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Access to phage therapy at Hospices Civils de Lyon in 2022: Implementation of the PHAGEinLYON Clinic programme 2022 年里昂平民医院的噬菌体疗法:PHAGEinLYON 诊所计划的实施。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-12-01 DOI: 10.1016/j.ijantimicag.2024.107372
Tristan Ferry , Myrtille Le Bouar , Thomas Briot , Tiphaine Roussel-Gaillard , Thomas Perpoint , Sandrine Roux , Florence Ader , Florent Valour , Behrouz Kassai , Inesse Boussaha , Marietou Ndiaye , Fabien Craighero , Clément Javaux , Sébastien Lustig , Cécile Batailler

Objectives

To describe the PHAGEinLYON Clinic programme, set up in 2022 to improve access to phage therapy in France using pharmaceutical-grade phages.

Methods

All phage therapy requests received during 2022 were collected prospectively, and reviewed retrospectively to analyse the decision and the patient care pathway (NCT05883995).

Results

Of 143 requests for phage therapy, the indication was confirmed at a multidisciplinary team meeting for 57 (40%) patients. Forty-four patients were infected with bacteria that could be targeted easily by phages in France. Finally, 33 patients were treated, including 26 at the study institution, through a compassionate access programme or in a clinical trial. The main indication were complex bone and joint infections, endovascular infection and lung infection. In order to manage these patients, 172 pharmaceutical phage cocktails targeting Staphylococcus aureus and/or Pseudomonas aeruginosa were prepared: 57 for local injection and 99 for intravenous injection. During follow-up, 18 (69%) patients showed a favourable clinical evolution, and six (23%) patients required subsequent phage therapy, either with the same phage with greater exposure, or with a different phage from elsewhere.

Conclusions

Implementation of the PHAGEinLYON Clinic programme in 2022 was associated with groundbreaking access to phage therapy in France.
目的:介绍 2022 年 PHAGEinLYON 诊所计划的设立情况:描述 2022 年 PHAGEinLYON 诊所项目的设立情况,该项目致力于在法国推广使用医药级噬菌体进行噬菌体治疗:我们描述了这一过程,前瞻性地收集了2022年收到的所有噬菌体治疗申请,并对其进行回顾性审查,以分析决策和患者护理路径(NCT05883995):在143份噬菌体治疗申请中,57份(40%)的适应症得到了多学科团队会议的确认,44份感染了法国噬菌体容易靶向的细菌。最后,33 名患者接受了治疗,其中 26 人在本机构接受了同情性使用或临床试验。主要适应症是复杂的骨关节感染、血管内感染和肺部感染。为治疗这些患者,我们配制了 172 种针对金黄色葡萄球菌和/或绿脓杆菌的药用噬菌体鸡尾酒;其中 57 种用于局部注射,99 种用于静脉注射。在随访过程中,18 名患者(69%)的临床疗效良好,6 名患者(23%)需要后续噬菌体治疗,使用相同的噬菌体,但噬菌体暴露量更大,或使用其他地方的不同噬菌体:结论:2022 年 PHAGEinLYON 诊所项目的实施为噬菌体疗法在法国的普及开创了先河。
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引用次数: 0
Monitoring of the cerebrospinal fluid voriconazole level in a patient with recurrent Candida meningitis after pituitary surgery 监测垂体手术后复发念珠菌脑膜炎患者脑脊液中伏立康唑的水平。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-12-01 DOI: 10.1016/j.ijantimicag.2024.107379
Mete Ucdal , Emre Kara , Mustafa Berker , Aslı Pinar , Dolunay Gulmez , Sevtap Arikan-Akdagli , Ahmet Cağkan Inkaya , Gokhan Metan
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引用次数: 0
Genomic and growth fitness study of extended-spectrum β-lactamase-producing Escherichia coli from bloodstream infections after introduction of a national 4C antimicrobial stewardship policy in Scotland 苏格兰引入国家 4C 抗菌药物管理政策后,对血流感染中产扩展谱 β-内酰胺酶大肠埃希菌的基因组和生长适应性研究。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-12-01 DOI: 10.1016/j.ijantimicag.2024.107380
Istifanus Nkene , Susanth Alapati , Antonio Ribeiro , Ijeoma Okoliegbe , Sreedevi Unnikrishnan , Corinne Ironside , Becky Wilson , Karolin Hijazi

Background

Extended-spectrum β-lactamase-producing Escherichia coli remains a major cause of hospital-acquired bloodstream infections in countries with high antimicrobial stewardship compliance.

Methods

Isolates from bloodstream infections that occurred between 2010 and 2020 in a tertiary-level hospital in North-East Scotland soon after introduction of the ‘4C’ antimicrobial stewardship policy were analysed for phylogenetic structure, antimicrobial resistance, plasmid, and virulence gene carriage. Growth fitness was measured in kinetic assays. Non-metric-multidimensional-scaling was used to evaluate clonal relationships, antimicrobial resistance, and virulence profiles in early and later years after the 4C policy introduction. Clonal and fitness trends over the study period were determined by generalised additive modelling. The relationship between clonal type, antimicrobial resistance, and fitness was evaluated by linear regression.

Results

Three hierarchical phylogenetic clusters were identified, with the most dominant cluster (O25:H4/fimH30) including all, and nearly exclusively, Clade C ST131 isolates as well as minor non-ST131 sequence types. The prevalence of ST131 was largely stable over the study period. Resistance to aminoglycosides and aztreonam in ST131 was lower (P = 0.019 and P = 0.004, respectively) during later years (2016–2020) by 28% on average compared to early years soon after 4C policy implementation (2010–2014). Carriage of virulence factors involved in bacterial adaptation was higher in ST131 compared to non-ST131 but mostly stable in early vs. later years. Growth fitness of ST131 was lower than non-ST131 and declined steadily in later years (P < 0.0001).

Conclusions

Despite stable virulence factor carriage, population structure, and resistance to cephalosporins, we show increased susceptibility of ST131 to aminoglycosides and aztreonam and concurrent fitness decline years after the introduction of the 4C policy.
背景:在抗菌药物管理达标率较高的国家,产广谱β-内酰胺酶大肠埃希菌仍是医院获得性血流感染的主要病因:方法: 对苏格兰东北部一家三级甲等医院 2010 年至 2020 年间发生的血流感染分离菌株进行了系统发育结构、抗菌药物耐药性、质粒和毒力基因携带分析,这些分离菌株是在 "4C "抗菌药物管理政策出台后不久发生的。生长适应性通过动力学实验进行测量。在 4C 政策出台后的早期和晚期,使用非计量多维标度评估克隆关系、抗菌药耐药性和毒力特征。通过广义加法模型确定了研究期间的克隆和适应性趋势。通过线性回归评估了克隆类型、抗菌药耐药性和适应性之间的关系:结果:确定了三个分层系统发育群,其中最主要的群组(O25:H4/fimH30)包括所有且几乎全部的C支系ST131分离株以及次要的非ST131序列类型。在研究期间,ST131 的流行率基本保持稳定。与 4C 政策实施后不久的早期(2010-2014 年)相比,晚期(2016-2020 年)ST131 对氨基糖苷类药物和阿曲南有较低的耐药性(p=0.019 和 p=0.004),平均降低了 28%。与非ST131相比,ST131携带的涉及细菌适应的毒力因子更高,但在早期与后期基本保持稳定。ST131 的生长适应性低于非 ST131,且在后期持续下降(p 结论:尽管细菌携带的毒力因子保持稳定,但 ST131 的生长适应性仍低于非 ST131:尽管毒力因子携带量、种群结构和对头孢菌素的耐药性保持稳定,但我们发现 ST131 对氨基糖苷类药物和阿曲南有更高的易感性,并且在 4C 政策实施多年后,其适应性也同时下降。
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引用次数: 0
Reviewer Thank You List 2024
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-12-01 DOI: 10.1016/j.ijantimicag.2024.107385
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引用次数: 0
International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗菌化疗学会 (ISAC) 新闻和信息页面
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-11-23 DOI: 10.1016/j.ijantimicag.2024.107391
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引用次数: 0
Model-Informed Drug Development (MIDD) for Antimicrobials 抗菌药物的模型信息药物开发 (MIDD)。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-11-15 DOI: 10.1016/j.ijantimicag.2024.107392
Yu-Wei Lin , S.Y. Amy Cheung
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引用次数: 0
Cefiderocol has immunoregulative effects in LPS-induced vitro experimental model via inhibiting inflammation and ferroptosis 在 LPS 诱导的体外实验模型中,头孢羟氨苄通过抑制炎症和铁蛋白沉积产生免疫调节作用。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-11-05 DOI: 10.1016/j.ijantimicag.2024.107374
Mohan Ju , Min Hao , Dongfang Lin, Shuang Liu

Background

Cefiderocol is a new catecholamine-containing siderophore cephalosporin. It, however, remains unclear how cefiderocol modulates the immune response of the host.

Objectives

This study elucidated whether cefiderocol exerts immunoprotective effects in an in vitro experimental model induced with lipopolysaccharide (LPS).

Methods

Mouse macrophage RAW 264.7 cells were exposed to LPS (100 ng/mL) or LPS + cefiderocol (40 mg/L) to assess the immunomodulatory effect of cefiderocol in vitro. ELISA was performed on cell culture supernatants to estimate cytokine levels. Ferroptosis level was also quantified by detecting intracellular reactive oxygen species and iron levels through flow cytometry analysis. Malondialdehyde and glutathione (GSH) levels were estimated by ELISA. We conducted western blotting assay for evaluating key ferroptosis pathway proteins.

Results

Cefiderocol alleviated LPS-induced inflammation by reducing IL-6, TNF-α, and IL-1β production levels and enhancing the IL-10 production level. Further analysis to determine the underlying mechanism revealed that cefiderocol inhibited ferroptosis; this was confirmed by reduced reactive oxygen species, malondialdehyde, and Fe2+ ion levels; increased GSH levels; upregulated expression of solute carrier family 7 member 11, GSH peroxidase 4, nuclear factor erythroid 2-related factor 2, and ferroptosis suppressor protein 1; and downregulated expression of acyl-CoA synthetase long-chain family member 4.

Conclusions

Cefiderocol may play a key role in reducing inflammation by decreasing inflammatory cytokine release and suppressing ferroptosis.
背景头孢羟氨苄是一种新的含儿茶酚胺的嗜苷头孢菌素。然而,目前仍不清楚头孢羟氨苄如何调节宿主的免疫反应:本研究阐明了头孢羟氨苄是否能在脂多糖(LPS)诱导的体外实验模型中发挥免疫保护作用:小鼠巨噬细胞 RAW 264.7 细胞暴露于 LPS(100 ng/mL)或 LPS + cefiderocol(40 mg/L),以评估 cefiderocol 在体外的免疫调节作用。对细胞培养上清液进行 ELISA 检测,以估算细胞因子水平。此外,还通过流式细胞仪分析检测细胞内活性氧(ROS)和铁水平,量化铁变态反应水平。丙二醛(MDA)和谷胱甘肽(GSH)水平是通过酶联免疫吸附法估算的。我们进行了 Western 印迹分析,以评估关键的铁变态反应通路蛋白:结果:头孢多巴通过降低IL-6、TNF-α和IL-1β的产生水平以及提高IL-10的产生水平,缓解了LPS诱导的炎症反应。为确定其潜在机制而进行的进一步分析表明,头孢可可可抑制铁变态反应;ROS、MDA 和 Fe2+ 离子水平的降低;GSH 水平的升高;溶质运载家族 7 成员 11、谷胱甘肽过氧化物酶 4、红细胞核因子 2 相关因子 2 和铁变态反应抑制蛋白 1 表达的上调;以及酰基-CoA 合成酶长链家族成员 4 表达的下调证实了这一点:结论:头孢羟氨苄可通过减少炎性细胞因子的释放和抑制铁绒毛膜促性腺激素的分泌,在减轻炎症方面发挥关键作用。
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引用次数: 0
Title Page & Editorial Board 扉页和编辑委员会
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-11-01 DOI: 10.1016/S0924-8579(24)00292-9
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引用次数: 0
Isoniazid prophylaxis based on tuberculosis risk factors in living kidney transplantation recipients: A retrospective cohort study 基于活体肾移植受者结核病风险因素的异烟肼预防:一项回顾性队列研究
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-31 DOI: 10.1016/j.ijantimicag.2024.107375
Hao Zhang , Jun Zeng , Tingting Zhu , Tao Lin , Turun Song

Background

Tuberculosis (TB) is a major and severe opportunistic infection among solid organ transplant recipients. Chemoprophylaxis is advised for those with latent tuberculosis infection. However, the effectiveness of an isoniazid (INH) prophylactic approach based on TB risk factors remains uncertain.

Methods

This study included all living-donor kidney transplant recipients between January 2016 and December 2022. The recipients were categorized into three groups: the risk group with INH (R-INH), the risk group without INH (R-NINH), and the non-risk group (NR), based on the presence of TB risk factors and INH usage. The R-INH group received a 6-month INH prophylactic regimen to prevent post-transplant TB infection. The incidence of active TB among the groups was assessed.

Results

A total of 1348 patients were divided into R-INH (n = 108), R-NINH (n = 371), and NR (n = 869). Forty-seven patients (3.49%) developed TB with an incidence rate of 16.0 per 1000 person-years. Compared to NR, the TB incidence in R-INH was not statistically different (hazard ratios, 0.55, 95% confidence interval, 0.07–4.21, P = 0.564), whereas it was significantly higher in R-NINH (hazard ratios, 5.04, 95% confidence interval, 2.64–9.62, P < 0.001). The median time from transplantation to TB was 19 months (interquartile range: 6–39), and 18 patients (38.3%) were diagnosed within 1 year of transplantation. Ninety-four patients (87.0%) completed INH prophylaxis, with adverse events including two cases of hepatotoxicity (1.85%) and one case of peripheral neuritis (0.93%).

Conclusions

A 6-month INH regimen based on TB risk factors is effective and well-tolerated for preventing post-transplant TB in kidney transplant recipients.
背景:结核病(TB)是实体器官移植受者中主要的严重机会性感染。建议潜伏肺结核感染者(LTBI)进行化学预防。然而,基于结核病风险因素的异烟肼(INH)预防方法的有效性仍不确定:本研究纳入了 2016 年 1 月至 2022 年 12 月期间的所有活体供肾移植受者(KTR)。根据是否存在结核病风险因素和 INH 使用情况,将受者分为三组:使用异烟肼的风险组(R-INH)、不使用异烟肼的风险组(R-NINH)和非风险组(NR)。R-INH 组接受为期 6 个月的 INH 预防治疗,以预防移植后结核病感染。对各组间活动性肺结核的发病率进行了评估:共有 1348 名患者被分为 R-INH 组(108 人)、R-NINH 组(371 人)和 NR 组(869 人)。47名患者(3.49%)患上了肺结核,发病率为每千人年16.0例。与 NR 相比,R-INH 的肺结核发病率没有统计学差异(HR,0.55,95% CI,0.07-4.21,P = 0.564),而 R-NINH 的发病率明显更高(HR,5.04,95% CI,2.64-9.62,P <0.001)。从移植到肺结核的中位时间为 19 个月(IQR:6-39),18 名患者(38.3%)在移植后一年内确诊。94名患者(87.0%)完成了INH预防治疗,不良反应包括2例肝脏毒性(1.85%)和1例周围神经炎(0.93%):结论:根据结核病风险因素制定的为期 6 个月的 INH 方案对预防 KTR 移植后结核病有效且耐受性良好。
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引用次数: 0
Machine learning accelerates the discovery of epitope-based dual-bioactive peptides against skin infections 机器学习加速发现抗皮肤感染的表皮双生物活性肽。
IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-31 DOI: 10.1016/j.ijantimicag.2024.107371
Le Fu , Xu Zheng , Jiawen Luo , Yiyu Zhang , Xue Gao , Li Jin , Wenting Liu , Chaoqun Zhang , Dongyu Gao , Bocheng Xu , Qingru Jiang , Shuli Chou , Liang Luo

Objectives

Skin injuries and infections are an inevitable part of daily human life, particularly with chronic wounds, becoming an increasing socioeconomic burden. In treating skin infections and promoting wound healing, bioactive peptides may hold significant potential, particularly those possessing antimicrobial and anti-inflammatory properties. However, obtaining these peptides solely through traditional wet laboratory experiments is costly and time-consuming, and peptides identified by current computer-assisted predictive models largely lack validation of their effects via wet laboratory experiments. Consequently, this study aimed to integrate computer-assisted methods and traditional wet laboratory experiments to identify anti-inflammatory and antimicrobial peptides.

Methods

We developed a computer-assisted mining pipeline to screen potential peptides from the epitopes of the major histocompatibility complex class II.

Results

The peptide AIMP1 was identified, with the ability to physically damage Escherichia coli by increasing bacterial cell membrane permeability, and with the ability to inhibit inflammation by binding to endotoxin-lipopolysaccharide. Additionally, in an LPS-induced inflammation animal model, AIMP1 slightly increased levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and in a skin wound infection animal model, AIMP1 effectively accelerated healing, reduced levels of these pro-inflammatory cytokines, and showed no acute hepatotoxicity or nephrotoxicity.

Conclusions

In conclusion, this study not only developed a computer-assisted mining pipeline for identifying anti-inflammatory and antimicrobial peptides but also successfully pinpointed the peptide AIMP1, demonstrating its therapeutic potential for skin injury treatment.
皮肤损伤和感染是人类日常生活中不可避免的一部分,尤其是慢性伤口,已成为日益沉重的社会经济负担。在治疗皮肤感染和促进伤口愈合方面,生物活性肽可能具有很大的潜力,尤其是那些具有抗菌和消炎特性的肽。然而,仅通过传统的湿实验室实验获取这些肽既昂贵又耗时,而且目前计算机辅助预测模型识别的肽大多缺乏湿实验室实验对其效果的验证。因此,本研究旨在将计算机辅助方法与传统的湿实验室实验相结合,以鉴定抗炎和抗菌肽。我们开发了一种计算机辅助挖掘管道,从主要组织相容性复合体 II 类(MHC-II)的表位筛选潜在的多肽。我们发现了肽 AIMP1,它能通过增加细菌细胞膜的通透性对大肠杆菌造成物理损伤,并能通过与内毒素-脂多糖结合抑制炎症。此外,在 LPS 诱导的炎症动物模型中,AIMP1 会轻微升高促炎细胞因子(TNF-α、IL-1β 和 IL-6)的水平;在皮肤伤口感染动物模型中,AIMP1 能有效加速伤口愈合,降低这些促炎细胞因子的水平,并且没有急性肝毒性或肾毒性。总之,本研究不仅开发了一种用于鉴定抗炎和抗菌多肽的计算机辅助挖掘管道,还成功地找到了多肽 AIMP1,证明了它在治疗皮肤损伤方面的治疗潜力。
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引用次数: 0
期刊
International Journal of Antimicrobial Agents
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