Journal of global antimicrobial resistance最新文献_第10页

Co-existence of mcr-1 and blaCTX−M from porcine-derived Escherichia coli isolated in China and selection of mcr-1 under cephalosporins pressure 猪源性大肠杆菌mcr-1与blaCTX-M的共存及头孢菌素压力下mcr-1的选择

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1016/j.jgar.2025.08.018

Zixian Wang , Lin Zheng , Lingwei Zhu , Jingyi Guo , Gejin Lu , Jie Jing , Shiwen Sun , Yang Sun , Xue Ji , Bowen Jiang , Bing Liang , Chuanfang Zhao , Xuejun Guo

Objectives

The usage of cephalosporins (CEFs) and the co-existence of the extended-spectrum β-lactamase gene bla_CTX−M in the same host may promote the prevalence of the colistin (CST) resistance gene mcr-1. This study aims to investigate the underlying mechanisms of how the mcr-1 and bla_CTX−M demonstrate significant co-occurrence in Escherichia coli (E. coli).

Methods

Conjugation assays were performed on 22 porcine-derived mcr-1-positive and bla_CTX−M-positive E. coli (MCRPEC::bla_CTX−_M⁺) isolates from China to assess co-transfer potential. Whole-genome sequencing characterized the genetic localization and context of mcr-1 and bla_CTX−M. Fitness cost and genetic stability were evaluated through the growth curve and antimicrobial resistance (AMR) gene stability rates measurements. Additionally, we examined mcr-1 selection during bla_CTX−M co-existence under CEFs’ pressure by monitoring fitness and stability variations in mcr-1.

Results

Successful co-transfer of mcr-1 and bla_CTX−M occurred in 36% (8/22) of isolates, demonstrating co-transfer efficiency ranging from 1.3 × 10^–5 to 1.5 × 10^–3. Predominant plasmid combinations facilitating co-transfer were the IncI2(mcr-1) + IncI1(bla_CTX−M) combination. Notably, we report the first identification of bla_CTX−M-positive E. coli (CTX-M-EC) carrying dual mcr-1 copies on plasmids. The mcr-1 and bla_CTX−M did not exhibit fitness costs in 63% (5/8) of transconjugants, with 88% (7/8) maintaining over 70% stable rate in 10 d. CEFs’ pressure enhanced both the fitness and stability of mcr-1 in bla_CTX−M co-harbouring transconjugants.

Conclusions

The observed high co-transfer efficiency, high stability rates, and low fitness costs of mcr-1 and bla_CTX−M across distinct plasmid types and the mcr-1 selection driven by CEFs support the co-existence of mcr-1 and bla_CTX−M in E. coli hosts. Our findings support the suggestion that there is an urgent need for coordinated antibiotic stewardship targeting both drug classes to curb multidrug-resistant (MDR) bacteria spread.

目的：头孢菌素（CEFs）的使用和广谱β-内酰胺酶（ESBL）基因blaCTX-M在同一宿主体内共存可能促进粘菌素（CST）耐药基因mcr-1的流行。本研究旨在探讨mcr-1和blaCTX-M在大肠杆菌中显著共存的潜在机制。方法：对22株猪源性mcr-1阳性和blaCTX-M阳性大肠杆菌（MCRPEC::blaCTX-M+）进行偶联试验，评估共转移潜力。全基因组测序鉴定了mcr-1和blaCTX-M的遗传定位和背景。通过生长曲线和抗菌素耐药性（AMR）基因稳定率的测定来评价适应度成本和遗传稳定性。此外，我们通过监测mcr-1的适应性和稳定性变化，研究了CEFs压力下blaCTX-M共存期间mcr-1的选择。结果：mcr-1与blaCTX-M共转移成功率为36%(8/22)，共转移效率为1.3×10-5 ~ 1.5×10-3。促进共转移的主要质粒组合是IncI2（mcr-1） + IncI1（blaCTX-M）组合。值得注意的是，我们报告了首次鉴定的blactx - m阳性大肠杆菌（CTX-M-EC）在质粒上携带双mcr-1拷贝。63%（5/8）的转共轭体mcr-1和blaCTX-M不表现出适应成本，88%（7/8）的转共轭体在10天内保持70%以上的稳定率。CEFs压力增强了blaCTX-M共载转共轭子中mcr-1的适应性和稳定性。结论：观察到mcr-1和blaCTX-M在不同质粒类型间的高共转移效率、高稳定性和低适应成本，以及CEFs驱动的mcr-1选择支持mcr-1和blaCTX-M在大肠杆菌宿主中共存。我们的研究结果支持了一项建议，即迫切需要针对这两种药物进行协调的抗生素管理，以遏制多重耐药细菌的传播。

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引用次数: 0

Dispensing of antibiotics without prescription in community drug retail outlets of Bahir Dar City in Northwest Ethiopia: A simulated client visit before and after educational intervention 埃塞俄比亚西北部巴希尔达尔市社区药品零售网点无处方分发抗生素：模拟客户访问前后的教育干预。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1016/j.jgar.2025.08.017

Masho Tigabe Tekle , Faisel Dula Sema , Minichil Chanie Worku , Abdisa Gemedi Jara , Worku Endalamaw Ayenew

Objectives

The non-prescription supply of antibiotics in community drug retail outlets (CDROs) significantly contributes to antibiotic resistance (ABR). This study aimed to assess the effectiveness of an educational intervention for pharmacy practitioners (PPs) in reducing over-the-counter (OTC) antibiotic sales.

Methods

From 1 August 2022, to 30 January 2023, a total of 80 simulated client (SC) visits (40 pre-intervention, 40:post-intervention) were made in 40 CDROs of Bahir Dar City, to determine the baseline and post-intervention extent of the OTC sale of antibiotics. Verbally a 30-minute one-time onsite education regarding antimicrobials, antibiotics, ABR, rational use of antibiotics, role of community PPs in ensuring rational use of antibiotics, and good antibiotic dispensing practice as an intervention was provided to 70 PPs who were working in the 40 CDROs. The education was guided by written informational material which was delivered to each PPs. Two months after the intervention, its effectiveness was tested using McNemar χ² test, and a P value <0.05 was considered statistically significant.

Results

The intervention resulted in significant improvements in reducing non-prescription sale of antibiotics in CDROs (55 % pre-intervention vs. 20 % post-intervention), increasing the request for prescription paper (35 % vs. 75 %), insisting that antibiotics must be dispensed with prescription paper (33.3 % vs. 68.7 %), and reducing dispensing of antibiotics at level 1 demand (50 % vs. 25 %).

Conclusions

Educational intervention provided to PPs was effective in reducing the non-prescription sale of antibiotics, and it improved the practice of dispensing antibiotics.

目的：社区药品零售网点（CDROs）非处方抗生素供应对抗生素耐药（ABR）有显著影响。本研究旨在评估教育干预对药房从业人员（PPs）减少非处方（OTC）抗生素销售的有效性。方法：于2022年8月1日至2023年1月30日，对巴希尔达尔市40家cdro进行80次模拟客户（SC）访诊（干预前40次，干预后40次），确定抗生素OTC销售基线及干预后程度。对在40个CDROs工作的70名pp进行了30分钟的现场口头教育，内容包括抗菌剂、抗生素、ABR、抗生素合理使用、社区pp在确保抗生素合理使用中的作用以及良好的抗生素配药规范（GADP）作为干预措施。教育工作由一份书面信息材料指导，该材料已分发给每个pp。干预2个月后，采用McNemar卡方检验进行有效性检验，p值< 0.05为差异有统计学意义。结果：干预显著改善；减少cdro中抗生素的非处方销售（干预前55% Vs干预后20%），增加处方纸的需求（35% Vs 75%），坚持抗生素必须配处方纸分发（33.3% Vs 68.7%），并减少一级需求抗生素的分发（50% Vs 25%）。结论：对PPs进行教育干预可有效减少非处方销售抗菌药物，提高抗菌药物调剂工作质量。

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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

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub 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。

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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

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub 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 , Wenyue Zhang , Ying Shi , Haiqin Jiang , Jingshu Xiong , Youming Mei , Tian Gan , 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":"2025-12-01","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

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

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub 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

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

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub 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 bla_NDM-1, bla_CTX-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: bla_NDM-1, bla_CTX-M-30, mcr-9.1, armA, rmtC, and rmtD. The bla_NDM-1 gene was embedded in a Tn125-like transposon contained in an IncC-type plasmid alongside the bla_CTX-M-30, rmtC, and tet(G) genes. The bla_CTX-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 bla_NDM-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。

{"title":"Genomic characterization of a carbapenem-resistant Citrobacter freundii complex strain co-carrying blaNDM-1, blaCTX-M-30, armA, rmtC, and rmtD from Chile","authors":"Isidora Manríquez-Cuadra , Maximiliano Matus-Köhler , Alejandro Aguayo-Reyes , Mario Quezada-Aguiluz , Felipe Morales-Leon , Gerardo González-Rocha , Andrés Opazo-Capurro","doi":"10.1016/j.jgar.2025.10.021","DOIUrl":"10.1016/j.jgar.2025.10.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Carbapenem- and third-generation cephalosporin-resistant <em>Enterobacterales</em>, including the <em>Citrobacter freundii</em> complex, are classified as a World Health Organization ‘critical priority’ due to their public health threat. This study reports a <em>C. freundii</em> complex isolate (Cit-107) co-harbouring the <em>bla</em><sub>NDM-1</sub>, <em>bla</em><sub>CTX-M-30</sub>, <em>armA, rmtC</em>, and <em>rmtD</em> genes, recovered from a rectal swab in 2022 in Concepción, Chile.</div></div><div><h3>Methods</h3><div>Antimicrobial susceptibility was assessed via disk diffusion. Whole-genome sequencing was performed using the Illumina NextSeq 2000 platform and annotated with Bakta. <em>In silico</em> analyses included JSpeciesWS, PubMLST, ABRicate, AMRFinderPlus, and MOB-suite. Phylogenetic analysis of Cit-107 and 50 <em>C. freundii</em> complex genomes from the Americas was conducted using IQ-TREE and visualized with iTOL.</div></div><div><h3>Results</h3><div>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: <em>bla</em><sub>NDM-1</sub>, <em>bla</em><sub>CTX-M-30</sub>, <em>mcr-9.1, armA, rmtC</em>, and <em>rmtD</em>. The <em>bla</em><sub>NDM-1</sub> gene was embedded in a Tn<em>125</em>-like transposon contained in an IncC-type plasmid alongside the <em>bla</em><sub>CTX-M-30</sub>, <em>rmtC</em>, and <em>tet(G)</em> genes. The <em>bla</em><sub>CTX-M-30</sub> was harboured in an IncN-type plasmid, while <em>armA, msr(E)</em>, and <em>mph(E)</em> were co-carried in an IncHI2A-type plasmid. Phylogenetic analysis revealed Cit-107 as a divergent lineage within the <em>C. freundii</em> complex.</div></div><div><h3>Conclusions</h3><div>This is the first report of a carbapenem-resistant <em>C. freundii</em> complex isolate carrying <em>bla</em><sub>NDM-1</sub> 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 <em>C. freundii</em> strains in clinical settings.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 290-293"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401026","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

Convergence of genetic variants in MCR-1 and O-antigen conferring polymyxin resistance and fitness cost MCR-1和o抗原遗传变异的趋同，赋予多粘菌素抗性和适应成本。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI: 10.1016/j.jgar.2025.10.005

Jinfeng Lu , Aiping Zhou , Dongjiang Wang , Shuang Wan , Yuting Yang , Na Lv , Jun Li , Guoping Wu

Objective

The emergence of multidrug-resistant bacteria alongside the extensive spread of opportunistic pathogens with a diversity of serotypes threatens public health. Fitness cost and morphological variation are hypothesised to result from O-antigen diversity and lipid A modification, whereas these reconfigurations within lipopolysaccharides (LPS) confer polymyxin resistance.

Methods

In this study, a multidrug-resistant Escherichia coli named EcE.CRE.COL was isolated from a patient undergoing therapeutic laparoscope for liver cancer. Antibiotic susceptibility was measured using the VITEK 2 system (bioMérieux, Marcy-l'Étoile, France), and whole-genome sequencing revealed a chromosome and three plasmids (namely pEcE.CRE.COL015, pEcE.CRE.COL016, and pEcE.CRE.COL032). Comparative genomics was then conducted to identify genetic determinants accounting for multi-drug resistance.

Results

This isolate exhibited characteristic resistance to carbapenems and polymyxin. Interestingly, pEcE.CRE.COL015 and pEcE.CRE.COL032 were shown to harbour bla_NDM-5 and mcr-1, accounting for corresponding antimicrobial resistance. We consequently proposed an evolutionary pattern for the spread of mcr-1, demonstrating that transposon-like architecture could play a key role in the dissemination of polymyxin resistance driven by mcr-1. In addition, a novel serotype gene cluster related to defective O-antigen synthesis was determined, likely resulting from a genetic insertion. SDS-PAGE indicated LPS defectiveness within this isolate, suggesting a variable charge on the membrane surface of EcE.CRE.COL.

Conclusions

Collectively, the co-occurrence of plasmid-borne mcr-1 and bla_NDM-5 was determined, with genetic variations in LPS biosynthesis genes potentially contributing to a synergistic change in bacterial surface charge and corresponding electrostatics to polymyxin.

目的：多药耐药细菌的出现，以及多种血清型的机会性病原体的广泛传播，威胁着公共卫生。适应度成本和形态变化可能是由o抗原多样性和脂质A修饰引起的，而脂多糖（LPS）中的这些重新配置赋予了多粘菌素抗性。方法：从肝癌腹腔镜治疗患者中分离出一株多重耐药大肠杆菌EcE.CRE.COL。采用VITEK 2系统检测抗生素敏感性。全基因组测序发现一条染色体，三个质粒（即pEcE.CRE）。COL015 pEcE.CRE。COL016和pEcE.CRE。分别为COL032)。进行比较基因组学以确定多药耐药的遗传决定因素。结果：该分离株对碳青霉烯类和多粘菌素具有明显的耐药性。有趣的是,pEcE.CRE。COL015和pEcE.CRE。COL032含有blaNDM-5和mcr-1，分别占相应的抗菌素耐药性。因此，我们提出了mcr-1传播的进化模式，其中转座子样结构可能在mcr-1驱动的多粘菌素耐药性传播中发挥关键作用。此外，确定了与o抗原合成缺陷相关的新血清型基因簇，可能是由遗传插入引起的。结果，SDS-PGAE显示该分离物存在LPS缺陷，表明ece . cree . col膜表面的电荷不同。结论：质粒携带的mcr-1和blaNDM-5共同存在，LPS生物合成基因的遗传变异可能导致细菌表面电荷及其对多粘菌素产生的静电协同变化。

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引用次数: 0

Pharmacokinetic/pharmacodynamic targets of ß-lactams associated with bacterial killing and suppression of the resistance emergence in the hollow fiber infection model: A systematic review 中空纤维感染模型中ß-内酰胺类药物的药代动力学/药效学靶点与细菌杀伤和耐药性抑制相关：系统综述

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI: 10.1016/j.jgar.2025.10.009

Charles Baulier , Marion Giry , Manuel Etienne , Julien Kallout , Kévin Alexandre

Introduction

The hollow-fibre infection model (HFIM) is an in vitro model used to study pharmacokinetic/pharmacodynamic (PK/PD) interactions between antibiotics and bacteria. However, its external validity remains poorly assessed. This study aimed to identify PK/PD targets and experimental variables associated with bacterial killing and prevention of resistance emergence during β-lactam treatment in HFIM.

Methods

Systematic review of studies using HFIM and β-lactams, with literature search conducted in 4 databases, following PRISMA guidelines. After a quality assessment (modified ToxRtools scale) of the included studies, univariate and multivariate analyses identified factors associated with the prevention of resistance emergence. CART analysis determined values of PK/PD indices best predicting this outcome.

Results

Of the 497 screened studies, 41 were included. A total of 367 experiments were analysed, mainly involving Pseudomonas aeruginosa (51%) and carbapenems (46%). Antibiotic exposure through minimal or steady-state free concentrations (fC_min,ss/MIC) (OR 0.78, 95% CI [0.70–0.85], P < 0.001), the initial inoculum size (OR 1.48, 95% CI [1.08–2.06], P = 0.017) and the use of a combination therapy (OR 0.33, CI [0.17–0.64], P = 0.001) remained significantly associated with resistance emergence in multivariate analysis. For carbapenems in monotherapy, the prevention of resistance emergence was likely with fC_min,ss/MIC > 5.7.

Conclusions

Stringent PK/PD indices thresholds were necessary to prevent resistance emergence in HFIM experiments.

简介：中空纤维感染模型（HFIM）是一种用于研究抗生素与细菌药代动力学/药效学（PK/PD）相互作用的体外模型。然而，其外部有效性仍然缺乏评估。本研究旨在确定β-内酰胺治疗HFIM期间与细菌杀灭和预防耐药性产生相关的PK/PD靶点和实验变量。方法：系统回顾使用HFIM和β-内酰胺的研究，并在4个数据库中进行文献检索，遵循PRISMA指南。在对纳入的研究进行质量评估（改良的ToxRtools量表）后，单变量和多变量分析确定了与预防耐药性出现相关的因素。CART分析确定了PK/PD指数最能预测该结果的值。结果：在筛选的497项研究中，41项被纳入。共分析367个实验，主要涉及铜绿假单胞菌（51%）和碳青霉烯类（46%）。抗生素暴露通过最低或稳态游离浓度（fCmin,ss/MIC）（or 0.78, CI[0.70-0.85], pmin,ss/MIC>5.7）。结论：在HFIM实验中，严格的PK/PD指标阈值是防止耐药发生的必要条件。

{"title":"Pharmacokinetic/pharmacodynamic targets of ß-lactams associated with bacterial killing and suppression of the resistance emergence in the hollow fiber infection model: A systematic review","authors":"Charles Baulier , Marion Giry , Manuel Etienne , Julien Kallout , Kévin Alexandre","doi":"10.1016/j.jgar.2025.10.009","DOIUrl":"10.1016/j.jgar.2025.10.009","url":null,"abstract":"<div><h3>Introduction</h3><div>The hollow-fibre infection model (HFIM) is an in vitro model used to study pharmacokinetic/pharmacodynamic (PK/PD) interactions between antibiotics and bacteria. However, its external validity remains poorly assessed. This study aimed to identify PK/PD targets and experimental variables associated with bacterial killing and prevention of resistance emergence during β-lactam treatment in HFIM.</div></div><div><h3>Methods</h3><div>Systematic review of studies using HFIM and β-lactams, with literature search conducted in 4 databases, following PRISMA guidelines. After a quality assessment (modified ToxRtools scale) of the included studies, univariate and multivariate analyses identified factors associated with the prevention of resistance emergence. CART analysis determined values of PK/PD indices best predicting this outcome.</div></div><div><h3>Results</h3><div>Of the 497 screened studies, 41 were included. A total of 367 experiments were analysed, mainly involving <em>Pseudomonas aeruginosa</em> (51%) and carbapenems (46%). Antibiotic exposure through minimal or steady-state free concentrations (<em>f</em>C<sub>min,ss</sub>/MIC) (OR 0.78, 95% CI [0.70–0.85], <em>P</em> < 0.001), the initial inoculum size (OR 1.48, 95% CI [1.08–2.06], <em>P</em> = 0.017) and the use of a combination therapy (OR 0.33, CI [0.17–0.64], <em>P</em> = 0.001) remained significantly associated with resistance emergence in multivariate analysis. For carbapenems in monotherapy, the prevention of resistance emergence was likely with <em>f</em>C<sub>min,ss</sub>/MIC > 5.7.</div></div><div><h3>Conclusions</h3><div>Stringent PK/PD indices thresholds were necessary to prevent resistance emergence in HFIM experiments.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 220-227"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308259","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

A reappraisal of carbapenems dosing in febrile neutropenic patients 碳青霉烯类药物治疗发热性中性粒细胞减少症的再评价。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub Date: 2025-10-21 DOI: 10.1016/j.jgar.2025.10.006

Sun-Ting Qin , Meng-Yu Kong , Rui-Yun Ling , Jing Fu , Yao-Jie Chen , Yu-Han Zeng , Dan-Na Jiang , Xiu-Hua Zhang , Xu-Ben Yu , Hai-Na Zhang

Objective

This study aims to optimize carbapenem dosing strategies in febrile neutropenic (FN) patients by evaluating the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) using Monte Carlo simulations based on published population PK (PopPK) models and real-world covariate data.

Methods

A systematic review of published PopPK studies on carbapenems in FN patients was conducted to obtain relevant PK parameters. In parallel, retrospective clinical data from FN patients treated at the First Affiliated Hospital of Wenzhou Medical University between January 2022 and April 2024 were collected to provide covariates for Monte Carlo simulation. Monte Carlo simulations were then performed to evaluate the PTA for various dosing regimens. Dosing regimens were assessed based on achieving a PTA of ≥ 90%.

Results

A total of 96 studies were screened, of which 4 met the inclusion criteria. Separately, real-world covariate data were obtained from 163 FN patients to inform the Monte Carlo simulations. The simulation results showed that standard label dosages of carbapenems administered over 0.5-h infusions failed to consistently achieve a PTA ≥ 90% at the current CLSI breakpoint of 1 mg/L for Enterobacterales. Notably, increasing the dose did not consistently improve PTA, whereas extending the infusion duration to 3 h or using continuous infusion strategy markedly enhanced the likelihood of attaining the PK/PD target.

Conclusion

Standard carbapenem dosing with 0.5-h infusions may lead to suboptimal exposure in FN patients. Prolonging the infusion duration is an effective strategy to improve PTA and optimize efficacy.

目的：本研究旨在基于已发表的人群PK （PopPK）模型和现实世界的共变量数据，通过蒙特卡罗模拟评估药代动力学/药效学（PK/PD）目标达成（PTA）的概率，优化碳青霉烯类药物在发热性中性粒细胞减少症（FN）患者中的给药策略。方法：系统回顾已发表的FN患者碳青霉烯类药物的PopPK研究，获得相关的PK参数。同时，收集2022年1月至2024年4月在温州医科大学第一附属医院治疗的FN患者的回顾性临床数据，为蒙特卡罗模拟提供协变量。然后进行蒙特卡罗模拟以评估各种给药方案的PTA。以达到≥90%的PTA为基础评估给药方案。结果：共筛选96项研究，其中4项符合纳入标准。另外，从163名FN患者中获得真实世界的协变量数据，为蒙特卡罗模拟提供信息。模拟结果显示，在肠杆菌目前的CLSI断点为1 mg/L时，标准标签剂量的碳青霉烯类药物在0.5小时内输注未能始终达到PTA≥90%。值得注意的是，增加剂量并不能持续改善PTA，而延长输注时间至3小时或使用连续输注策略可显著提高达到PK/PD目标的可能性。结论：标准剂量的碳青霉烯输注0.5小时可能导致FN患者的次优暴露。延长输注时间是改善PTA、优化疗效的有效策略。

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引用次数: 0

30-d mortality risk factors in paediatric patients with bloodstream infection due to Enterobacterales: A retrospective observational cohort study 肠杆菌所致血流感染患儿30天死亡率危险因素：一项回顾性观察队列研究

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI: 10.1016/j.jgar.2025.09.014

Ojeda-Diezbarroso Karla , Jimenez-Juarez Rodolfo Norberto , Avilés-Robles Martha , Laris-González Almudena , Bonilla-Pellegrini Sergio , Pichardo-Villalón Liliana , Castellanos-Cruz Carmen

Objective

Data on paediatric bloodstream infection (BSI) in low- and middle-income countries remain scarce. Consequently, this study aims to elucidate the risk factors associated with mortality in paediatric patients with enterobacterial BSIs.

Methods

This was a retrospective analysis of patients with bloodstream infection due to Enterobacterales attended at Hospital Infantil de Mexico during 2013–2019. Factors influencing mortality were assessed. The baseline characteristics of the population, bloodstream infection and antimicrobial treatment were compared between survivors and non-survivors as well.

Results

Of 527 cases of BSIs, 63.6% (n = 335) were caused by Enterobacterales and 307 cases were included. The overall mortality rate was 11.1% (n = 34). In the multivariable regression model, septic shock/multiorgan failure (HR 9.69, 95% CI: 3.28–28.63), and empirical treatment failure (HR 3.4, 95% CI: 1.36–8.45) were associated with an increased mortality risk.

Conclusions

in this study, the mortality in paediatric BSIs was driven by severe clinical presentation and failure to control inflammatory response and infection. Improving outcomes requires proactive measures, including early detection of sepsis by caregivers, education of healthcare providers for timely recognition and treatment, vigilant monitoring of systemic inflammatory response with adaptable therapeutic approaches and reinforcement of antimicrobial stewardship programs.

目的：关于低收入和中等收入国家儿童血液感染（BSI）的数据仍然很少。因此，本研究旨在阐明与肠杆菌性脑损伤患儿死亡率相关的危险因素。方法：回顾性分析2013-2019年在墨西哥婴儿医院就诊的肠杆菌血流感染患者。评估影响死亡率的因素。在幸存者和非幸存者之间比较了人群、血液感染和抗菌治疗的基线特征。结果：527例bsi中，肠杆菌引起的占63.6%（335例），共307例。总死亡率为11.1% （n=34）。在多变量回归模型中，感染性休克/多器官衰竭（HR 9.69, 95% CI: 3.28-28.63）和经验性治疗失败（HR 3.4, 95% CI: 1.36-8.45）与死亡风险增加相关。结论：在本研究中，儿童脑损伤的死亡率是由严重的临床表现和未能控制炎症反应和感染引起的。改善结果需要采取积极的措施，包括护理人员早期发现败血症，教育医疗保健提供者及时识别和治疗，使用适应性治疗方法对全身炎症反应进行警惕监测，并加强抗菌药物管理计划。

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引用次数: 0