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Serotypes and antimicrobial resistance patterns of food-borne Salmonella isolates in the Jiaxing Region, China, from 2020 to 2024 2020 - 2024年嘉兴地区食源性沙门氏菌分离株血清型及耐药性分析
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.jgar.2025.10.023
Xiaoqin Niu , Liping Tu , Qinlong Yu , Binbin Lu , Junhua Tian , Wei Wang , Bailong Hou , Weifeng Shen

Background

Salmonella is a worldwide food-borne pathogen, which brings significant challenges to clinical practice due to the increase of antibiotic resistance.

Objective

This study aims to explore the serotype variety and antibiotic resistance of food-borne Salmonella in the Jiaxing region from 2020 to 2024.

Methods

The faecal samples of 8541 patients with food-borne diseases were investigated. The isolated Salmonella strains underwent MALDI-TOF, serological typing, and drug susceptibility testing.

Results

A total of 622 Salmonella strains were isolated from 8541 faecal samples, with 382 (61.4%) originating from patients under 6 y old. Summer and autumn were the peak seasons. 622 strains of Salmonella were divided into 53 serotypes, with the most common serotypes being Salmonella Typhimurium and Salmonella Enteritidis. The drug susceptibility test revealed that most strains were resistant to ampicillin (79.8%), while 38% exhibited resistance to trimethoprim/sulfamethoxazole. The susceptibility rate to cephalosporins and fluoroquinolones was over 84%. Only one strain was found to be resistant to carbapenems. Notably, 69.5% of the strains were resistant to at least one antibiotic, and 21.9% demonstrated multidrug resistance. Our findings also indicated an increasing trend in the resistance of isolated strains to ceftriaxone and cefepime over the past 5 y. Compared to S. Typhimurium, S. Enteritidis was more susceptible to a range of antibiotics, with the most notable difference in susceptibility to trimethoprim/sulfamethoxazole.

Conclusions

Salmonella serotypes exhibited varied patterns of drug susceptibility. Antibiotic selection should be based on the susceptibility profile of the pathogenic bacteria to effectively treat and prevent Salmonella infections.
背景:沙门氏菌是一种世界性的食源性致病菌,由于抗生素耐药性的增加,给临床实践带来了重大挑战。目的:了解2020 - 2024年嘉兴地区食源性沙门氏菌的血清型、品种及耐药性。方法:对8541例食源性疾病患者粪便标本进行调查。对分离的沙门氏菌进行MALDI-TOF、血清学分型和药敏试验。结果:从8541份粪便中分离出622株沙门氏菌,其中382株(61.4%)来自6岁以下患者。夏季和秋季是高峰期。622株沙门菌分为53种血清型,以鼠伤寒沙门菌和肠炎沙门菌最为常见。药敏试验结果显示,大多数菌株对氨苄西林耐药(79.8%),对甲氧苄啶/磺胺甲恶唑耐药(38%)。头孢菌素类和氟喹诺酮类药物的易感率均在84%以上。只有一种菌株被发现对碳青霉烯类具有耐药性。值得注意的是,69.5%的菌株至少对一种抗生素耐药,21.9%的菌株表现出多药耐药。我们的研究结果还表明,在过去的五年中,分离菌株对头孢曲松和头孢吡肟的耐药性呈上升趋势。与鼠伤寒沙门氏菌相比,肠炎沙门氏菌对一系列抗生素更敏感,其中对甲氧苄啶/磺胺甲恶唑的敏感性差异最显著。结论:沙门氏菌血清型具有不同的药敏模式。应根据病原菌的药敏特征选择抗生素,以有效治疗和预防沙门氏菌感染。
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引用次数: 0
Genomic characterization of a carbapenem-resistant Citrobacter freundii complex strain co-carrying blaNDM-1, blaCTX-M-30, armA, rmtC, and rmtD from Chile 智利一株共携带blaNDM-1、blaCTX-M-30、armA、rmtC和rmtD的耐碳青霉烯型弗氏柠檬酸杆菌复合体的基因组特征
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.jgar.2025.10.021
Isidora Manríquez-Cuadra , Maximiliano Matus-Köhler , Alejandro Aguayo-Reyes , Mario Quezada-Aguiluz , Felipe Morales-Leon , Gerardo González-Rocha , Andrés Opazo-Capurro

Introduction

Carbapenem- and third-generation cephalosporin-resistant Enterobacterales, including the Citrobacter freundii complex, are classified as a World Health Organization ‘critical priority’ due to their public health threat. This study reports a C. freundii complex isolate (Cit-107) co-harbouring the blaNDM-1, blaCTX-M-30, armA, rmtC, and rmtD genes, recovered from a rectal swab in 2022 in Concepción, Chile.

Methods

Antimicrobial susceptibility was assessed via disk diffusion. Whole-genome sequencing was performed using the Illumina NextSeq 2000 platform and annotated with Bakta. In silico analyses included JSpeciesWS, PubMLST, ABRicate, AMRFinderPlus, and MOB-suite. Phylogenetic analysis of Cit-107 and 50 C. freundii complex genomes from the Americas was conducted using IQ-TREE and visualized with iTOL.

Results

Cit-107 was resistant to clinically relevant antibiotics, such as carbapenems, cephalosporins, aminoglycosides, and fluoroquinolones. It belongs to sequence type (ST) ST112 and carries multiple resistance genes: blaNDM-1, blaCTX-M-30, mcr-9.1, armA, rmtC, and rmtD. The blaNDM-1 gene was embedded in a Tn125-like transposon contained in an IncC-type plasmid alongside the blaCTX-M-30, rmtC, and tet(G) genes. The blaCTX-M-30 was harboured in an IncN-type plasmid, while armA, msr(E), and mph(E) were co-carried in an IncHI2A-type plasmid. Phylogenetic analysis revealed Cit-107 as a divergent lineage within the C. freundii complex.

Conclusions

This is the first report of a carbapenem-resistant C. freundii complex isolate carrying blaNDM-1 in Chile alongside multiple antibiotic-resistance genes harboured in several plasmid types. Its unique resistome and phylogenetic profile underscore the need for surveillance of emerging multidrug-resistant C. freundii strains in clinical settings.
导论:碳青霉烯类和第三代耐头孢菌素肠杆菌,包括弗伦地柠檬酸杆菌复群,由于其对公共卫生的威胁,被列为世卫组织的“关键优先事项”。本研究报告了2022年在智利Concepción从直肠棉絮中分离出的一种弗氏梭菌复合分离物(ctc -107),该分离物共携带blaNDM-1、blaCTX-M-30、armA、rmtC和rmtD基因。方法:采用纸片扩散法进行药敏试验。使用Illumina NextSeq 2000平台进行全基因组测序(WGS),并使用Bakta进行注释。计算机分析包括JSpeciesWS、PubMLST、ABRicate、AMRFinderPlus和mobo -suite。利用IQ-TREE和iTOL对美洲Cit-107和50个弗氏线虫复合体基因组进行系统发育分析。结果:Cit-107对碳青霉烯类、头孢菌素类、氨基糖苷类、氟喹诺酮类等临床相关抗生素耐药。它属于序列型(ST) ST112,携带多种抗性基因:blaNDM-1、blaCTX-M-30、mcr-9.1、armA、rmtC和rmtD。blaNDM-1基因与blaCTX-M-30、rmtC和tet(G)基因一起嵌入incc型质粒中的tn125样转座子中。blaCTX-M-30包埋在incn型质粒中,而armA、msr(E)和mph(E)包埋在inchi2a型质粒中。系统发育分析表明Cit-107是弗氏胞杆菌复合体中的一个分支。结论:这是智利首次报道的一种碳青霉烯耐药的弗氏胞杆菌复合体分离物携带blaNDM-1,同时在几种质粒类型中携带多种抗生素耐药基因。其独特的抗性组和系统发育特征强调了在临床环境中监测新出现的多重耐药弗氏弓形虫菌株的必要性。
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引用次数: 0
in vitro antibacterial activity of nordihydroguaiaretic acid combined with ceftriaxone against carbapenem-resistant Klebsiella pneumoniae 北二氢愈创木酸联合头孢曲松对耐碳青霉烯肺炎克雷伯菌的体外抗菌活性研究。
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.jgar.2025.10.007
Chengjiao Luo , Hua Tan , Hang Sun , Xianwei Zhang , Qian Chen

Objective

This study investigated the interplay between biofilm formation and efflux pumps in carbapenem-resistant Klebsiella pneumoniae (CRKP) and evaluated the biofilm inhibition by nordihydroguaiaretic acid (NDGA) along with the efficacy of its combination with ceftriaxone (CRO) against CRKP, to inform the development of novel therapeutic strategies against multidrug-resistant infections.

Methods

Efflux pump genes were detected via PCR. Biofilm formation was quantified by crystal violet staining and categorized by the biofilm formation index (BFI) classification. Strong biofilm producers (BFI > 4 × negative control) were selected for in vitro models. Efflux pump gene expression was compared between biofilm and planktonic states using qRT-PCR. NDGA’s biofilm inhibition and NDGA-CRO synergy were assessed via checkerboard assays.

Results

Among the 86 CRKP isolates, 51.16% (44/86) were classified as strong biofilm producers, followed by moderate (17.44%, 15/86), weak (20.93%, 18/86), and negative (10.47%, 9/86) producers. Efflux pump genes (acrA, acrB, tolC, oqxA, oqxB) were detected in 100%, 100%, 100%, 97.7%, and 98.84% of isolates. Gene expression was significantly upregulated in biofilm versus planktonic state (P < 0.05). NDGA (≥16 µg/mL) inhibited biofilm formation, and its combination with CRO exhibited additive (63.64%) and synergistic (36.36%) effects.

Conclusion

Efflux pumps and biofilms synergistically enhance CRKP resistance. By inhibiting both efflux-mediated antibiotic extrusion and biofilm formation, NDGA resensitizes CRKP to CRO. This in vitro efficacy supports further development, pending in vivo safety studies in animal models.
目的:研究耐碳青霉烯肺炎克雷伯菌(CRKP)生物膜形成与外排泵之间的相互作用,评价去甲二氢愈创木酸(NDGA)对CRKP的生物膜抑制作用及其与头孢曲松(CRO)联合治疗CRKP的效果,为开发抗多重耐药感染的新治疗策略提供依据。方法:采用PCR法检测外排泵基因。采用结晶紫染色定量测定生物膜的形成,并采用生物膜形成指数(BFI)分类。体外模型选用强生物膜产生者(BFI bbb40 × 阴性对照)。采用qRT-PCR方法比较生物膜状态和浮游状态下外排泵基因的表达。通过棋盘法评估NDGA的生物膜抑制作用和NDGA- cro协同作用。结果:86株CRKP菌株中,强生膜菌株占51.16%(44/86),其次为中等(17.44%,15/86)、弱(20.93%,18/86)和阴性(10.47%,9/86)。外排泵基因acrA、acrB、tolC、oqxA、oqxB的检出率分别为100%、100%、100%、97.7%、98.84%。生物膜状态与浮游状态相比,基因表达显著上调(P < 0.05)。NDGA(≥16 μg/mL)抑制生物膜的形成,与CRO联用表现出加性(63.64%)和增效(36.36%)作用。结论:外排泵和生物膜协同增强CRKP耐药性。NDGA通过抑制外排介导的抗生素挤出和生物膜形成,使CRKP对CRO重新致敏。这种体外功效支持进一步的开发,有待于动物模型的体内安全性研究。
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引用次数: 0
Prevalence and molecular epidemiology of optrA-positive Enterococcus in herders and yaks from high-altitude Tibet, China
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-24 DOI: 10.1016/j.jgar.2025.10.016
Hanyu Wang , Xinyue Han , Aoxiao Chen , Zelin Yan , Rong Zhang , Yang Wang

Objectives

Antimicrobial resistance (AMR) in high-altitude environments remains understudied despite its growing global concern. This study investigates the molecular epidemiology of the optrA gene, which confers resistance to oxazolidinones and phenicols, in Enterococcus species isolated from herders and yak faecal samples in Nagqu, Tibet, China.

Methods

A total of 161 faecal samples from herders and 42 from yaks were collected and analysed for the presence of optrA-positive Enterococcus strains. Antimicrobial susceptibility testing (AST) was performed to determine resistance patterns. Whole-genome sequencing (WGS) and phylogenetic analysis were used to assess genetic relationships and the potential for clonal spread and horizontal gene transfer.

Results

The optrA gene was detected in 6.2% (10/161) of human samples and 9.5% (4/42) of yak samples, indicating a higher prevalence in yaks. Resistance was highest for tetracycline (100%), erythromycin (92.9%), and linezolid (92.9%). Phylogenetic analysis revealed clonal dissemination, with some isolates exhibiting high genetic homology. Notably, one E. faecalis strain belonged to ST16, a sequence type commonly found in low-altitude cities, suggesting potential transmission between regions. The optrA gene was frequently associated with mobile genetic elements, indicating a risk of horizontal gene transfer and further dissemination of resistance.

Conclusion

The presence of optrA-positive Enterococcus in both human and animal populations in this high-altitude region underscores the role of human-animal interactions in AMR transmission. The increasing prevalence of resistant strains in yaks, coupled with genetic evidence of clonal expansion, highlights the need for a comprehensive One Health approach to AMR surveillance and mitigation in remote, high-altitude environments.
背景:高海拔环境下的抗菌素耐药性(AMR)尽管日益受到全球关注,但研究仍不足。方法:采集161份牧民粪便和42份牦牛粪便,检测optra阳性肠球菌。采用药敏试验(AST)确定耐药模式。采用全基因组测序(WGS)和系统发育分析来评估遗传关系以及克隆传播和水平基因转移的可能性。结果:optrA基因在6.2%(10/161)的人样本和9.5%(4/42)的牦牛样本中检出,表明该基因在牦牛中的检出率较高。耐药率最高的是四环素(100%)、红霉素(92.9%)和利奈唑胺(92.9%)。系统发育分析显示克隆传播,部分分离株具有较高的遗传同源性。值得注意的是,1株粪肠球菌属于ST16型,这是一种常见于低海拔城市的序列型,提示可能存在区域间传播。optrA基因经常与移动遗传元件相关,表明存在水平基因转移和耐药性进一步传播的风险。结论:在该高海拔地区的人和动物种群中均存在optra阳性肠球菌,说明人-动物相互作用在AMR传播中的作用。耐药菌株在牦牛中日益流行,再加上克隆扩增的遗传证据,突出表明需要在偏远、高海拔环境中对抗菌素耐药性监测和缓解采取全面的“同一个健康”方法。
{"title":"Prevalence and molecular epidemiology of optrA-positive Enterococcus in herders and yaks from high-altitude Tibet, China","authors":"Hanyu Wang ,&nbsp;Xinyue Han ,&nbsp;Aoxiao Chen ,&nbsp;Zelin Yan ,&nbsp;Rong Zhang ,&nbsp;Yang Wang","doi":"10.1016/j.jgar.2025.10.016","DOIUrl":"10.1016/j.jgar.2025.10.016","url":null,"abstract":"<div><h3>Objectives</h3><div>Antimicrobial resistance (AMR) in high-altitude environments remains understudied despite its growing global concern. This study investigates the molecular epidemiology of the <em>optrA</em> gene, which confers resistance to oxazolidinones and phenicols, in <em>Enterococcus</em> species isolated from herders and yak faecal samples in Nagqu, Tibet, China.</div></div><div><h3>Methods</h3><div>A total of 161 faecal samples from herders and 42 from yaks were collected and analysed for the presence of <em>optrA</em>-positive <em>Enterococcus</em> strains. Antimicrobial susceptibility testing (AST) was performed to determine resistance patterns. Whole-genome sequencing (WGS) and phylogenetic analysis were used to assess genetic relationships and the potential for clonal spread and horizontal gene transfer.</div></div><div><h3>Results</h3><div>The <em>optrA</em> gene was detected in 6.2% (10/161) of human samples and 9.5% (4/42) of yak samples, indicating a higher prevalence in yaks. Resistance was highest for tetracycline (100%), erythromycin (92.9%), and linezolid (92.9%). Phylogenetic analysis revealed clonal dissemination, with some isolates exhibiting high genetic homology. Notably, one <em>E. faecalis</em> strain belonged to ST16, a sequence type commonly found in low-altitude cities, suggesting potential transmission between regions. The <em>optrA</em> gene was frequently associated with mobile genetic elements, indicating a risk of horizontal gene transfer and further dissemination of resistance.</div></div><div><h3>Conclusion</h3><div>The presence of <em>optrA</em>-positive <em>Enterococcus</em> in both human and animal populations in this high-altitude region underscores the role of human-animal interactions in AMR transmission. The increasing prevalence of resistant strains in yaks, coupled with genetic evidence of clonal expansion, highlights the need for a comprehensive One Health approach to AMR surveillance and mitigation in remote, high-altitude environments.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 1-5"},"PeriodicalIF":3.2,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Ceftolozane/tazobactam in action: Prescribing patterns, effectiveness, and healthcare utilisation across seven countries 头孢唑烷/他唑巴坦在行动:七个国家的处方模式、有效性和医疗保健利用
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-24 DOI: 10.1016/j.jgar.2025.10.013
Emre Yucel , Alex Soriano , David L. Paterson , Florian Thalhalmmer , Stefan Kluge , Pierluigi Viale , Mike Allen , Brune Akrich , Jessica Levy , Huina Yang , Sunny Kaul

Objectives

Infections by antimicrobial-resistant, Gram-negative bacteria present significant global challenge, resulting in difficult treatment scenarios and poor clinical outcomes. Although ceftolozane/tazobactam (C/T) has been approved for the treatment of hospital-acquired HABP/VABP, cUTI, and cIAI, data on real-world use remains limited. This study presents real-world use of C/T across various countries.

Methods

The Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam: Real-world Analysis (SPECTRA) was a retrospective, observational study involving 617 adult inpatients across seven countries who were treated with C/T for at least 48 hours between 2016 and 2020. The primary objective was to describe real-world utilisation of C/T, focusing on sociodemographic and clinical characteristics, treatment patterns, clinical outcomes, and resource utilisation.

Results

617 patients from seven countries were included. Prevalence of at least one comorbidity ranged from 55.9% (Mexico) to 91.7% (Austria), with mean number of comorbidities from 1.0 (Mexico) to 2.7 (UK). Culture results from 72.7% patients identified MDR Pseudomonas aeruginosa, ranging from 55.9% (Italy) to 80.6% (Spain). Median hospital length of stay ranged from 23 (Mexico) to 53.5 (Austria) days. Clinical success rate for treating the index infection with C/T was 64.8%, with 51.1% of cases treated within the ICU.

Conclusions

This multi-national, retrospective, observational study demonstrates the real-world use and healthcare resource utilisation (HCRU) of C/T in patients with Gram-negative infections across seven countries. These findings provide valuable insights into prescribing patterns and resource implications of C/T treatment, underscoring the importance of real-world data to inform clinical practice and optimise antimicrobial therapy in diverse healthcare settings.
目的耐药革兰氏阴性菌感染是全球面临的重大挑战,导致治疗困难和临床结果不佳。虽然头孢唑烷/他唑巴坦(C/T)已被批准用于治疗医院获得性HABP/VABP、cUTI和cIAI,但实际使用数据仍然有限。本研究展示了各国实际使用的C/T。方法头孢唑烷/他唑巴坦的处方模式和有效性研究:真实世界分析(SPECTRA)是一项回顾性观察性研究,涉及7个国家的617名成人住院患者,这些患者在2016年至2020年期间接受了至少48小时的C/T治疗。主要目的是描述C/T在现实世界中的使用情况,重点关注社会人口学和临床特征、治疗模式、临床结果和资源利用。结果共纳入来自7个国家的617例患者。至少一种合并症的患病率从55.9%(墨西哥)到91.7%(奥地利)不等,平均合并症数从1.0(墨西哥)到2.7(英国)不等。72.7%的患者培养结果发现耐多药铜绿假单胞菌,从55.9%(意大利)到80.6%(西班牙)不等。住院时间中位数从23天(墨西哥)到53.5天(奥地利)不等。C/T治疗指数感染的临床成功率为64.8%,其中51.1%的病例在ICU内治疗。这项跨国、回顾性、观察性研究显示了七个国家革兰氏阴性感染患者中C/T的实际使用情况和医疗资源利用率(HCRU)。这些发现为C/T治疗的处方模式和资源含义提供了有价值的见解,强调了现实世界数据对临床实践和优化不同医疗保健环境中的抗菌治疗的重要性。
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引用次数: 0
Rapid clonal replacement by ST773 with NDM-1 among carbapenem-resistant Pseudomonas aeruginosa in South Korea 韩国耐碳青霉烯假单胞菌中ST773快速克隆替代NDM-1
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-23 DOI: 10.1016/j.jgar.2025.10.010
Yonggeun Cho , Kyung-Wook Hong , Min-Kyoung Shin , Sunjoo Kim , Jung-Hyun Byun
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引用次数: 0
Elucidating artemisinin (ART)-heme as a biomarker for ART resistance and ATP-dependent transport of ART in Plasmodium falciparum 阐明青蒿素血红素作为恶性疟原虫抗逆转录病毒耐药性和抗逆转录病毒atp依赖性转运的生物标志物。
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-23 DOI: 10.1016/j.jgar.2025.10.017
Hui Liu , Hongchang Zhou , Yuan Cai , Shanshan Du , Zhenghui Huang , Kun Xu , Jie Xing

Objectives

Artemisinin (ART) resistance is widespread in Southeast Asia and emerging in Africa. In this study, the potential biomarker for ART resistance was first characterised in P. falciparum, and the roles of several molecular pathways (e.g., Hb endocytosis) in ART resistance were then evaluated.

Methods

The metabolic profiles of ART and its pharmacokinetics were studied in Plasmodium falciparum (P. falciparum) incubated in vitro. Several strains of P. falciparum (ART-sensitive strains Pf3D7/PfDd2, and ART-resistance strain Pf6320 carrying K13 mutation C580Y) synchronised at different stages (ring and trophozoite) were used. The antimalarial activity of ART-heme adduct was evaluated. Several molecular pathways (i.e., Hb endocytosis) were evaluated for their roles in ART resistance using (non)selective inhibitors.

Results

ART-heme adduct was identified as a major metabolite for ART in P. falciparum, and it exhibited weak antimalarial activity (µM level). In ART-sensitive parasites, the formation of ART-heme was rapid, and both time- and concentration-dependent (50–450 nM). In contrast, ART-heme formation in ART-resistant parasites was independent of ART concentration. ART-heme formation was susceptible to orthovanadate (an inhibitor of P-type ATPase). Hb endocytosis/degradation, SERCA and the efflux transporter played roles in ART-heme formation to some extent. Synergistic antiplasmodial effect existed between ART and verapamil (an inhibitor of the efflux transporter).

Conclusions

ART-heme adduct displayed weak antiplasmodial activity but may still serve as a biomarker for both the antiplasmodial efficacy of ART and its resistance. ART transport in P. falciparum was ATP-dependent, and inhibition of efflux transporter may be a strategy to enhance ART potency.
背景:青蒿素耐药性在东南亚广泛存在,并在非洲出现。在这项研究中,首先在恶性疟原虫中鉴定了抗逆转录病毒耐药性的潜在生物标志物,然后评估了几种分子途径(如Hb内吞作用)在抗逆转录病毒耐药性中的作用。方法:研究ART在体外培养的恶性疟原虫体内的代谢谱及药代动力学。采用在不同阶段(环体和滋养体)同步的几种恶性疟原虫(art敏感株Pf3D7/PfDd2和携带K13突变C580Y的art抗性株Pf6320)。对art -血红素加合物的抗疟活性进行了评价。使用(非)选择性抑制剂评估了几种分子途径(即Hb内吞作用)在抗逆转录病毒药物耐药性中的作用。结果:ART-血红素加合物是恶性疟原虫ART的主要代谢物,其抗疟活性较弱(μM水平)。在ART敏感的寄生虫中,ART血红素的形成是快速的,并且具有时间和浓度依赖性(50-450 nM)。相反,抗ART寄生虫中ART血红素的形成与ART浓度无关。art -血红素的形成易受正钒酸盐(p型atp酶的抑制剂)的影响。Hb内吞/降解、SERCA和外排转运体在art -血红素的形成中发挥了一定的作用。抗逆转录病毒治疗与维拉帕米(一种外排转运蛋白抑制剂)之间存在协同抗疟原虫作用。结论:ART-血红素加合物表现出较弱的抗疟原虫活性,但仍可作为ART抗疟原虫疗效和耐药性的生物标志物。恶性疟原虫的抗逆转录病毒转运依赖于atp,抑制外排转运蛋白可能是提高抗逆转录病毒效力的一种策略。
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引用次数: 0
Efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations for the treatment of complicated urinary tract infections or acute pyelonephritis: A systematic review and meta-analysis 新型β-内酰胺/β-内酰胺酶抑制剂联合治疗复杂性尿路感染或急性肾盂肾炎的疗效和安全性:系统综述和荟萃分析
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-22 DOI: 10.1016/j.jgar.2025.10.011
Sirui Tang , Yuxuan Song , Caipeng Qin , Tao Xu

Objectives

The increasing resistance of gram-negative bacteria in complicated urinary tract infections (cUTI) and acute pyelonephritis (APN) poses major treatment challenges. This study aimed to evaluated the efficacy and safety of novel β-Lactam/β-Lactamase inhibitor combinations compared with conventional antibiotics.

Methods

We systematically searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and FDA.gov for randomized controlled trials (RCTs) published up to July 15, 2025. Eligible studied included patients with cUTI or APN. Primary outcomes were clinical and microbiological response rates at the test-of-cure (TOC) or the end-of-treatment visit. Secondary outcomes included adverse events (AEs), serious AEs (SAEs), and treatment discontinuations due to AEs. Risk of bias was assessed using the Cochran tool.

Results

Eleven RCTs with a total of 4986 patients (2719 in the experimental group and 2267 in the control group) were included. Novel β-Lactam/β-Lactamase inhibitors significantly improved clinical response in the microbiological modified intent-to-treat population (OR = 1.64, 95% CI [1.43–1.88], P < 0.001). The incidence of overall AEs and SAEs was similar between groups, though drug-related AEs were more common in the experimental group (OR = 1.38, 95% CI [1.11–1.72], P = 0.003).

Conclusions

Novel β-Lactam/β-Lactamase inhibitor combinations demonstrated superior efficacy and comparable safety to conventional antibiotics in treating cUTI and APN, particularly at the TOC stage.
背景:复杂性尿路感染(cUTI)和急性肾盂肾炎(APN)中革兰氏阴性菌耐药性的增加给治疗带来了重大挑战。本研究旨在评价新型β-内酰胺/β-内酰胺酶抑制剂联合使用与传统抗生素的疗效和安全性。方法:我们系统地检索PubMed、Embase、Cochrane Library、Web of Science、ClinicalTrials.gov和FDA.gov,检索截至2025年7月15日发表的随机对照试验(RCTs)。符合条件的研究包括cUTI或APN患者。主要结果是临床和治愈试验(TOC)或治疗结束时的微生物反应率。次要结局包括不良事件(ae)、严重ae (sae)和因ae而停止治疗。使用Cochran工具评估偏倚风险。结果:纳入11项随机对照试验,共4986例患者(实验组2719例,对照组2267例)。新型β-内酰胺/β-内酰胺酶抑制剂显著改善了微生物修饰的意图治疗人群的临床反应(OR=1.64, 95% CI[1.43-1.88])。结论:新型β-内酰胺/β-内酰胺酶抑制剂联合治疗cUTI和APN具有优于传统抗生素的疗效和相当的安全性,特别是在TOC期。
{"title":"Efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations for the treatment of complicated urinary tract infections or acute pyelonephritis: A systematic review and meta-analysis","authors":"Sirui Tang ,&nbsp;Yuxuan Song ,&nbsp;Caipeng Qin ,&nbsp;Tao Xu","doi":"10.1016/j.jgar.2025.10.011","DOIUrl":"10.1016/j.jgar.2025.10.011","url":null,"abstract":"<div><h3>Objectives</h3><div>The increasing resistance of gram-negative bacteria in complicated urinary tract infections (cUTI) and acute pyelonephritis (APN) poses major treatment challenges. This study aimed to evaluated the efficacy and safety of novel β-Lactam/β-Lactamase inhibitor combinations compared with conventional antibiotics.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and FDA.gov for randomized controlled trials (RCTs) published up to July 15, 2025. Eligible studied included patients with cUTI or APN. Primary outcomes were clinical and microbiological response rates at the test-of-cure (TOC) or the end-of-treatment visit. Secondary outcomes included adverse events (AEs), serious AEs (SAEs), and treatment discontinuations due to AEs. Risk of bias was assessed using the Cochran tool.</div></div><div><h3>Results</h3><div>Eleven RCTs with a total of 4986 patients (2719 in the experimental group and 2267 in the control group) were included. Novel β-Lactam/β-Lactamase inhibitors significantly improved clinical response in the microbiological modified intent-to-treat population (OR = 1.64, 95% CI [1.43–1.88], <em>P</em> &lt; 0.001). The incidence of overall AEs and SAEs was similar between groups, though drug-related AEs were more common in the experimental group (OR = 1.38, 95% CI [1.11–1.72], <em>P</em> = 0.003).</div></div><div><h3>Conclusions</h3><div>Novel β-Lactam/β-Lactamase inhibitor combinations demonstrated superior efficacy and comparable safety to conventional antibiotics in treating cUTI and APN, particularly at the TOC stage.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 268-281"},"PeriodicalIF":3.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Antimicrobial susceptibility patterns and genotypic characteristics of Mycobacterium marinum and Mycobacterium abscessus isolated from cutaneous infections: A retrospective study 皮肤感染分离的海洋分枝杆菌和脓肿分枝杆菌的抗微生物药敏模式和基因型特征:一项回顾性研究。
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-22 DOI: 10.1016/j.jgar.2025.10.001
Jiayi Peng , Wenyue Zhang , Ying Shi , Haiqin Jiang , Jingshu Xiong , Youming Mei , Tian Gan , Hongsheng Wang

Objectives

Antimicrobial susceptibility data for cutaneous mycobacteria remain limited. This study investigated the antimicrobial susceptibility patterns and molecular resistance mechanisms of Mycobacterium marinum and Mycobacterium abscessus isolates from a dermatology specialized hospital in China.

Methods

Antimicrobial susceptibility testing was performed on 200 M. marinum and 50 M. abscessus clinical isolates using broth microdilution method. M. abscessus subspecies were identified through hsp65, erm (41), and rpoB gene sequencing. For M. abscessus isolates, resistance-associated mutations for clarithromycin, amikacin, and fluoroquinolones were analysed by sequencing erm (41), rrl, rrs, gyrA, and gyrB genes.

Results

M. marinum demonstrated high susceptibility (82.5%–100%) to clarithromycin, rifampin, rifabutin, moxifloxacin, linezolid, trimethoprim-sulfamethoxazole, with moderate susceptibility to tetracyclines and ciprofloxacin. Ethambutol showed favourable activity against M. marinum with MIC90 of 2 µg/mL. Among M. abscessus isolates (23 M. abscessus subsp. abscessus, 26 M. abscessus subsp. massiliense, 1 M. abscessus subsp. bolletii), overall susceptibility to clarithromycin and amikacin was 78% and 82%, respectively. Tigecycline and clofazimine were effective against M. abscessus with MIC90 1 and 0.5 µg/mL, respectively. In contrast, M. abscessus isolates demonstrated high-level of resistance to multiple antibiotics, including linezolid, fluoroquinolones, and tetracyclines. M. abscessus subsp. massiliense exhibited higher clarithromycin susceptibility (100%) compared to M. abscessus subsp. abscessus (56.5%). Clarithromycin resistance of M. abscessus isolates correlated with functional T28 sequevar in the erm (41) gene.

Conclusions

Our findings elucidate distinct antimicrobial susceptibility profiles of M. marinum and M. abscessus isolated from cutaneous infection in China, providing critical guidance for clinical treatment. Cutaneous M. abscessus isolates exhibit extensive drug resistance patterns. Subtyping and erm (41) polymorphism detection serve as reliable predictors of clarithromycin resistance in M. abscessus.
目的:皮肤分枝杆菌的药敏数据仍然有限。本研究对中国某皮肤科专科医院分离的海洋分枝杆菌和脓肿分枝杆菌的药敏模式和分子耐药机制进行了研究。方法:采用微量肉汤稀释法对200株海洋分枝杆菌和50株脓肿分枝杆菌临床分离株进行药敏试验。通过hsp65、erm(41)和rpoB基因测序鉴定脓肿支原体亚种。对分离的脓肿分枝杆菌进行erm(41)、rrl、rrs、gyrA和gyrB基因测序,分析克拉霉素、氨卡星和氟喹诺酮类药物耐药相关突变。结果:海芽孢杆菌对克拉霉素、利福平、利福布汀、莫西沙星、利奈唑胺、甲氧苄啶-磺胺甲恶唑敏感性高(82.5% ~ 100%),对四环素类和环丙沙星敏感性中等。乙胺丁醇对海洋分枝杆菌有较好的抑制作用,MIC90为2μg/mL。在脓肿支原体分离株中,有23株为脓肿支原体。脓肿,26 M.脓肿子粗毛状,1脓肿分枝。对克拉霉素和阿米卡星的总体敏感性分别为78%和82%。替加环素和氯法齐明分别以MIC90 1和0.5 μg/mL对脓肿支原体有效。相比之下,脓肿分枝杆菌对包括利奈唑胺、氟喹诺酮类药物和四环素类药物在内的多种抗生素表现出高度耐药性。脓肿支原体马尾蚴对克拉霉素的敏感性为100%,高于脓肿分枝杆菌。脓肿(56.5%)。脓疡分枝杆菌对克拉霉素的耐药性与erm(41)基因T28的功能序列相关。结论:我们的研究结果阐明了中国皮肤感染分离的海洋分枝杆菌和脓肿分枝杆菌不同的抗菌药物敏感性特征,为临床治疗提供了重要指导。皮肤脓肿分枝杆菌分离株表现出广泛的耐药模式。亚型分型和erm(41)多态性检测可作为脓疡分枝杆菌耐药的可靠预测指标。
{"title":"Antimicrobial susceptibility patterns and genotypic characteristics of Mycobacterium marinum and Mycobacterium abscessus isolated from cutaneous infections: A retrospective study","authors":"Jiayi Peng ,&nbsp;Wenyue Zhang ,&nbsp;Ying Shi ,&nbsp;Haiqin Jiang ,&nbsp;Jingshu Xiong ,&nbsp;Youming Mei ,&nbsp;Tian Gan ,&nbsp;Hongsheng Wang","doi":"10.1016/j.jgar.2025.10.001","DOIUrl":"10.1016/j.jgar.2025.10.001","url":null,"abstract":"<div><h3>Objectives</h3><div>Antimicrobial susceptibility data for cutaneous mycobacteria remain limited. This study investigated the antimicrobial susceptibility patterns and molecular resistance mechanisms of <em>Mycobacterium marinum</em> and <em>Mycobacterium abscessus</em> isolates from a dermatology specialized hospital in China.</div></div><div><h3>Methods</h3><div>Antimicrobial susceptibility testing was performed on 200 <em>M. marinum</em> and 50 <em>M. abscessus</em> clinical isolates using broth microdilution method. <em>M. abscessus</em> subspecies were identified through <em>hsp65, erm (41),</em> and <em>rpoB</em> gene sequencing. For <em>M. abscessus</em> isolates, resistance-associated mutations for clarithromycin, amikacin, and fluoroquinolones were analysed by sequencing <em>erm (41), rrl, rrs, gyrA, and gyrB</em> genes.</div></div><div><h3>Results</h3><div><em>M. marinum</em> demonstrated high susceptibility (82.5%–100%) to clarithromycin, rifampin, rifabutin, moxifloxacin, linezolid, trimethoprim-sulfamethoxazole, with moderate susceptibility to tetracyclines and ciprofloxacin. Ethambutol showed favourable activity against <em>M. marinum</em> with MIC<sub>90</sub> of 2 µg/mL. Among <em>M. abscessus</em> isolates (23 <em>M. abscessus subsp. abscessus</em>, 26 <em>M. abscessus subsp. massiliense</em>, 1 <em>M. abscessus subsp. bolletii</em>), overall susceptibility to clarithromycin and amikacin was 78% and 82%, respectively. Tigecycline and clofazimine were effective against <em>M. abscessus</em> with MIC<sub>90</sub> 1 and 0.5 µg/mL, respectively. In contrast, <em>M. abscessus</em> isolates demonstrated high-level of resistance to multiple antibiotics, including linezolid, fluoroquinolones, and tetracyclines. <em>M. abscessus subsp. massiliense</em> exhibited higher clarithromycin susceptibility (100%) compared to <em>M. abscessus subsp. abscessus</em> (56.5%). Clarithromycin resistance of <em>M. abscessus</em> isolates correlated with functional T28 sequevar in the <em>erm (41)</em> gene.</div></div><div><h3>Conclusions</h3><div>Our findings elucidate distinct antimicrobial susceptibility profiles of <em>M. marinum</em> and <em>M. abscessus</em> isolated from cutaneous infection in China, providing critical guidance for clinical treatment. Cutaneous <em>M. abscessus</em> isolates exhibit extensive drug resistance patterns. Subtyping and <em>erm (41)</em> polymorphism detection serve as reliable predictors of clarithromycin resistance in <em>M. abscessus</em>.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 240-247"},"PeriodicalIF":3.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
blaNDM-5 is the predominant variant of blaNDM gene in Klebsiella species detected in Mississippi, USA blaNDM-5是在美国密西西比州克雷伯菌中检测到的blaNDM基因的显性变异。
IF 3.2 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-10-21 DOI: 10.1016/j.jgar.2025.10.014
Srimadhav Nallani , Saihou Ceesay , Abiye Iyo, Lucersia Nichols, Daphne Ware, Beata Karolewicz

Objectives

The Mississippi Public Health Laboratory conducts active surveillance of carbapenem-resistant Enterobacterales (CRE) infections as part of the Antimicrobial Resistance Laboratory Network (ARLN) program implemented by the United States Centers for Disease Control and Prevention (CDC). Here, we describe the prevalence of New Delhi Metallo-β-lactamase (blaNDM) genes in Klebsiella, a major pathogen of the Enterobacterales order linked to nosocomial infections, between January 2022 and June 2025.

Methods

Carbapenemase activity was confirmed using the Modified Carbapenem Inactivation Method (mCIM). PCR was then performed on carbapenemase-positive isolates to detect blaNDM genes. Whole-genome sequencing (WGS) was performed on 35 blaNDM-positive isolates to identify blaNDM gene variants, other antimicrobial resistance (AMR) determinants, virulence factors, and plasmids. Antibiotic susceptibility testing (AST) was determined by the Kirby-Bauer disk diffusion assay.

Results

Among the 35 NDM-positive Klebsiella species, the blaNDM-5 variant was identified in 23 (65.7%) isolates, followed by blaNDM-1 and blaNDM-7 genes which were identified in 6/35 (17%) and 6/35 (17%) cases, respectively. A significant proportion of blaNDM-5 cases also harbored additional β-lactamase genes such as blaSHV family (18/23; 78%) and blaTEM-1 (9/23; 39%) indicating multi-drug resistance. All 23 blaNDM-5-positive isolates were resistant to carbapenems and broad-spectrum cephalosporins, but 13/23 (56.5%) remained susceptible to aztreonam. PlasmidFinder analysis identified IncX3 (20/23) and IncFIB(K) (19/23) as the predominant plasmid replicons among these isolates.

Conclusion

The emergence and spread of bacteria carrying blaNDM-5 gene poses a significant threat to public health in Mississippi. Our dataset warrants further study to investigate the potential role of plasmids in blaNDM-5 dissemination.
目的:密西西比公共卫生实验室对碳青霉烯耐药肠杆菌(CRE)感染进行积极监测,作为美国疾病控制和预防中心(CDC)实施的抗菌素耐药性实验室网络(ARLN)计划的一部分。在这里,我们描述了2022年1月至2025年6月期间克雷伯氏菌中新德里金属β-内酰胺酶(blaNDM)基因的流行情况,克雷伯氏菌是与医院感染相关的肠杆菌目的主要病原体。方法:采用改良碳青霉烯酶失活法(mCIM)测定碳青霉烯酶活性。然后对碳青霉烯酶阳性分离株进行PCR检测blaNDM基因。对35株blaNDM阳性分离株进行全基因组测序(WGS),以鉴定blaNDM基因变异、其他抗微生物药物耐药性(AMR)决定因素、毒力因子和质粒。采用Kirby-Bauer纸片扩散法进行药敏试验(AST)。结果:35株ndm阳性克雷伯菌中,检出blaNDM-5基因的有23株(65.7%),检出blaNDM-1基因的有6/35(17%),检出blaNDM-7基因的有6/35(17%)。相当比例的blaNDM-5病例还携带额外的β-内酰胺酶基因,如blaSHV家族(18/23;78%)和blandm -1(9/23; 39%),表明多药耐药。23株blandm -5阳性菌株均对碳青霉烯类和广谱头孢菌素耐药,13/23株(56.5%)对氨曲南敏感。PlasmidFinder分析发现IncX3(20/23)和IncFIB(K)(19/23)是这些分离株中主要的质粒复制子。结论:携带blaNDM-5基因的细菌的出现和传播对密西西比州的公共卫生构成了重大威胁。我们的数据集值得进一步研究,以调查质粒在blaNDM-5传播中的潜在作用。
{"title":"blaNDM-5 is the predominant variant of blaNDM gene in Klebsiella species detected in Mississippi, USA","authors":"Srimadhav Nallani ,&nbsp;Saihou Ceesay ,&nbsp;Abiye Iyo,&nbsp;Lucersia Nichols,&nbsp;Daphne Ware,&nbsp;Beata Karolewicz","doi":"10.1016/j.jgar.2025.10.014","DOIUrl":"10.1016/j.jgar.2025.10.014","url":null,"abstract":"<div><h3>Objectives</h3><div>The Mississippi Public Health Laboratory conducts active surveillance of carbapenem-resistant <em>Enterobacterales</em> (CRE) infections as part of the Antimicrobial Resistance Laboratory Network (ARLN) program implemented by the United States Centers for Disease Control and Prevention (CDC). Here, we describe the prevalence of New Delhi Metallo-β-lactamase (<em>bla</em><sub>NDM</sub>) genes in <em>Klebsiella</em>, a major pathogen of the <em>Enterobacterales</em> order linked to nosocomial infections, between January 2022 and June 2025.</div></div><div><h3>Methods</h3><div>Carbapenemase activity was confirmed using the Modified Carbapenem Inactivation Method (mCIM). PCR was then performed on carbapenemase-positive isolates to detect <em>bla</em><sub>NDM</sub> genes. Whole-genome sequencing (WGS) was performed on 35 <em>bla</em><sub>NDM</sub>-positive isolates to identify <em>bla</em><sub>NDM</sub> gene variants, other antimicrobial resistance (AMR) determinants, virulence factors, and plasmids. Antibiotic susceptibility testing (AST) was determined by the Kirby-Bauer disk diffusion assay.</div></div><div><h3>Results</h3><div>Among the 35 NDM-positive <em>Klebsiella</em> species, the <em>bla</em><sub>NDM-5</sub> variant was identified in 23 (65.7%) isolates, followed by <em>bla</em><sub>NDM-1</sub> and <em>bla</em><sub>NDM-7</sub> genes which were identified in 6/35 (17%) and 6/35 (17%) cases, respectively. A significant proportion of <em>bla</em><sub>NDM-5</sub> cases also harbored additional β-lactamase genes such as <em>bla</em><sub>SHV</sub> family (18/23; 78%) and <em>bla</em><sub>TEM-1</sub> (9/23; 39%) indicating multi-drug resistance. All 23 <em>bla</em><sub>NDM-5</sub>-positive isolates were resistant to carbapenems and broad-spectrum cephalosporins, but 13/23 (56.5%) remained susceptible to aztreonam. PlasmidFinder analysis identified IncX3 (20/23) and IncFIB(K) (19/23) as the predominant plasmid replicons among these isolates.</div></div><div><h3>Conclusion</h3><div>The emergence and spread of bacteria carrying <em>bla</em><sub>NDM-5</sub> gene poses a significant threat to public health in Mississippi. Our dataset warrants further study to investigate the potential role of plasmids in <em>bla</em><sub>NDM-5</sub> dissemination.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 282-286"},"PeriodicalIF":3.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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Journal of global antimicrobial resistance
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