Journal of global antimicrobial resistance最新文献_第3页

Antimicrobial resistance in India: Integrating the response into health systems for universal health coverage 印度的抗菌素耐药性：将应对措施纳入全民健康覆盖的卫生系统。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.001

Sudha Chandrashekar , Shambhavi Nimisha Prasad , Ramesh Masthi N R , Sheilja Walia , Anushree Trikha , Rajeev Sadanandan

Background

Antimicrobial resistance (AMR) poses a formidable threat to public health in India, requiring a multidimensional response that bridges policy, innovation and intersectoral collaborations. The rapid emergence and spread of multidrug-resistant pathogens driven by the misuse of antimicrobials in human health, animal health, agriculture and environmental settings has rendered many existing therapies obsolete, leaving the population vulnerable to untreatable infections.

Objectives

To examine the multifactorial drivers of AMR in India, review current national and state-level policies and explore the potential role of artificial intelligence (AI) in AMR surveillance, prevention and control.

Methods

This review synthesises evidence from published literature, reports and policy documents. It analyses AMR determinants across human, animal and environmental sectors, evaluates policy frameworks such as India’s National Action Plan and State Action Plans to combat AMR.

Results

Key AMR drivers include antibiotic misuse, inadequate regulation, over-the-counter availability, pharmaceutical and hospital wastewater contamination and gaps in infection prevention. India has come up with national and six state level action plans for AMR containment. The measures include stewardship programs, laboratory network strengthening, spreading awareness and intersectoral coordination. The role of AI in strengthening AMR surveillance and clinical decision-making by integrating complex, high-dimensional data for predictive modelling has been explored.

Conclusion

While India has made significant policy and surveillance advances, enforcement gaps, limited awareness and fragmented data hinder progress. Strengthening governance, expanding One Health surveillance, integrating AI and embedding AMR strategies into universal health coverage are critical to mitigating AMR’s health and economic burden.

背景：抗微生物药物耐药性（AMR）对印度的公共卫生构成巨大威胁，需要在政策、创新和部门间合作之间建立桥梁，采取多方面的应对措施。由于在人类卫生、动物卫生、农业和环境环境中滥用抗微生物药物，导致耐多药病原体的迅速出现和传播，使许多现有疗法过时，使人群容易受到无法治疗的感染。目的：研究印度抗菌素耐药性的多因素驱动因素，审查当前的国家和州一级政策，并探索人工智能（AI）在抗菌素耐药性监测、预防和控制中的潜在作用。方法：本综述综合了已发表的文献、报告和政策文件的证据。报告分析了人类、动物和环境部门的抗微生物药物耐药性决定因素，评估了印度《国家行动计划》和《国家抗微生物药物耐药性行动计划》等政策框架。结果：抗生素耐药性的主要驱动因素包括抗生素滥用、监管不足、非处方药可及性、制药和医院废水污染以及感染预防方面的差距。印度已经提出了国家和六个邦一级的抗微生物药物耐药性控制行动计划。这些措施包括管理计划、加强实验室网络、传播意识和部门间协调。通过整合复杂的高维数据进行预测建模，人工智能在加强抗菌素耐药性监测和临床决策中的作用已经得到了探索。结论：虽然印度在政策和监督方面取得了重大进展，但执法差距、意识有限和数据碎片化阻碍了进展。加强治理、扩大“一种健康”监测、整合人工智能以及将抗菌素耐药性战略纳入全民健康覆盖，对于减轻抗菌素耐药性的健康和经济负担至关重要。

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引用次数: 0

Clinical outcome comparison between adjunctive clindamycin vs. linezolid for invasive group A streptococcal infection 辅助克林霉素与利奈唑胺治疗侵袭性A组链球菌感染的临床结果比较。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.013

Eriko Hashimoto , Sayaka Yoshida , Taito Kitano

Purpose

Although the non-inferiority of adjunctive linezolid (LZD) was indicated for the treatment of invasive group A streptococcal (iGAS) infection, compared with adjunctive clindamycin (CLDM), additional evaluation of comparative effectiveness by subpopulation may further strengthen the evidence. We compared the efficacy of CLDM and LZD combination therapy for iGAS infection.

Methods

In this retrospective cohort study, data were extracted and analysed using TriNetX, a multicentre database. Data were extracted from 1 January 2015 to 30 April 2025, creating two cohorts (adjunctive CLDM and LZD groups). The primary endpoint was mortality within 90 d from diagnosis, which was compared between groups using propensity score matching. Subgroup analyses were conducted according to age, concomitant intravenous immunoglobulin treatment, and study period.

Results

For analysis, 5841 cases were identified in the CLDM combination group and 1426 in the LZD group. The primary endpoint was observed in 170 (12.0%) cases in the CLDM group and 195 (13.8%) in the LZD group. Odds ratio was 0.854 (95% confidence interval 0.685–1.065, P = 0.161), with odds ratio <1 indicating a CLDM-favourable result.

Conclusions

Clinical efficacy of adjunctive CLDM and LZD was compared in patients with iGAS infection. No significant difference in mortality was observed in the overall population. LZD may be a potential alternative in cases where CLDM use is limited by resistance, intolerance, or contraindications.

目的：虽然与辅助克林霉素（CLDM）相比，辅助利奈唑胺（LZD）治疗侵袭性A组链球菌（iGAS）感染具有非劣效性，但对亚群比较效果的额外评价可能会进一步加强证据。我们比较了CLDM和LZD联合治疗iGAS感染的疗效。方法：在这项回顾性队列研究中，使用TriNetX多中心数据库提取数据并进行分析。数据从2015年1月1日至2025年4月30日提取，创建两个队列（辅助CLDM组和LZD组）。主要终点是诊断后90天内的死亡率，使用倾向评分匹配（PSM）进行组间比较。根据年龄、同时静脉注射免疫球蛋白（IVIG）治疗和研究时间进行亚组分析。结果：在分析中，CLDM联合组有5841例，LZD组有1426例。CLDM组170例（12.0%）和LZD组195例（13.8%）观察到主要终点。优势比（OR）为0.854(95%可信区间0.685-1.065,p=0.161)， OR。结论：比较iGAS感染患者辅助CLDM与LZD的临床疗效。在总体人群中没有观察到死亡率的显著差异。如果CLDM的使用受到耐药性、不耐受或禁忌症的限制，LZD可能是一种潜在的替代方案。

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引用次数: 0

Undetected rifampicin-resistant tuberculosis associated with rpoB I491F and V170F mutations in Botswana: Diagnostic implications 博茨瓦纳与rpoB I491F和V170F突变相关的未检出的利福平耐药结核病：诊断意义

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.005

Tuelo Mogashoa , Justice T. Ngom , Johannes Loubser , Kedumetse Seru , Tuduetso Molefi , One Stephen , Rosemary M. Musonda , Simani Gaseitsiwe , Robin M. Warren , Anzaan Dippenaar , Elizabeth M. Streicher , Sikhulile Moyo

Background

Undetected rifampicin resistance is a threat to global tuberculosis (TB) control efforts by delaying effective treatment. In different studies, non-canonical rpoB mutations outside the rifampicin resistance-determining region have been reported at varying prevalences by country. Here, we report cases of rifampicin resistance in Botswana that were missed by the routine molecular diagnostic assays.

Methods

Individuals were tested under routine programme conditions, in accordance with national guidelines, at four designated drug-resistant TB clinics from 2017 to 2022. Initial testing at the facilities included GeneXpert MTB/RIF ultra and later phenotypic drug susceptibility testing (pDST), as well as the Hain MTBDRsl line probe assay, at the National Tuberculosis Reference Laboratory. A total of nine isolates were subsequently sequenced on the Illumina NextSeq 2000 instrument.

Results

At the point of care, routine molecular tests classified all nine individuals as susceptible to rifampicin. Subsequent culture and phenotypic drug susceptibility testing confirmed rifampicin resistance. Whole-genome sequencing identified non-canonical rpoB mutations outside the rifampicin resistance-determining region I49F and V170F, which are associated with low-level rifampicin resistance. Of the nine isolates sequenced, 4 (44%) harboured the rpoB V170F mutation, while 5 (56%) harboured the rpoB I491F mutation.

Conclusions

These results highlight a diagnostic gap within the current algorithms and show the value of sequencing-based approaches for accurately detecting drug resistance. Incorporating sequencing into routine clinical practice could help guide the selection of TB treatment and improve treatment outcomes in patients who do not respond to first-line therapy.

背景：未被发现的利福平耐药性延误了有效治疗，对全球结核病控制工作构成威胁。在不同的研究中，在利福平耐药决定区以外的非规范rpoB突变在不同国家的流行率不同。在这里，我们报告的病例利福平耐药在博茨瓦纳漏掉了常规分子诊断分析。方法：根据国家指南，于2017年至2022年在四个指定的耐药结核病诊所在常规规划条件下对个体进行检测。这些设施的初步检测包括GeneXpert MTB/RIF超和后来的表型药敏试验（pDST），以及国家结核病参考实验室的Hain MTBDRsl系探针测定。随后，共有9个分离株在Illumina NextSeq 2000仪器上测序。结果：在护理点，常规分子测试将所有9个人分类为利福平敏感。随后的培养和表型药敏试验证实利福平耐药。全基因组测序鉴定出在利福平耐药决定区I49F和V170F之外的非规范rpoB突变，这与低水平的利福平耐药有关。测序的9株分离株中，4株（44%）携带rpoB V170F突变，5株（56%）携带rpoB I491F突变。结论：这些结果突出了当前算法的诊断差距，并显示了基于测序的方法在准确检测耐药性方面的价值。将测序纳入常规临床实践可能有助于指导结核病治疗的选择，并改善对一线治疗无反应的患者的治疗结果。

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引用次数: 0

Impact of antimicrobial prophylaxis in colorectal cancer surgery on the gut and oral microbiome and resistome: A prospective observational cohort study 结直肠癌手术中抗菌素预防对肠道和口腔微生物组和抵抗组的影响：一项前瞻性观察队列研究

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.014

Hiroki Kitagawa , Toshiki Kajihara , Koji Yahara , Norikazu Kitamura , Norifumi Shigemoto , Hirofumi Doi , Kensuke Shimbara , Kosuke Yoshimura , Ikki Nakashima , Shinnosuke Uegami , Yusuke Watadani , Miki Kawada-Matsuo , Hitoshi Komatsuzawa , Hiroki Ohge , Motoyuki Sugai

Background

The use of antibiotics may facilitate the colonisation of antimicrobial-resistant organisms and genes within the host microbiome. However, studies on the effects of antibiotics on microbiomes and resistomes in clinical settings are limited.

Aim

The aim of this study was to determine the effects of antibiotic prophylaxis during colorectal cancer surgery on the oral and gut microbiomes and resistomes of patients.

Methods

We conducted a single-centre prospective observational cohort study on patients who underwent colorectal cancer surgery with antibiotic prophylaxis. DNA was extracted from oral and stool samples 1 day prior to the procedure and on postoperative days 1, 7, and 28. Subsequently, metagenomic sequencing was performed.

Findings

Among the eight patients with colorectal cancer, α-diversity in the oral and stool samples significantly decreased from baseline to each of the three post-administration time points. The abundance of anaerobic genera significantly decreased from baseline to Day 7. In the stool samples, Enterococcus, Limosilactobacillus, and Lacticaseibacillus abundances were markedly increased. Total antibiotic resistance gene (ARG) abundance significantly increased from the baseline to Day 7 in both oral and stool samples. The impact of the increase observed on Day 7 decreased but still persisted until Day 28 for diversity and total abundance of ARGs.

Conclusions

Oral and gut microbiomes and resistomes exhibited marked alterations that gradually reversed over time. Changes in the microbiome were associated with the spectrum of antibiotics used.

背景：抗生素的使用可能促进抗菌素耐药生物和基因在宿主微生物群中的定植。然而，关于抗生素在临床环境中对微生物组和抵抗组的影响的研究是有限的。目的：本研究的目的是确定结肠直肠癌手术期间抗生素预防对患者口腔和肠道微生物组和抵抗组的影响。方法：我们对接受结肠直肠癌手术的患者进行了单中心前瞻性观察队列研究。术前1天和术后第1、7和28天分别从口腔和粪便样本中提取DNA。随后，进行宏基因组测序。结果：在8例结直肠癌患者中，口服和粪便样品中的α-多样性从基线到三个给药后时间点均显著降低。从基线到第7天，厌氧菌的丰度显著下降。粪便样品中肠球菌、乳酸杆菌和乳酸菌丰度明显升高。从基线到第7天，口腔和粪便样本中的总抗生素耐药基因（ARG）丰度显著增加。第7天观察到的增加对ARGs的多样性和总丰度的影响有所下降，但仍持续到第28天。结论：口腔和肠道微生物组和抗性组表现出明显的变化，随着时间的推移逐渐逆转。微生物组的变化与使用的抗生素种类有关。

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引用次数: 0

Detection of clinical isolates of tigecycline-resistant Escherichia coli harbouring tet(X4) in Myanmar 缅甸耐替加环素携带tet（X4）大肠杆菌临床分离株检测。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.006

Maiko Kirikae , Satomi Takei , Thi Thi Htoon , Pan Ei Soe , Nang Sarm Hom , San Yu Maw , May Yee Aung , Shino Hosoya , Swe Setk , Htay Htay Tin , Yuki Uehara , Teruo Kirikae , Tatsuya Tada

Objectives

Tigecycline is one of the last-resort antibiotics for treating serious infections caused by multidrug-resistant pathogens. This is the first report of clinical isolates of tigecycline-resistant Escherichia coli harbouring tet(X4) in Myanmar.

Methods

Two E. coli isolates were obtained from two patients at two hospitals in Myanmar from November 2023 to May 2024. They were identified using MALDI-TOF MS, and minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Genomic DNA was extracted and sequenced using next generation sequencing. Drug resistance factors were determined, and the genetic environments surrounding tet(X4) and bla_NDM-5 were analysed. Conjugation rates of plasmids harbouring tet(X4) and bla_NDM-5 were calculated.

Results

One strain, TGH62, was resistant to tigecycline (MIC 8 µg/mL) and meropenem (MIC 128 µg/mL), whereas the other, YGH433, was resistant to tigecycline (MIC 4 µg/mL). Whole-genome sequencing revealed that both strains harboured tet(X4) on plasmids and TGH62 also harboured bla_NDM-5 on a plasmid. The plasmids carrying tet(X4) in TGH62 and YGH433 belonged to the IncI and IncFII incompatibility groups, respectively. The plasmid carrying bla_NDM-5 belonged to the IncFIA incompatibility group. The conjugation efficiencies of the plasmids harbouring tet(X4) in YGH433 and bla_NDM-5 in TGH62 were relatively high, whereas that harbouring tet(X4) in TGH62 was low.

Conclusions

Tigecycline-resistant Enterobacteriaceae harbouring tet(X4) may spread in hospitals in Myanmar. Further studies are needed to detect tet(X4) conferring tigecycline resistance in hospitals as well as environmental settings in Myanmar.

目的：替加环素是治疗多重耐药病原菌引起的严重感染的最后抗生素之一。这是缅甸首次报道携带tet（X4）的耐替加环素大肠杆菌临床分离株。方法：2023年11月至2024年5月，从缅甸两家医院的2例患者中分离出2株大肠杆菌。用MALDI-TOF质谱法鉴定，用肉汤微量稀释法测定最低抑菌浓度（mic）。提取基因组DNA，采用下一代测序技术进行测序。测定耐药因素，分析tet（X4）和blaNDM-5的遗传环境。计算携带tet（X4）和blaNDM-5的质粒的结合率。结果：菌株TGH62对替加环素（MIC为8µg/ml）和美罗培南（MIC为128µg/ml）耐药，菌株YGH433对替加环素（MIC为4µg/ml）耐药。全基因组测序显示，这两种菌株的质粒上都含有tet(X4)， TGH62的质粒上也含有blaNDM-5。TGH62和YGH433中携带tet（X4）的质粒分别属于IncI和IncFII不相容组。携带blaNDM-5的质粒属于IncFIA不相容组。在YGH433中携带tet（X4）的质粒和在TGH62中携带blaNDM-5的质粒结合效率较高，而在TGH62中携带tet（X4）的质粒结合效率较低。结论：携带tet（X4）的耐替加环素肠杆菌科可能在缅甸医院传播。需要进一步的研究来发现在缅甸的医院和环境环境中造成替加环素耐药性的tet（X4）。

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引用次数: 0

Dissemination of NDM-1-producing Pseudomonas aeruginosa ST308 and ST274 high-risk clones in Argentina 产ndm -1铜绿假单胞菌ST308和ST274高危无性系在阿根廷的传播

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.011

Melina Rapoport , Nahir Gattoni , Celeste Lucero , Juan Manuel de Mendieta

Objective

This study describes the phenotypic, molecular, and genomic characterisation of emerging bla_NDM-1-producing Pseudomonas aeruginosa in Argentina, mainly driven by ST308 and ST274 clones.

Methods

Nineteen clinical isolates submitted to the National and Regional Reference Laboratory on Antimicrobial Resistance between 2018 and 2024 from nine hospitals were analysed. Antimicrobial susceptibility and carbapenemase activity were evaluated. In-house PCR assays were used to detect relevant resistance determinants. Genetic relatedness was assessed by SpeI-PFGE, and whole-genome sequencing was performed on nine isolates using Illumina and Oxford Nanopore technologies.

Results

All isolates were resistant to all β-lactams tested, except two, M28149 and M28715, that remained susceptible to aztreonam. All carried bla_NDM-1. PFGE identified six pulsotypes, with 13 isolates in one dominant type. Whole-genome sequencing revealed six ST308, two ST274, and one ST3243; five ST308 isolates also harboured the rmtD 16S methylase gene. Phylogenetic analysis of ST308 isolates showed they formed a distinct cluster compared with those from other countries.

Conclusions

The emergence of bla_NDM-1-producing P. aeruginosa associated with ST308 and ST274 clones represents a public health concern, particularly given the scarcity of effective treatment options for severe infections caused by these high-risk clones.

背景:。铜绿假单胞菌是一种主要的医院病原体，可引起广泛的急性和慢性感染。当分离株是碳青霉烯酶的生产者，通常对大多数或所有一线抗生素具有耐药性时，抗菌治疗变得特别具有挑战性。blaNDM是一种广泛存在于肠杆菌中的金属β-内酰胺酶，但仅在铜绿假单胞菌中偶有报道。目的:。本研究描述了阿根廷产blandm -1假单胞菌（P. aeruginosa）的表型、分子和基因组特征，主要由ST308和ST274克隆驱动。方法:。对9家医院2018 - 2024年提交给国家和地区抗微生物药物耐药性参考实验室的19株临床分离株进行分析。评估了药物敏感性和碳青霉烯酶活性。采用内部PCR检测相关的耐药决定因素。通过SpeI-PFGE评估遗传亲缘性，并使用Illumina和Oxford Nanopore技术对9个分离株进行全基因组测序。结果:。除2株（M28149、M28715）对氨曲南敏感外，其余菌株均对β-内酰胺类耐药。都携带了blaNDM-1。PFGE鉴定出6个脉冲型，其中1个优势型有13个分离株。WGS发现6个ST308, 2个ST274, 1个ST3243；5株ST308菌株还携带rmtD 16S甲基化酶基因。系统发育分析表明，ST308分离株与其他国家分离株形成明显的聚类。结论:。与ST308和ST274克隆相关的产生blandm -1的铜绿假单胞菌的出现引起了公共卫生关注，特别是考虑到这些高风险克隆引起的严重感染缺乏有效的治疗方案。

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引用次数: 0

Evaluating the performance of the InnowaveDx MTB/RIF/INH for simultaneous detection of Mycobacterium tuberculosis and resistance to rifampicin and isoniazid 评估InnowaveDx MTB/RIF/INH同时检测结核分枝杆菌和对利福平和异烟肼的耐药性的性能。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.016

Dapeng Fan, Hao Li, Xuechai Shang, Miaofen Yang, Huanyu Li, Yongning Yue, Long Cai

Objective

To evaluate the diagnostic performance of the InnowaveDx MTB/RIF/INH assay for the simultaneous detection of Mycobacterium tuberculosis and resistance to rifampicin and isoniazid.

Methods

We evaluated the performance of the InnowaveDx MTB/RIF/INH (InnowaveDx) assay in diagnosing pulmonary tuberculosis and detecting rifampicin and isoniazid resistance at the Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine.

Results

Using the clinical final diagnosis as the standard, the sensitivity of InnowaveDx was 68.0%, which was higher than that of acid-fast bacilli smear, MGIT culture, and Xpert (P < .001). The specificity was 97.1%, which was higher than acid-fast bacilli smear (P < .001). The agreement between InnowaveDx and MGIT phenotypic drug sensitivity, as well as Xpert, for detecting rifampicin resistance, had kappa values of 0.783 and 0.940, respectively. The agreement between InnowaveDx and MGIT phenotypic drug sensitivity, as well as multicolor melting curve analysis, for detecting isoniazid resistance, had kappa values of 0.915 and 1. The discrepancies in rifampicin- and isoniazid-resistance detection were observed in 11 and 4 cases, respectively.

Conclusions

The InnowaveDx MTB/RIF/INH assay demonstrates good performance in detecting M. tuberculosis as well as rifampicin and isoniazid resistance. The discrepancies in rifampicin-resistance results and phenotypic resistance are mainly the result of borderline resistance mutations.

背景：在中国，耐多药或利福平耐药结核病（MDR/RR-TB）的早期准确诊断对于确保适当治疗至关重要。迫切需要开发一种同时检测结核分枝杆菌（MTB）以及对利福平和异烟肼耐药的诊断方法。方法：评价InnowaveDx MTB/RIF/INH （InnowaveDx）检测在浙江省中西医结合医院诊断肺结核及检测利福平和异烟肼耐药中的表现。结果：以临床最终诊断为标准，InnowaveDx的敏感性为68.0%，高于AFB涂片、MGIT培养和Xpert （P < 0.001）。特异性为97.1%，高于AFB涂片（P < 0.001）。InnowaveDx与MGIT表型药物敏感性（pDST）和Xpert检测利福平耐药的Kappa值一致性分别为0.783和0.940。InnowaveDx与MGIT pDST以及MMCA检测异烟肼耐药性的Kappa值分别为0.915和1。利福平耐药和异烟肼耐药检测差异分别为11例和4例。结论：InnowaveDx MTB/RIF/INH检测方法对MTB以及利福平和异烟肼耐药具有良好的检测效果。利福平耐药结果与表型耐药差异主要是由于临界耐药突变所致。

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引用次数: 0

Impact of DNA methyltransferases on bacterial fitness and genome stability in Escherichia coli DNA甲基转移酶对大肠杆菌细菌适应度和基因组稳定性的影响

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.009

Jee Hong KIM , Hyunkeun KIM , Kwan Soo KO

Objective

DNA methylation, catalysed by DNA methyltransferases (MTases), plays a crucial role in bacterial physiology. In this study, we investigated the effects of the DNA MTases, DNA adenine methyltransferase (Dam) and DNA cytosine methyltransferase (Dcm), on bacterial fitness and mutation rates in Escherichia coli.

Methods

We constructed an E. coli K-12 MG1655 strain lacking both the dam and dcm genes (ΔdamΔdcm). The bacterial fitness was assessed using growth curves and competition assays. Antibiotic susceptibility and persister cell formation were also evaluated. Additionally, the spontaneous mutation rates and mutation types in response to rifampicin and colistin were analysed.

Results

The MTase-deficient mutant ΔdamΔdcm exhibited significantly reduced growth rates and competitiveness compared to the wild-type (WT) strain. However, no significant differences in antibiotic resistance or persister cell formation rates were observed between the mutant and WT strains. Mutation frequencies in ΔdamΔdcm were significantly higher than in the WT when exposed to both rifampicin and colistin. Furthermore, a higher ratio of transition mutations in the rpoB and pmrAB genes was observed in rifampicin-resistant and colistin-resistant colonies derived from ΔdamΔdcm, respectively. DNA methylation influences bacterial growth and competitiveness, and the absence of MTases leads to increased spontaneous mutation rates under antibiotic pressure.

Conclusions

These findings suggest that DNA methylation plays a critical role in maintaining genomic stability and contributing to the development of antibiotic resistance.

目的：DNA甲基化是由DNA甲基转移酶（MTases）催化的，在细菌生理中起着至关重要的作用。在本研究中，我们研究了DNA mtase， DNA腺嘌呤甲基转移酶（Dam）和DNA胞嘧啶甲基转移酶（Dcm）对大肠杆菌细菌适合度和突变率的影响。方法：构建一株同时缺乏dam和dcm基因的大肠杆菌K-12 MG1655菌株（ΔdamΔdcm）。采用生长曲线和竞争试验评估细菌适合度。抗生素敏感性和持久性细胞形成也进行了评估。此外，还分析了利福平和粘菌素的自发突变率和突变类型。结果：与野生型（WT）菌株相比，mtase缺陷突变体ΔdamΔdcm的生长速度和竞争力显著降低。然而，突变菌株和WT菌株在抗生素耐药性和持久性细胞形成率方面没有显著差异。当暴露于利福平和粘菌素时，ΔdamΔdcm的突变频率显著高于WT。此外，在来自ΔdamΔdcm的利福平耐药菌落和粘菌素耐药菌落中，rpoB和pmrAB基因的过渡突变比例更高。DNA甲基化影响细菌的生长和竞争，并且mtase的缺乏导致抗生素压力下自发突变率增加。结论：这些发现表明DNA甲基化在维持基因组稳定性和促进抗生素耐药性的发展中起着关键作用。

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引用次数: 0

A combination of Mycobacterium tuberculosis-derived sRNA and endogenous miRNA in circulation as novel auxiliary diagnostic markers for patients with multidrug-resistant tuberculosis 结核分枝杆菌衍生的sRNA和循环中内源性miRNA联合作为耐多药结核病患者新的辅助诊断标记。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.015

Xiang-Dong Wang , Dongmei Niu , Wei Lv , Lei Wang , Chen-Yu Zhang , Chunni Zhang , Jiaxi Song , Xueling Hu , Cheng Wang

Objective

Circulating non-coding small RNAs (sRNAs) have recently emerged as promising biomarkers for Mycobacterium tuberculosis (Mtb). However, little is known about the expression patterns and combined diagnostic potential of M. tuberculosis-derived sRNA (TB-sRNA) and endogenous miRNA in the circulation of patients with multidrug-resistant tuberculosis (MDR-TB).

Methods

Illumina sequencing by synthesis technology and quantitative real-time polymerase chain reaction were used to identify TB-sRNAs in serum and sputum from patients infected with drug-resistant TB, drug-sensitive TB (DS-TB), and controls. Simultaneously, four endogenous miRNAs – miR-29c, miR-132, miR-320b, and miR-548e – were chosen for further study. The diagnostic performance of significantly altered sRNAs and miRNAs was analysed using receiver operating characteristic (ROC) curves.

Results

Illumina sequencing by synthesis combined with individual quantitative real-time polymerase chain reaction verification successfully identified one TB-encoded sRNA, named TB-sRNA015, and endogenous miR-132 were significantly elevated in patients with MDR-TB compared to patients with DS-TB and controls (P < 0.01). ROC analyses showed that the area under the ROC curve (AUC) for serum sRNA015 discriminating patients with MDR-TB from controls and patients with DS-TB were 0.774 (95% confidence interval [CI], 0.653–0.895) and 0.692 (95% CI, 0.560–0.825), respectively. For serum miR-132, the AUCs were 0.841 (95% CI, 0.735–0.946) for MDR-TB vs. controls and 0.655 (95% CI, 0.518–0.793) for MDR-TB vs. DS-TB. Importantly, combining sRNA015 with miR-132 increased the AUC to 0.860 (95% CI, 0.760–0.960) for discriminating MDR-TB from controls.

Conclusions

The combination of serum sRNA015 and miR-132 may serve as an auxiliary diagnostic tool for MDR-TB infection.

目的：循环非编码小rna （sRNAs）最近成为结核分枝杆菌（Mtb）的有希望的生物标志物。然而，对于mtb衍生的sRNA （TB-sRNA）和内源性miRNA在耐多药结核病（MDR-TB）患者循环中的表达模式和联合诊断潜力知之甚少。方法：采用Illumina合成测序（SBS）技术和实时定量聚合酶链反应（qRT-PCR）技术对耐药结核病（DR-TB）、药敏结核病（DS-TB）和对照患者血清和痰液中的TB- srnas进行鉴定。同时，我们选择了四种内源性mirna - mir -29c、miR-132、miR-320b和mir -548e进行进一步研究。使用受试者工作特征（ROC）曲线分析显著改变的sRNAs和miRNAs的诊断性能。结果：Illumina SBS联合个体qRT-PCR验证成功鉴定了一个tb编码的sRNA，命名为TB-sRNA015，耐多药结核病患者中内源性miR-132与DS-TB患者和对照组相比显著升高（P < 0.01）。ROC分析显示，血清sRNA015区分耐多药结核病患者与对照组和DS-TB患者的ROC曲线下面积（AUC）分别为0.774（95%可信区间[CI]， 0.653-0.895）和0.692 （95% CI, 0.56 -0.825）。对于血清miR-132，耐多药结核病与对照组的auc为0.841 (95% CI, 0.735-0.946)，耐多药结核病与DS-TB的auc为0.655 （95% CI, 0.518-0.793）。重要的是，将sRNA015与miR-132联合使用将区分耐多药结核病与对照组的AUC提高到0.860 （95% CI, 0.76 -0.960）。结论：血清sRNA015与miR-132联合检测可作为耐多药结核感染的辅助诊断工具。

{"title":"A combination of Mycobacterium tuberculosis-derived sRNA and endogenous miRNA in circulation as novel auxiliary diagnostic markers for patients with multidrug-resistant tuberculosis","authors":"Xiang-Dong Wang , Dongmei Niu , Wei Lv , Lei Wang , Chen-Yu Zhang , Chunni Zhang , Jiaxi Song , Xueling Hu , Cheng Wang","doi":"10.1016/j.jgar.2025.12.015","DOIUrl":"10.1016/j.jgar.2025.12.015","url":null,"abstract":"<div><h3>Objective</h3><div>Circulating non-coding small RNAs (sRNAs) have recently emerged as promising biomarkers for <em>Mycobacterium tuberculosis</em> (Mtb). However, little is known about the expression patterns and combined diagnostic potential of <em>M. tuberculosis</em>-derived sRNA (TB-sRNA) and endogenous miRNA in the circulation of patients with multidrug-resistant tuberculosis (MDR-TB).</div></div><div><h3>Methods</h3><div>Illumina sequencing by synthesis technology and quantitative real-time polymerase chain reaction were used to identify TB-sRNAs in serum and sputum from patients infected with drug-resistant TB, drug-sensitive TB (DS-TB), and controls. Simultaneously, four endogenous miRNAs – miR-29c, miR-132, miR-320b, and miR-548e – were chosen for further study. The diagnostic performance of significantly altered sRNAs and miRNAs was analysed using receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>Illumina sequencing by synthesis combined with individual quantitative real-time polymerase chain reaction verification successfully identified one TB-encoded sRNA, named TB-sRNA015, and endogenous miR-132 were significantly elevated in patients with MDR-TB compared to patients with DS-TB and controls (<em>P</em> < 0.01). ROC analyses showed that the area under the ROC curve (AUC) for serum sRNA015 discriminating patients with MDR-TB from controls and patients with DS-TB were 0.774 (95% confidence interval [CI], 0.653–0.895) and 0.692 (95% CI, 0.560–0.825), respectively. For serum miR-132, the AUCs were 0.841 (95% CI, 0.735–0.946) for MDR-TB vs. controls and 0.655 (95% CI, 0.518–0.793) for MDR-TB vs. DS-TB. Importantly, combining sRNA015 with miR-132 increased the AUC to 0.860 (95% CI, 0.760–0.960) for discriminating MDR-TB from controls.</div></div><div><h3>Conclusions</h3><div>The combination of serum sRNA015 and miR-132 may serve as an auxiliary diagnostic tool for MDR-TB infection.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 264-272"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948922","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

Multiplex PCR pneumonia panel compared to standard culture of respiratory specimens: Retrospective results from a transplant centre 多重PCR肺炎组与标准培养呼吸道标本的比较：来自移植中心的回顾性结果。

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance

Pub Date : 2026-01-01 DOI: 10.1016/j.jgar.2025.12.004

Muhammad Sharjeel , Memoona Irshad , Azka Rizvi , Altaf Ahmed , Muhammad Jan Leghari

Objective

Rapid identification of lower respiratory tract infection pathogens is critical for initiating early antimicrobial therapy. This study aimed at evaluating the role of multiplex polymerase chain reaction (mPCR) in detecting respiratory pathogens and antimicrobial resistance at a transplant centre.

Methods

The study was a single-centre, retrospective analysis, completed at a tertiary care transplant centre. Data were included from 242 patients admitted with lower respiratory tract infection during a 24-month period. Respiratory specimens were analysed through BioFire PCR. Blood mPCR specimens were excluded (n = 44). Multiplex PCR results were compared with the gold standard of culture and sensitivity testing.

Results

A total of 198 patients were included in the study. The majority had a history of chronic hepatic or renal impairment (n = 95; 48%) or liver/kidney transplantation (n = 57; 28.8%). Chest imaging (n = 162) predominantly revealed pleural effusions (35.2%) and parenchymal infiltrates (28.4%). Most common sample types included sputum (n = 101; 51.0%) and tracheal aspirates (n = 93; 47.0%). Standard culture detected the following pathogens: 290 typical bacteria, 2 atypical organisms, and 95 viral detections. Klebsiella pneumoniae (32.3%) and Escherichia coli (28.8%) were most frequently identified. In n = 102 patients with corresponding culture results, mPCR had sensitivity of 76% and specificity of 59%, with 66.7% concordance between methods. Multiplex PCR and culture identified multiple bacterial species in 38 (37.3%) and 17 (16.7%) cases, respectively. Antimicrobial resistance gene analysis revealed high prevalence of CTX-M (30%), NDM (28%), and OXA-48-like (22%) mutations.

Conclusions

Multiplex PCR pneumonia panel demonstrated high sensitivity in detecting respiratory pathogens but had limitations in its specificity when compared to culture methods.

目的：快速识别下呼吸道感染（LRTI）病原体是启动早期抗菌治疗的关键。本研究旨在评估多重聚合酶链反应（mPCR）在移植中心检测呼吸道病原体和抗菌素耐药性（AMR）中的作用。方法：本研究为单中心回顾性分析，在三级保健移植中心完成。数据来自242例24个月内入院的LRTI患者。呼吸标本通过BioFire®PCR进行分析。排除血液mPCR标本（n=44）。将多重PCR结果与培养和敏感性试验金标准进行比较。结果：纳入n=198例患者的数据。大多数患者有慢性肝肾损害史（n=95, 48%）或肝/肾移植史（n=57, 28.8%）。胸部显像（n=162）主要显示胸腔积液（35.2%）和实质浸润（28.4%）。最常见的样本类型包括痰液（n=101, 51.0%）和气管吸入物（n=93, 47.0%）。病原菌检测结果如下：典型菌290例，非典型菌2例，病毒95例。肺炎克雷伯菌（32.3%）和大肠埃希菌（28.8%）最为常见。在n=102例有相应培养结果的患者中，mPCR的敏感性为76%，特异性为59%，两种方法的一致性为66.7%。多重PCR和培养分别检出38例（37.3%）和17例（16.7%）多菌种。AMR基因分析显示CTX-M（30%）、NDM（28%）和oxa -48样（22%）突变的高患病率。结论：多重PCR肺炎检测方法对呼吸道病原菌的检测具有较高的敏感性，但与培养方法相比，其特异性存在局限性。

{"title":"Multiplex PCR pneumonia panel compared to standard culture of respiratory specimens: Retrospective results from a transplant centre","authors":"Muhammad Sharjeel , Memoona Irshad , Azka Rizvi , Altaf Ahmed , Muhammad Jan Leghari","doi":"10.1016/j.jgar.2025.12.004","DOIUrl":"10.1016/j.jgar.2025.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>Rapid identification of lower respiratory tract infection pathogens is critical for initiating early antimicrobial therapy. This study aimed at evaluating the role of multiplex polymerase chain reaction (mPCR) in detecting respiratory pathogens and antimicrobial resistance at a transplant centre.</div></div><div><h3>Methods</h3><div>The study was a single-centre, retrospective analysis, completed at a tertiary care transplant centre. Data were included from 242 patients admitted with lower respiratory tract infection during a 24-month period. Respiratory specimens were analysed through BioFire PCR. Blood mPCR specimens were excluded (<em>n</em> = 44). Multiplex PCR results were compared with the gold standard of culture and sensitivity testing.</div></div><div><h3>Results</h3><div>A total of 198 patients were included in the study. The majority had a history of chronic hepatic or renal impairment (<em>n</em> = 95; 48%) or liver/kidney transplantation (<em>n</em> = 57; 28.8%). Chest imaging (<em>n</em> = 162) predominantly revealed pleural effusions (35.2%) and parenchymal infiltrates (28.4%). Most common sample types included sputum (<em>n</em> = 101; 51.0%) and tracheal aspirates (<em>n</em> = 93; 47.0%). Standard culture detected the following pathogens: 290 typical bacteria, 2 atypical organisms, and 95 viral detections. <em>Klebsiella pneumoniae</em> (32.3%) and <em>Escherichia coli</em> (28.8%) were most frequently identified. In <em>n</em> = 102 patients with corresponding culture results, mPCR had sensitivity of 76% and specificity of 59%, with 66.7% concordance between methods. Multiplex PCR and culture identified multiple bacterial species in 38 (37.3%) and 17 (16.7%) cases, respectively. Antimicrobial resistance gene analysis revealed high prevalence of CTX-M (30%), NDM (28%), and OXA-48-like (22%) mutations.</div></div><div><h3>Conclusions</h3><div>Multiplex PCR pneumonia panel demonstrated high sensitivity in detecting respiratory pathogens but had limitations in its specificity when compared to culture methods.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"46 ","pages":"Pages 179-186"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723937","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