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N-acetylcysteine effects on extracellular polymeric substances of Xylella fastidiosa: A spatiotemporal investigation with implications for biofilm disruption N-Acetylcysteine 对 Xylella fastidiosa 细胞外聚合物质的影响:时空研究及其对生物膜破坏的影响。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-17 DOI: 10.1016/j.ijantimicag.2024.107340
Aldeliane M. da Silva , Duber M. Murillo , Silambarasan Anbumani , Antonio Augusto von Zuben , Alessandro Cavalli , Helio T. Obata , Eduarda Regina Fischer , Mariana de Souza e Silva , Erik Bakkers , Alessandra A. Souza , Hernandes F. Carvalho , Mônica A. Cotta

Background

The matrix of extracellular polymeric substances (EPS) present in biofilms greatly amplifies the problem of bacterial infections, protecting bacteria against antimicrobial treatments and eventually leading to bacterial resistance. The need for alternative treatments that destroy the EPS matrix becomes evident. N-acetylcysteine (NAC) is one option that presents diverse effects against bacteria; however, the different mechanisms of action of NAC in biofilms have yet to be elucidated.

Objectives

In this work, we performed microscopy studies at micro and nano scales to address the effects of NAC at single cell level and early-stage biofilms of the Xylella fastidiosa phytopathogen.

Methods

We show the physical effects of NAC on the adhesion surface and the different types of EPS, as well as the mechanical response of individual bacteria to NAC concentrations between 2 and 20 mg/mL.

Results

NAC modified the conditioning film on the substrate, broke down the soluble EPS, resulting in the release of adherent bacteria, decreased the volume of loosely bound EPS, and disrupted the biofilm matrix. Tightly bound EPS suffered structural alterations despite no solid evidence of its removal. In addition, bacterial force measurements upon NAC action performed with InP nanowire arrays showed an enhanced momentum transfer to the nanowires due to increased cell mobility resulting from EPS removal.

Conclusions

Our results clearly show that conditioning film and soluble EPS play a key role in cell adhesion control and that NAC alters EPS structure, providing solid evidence that NAC actuates mainly on EPS removal, both at single cell and biofilm levels.
生物膜中存在的胞外高分子物质(EPS)基质大大加剧了细菌感染问题,保护细菌免受抗菌治疗,并最终导致细菌产生抗药性。因此,显然需要能破坏 EPS 基质的替代治疗方法。N- 乙酰半胱氨酸(NAC)是一种能对细菌产生多种作用的选择;然而,NAC 在生物膜中的不同作用机制仍有待阐明。在这项工作中,我们进行了微米和纳米尺度的显微镜研究,以探讨 NAC 在单细胞水平和 Xylella fastidiosa 植物病原体早期生物膜中的作用。我们展示了 NAC 对粘附表面和不同类型 EPS 的物理效应,以及单个细菌对 2 至 20 mg/mL NAC 浓度的机械响应。NAC 改变了基质上的调节膜,分解了可溶性 EPS,导致附着细菌释放,减少了松散结合 EPS 的体积,并破坏了生物膜基质。尽管没有确凿证据表明 EPS 被清除,但紧密结合的 EPS 结构发生了改变。此外,在使用 InP 纳米线阵列进行 NAC 作用时的细菌力测量结果表明,由于 EPS 被清除,细胞流动性增加,因此纳米线的动量传递增强。我们的研究结果清楚地表明,调节膜和可溶性 EPS 在细胞粘附控制中起着关键作用,而 NAC 改变了 EPS 的结构,从而提供了确凿的证据,证明 NAC 在单细胞和生物膜水平上的作用主要是去除 EPS。
{"title":"N-acetylcysteine effects on extracellular polymeric substances of Xylella fastidiosa: A spatiotemporal investigation with implications for biofilm disruption","authors":"Aldeliane M. da Silva ,&nbsp;Duber M. Murillo ,&nbsp;Silambarasan Anbumani ,&nbsp;Antonio Augusto von Zuben ,&nbsp;Alessandro Cavalli ,&nbsp;Helio T. Obata ,&nbsp;Eduarda Regina Fischer ,&nbsp;Mariana de Souza e Silva ,&nbsp;Erik Bakkers ,&nbsp;Alessandra A. Souza ,&nbsp;Hernandes F. Carvalho ,&nbsp;Mônica A. Cotta","doi":"10.1016/j.ijantimicag.2024.107340","DOIUrl":"10.1016/j.ijantimicag.2024.107340","url":null,"abstract":"<div><h3>Background</h3><div>The matrix of extracellular polymeric substances (EPS) present in biofilms greatly amplifies the problem of bacterial infections, protecting bacteria against antimicrobial treatments and eventually leading to bacterial resistance. The need for alternative treatments that destroy the EPS matrix becomes evident. N-acetylcysteine (NAC) is one option that presents diverse effects against bacteria; however, the different mechanisms of action of NAC in biofilms have yet to be elucidated.</div></div><div><h3>Objectives</h3><div>In this work, we performed microscopy studies at micro and nano scales to address the effects of NAC at single cell level and early-stage biofilms of the <em>Xylella fastidiosa</em> phytopathogen.</div></div><div><h3>Methods</h3><div>We show the physical effects of NAC on the adhesion surface and the different types of EPS, as well as the mechanical response of individual bacteria to NAC concentrations between 2 and 20 mg/mL.</div></div><div><h3>Results</h3><div>NAC modified the conditioning film on the substrate, broke down the soluble EPS, resulting in the release of adherent bacteria, decreased the volume of loosely bound EPS, and disrupted the biofilm matrix. Tightly bound EPS suffered structural alterations despite no solid evidence of its removal. In addition, bacterial force measurements upon NAC action performed with InP nanowire arrays showed an enhanced momentum transfer to the nanowires due to increased cell mobility resulting from EPS removal.</div></div><div><h3>Conclusions</h3><div>Our results clearly show that conditioning film and soluble EPS play a key role in cell adhesion control and that NAC alters EPS structure, providing solid evidence that NAC actuates mainly on EPS removal, both at single cell and biofilm levels.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107340"},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The efficacy of keverprazan-based quadruple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind, multicentre trial 基于开瑞坦的根除幽门螺旋杆菌四联疗法的疗效:一项 III 期随机、双盲、多中心试验。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-16 DOI: 10.1016/j.ijantimicag.2024.107320
Niandi Tan , Hao Wu , Cheng Lan , Chengxia Liu , Aijun Liao , Zhiyong Jiao , Dongxing Su , Xiaomei Zhang , Zhe Zhang , Weiming Xiao , Fangfang Li , Xing Li , Min Xia , Rongyuan Qiu , Huixin Chen , Youli Liu , Mei Su , Minhu Chen , Yinglian Xiao

Introduction

Keverprazan is a novel potassium-competitive acid blocker. The advantages of keverprazan as a potent acid suppressor in Helicobacter pylori eradication have not yet been demonstrated. The aim of this study was to evaluate the efficacy of keverprazan as a component of bismuth quadruple therapy in H. pylori treatment.

Methods

Adult patients with H. pylori infection were enrolled and randomised to take keverprazan (KEV group)- or esomeprazole (ESO group)-quadruple therapy. The regimens contained keverprazan 20 mg or esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 240 mg and were administered twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment.

Results

The full analysis set showed that the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for the KEV and ESO groups, respectively (difference: 5.29%; 95% confidence interval [CI]: -0.55–11.18). Keverprazan was superior to esomeprazole in terms of eradication rate in the per protocol set (P=0.0382). The eradication rates for patients resistant or non-resistant to clarithromycin were both numerically higher in the KEV group than the ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 92.31% vs. 88.16% for clarithromycin-non-resistance). The incidence of adverse events was similar in the KEV and ESO groups (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity. No TEAEs led to death in either group.

Conclusions

Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy, provided effective H. pylori eradication and was non-inferior to an esomeprazole-based regimen.
简介Keverprazan是一种新型钾竞争性酸阻滞剂,其作为强效酸抑制剂根除幽门螺旋杆菌(H. pylori)的优势尚未得到证实。本研究旨在评估 Keverprazan 作为四联铋剂治疗幽门螺杆菌的疗效:成年幽门螺杆菌感染患者入组并随机接受开瑞普拉赞(KEV组)或埃索美拉唑(ESO组)-四联疗法(治疗方案包括开瑞普拉赞20毫克或埃索美拉唑20毫克、克拉霉素500毫克、阿莫西林1000毫克、枸橼酸铋钾240毫克),每日两次,共14天。主要终点是治疗后 4 周的幽门螺杆菌根除率:全套分析结果显示,KEV 组和 ESO 组的幽门螺杆菌根除率分别为 87.8%(252/287)和 82.52%(236/286)(差异:5.29%;95% CI:-0.55% 至 11.18%)。就根除率而言,按方案组观察到开维普拉赞优于埃索美拉唑(P=0.0382)。KEV组对克拉霉素耐药或不耐药患者的根除率均高于ESO组(克拉霉素耐药患者的根除率为83.45%,ESO组为76.98%;克拉霉素不耐药患者的根除率为96.67%,ESO组为93.38%)。KEV组和ESO组的不良反应发生率相似(76.31% vs. 77.62%),大多数不良反应(>90%)的严重程度较轻,没有导致死亡:结论:Keverprazan 20 毫克,每日两次,作为铋剂四联疗法的一部分,可有效根除幽门螺杆菌,其疗效不劣于以埃索美拉唑为基础的治疗方案。
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引用次数: 0
Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: In vitro and in vivo proof-of-concept studies 异巴伐醌提高耐大肠菌素肺炎克雷伯氏菌的敏感性:体外和体内概念验证研究。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-16 DOI: 10.1016/j.ijantimicag.2024.107338
Xiang Geng , Yuxi Li , Ruochen Hao , Chunyan Xu , Zhun Li , Yajun Yang , Xiwang Liu , Jianyong Li , Wanxia Pu

Objective

Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae (K. pneumoniae) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo.

Results

The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro concurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone.

Conclusion

These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae-associated infections.
抗生素耐药性引起了全世界的广泛关注,尤其是在临床环境中,肺炎克雷伯氏菌等耐药革兰氏阴性菌构成了重大挑战。本研究旨在探讨异巴伐醌(IBC)在体外恢复肺炎克雷伯菌对可乐定敏感性的机制,并在体内验证其协同治疗效果。结果表明,在体外和体内联合使用可乐定和 IBC 都能显示出强大的抗菌效果。体外同时给予可乐定和 IBC 会导致膜通透性增加、细胞完整性受损、膜流动性降低以及膜平衡被破坏。此外,这种组合还减少了生物膜的生成,抑制了 AI-2 因子的合成,改变了膜电位,影响了活性氧和三磷酸腺苷的合成水平,最终导致细菌死亡。在小白蛾和小鼠身上进行的体内实验表明,与单独使用可乐定相比,联合使用可乐定和 IBC 可提高存活率并显著减少病理损伤。这些结果表明,IBC 通过诱导细菌膜的物理破坏和氧化应激,有效地恢复了可乐定的敏感性。可乐定和 IBC 的联合疗法为抗击耐药肺炎双球菌相关感染提供了一种可行而安全的策略。
{"title":"Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: In vitro and in vivo proof-of-concept studies","authors":"Xiang Geng ,&nbsp;Yuxi Li ,&nbsp;Ruochen Hao ,&nbsp;Chunyan Xu ,&nbsp;Zhun Li ,&nbsp;Yajun Yang ,&nbsp;Xiwang Liu ,&nbsp;Jianyong Li ,&nbsp;Wanxia Pu","doi":"10.1016/j.ijantimicag.2024.107338","DOIUrl":"10.1016/j.ijantimicag.2024.107338","url":null,"abstract":"<div><h3>Objective</h3><div>Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like <em>Klebsiella pneumoniae</em> (<em>K. pneumoniae</em>) present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of <em>K. pneumoniae</em> to colistin in vitro and to validate the synergistic therapeutic effect in vivo.</div></div><div><h3>Results</h3><div>The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro <em>c</em>oncurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the autoinducer factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on <em>Galleria mellonella</em> and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone.</div></div><div><h3>Conclusion</h3><div>These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant <em>K. pneumoniae</em>-associated infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107338"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens 抗癌剂 5-氟尿嘧啶可逆转耐碳青霉烯类革兰氏阴性病原体对美罗培南的耐药性。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-16 DOI: 10.1016/j.ijantimicag.2024.107337
Muchen Zhang , Siyuan Yang , Yongqing Liu , Zhiyu Zou , Yan Zhang , Yunrui Tian , Rong Zhang , Dejun Liu , Congming Wu , Jianzhong Shen , Huangwei Song , Yang Wang
The global increasing incidence of clinical infections caused by carbapenem-resistant Gram-negative pathogens requires urgent and effective treatment strategies. Antibiotic adjuvants represent a promising approach to enhance the efficacy of meropenem against carbapenem-resistant bacteria. This study shows that the anticancer agent 5-fluorouracil (5-FU, 50 µM) significantly reduced the minimum inhibitory concentration of meropenem against blaNDM-5 positive Escherichia coli by 32-fold through cell-based high-throughput screening. Further pharmacological studies indicated that 5-FU exhibited potentiation effects on carbapenem antibiotics against 42 Gram-negative bacteria producing either metallo-β-lactamases (MBLs), such as NDM and IMP, or serine β-lactamases (Ser-BLs), like KPC and OXA. These bacteria included E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp., 32 of which were obtained from human clinical samples. Mechanistic investigations revealed that 5-FU inhibited the transcription and expression of the blaNDM-5 gene. In addition, 5-FU combined with meropenem enhanced bacterial metabolism, and stimulated the production of reactive oxygen species (ROS), thereby rendering bacteria more susceptible to meropenem. In a mouse systemic infection model, 5-FU combined with meropenem reduced bacterial loads and effectively elevated the survival rate of 83.3%, compared with 16.7% with meropenem monotherapy. Collectively, these findings indicate the potential of 5-FU as a novel meropenem adjuvant to improve treatment outcomes against infections caused by carbapenem-resistant bacteria.
耐碳青霉烯类革兰氏阴性病原体引起的临床感染发病率在全球范围内不断上升,迫切需要有效的治疗策略。抗生素辅助剂是提高美罗培南对耐碳青霉烯类细菌疗效的一种可行方法。在此,我们通过基于细胞的高通量筛选,发现抗癌剂 5-氟尿嘧啶(5-FU,50 µM)能将美罗培南对 blaNDM-5 阳性大肠杆菌的最小抑菌浓度显著降低 32 倍。进一步的药理学研究表明,5-FU 对 42 种产生金属-β-内酰胺酶(MBLs)(如 NDM 和 IMP)或丝氨酸 β-内酰胺酶(Ser-BLs)(如 KPC 和 OXA)的革兰氏阴性细菌具有碳青霉烯类抗生素的增效作用。这些细菌包括大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和不动杆菌,其中 32 种细菌来自人类临床样本。机理研究发现,5-FU 可抑制 blaNDM-5 基因的转录和表达水平。此外,5-FU 与美罗培南合用可增强细菌的新陈代谢,刺激活性氧(ROS)的产生,从而使细菌更易受美罗培南的影响。在小鼠全身感染模型中,与美罗培南单药治疗相比,这种药物组合能有效地将存活率从 16.7% 提高到 83.3%,并减少组织中的细菌数量。总之,这些发现揭示了 5-FU 作为一种新型美罗培南辅助药物改善耐碳青霉烯类细菌感染治疗效果的潜力。
{"title":"Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens","authors":"Muchen Zhang ,&nbsp;Siyuan Yang ,&nbsp;Yongqing Liu ,&nbsp;Zhiyu Zou ,&nbsp;Yan Zhang ,&nbsp;Yunrui Tian ,&nbsp;Rong Zhang ,&nbsp;Dejun Liu ,&nbsp;Congming Wu ,&nbsp;Jianzhong Shen ,&nbsp;Huangwei Song ,&nbsp;Yang Wang","doi":"10.1016/j.ijantimicag.2024.107337","DOIUrl":"10.1016/j.ijantimicag.2024.107337","url":null,"abstract":"<div><div>The global increasing incidence of clinical infections caused by carbapenem-resistant Gram-negative pathogens requires urgent and effective treatment strategies. Antibiotic adjuvants represent a promising approach to enhance the efficacy of meropenem against carbapenem-resistant bacteria. This study shows that the anticancer agent 5-fluorouracil (5-FU, 50 µM) significantly reduced the minimum inhibitory concentration of meropenem against <em>bla</em><sub>NDM-5</sub> positive <em>Escherichia coli</em> by 32-fold through cell-based high-throughput screening. Further pharmacological studies indicated that 5-FU exhibited potentiation effects on carbapenem antibiotics against 42 Gram-negative bacteria producing either metallo-β-lactamases (MBLs), such as NDM and IMP, or serine β-lactamases (Ser-BLs), like KPC and OXA. These bacteria included <em>E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa</em> and <em>Acinetobacter spp.</em>, 32 of which were obtained from human clinical samples. Mechanistic investigations revealed that 5-FU inhibited the transcription and expression of the <em>bla</em><sub>NDM-5</sub> gene. In addition, 5-FU combined with meropenem enhanced bacterial metabolism, and stimulated the production of reactive oxygen species (ROS), thereby rendering bacteria more susceptible to meropenem. In a mouse systemic infection model, 5-FU combined with meropenem reduced bacterial loads and effectively elevated the survival rate of 83.3%, compared with 16.7% with meropenem monotherapy. Collectively, these findings indicate the potential of 5-FU as a novel meropenem adjuvant to improve treatment outcomes against infections caused by carbapenem-resistant bacteria.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107337"},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetics and safety of colistin sulfate after single and multiple intravenous doses in healthy Chinese subjects 中国健康受试者单次和多次静脉注射硫酸可乐定的药代动力学和安全性。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-12 DOI: 10.1016/j.ijantimicag.2024.107326
Xiaolan Huang , Xiaofen Liu , Yaxin Fan , Yu Wang , Beining Guo , Jingjing Wang , Jicheng Yu , Qiong Wei , Xiaojie Wu , Haihui Huang , Jing Zhang

Objective

Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear.

Methods

This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10,000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group, n = 12) or the same dose q12h for 7 days (multi-dose group, n = 12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis.

Results

After a single dose the peak concentration (Cmax), area under the curve from 0 to 12 h (AUC0-12h), terminal half-life (T1/2), volume of distribution (Vd), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported.

Conclusions

This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice.
背景:抗菌药耐药性的不断增加导致多粘菌素类药物作为治疗耐多药革兰氏阴性菌感染的最后选择而重新兴起。硫酸可乐定的肠外制剂仅在中国有售。虽然静脉注射可乐定的起效时间可能比其原药 CMS 更快,但其药代动力学(PK)特征仍不清楚:这项单中心、开放标签、单剂量和多剂量的 1 期试验研究了硫酸可乐定在中国健康成人中的药代动力学和安全性。参试者通过2小时静脉输注接受单剂量10000单位/千克(相当于0.452毫克/千克)的硫酸可乐定(单剂量组,12人)或连续7天每12小时接受相同剂量的硫酸可乐定(多剂量组,12人)。使用 LC-MS/MS 测定血浆和尿液中的秋水仙素浓度,并使用非室分析法计算 PK 参数:单次给药后,可乐定的峰值浓度(Cmax)、0-12 h曲线下面积(AUC0-12h)、终末半衰期(T1/2)、分布容积(Vd)和全身清除率(CL)分别为 1.08 ± 0.18 mg/L、4.73 ± 0.89 h-mg/L、3.65 ± 0.55 h、16.82 ± 2.70 L 和 3.24 ± 0.51 L/h。多次给药后未观察到可乐定蓄积。多剂量给药后 24 小时内,可乐定的累积尿回收率为 0.9 ± 0.7%。无肾毒性报告:本研究首次报道了中国健康受试者单次和多次服用硫酸秋司汀后的秋司汀PK。结论:该研究首次报道了中国健康受试者单次和多次服用硫酸可乐定后的 PK 和安全性数据,为临床实践中选择最佳剂量提供了依据。
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引用次数: 0
Past, Present, and Future Biomarkers of Kidney Function and Injury: The Relationship With Antibiotics 肾功能和肾损伤的过去、现在和未来生物标志物:与抗生素的关系。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-07 DOI: 10.1016/j.ijantimicag.2024.107332
Jack Chang , Gwendolyn M. Pais , Erin F. Barreto , Bryce Young , Haley Scott , Zachary Schwartz , Collin Cartwright , Raymond Jubrail , Anand Srivastava , Marc H. Scheetz
Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing.
常规使用的肾脏损伤和功能生物标志物,如血清肌酐和尿白蛋白与肌酐比值,既不敏感也不特异。目前正在开发用于临床的未来生物标志物,并已将其纳入美国食品药品管理局和预测安全性测试联盟等组织的指南中。这些生物标志物对于早期识别肾损伤和更准确地测量肾功能具有重要意义。许多抗生素要么会被肾脏排出体外,要么会引起明显的临床肾毒性。因此,临床医生应该熟悉肾功能和肾损伤的新生物标记物、它们在临床实践中的地位以及在抗生素剂量中的应用。
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引用次数: 0
In-host intra- and inter-species transfer of blaKPC-2 and blaNDM-1 in Serratia marcescens and its local and global epidemiology Serratia marcescens 中 blaKPC-2 和 blaNDM-1 的宿主内和种间转移及其地方和全球流行病学。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-07 DOI: 10.1016/j.ijantimicag.2024.107327
Feilong Zhang , Zhihua Li , Xinmeng Liu , Ziyao Li , Zichen Lei , Jiankang Zhao , Yulin Zhang , Yongli Wu , Xinrui Yang , Binghuai Lu

Objectives

The aim of this study was to investigate interspecies transfer of resistance gene blaNDM-1 and intraspecies transfer of resistance gene blaKPC-2 in Serratia marcescens, and explore the epidemical and evolutionary characteristics of carbapenemase-producing S. marcescens (CPSM) regionally and globally.

Methods

Interspecies and intraspecies transfer of blaKPC-2- or blaNDM-1 were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.

Results

CPSM S50079 strain, co-carrying blaKPC-2 and blaNDM-1 on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either blaKPC-2 or blaNDM-1. The interspecies transfer of blaNDM-1-carrying plasmid from Providencia rettgeri P50213, producing the identical blaNDM-1-carrying TUs, to S. marcescens S50079K, an S50079 variant via plasmid curing, was identified through blaNDM-1-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of blaKPC-2, mediated by IS26 from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of blaNDM-1 carried by IncX3 plasmid was identified among S. marcescens and Citrobacter freundii as well as Enterobacter hormaechei via plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive S. marcescens strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from blaKPC-2 to both blaKPC-2 and blaNDM-1, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive S. marcescens genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.

Conclusions

Interspecies transfer of resistance gene blaNDM-1 and intraspecies transfer of resistance gene blaKPC-2 in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.
研究目的本研究旨在调查产碳青霉烯酶沙雷氏菌耐药基因 blaNDM-1 的种间转移和 blaKPC-2 的种内转移,并探讨产碳青霉烯酶沙雷氏菌(CPSM)在区域和全球范围内的流行和进化特征:方法:通过抗菌药物敏感性测试、质粒共轭和固化、发现转座单元(TU)、外膜囊泡(OMV)、qPCR、全基因组测序和生物信息学分析,确定了 blaKPC-2- 或 blaNDM-1 的种间和种内转移。通过 cgSNP 和最大似然系统发生树探讨了 CPSM 菌株的基因组进化:结果:从一名急性胰腺炎患者的血液中分离出了CPSM S50079菌株,它在一个质粒上同时携带blaKPC-2和blaNDM-1,并能产生携带blaKPC-2或blaNDM-1的TU。我们确定了携带 blaNDM-1 的质粒通过质粒固化、blaNDM-1-harboring 质粒共轭和 OMVs 转移,从产生相同携带 blaNDM-1 的 TU 的普罗维登斯菌(Providencia rettgeri)P50213 转移到 S. marcescens S50079K(一种 S50079 变种)。此外,在 S50079 中还发现了由 IS26 介导的 blaKPC-2 从质粒到染色体的种内转移。可能的是,在另一名肺移植患者中,也发现了由 IncX3 质粒携带的 blaNDM-1 通过质粒转移在 S. marcescens 和 Citrobacter freundii 以及 Enterobacter hormaechei 之间进行种间转移。此外,在同一家医院的 349 株非重复性 S. marcescens 菌株中发现了 11 个 CPSM,在这 8 个 CPSM 中发现了碳青霉烯酶从 blaKPC-2 演化为 blaKPC-2 和 blaNDM-1 的克隆传播,时间跨度长达四年。最后,对从 NCBI 数据库中检索到的 835 个非重复性 S. marcescens 基因组中的 236 个全球 CPSM 进行分析后发现,碳青霉烯酶在全球范围内长期传播和进化,并将导致更多的碳青霉烯酶基因趋同:结论:在CPSM中发现了耐药基因blaNDM-1的种间转移和耐药基因blaKPC-2的种内转移。结论:发现了CPSM中耐药基因blaNDM-1的种间转移和耐药基因blaKPC-2的种内转移,揭示了CPSM的本地传播和全球传播,需要进行更紧迫的监测。
{"title":"In-host intra- and inter-species transfer of blaKPC-2 and blaNDM-1 in Serratia marcescens and its local and global epidemiology","authors":"Feilong Zhang ,&nbsp;Zhihua Li ,&nbsp;Xinmeng Liu ,&nbsp;Ziyao Li ,&nbsp;Zichen Lei ,&nbsp;Jiankang Zhao ,&nbsp;Yulin Zhang ,&nbsp;Yongli Wu ,&nbsp;Xinrui Yang ,&nbsp;Binghuai Lu","doi":"10.1016/j.ijantimicag.2024.107327","DOIUrl":"10.1016/j.ijantimicag.2024.107327","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this study was to investigate interspecies transfer of resistance gene <em>bla</em><sub>NDM-1</sub> and intraspecies transfer of resistance gene <em>bla</em><sub>KPC-2</sub> in <em>Serratia marcescens</em>, and explore the epidemical and evolutionary characteristics of carbapenemase-producing <em>S. marcescens</em> (CPSM) regionally and globally.</div></div><div><h3>Methods</h3><div>Interspecies and intraspecies transfer of <em>bla</em><sub>KPC-2</sub>- or <em>bla</em><sub>NDM-1</sub> were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.</div></div><div><h3>Results</h3><div>CPSM S50079 strain, co-carrying <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>NDM-1</sub> on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either <em>bla</em><sub>KPC-2</sub> or <em>bla</em><sub>NDM-1</sub>. The interspecies transfer of <em>bla</em><sub>NDM-1</sub>-carrying plasmid from <em>Providencia rettgeri</em> P50213, producing the identical <em>bla</em><sub>NDM-1</sub>-carrying TUs, to <em>S. marcescens</em> S50079K, an S50079 variant <em>via</em> plasmid curing, was identified through <em>bla</em><sub>NDM-1</sub>-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of <em>bla</em><sub>KPC-2</sub>, mediated by IS<em>26</em> from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of <em>bla</em><sub>NDM-1</sub> carried by IncX3 plasmid was identified among <em>S. marcescens</em> and <em>Citrobacter freundii</em> as well as <em>Enterobacter hormaechei via</em> plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive <em>S. marcescens</em> strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from <em>bla</em><sub>KPC-2</sub> to both <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>NDM-1</sub>, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive <em>S. marcescens</em> genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.</div></div><div><h3>Conclusions</h3><div>Interspecies transfer of resistance gene <em>bla</em><sub>NDM-1</sub> and intraspecies transfer of resistance gene <em>bla</em><sub>KPC-2</sub> in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107327"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis vonoprazan和大剂量阿莫西林双重疗法根除幽门螺旋杆菌的有效性和安全性:系统回顾和荟萃分析。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-07 DOI: 10.1016/j.ijantimicag.2024.107331
Ju Zhang , Huan Zhang , Xiao-Jing Zhu , Nuo Yao , Ju-Mei Yin , Jian Liu , Han-Jun Dan , Qi-Meng Pang , Zhi-Hua Liu , Yong-Quan Shi

Background

Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating Helicobacter pylori. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis.

Materials and Methods

A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing H. pylori eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis.

Results

Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior H. pylori eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07–1.73; P=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07–1.88; P=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35–0.68, P<0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98–1.64; P=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03–3.00; P=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55–0.75), 92% (95% CI 0.91–0.94) and 93% (95% CI 0.90–0.97), respectively.

Conclusion

VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.
背景:新型抑酸药物沃诺普拉赞为根除幽门螺杆菌提供了更多选择。因此,沃诺普拉赞和大剂量阿莫西林双重疗法是否更有效、更安全,需要进行系统分析:对截至 2024 年 5 月 16 日的 PubMed、Embase、Cochrane Library 和 Web of Science 数据库中的文献进行了全面检索。纳入了评估VHA双重疗法与其他疗法相比的幽门螺杆菌根除率、不良事件和依从性的研究。使用RevMan 5.4进行统计分析:结果:共纳入11项研究性临床试验和2项回顾性临床研究,4570个样本。VHA双重疗法具有更高的幽门螺杆菌根除率(ITT:86.0% vs 80.7%,OR=1.36,95%CI 1.07-1.73,P=0.01;PP:90.6% vs 85.7%,OR=1.42,95%CI 1.07-1.88,P=0.02)、更少的不良反应(15.4% vs 27.7%,OR=0.49,95%CI 0.35-0.68,PConclusion):与指南推荐的疗法相比,VHA 10 天或 14 天双重疗法的疗效和安全性更佳,应优先采用。
{"title":"Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis","authors":"Ju Zhang ,&nbsp;Huan Zhang ,&nbsp;Xiao-Jing Zhu ,&nbsp;Nuo Yao ,&nbsp;Ju-Mei Yin ,&nbsp;Jian Liu ,&nbsp;Han-Jun Dan ,&nbsp;Qi-Meng Pang ,&nbsp;Zhi-Hua Liu ,&nbsp;Yong-Quan Shi","doi":"10.1016/j.ijantimicag.2024.107331","DOIUrl":"10.1016/j.ijantimicag.2024.107331","url":null,"abstract":"<div><h3>Background</h3><div>Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating <em>Helicobacter pylori</em>. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis.</div></div><div><h3>Materials and Methods</h3><div>A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing <em>H. pylori</em> eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis.</div></div><div><h3>Results</h3><div>Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior <em>H. pylori</em> eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07–1.73; <em>P</em>=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07–1.88; <em>P</em>=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35–0.68, <em>P</em>&lt;0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98–1.64; <em>P</em>=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03–3.00; <em>P</em>=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55–0.75), 92% (95% CI 0.91–0.94) and 93% (95% CI 0.90–0.97), respectively.</div></div><div><h3>Conclusion</h3><div>VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107331"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286361","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}
引用次数: 0
Advances in Virus-Specific T-Cell Therapy for Polyomavirus Infections: A Comprehensive Review 多瘤病毒感染的病毒特异性 T 细胞疗法进展:全面回顾。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-07 DOI: 10.1016/j.ijantimicag.2024.107333
Baran Alkan , M. Asli Tuncer , A. Çağkan İnkaya
Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.
多瘤病毒是一类小型、无包膜、双链 DNA 病毒,可感染包括人类在内的各种宿主。已知 BKPyV 可导致人类多瘤病毒相关性肾病(HPyVAN)、人类多瘤病毒相关性出血性膀胱炎(HPyVHC)和人类多瘤病毒相关性尿道癌(HPyVUC)等疾病。另一方面,JCPyV 可导致进行性多灶性白质脑病(PML),这是一种严重的中枢神经系统脱髓鞘疾病。PML 主要影响免疫力低下的人群,包括艾滋病毒感染者、某些免疫抑制疗法的接受者和移植患者。人类乳头瘤病毒感染的治疗方案一直很有限,但病毒特异性 T 细胞(VST)疗法的最新进展已显示出希望。虽然 VST 疗法在治疗 BKPyV 和 JCPyV 感染方面已显示出希望,但仍存在一些挑战。这些挑战包括:VST 的制备耗时且成本高昂、需要先进的生产设备,以及最佳细胞类型和输注频率的不确定性。据我们所知,有 85 名出血性膀胱炎患者、27 名 BKPyV 病毒血症患者、2 名 BKPyV 肾炎患者、14 名出血性膀胱炎和 BKPyV 病毒血症患者以及 32 名 PML 患者接受了 VST 治疗。完全应答、部分应答、无应答和无结果报告(NA)分别为 82 例、33 例、35 例和 10 例。总之,本综述强调了VST疗法作为一种治疗多瘤病毒感染的有前途的方法的重要性,并强调需要继续开展研究和临床试验,以完善和扩展这种创新的免疫治疗策略。
{"title":"Advances in Virus-Specific T-Cell Therapy for Polyomavirus Infections: A Comprehensive Review","authors":"Baran Alkan ,&nbsp;M. Asli Tuncer ,&nbsp;A. Çağkan İnkaya","doi":"10.1016/j.ijantimicag.2024.107333","DOIUrl":"10.1016/j.ijantimicag.2024.107333","url":null,"abstract":"<div><div>Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107333"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epidemiology of Subsequent Carbapenem-Resistant Enterobacterales (CRE) Infection Among Rectal Carriers: A Meta-Analysis of Incidence, Risk Factors and Their Association With Geographic Region and Age 直肠带菌者继发耐碳青霉烯类肠杆菌 (CRE) 感染的流行病学:发病率、风险因素及其与地理区域和年龄关系的荟萃分析。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-07 DOI: 10.1016/j.ijantimicag.2024.107335
Yuhan Wei , Huijuan Luo , Xia Chen , Qun Yan

Background

This study aimed to assess the incidence and risk factors of subsequent carbapenem-resistant Enterobacterales (CRE) infection among rectal carriers, and their association with geographic region and age.

Methods

A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to 31 January 2024). This study is registered with PROSPERO (CRD42023444420).

Results

Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9–25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2–34.5), followed by Europe (20.9%, 95% CI 12.5–30.8) and Asia (19.8%, 95% CI 12.7–27.9). Children had a greater incidence (26.7%, 95% CI 21.3–32.3) than adults (19.8%, 95% CI 14.9–25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (odds ratio [OR] 4.95 95% CI 1.87–13.11). In Europe, admission to the intensive care unit was prominent (OR 2.76 95% CI 1.14–6.65). In the America, the use of a urinary Foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to the intensive care unit was most notable in adults (OR 3.01 95% CI 1.80–5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39–55.47).

Conclusions

Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help in developing more potent prevention and control measures to reduce CRE infection.
研究目的本研究旨在评估直肠带菌者继发 CRE 感染的发生率和风险因素,以及它们与地理区域和年龄的关系:对调查直肠带菌者CRE后续感染发生率和/或风险因素的研究进行了荟萃分析,并按地理区域和年龄进行了亚组分析。研究人员检索了 PubMed、Embase、Web of Science 和 Cochrane Library(发表时间从开始到 2024 年 1 月 31 日)。本研究已在 PROSPERO 注册,编号为 CRD42023444420:结果:在确定的 4459 项研究中,纳入了 24 项研究,共有 8188 名 CRE 直肠携带者。CRE后续感染的总发生率为20.6%(95% CI 15.9-25.8)。美国的发病率最高(23.6%,95% CI 14.2-34.5),其次是欧洲(20.9%,95% CI 12.5-30.8)和亚洲(19.8%,95% CI 12.7-27.9)。儿童的发病率(26.7%,95% CI 21.3-32.3)高于成人(19.8%,95% CI 14.9-25.2)。有 14 个因素与随后的 CRE 感染有关。在亚洲,最显著的风险因素是胃炎(OR 4.95 95% CI 1.87-13.11)。在欧洲,入住重症监护室是最重要的因素(OR 2.76 95% CI 1.14-6.65)。在美国,使用输尿导管(OR 4.33 95% CI 1.06-17.70)是主要原因。入住重症监护室在成人中最显著(OR 3.01 95% CI 1.80-5.02),而机械通气在儿童中最显著(OR 15.61 95% CI 4.39-55.47):结论:直肠带菌者继发 CRE 感染的风险至关重要。结论:直肠携带者继发 CRE 感染的风险至关重要,确定继发感染的风险因素有助于制定更有效的预防和控制措施,减少 CRE 感染。
{"title":"Epidemiology of Subsequent Carbapenem-Resistant Enterobacterales (CRE) Infection Among Rectal Carriers: A Meta-Analysis of Incidence, Risk Factors and Their Association With Geographic Region and Age","authors":"Yuhan Wei ,&nbsp;Huijuan Luo ,&nbsp;Xia Chen ,&nbsp;Qun Yan","doi":"10.1016/j.ijantimicag.2024.107335","DOIUrl":"10.1016/j.ijantimicag.2024.107335","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to assess the incidence and risk factors of subsequent carbapenem-resistant Enterobacterales (CRE) infection among rectal carriers, and their association with geographic region and age.</div></div><div><h3>Methods</h3><div>A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to 31 January 2024). This study is registered with PROSPERO (CRD42023444420).</div></div><div><h3>Results</h3><div>Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9–25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2–34.5), followed by Europe (20.9%, 95% CI 12.5–30.8) and Asia (19.8%, 95% CI 12.7–27.9). Children had a greater incidence (26.7%, 95% CI 21.3–32.3) than adults (19.8%, 95% CI 14.9–25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (odds ratio [OR] 4.95 95% CI 1.87–13.11). In Europe, admission to the intensive care unit was prominent (OR 2.76 95% CI 1.14–6.65). In the America, the use of a urinary Foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to the intensive care unit was most notable in adults (OR 3.01 95% CI 1.80–5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39–55.47).</div></div><div><h3>Conclusions</h3><div>Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help in developing more potent prevention and control measures to reduce CRE infection.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 5","pages":"Article 107335"},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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International Journal of Antimicrobial Agents
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