immediate pacemaker removal. After adding FOM to DAP, the blood culture became negative on day 38. In case 3, a 57-year-old woman developed persistent MRSA bacteremia due to pulmonary valve endocarditis and pulmonary artery thrombosis after total esophagectomy for esophageal cancer. The bacteremia continued for 50 days despite treatment with DAP, followed by VCM, VCM plus minocycline, DAP plus linezolid (LZD), and VCM plus LZD. She was managed conservatively because of surgical complications. After adding FOM to VCM on day 51, the blood culture became negative on day 58. FOM combination therapy may be effective in eliminating bacteria and can serve as salvage therapy for refractory MRSA bacteremia.
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  • 文章类型: Journal Article
    混合感染中的病毒间关系和病毒-干旱关系在农业和自然植被中很重要。在这次定量审查中,我们对已发表的阶乘实验进行抽样,以探索与可加性零假设的关系。我们的样本捕获了拮抗剂,双重感染中的加性和协同性病毒间关系。我们样本中的病毒-干旱关系是加性或拮抗性的,强化了病毒对干旱植物有中性或积极影响的观点,或者干旱增强了植物对病毒的耐受性。病毒间和病毒-干旱的关系都因病毒种类而异,寄主植物达到品种或加入的水平,感染时间,植物年龄和性状和生长条件。这些关系的性状依赖性对植物的资源分配具有影响。由于理论滞后,这些领域更多的实验研究必然会回归现象学结果。理论工作可以朝着两个互补的方向发展。首先,有效理论对系统的行为进行建模,而不指定导致系统状态变化的所有根本原因。第二,机械理论基于明确考虑向下因果关系的植物表型的细致入微的观点;植物表型对病毒间关系的影响,反之亦然;时间的影响,干旱与病毒相互作用以调节植物表型的强度和持续时间;干旱的土壤(水分)和大气(蒸气压不足)方面。理论应该随时间变化,从短期到完整的生长季节,以及相关特征的组织水平:农业中的作物产量和自然界中的适应性。
    Inter-virus relationships in mixed infections and virus-drought relationships are important in agriculture and natural vegetation. In this quantitative review, we sampled published factorial experiments to probe for relationships against the null hypothesis of additivity. Our sample captured antagonistic, additive and synergistic inter-virus relationships in double infections. Virus-drought relationships in our sample were additive or antagonistic, reinforcing the notion that viruses have neutral or positive effects on droughted plants, or that drought enhances plant tolerance to viruses. Both inter-virus and virus-drought relationships vary with virus species, host plant to the level of cultivar or accession, timing of infection, plant age and trait and growing conditions. The trait-dependence of these relationships has implications for resource allocation in plants. Owing to lagging theories, more experimental research in these fields is bound to return phenomenological outcomes. Theoretical work can advance in two complementary directions. First, the effective theory models the behaviour of the system without specifying all the underlying causes that lead to system state change. Second, mechanistic theory based on a nuanced view of the plant phenotype that explicitly considers downward causation; the influence of the plant phenotype on inter-virus relations and vice versa; the impact of timing, intensity and duration of drought interacting with viruses to modulate the plant phenotype; both the soil (moisture) and atmospheric (vapour pressure deficit) aspects of drought. Theories should scale in time, from short term to full growing season, and in levels of organisation up to the relevant traits: crop yield in agriculture and fitness in nature.
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  • 文章类型: Systematic Review
    耐碳青霉烯类肠杆菌(CRE)和耐多药铜绿假单胞菌(MDR-PA)感染与高发病风险相关,死亡率,和治疗费用。我们的目的是在体外评估,比较头孢他啶-阿维巴坦(CZA)联合方案与单独CZA对CRE和/或MDR-PA分离株或感染的疗效的体内和临床研究。
    我们系统地回顾了CINAHL/MEDLINE的相关文献,Pubmed,科克伦,WebofScience,Embase,和Scopus,直到2022年12月1日。评论文章,灰色文学,摘要,注释,社论,非同行评审文章,非英语文章,并排除了对单个分离株进行的体外协同作用研究。
    22在体外,评价了7项体内研究和20项临床研究。体外研究表明,CZA和氨曲南之间对产金属β-内酰胺酶(MBL)的分离株具有可靠的协同作用。一些研究表明CZA和阿米卡星之间具有良好的体外协同作用,美罗培南,磷霉素和多粘菌素对CRE分离株。对于MDR-PA分离株,体外或体内研究相对较少。在观察性临床研究中,死亡率,临床治愈,不良事件,单药治疗组和联合治疗组暴露后CZA耐药的发展大致相似.然而,在接受CZA联合治疗的患者中,抗生素相关的肾毒性和感染复发率较高.
    好处,如果有的话,MDR-PA感染中的CZA组合方案难以捉摸,因为很少有临床研究包括这些感染。目前没有关于使用CZA组合方案而不是CZA单一疗法的文献记载的临床益处。CZA联合氨曲南用于MBL生产者引起的严重感染应通过随机对照试验进行评估。
    https://www.crd.约克。AC.uk/prospro/display_record.php?RecordID=278552,CRD42021278552。
    UNASSIGNED: Carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections.
    UNASSIGNED: We systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded.
    UNASSIGNED: 22 in vitro, 7 in vivo and 20 clinical studies were evaluated. In vitro studies showed reliable synergy between CZA and aztreonam against metallo-β-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer in vitro or in vivo studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies.
    UNASSIGNED: The benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials.
    UNASSIGNED: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552.
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