International Journal of Antimicrobial Agents最新文献_第9页

Consumption and expenditure on fidaxomicin and oral vancomycin for Clostridioides difficile infection: A 12-year longitudinal study of 43 countries and regions 非达霉素和口服万古霉素治疗艰难梭菌感染的消费和支出：43个国家和地区的12年纵向研究。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-05 DOI: 10.1016/j.ijantimicag.2025.107664

Yin Zhang , Xue Li , Angel Y.S. Wong , Vincent K.C. Yan , Joseph E. Blais , Jiaqi Wong , Esther W. Chan , Wai K. Leung

Background

Current treatment guidelines recommend fidaxomicin and oral vancomycin as first-line treatments for Clostridioides difficile infection (CDI). Disparities in the prevalence of CDI and the availability of novel treatments necessitate understanding the contemporary trends in their consumption at the global level.

Methods

This longitudinal study used global pharmaceutical sales from IQVIA-MIDAS for fidaxomicin and oral vancomycin in 43 countries from 2012 to 2023. We measured defined daily doses per 100,000 inhabitants per year (DDD/100K) and manufacture-level prices, calculating changes using compound annual growth rates (CAGR). We conducted interrupted time-series analyses to assess the impact of guideline updates by Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA) on quarterly consumption.

Results

Overall fidaxomicin consumption increased from 21.68 DDD/100K in 2012 to 126.86 DDD/100K in 2023 (CAGR = 17.42%) and similar increases in expenditure (0.07–0.34 USD/capita; CAGR = 14.96%). Oral vancomycin consumption increased from 71.61 to 120.82 DDD/100K (CAGR = 4.87%), although with a decreasing trend in expenditure (0.20–0.03 USD/capita; CAGR = −15.16%). The earliest adoption of fidaxomicin in middle-income economies occurred five years later than in high-income economies. Despite higher CAGRs, consumption of fidaxomicin and oral vancomycin in middle-income economies was only 1.9% and 2.3%, respectively, of that in high-income economies in 2023. Following the IDSA/SHEA guideline updates, fidaxomicin consumption in Northern America increased immediately.

Conclusion

Consumption of fidaxomicin and oral vancomycin continues to increase globally; however, significant economic and geographical disparities in utilization highlight inequitable access to first-line CDI treatments.

背景：目前的治疗指南推荐非达索霉素和口服万古霉素作为艰难梭菌感染（CDI）的一线治疗。CDI患病率的差异和新治疗方法的可得性需要了解其在全球范围内的消费趋势。方法：这项纵向研究使用了2012年至2023年在43个国家通过IQVIA-MIDAS销售的非达霉素和口服万古霉素的全球药品。我们测量了每年每10万居民的定义日剂量（DDD/100K）和制造级价格，使用复合年增长率（CAGR）计算变化。我们进行了中断时间序列分析，以评估美国传染病学会和美国卫生保健流行病学学会（IDSA/SHEA）指南更新对季度消费的影响。结果：非达霉素总消费量从2012年的21.68 DDD/100K增加到2023年的126.86 DDD/100K (CAGR = 17.42%)，支出也有类似的增长（0.07 ~ 0.34 USD/人均，CAGR = 14.96%）。口服万古霉素用量从71.61 DDD/100K增加到120.82 DDD/100K（复合年增长率 = 4.87%），支出呈下降趋势（0.20 - 0.03 USD/人均，复合年增长率 = -15.16%）。中等收入经济体最早采用非达索霉素的时间比高收入经济体晚5年。尽管复合年增长率更高，但2023年中等收入经济体的非达霉素和口服万古霉素消费量分别仅为高收入经济体的1.9%和2.3%。在IDSA/SHEA指南更新后，北美的非达霉素消费量立即增加。结论：全球非达霉素和万古霉素口服用量持续增加；然而，利用方面的重大经济和地理差异突出了一线CDI治疗的不公平获取。

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引用次数: 0

An easy-to-use predictive score for identifying patients at risk of suboptimal linezolid exposure and candidates for therapeutic drug monitoring 一个易于使用的预测评分，用于识别有亚理想利奈唑胺暴露风险的患者和治疗药物监测的候选患者。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-04 DOI: 10.1016/j.ijantimicag.2025.107661

Daniel Fresán , Luisa Sorlí , Jaume Barceló-Vidal , Ana Rodrigo-Moreno , Rosana Muñoz , Isaac Subirana , Antoni Ferrer , Camila Velasco , Jason Roberts , Adela Benítez-Cano , Sonia Luque , PK/PD of Anti-Infectives Study Group of the European Society of Clinical Microbiology and Infectious Diseases (EPASG)

Objectives

Due to the high interindividual pharmacokinetic variability, only between 34.5–57.5% patients treated with linezolid fall within its therapeutic range with standard dosing. This study aimed to develop and validate a simple-to-use predictive score to identify patients at risk of sub- or supra-therapeutic linezolid exposure who may benefit from therapeutic drug monitoring (TDM).

Methods

A retrospective observational study was conducted using data from 819 patients treated with linezolid and undergoing TDM (2011–2022). Linezolid trough concentrations were classified as sub-therapeutic, therapeutic and supra-therapeutic (< 2 mg/L, between 2 and 7 mg/L and > 7 mg/L, respectively). A multinomial logistic regression model was used to develop a predictive score, which was externally validated in a separate cohort of 73 patients. Discrimination performance was assessed using ROC curve.

Results

Only 31.5% of patients achieved therapeutic concentrations. Median linezolid trough concentrations were 3.9 mg/L (range: 0.5–63.7 mg/L). Independent predictors of sub-therapeutic concentrations were a younger age, a low linezolid dose/body weight, augmented renal clearance and intensive care unit admission. Predictors of supra-therapeutic concentrations were a higher dose/body weight, renal impairment and liver cirrhosis. The predictive model showed high accuracy for identifying patients at risk of supra-therapeutic exposure (AUC 82% derivation; 90% validation), while performance was moderate for underexposure (AUC 63% derivation; 49% validation). An online calculator was implemented to facilitate score use in clinical practice.

Conclusions

The predictive score provides clinicians with an effective tool to support individualised linezolid therapy and guide TDM implementation, reducing the risk of toxicity or treatment failure.

背景和目的：由于个体间药代动力学的高度变异性，只有34.5-57.5%接受利奈唑胺治疗的患者在其标准剂量的治疗范围内。本研究旨在开发和验证一种简单易用的预测评分，以识别有亚治疗或超治疗利奈唑胺暴露风险的患者，这些患者可能受益于治疗性药物监测（TDM）。方法：对2011-2022年接受利奈唑胺治疗并接受TDM的819例患者进行回顾性观察研究。利奈唑胺谷浓度分为亚治疗性、治疗性和超治疗性（分别为< 2 mg/L、2-7 mg/L和0 -7 mg/L）。使用多项逻辑回归模型建立预测评分，并在73例患者的单独队列中进行外部验证。采用ROC曲线评估辨别力。结果：只有31.5%的患者达到治疗浓度。中位利奈唑胺谷浓度为3.9 mg/L（范围：0.5 ~ 63.7 mg/L）。亚治疗浓度的独立预测因子为年龄较小、利奈唑胺剂量/体重较低、肾脏清除率增强和入住重症监护室。超治疗浓度的预测因子是更高的剂量/体重、肾功能损害和肝硬化。该预测模型在识别超治疗暴露风险患者方面显示出很高的准确性（AUC偏差82%，验证率90%），而在暴露不足方面表现中等（AUC偏差63%，验证率49%）。为了便于临床应用，我们设计了一个在线计算器。结论：预测评分为临床医生提供了支持个体化利奈唑胺治疗和指导TDM实施的有效工具，降低了毒性或治疗失败的风险。

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引用次数: 0

Two Tail Protein-Derived Capsule Depolymerases From Phage vB_KpnS_GH-K1 are Effective Against Pneumonia Caused by K2 Serotype Klebsiella pneumoniae 噬菌体vB_KpnS_GH-K1的两种尾蛋白衍生胶囊解聚合酶对K2血清型肺炎克雷伯菌引起的肺炎有效。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-04 DOI: 10.1016/j.ijantimicag.2025.107662

Guiyang Ge , Hongbei Ge , Jianhui Xu , Bing Yue , Qizhu Yang , Zewei Cheng , Zhimin Guo , Hewen Deng , Haozhe Hou , Shang Shi , Jiaquan Li , Meng Yu , Jiaming Niu , Ruopeng Cai , Rui Du

Objectives

Hypervirulent Klebsiella pneumoniae (hvKP) poses an escalating threat to public health and animal husbandry, underscoring the urgent need for novel antimicrobial alternatives. This study aimed to isolate and characterize depolymerases from a Klebsiella phage and evaluate their therapeutic potential against acute pneumonia caused by the K2 serotype hvKP

Methods

We isolated and characterized the bacteriophage vB_KpnS_GH-K1 (GH-K1) of the “KP36likevirus” genus. Genomic analysis led to the identification of two putative phage-derived depolymerases: tail fiber protein (TFP41) and tail spike protein (TSP42). The enzymatic activity of the expressed and purified proteins was assessed through spot assays and mucoviscosity measurements. Their ability to enhance host immune clearance was evaluated via macrophage phagocytosis assays, analysis of mitogen-activated protein kinase (MAPK) signaling pathway activation, and cytokine profiling. The therapeutic efficacy was ultimately determined in a murine model of acute pneumonia, where survival rates, lung bacterial loads, and pathological changes were monitored following intranasal administration of the depolymerases.

Results

Both depolymerases exhibited potent activity in degrading the capsular polysaccharides (CPS) of K2 serotype K. pneumoniae. Capsule degradation by TFP41 and TSP42 enhances macrophage-mediated phagocytosis of K2 serotype strains, leading to potentiated activation of the MAPK signaling pathway. In vivo experiments demonstrated the exceptional therapeutic efficacy of TSP42, where a single 20 µg dose ensured over 80 % survival in mice within 12 h of intranasal infection, achieving complete survival when administered within 2 h. Importantly, TSP42 demonstrates superior therapeutic efficacy against acute pneumonia caused by K2 strains compared to other depolymerases in “KP36likevirus”. Although TFP41 exhibited slightly weaker efficacy, daily administration for three consecutive days also resulted in 100 % survival, and notably represents the first tail fiber depolymerase with demonstrated therapeutic efficacy in the “KP36likevirus” genus, expanding the functional diversity of phage-derived depolymerases beyond well-characterized tail spike proteins.

Conclusion

These findings underscore the potential of phage-derived depolymerases as innovative therapeutic agents against hvKP infections and position TSP42 as an exceptionally promising antibiotic alternative

高致病性肺炎克雷伯菌（hvKP）对公共卫生和畜牧业构成日益严重的威胁。本研究分离并鉴定了“kp36样病毒”属噬菌体vB_KpnS_GH-K1 (GH-K1)，鉴定出两种噬菌体衍生的解聚合酶：尾纤维蛋白- tfp41和尾刺蛋白- tsp42。这两种解聚合酶在K2血清型肺炎克雷伯菌的荚膜多糖（CPS）降解中表现出强大的活性。TFP41和TSP42对胶囊的降解增强了K2血清型菌株巨噬细胞介导的吞噬作用，从而增强了丝裂原活化蛋白激酶（MAPK）信号通路的激活。体内实验证明了TSP42的特殊治疗效果，单次20 μg剂量可确保小鼠在鼻内感染12小时内存活80%以上，在2小时内完全存活。重要的是，与“kp36样病毒”中的其他解聚合酶相比，TSP42对由K2菌株引起的急性肺炎具有更好的治疗效果。虽然TFP41的疗效稍弱，但连续3天每天给药也能达到100%的存活率，并且值得注意的是，TFP41是“kp36样病毒”属中第一个显示出治疗效果的尾纤维解聚合酶，扩大了噬菌体衍生的解聚合酶的功能多样性，超出了已知的尾刺蛋白。这些发现强调了噬菌体衍生解聚合酶作为抗hvKP感染的创新治疗剂的潜力，并将TSP42定位为一种非常有前途的抗生素替代品。

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引用次数: 0

Combined disk-based tests for phenotypic identification of KPC variants in Enterobacterales 肠杆菌中KPC变异表型鉴定的联合圆盘试验。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-04 DOI: 10.1016/j.ijantimicag.2025.107663

Feng Yang , Li Ding , Siquan Shen , Chengkang Tang , Weiwei Yang , Qingyu Shi , Renru Han , Dandan Yin , Yan Guo , Fupin Hu

Objective

The identification of Klebsiella pneumoniae carbapenemase (KPC) variants is challenging due to their atypical resistance profiles, especially in resource-limited settings where molecular diagnostics are not readily available.

Methods

In this study, we developed a combination of disk-based phenotypic assays to identify KPC variant-positive Enterobacterales, including standard disk diffusion, the 3-aminophenylboronic acid (APB)/EDTA inhibition test, and the ESBL confirmatory test.

Results

In the disk diffusion test, all 18 KPC variant-producing strains analysed in this study were resistant to ceftazidime-avibactam and ertapenem, and 22.2 % (4 of 18) were resistant to imipenem, including those producing KPC-79, KPC-93, KPC-112, and KPC-157. For the APB/EDTA inhibition test, all strains were non-susceptible to meropenem (17 resistant and 1 intermediate) but showed no ≥5 mm increase in inhibition zone diameter with APB, EDTA, or both, thus yielding negative results according to criteria for wild-type carbapenemases. For the ESBL confirmatory test, four strains (producing KPC-79, KPC-93, KPC-112, and KPC-157) were negative, consistent with their imipenem resistance in disk diffusion, suggesting a potential phenotypic linkage. Based on these findings, two distinct disk-based phenotypic patterns of the KPC variants were identified. Both patterns shared resistance to ceftazidime-avibactam and ertapenem, along with a negative APB/EDTA inhibition result but differed in imipenem susceptibility and ESBL test results: one showed imipenem susceptibility with a positive ESBL test, whereas the other showed imipenem resistance with a negative ESBL test.

Conclusions

In conclusion, this study proposes a simple disk-based approach for the phenotypic identification of KPC variants in Enterobacterales, which may aid preliminary screening in clinical laboratories and warrants further validation.

肺炎克雷伯菌碳青霉烯酶（KPC）变体的鉴定具有挑战性，因为它们的非典型耐药谱，特别是在资源有限的环境中，分子诊断不容易获得。在这项研究中，我们开发了基于磁盘的表型分析组合来鉴定KPC变异阳性肠杆菌，包括标准磁盘扩散，APB/EDTA抑制试验和ESBL验证试验。在纸片扩散试验中，本研究分析的18株KPC变异体菌株对头孢他啶-阿维巴坦和埃他培南均耐药，对亚胺培南耐药的菌株占22.2%(4/18)，包括产KPC-79、KPC-93、KPC-112和KPC-157。在APB/EDTA抑制试验中，所有菌株对美罗培南不敏感（17株耐药，1株中间），但APB、EDTA或两者均未显示抑制区直径增加≥5 mm，因此根据野生型碳青霉烯酶标准为阴性。在ESBL验证试验中，4株菌株（产生KPC-79、KPC-93、KPC-112和KPC-157）呈阴性，与它们在磁盘扩散中的亚胺培南耐药性一致，提示可能存在表型连锁。基于这些发现，确定了KPC变异的两种不同的基于磁盘的表型模式。两组患者对头孢他啶-阿维巴坦和厄他培南均有耐药性，APB/EDTA抑制结果均为阴性，但亚胺培南敏感性和ESBL试验结果不同：一组患者对亚胺培南敏感，ESBL试验呈阳性，而另一组患者对亚胺培南耐药，ESBL试验呈阴性。总之，本研究提出了一种简单的基于磁盘的方法来鉴定肠杆菌中KPC变异的表型，这可能有助于临床实验室的初步筛选，值得进一步验证。

{"title":"Combined disk-based tests for phenotypic identification of KPC variants in Enterobacterales","authors":"Feng Yang , Li Ding , Siquan Shen , Chengkang Tang , Weiwei Yang , Qingyu Shi , Renru Han , Dandan Yin , Yan Guo , Fupin Hu","doi":"10.1016/j.ijantimicag.2025.107663","DOIUrl":"10.1016/j.ijantimicag.2025.107663","url":null,"abstract":"<div><h3>Objective</h3><div>The identification of <em>Klebsiella pneumoniae</em> carbapenemase (KPC) variants is challenging due to their atypical resistance profiles, especially in resource-limited settings where molecular diagnostics are not readily available.</div></div><div><h3>Methods</h3><div>In this study, we developed a combination of disk-based phenotypic assays to identify KPC variant-positive Enterobacterales, including standard disk diffusion, the 3-aminophenylboronic acid (APB)/EDTA inhibition test, and the ESBL confirmatory test.</div></div><div><h3>Results</h3><div>In the disk diffusion test, all 18 KPC variant-producing strains analysed in this study were resistant to ceftazidime-avibactam and ertapenem, and 22.2 % (4 of 18) were resistant to imipenem, including those producing KPC-79, KPC-93, KPC-112, and KPC-157. For the APB/EDTA inhibition test, all strains were non-susceptible to meropenem (17 resistant and 1 intermediate) but showed no ≥5 mm increase in inhibition zone diameter with APB, EDTA, or both, thus yielding negative results according to criteria for wild-type carbapenemases. For the ESBL confirmatory test, four strains (producing KPC-79, KPC-93, KPC-112, and KPC-157) were negative, consistent with their imipenem resistance in disk diffusion, suggesting a potential phenotypic linkage. Based on these findings, two distinct disk-based phenotypic patterns of the KPC variants were identified. Both patterns shared resistance to ceftazidime-avibactam and ertapenem, along with a negative APB/EDTA inhibition result but differed in imipenem susceptibility and ESBL test results: one showed imipenem susceptibility with a positive ESBL test, whereas the other showed imipenem resistance with a negative ESBL test.</div></div><div><h3>Conclusions</h3><div>In conclusion, this study proposes a simple disk-based approach for the phenotypic identification of KPC variants in Enterobacterales, which may aid preliminary screening in clinical laboratories and warrants further validation.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107663"},"PeriodicalIF":4.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanomedicine for phage therapy: Encapsulation strategies for enhanced antimicrobial efficacy 用于噬菌体治疗的纳米药物：增强抗菌功效的包封策略。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-04 DOI: 10.1016/j.ijantimicag.2025.107660

Alexis Dorta-Gorrín , Verónica Salgueiriño , Lorena García-Hevia

Antibiotic resistance is a growing global health crisis, driving the need for alternative antimicrobial strategies. Phage therapy has re-emerged as a promising approach due to its specificity and ability to evolve against bacterial resistance mechanisms. However, therapeutic implementation is often challenged by factors such as phage stability, immune clearance, and site-specific delivery. Encapsulation technologies offer a potential solution, enhancing phage bioavailability, systemic circulation, and therapeutic action at the infection site.

This review explores the latest advancements in phage encapsulation within the context of nanomedicine-based delivery systems, including polymeric nanoparticles, liposomes, hydrogels, nanofibers, and inorganic nanoparticles. Each system is analyzed regarding its impact on phage stability, pharmacokinetics, and host-pathogen interactions, with a particular focus on applications in clinical and preclinical models of phage therapy. Liposomal and polymeric nanoparticle encapsulation enhance phage persistence in systemic circulation and protect them from degradation. Hydrogels and nanofibers improve localized phage delivery for wound healing applications, while inorganic nanoparticles and stimuli-responsive nanocarriers facilitate targeted delivery for intracellular and respiratory infections.

By leveraging nanotechnology-driven encapsulation, phage therapy can overcome key delivery challenges, expanding its potential for treating multidrug-resistant bacterial infections. This approach opens new possibilities for precision antimicrobial therapies, reinforcing phage therapy as a viable alternative to conventional antibiotics.

抗生素耐药性是一个日益严重的全球健康危机，推动了对替代抗微生物战略的需求。噬菌体疗法由于其特异性和进化能力而重新成为一种有前途的方法，可以对抗细菌的耐药机制。然而，治疗的实施经常受到诸如噬菌体稳定性、免疫清除和部位特异性递送等因素的挑战。包封技术提供了一种潜在的解决方案，增强了噬菌体的生物利用度、体循环和感染部位的治疗作用。本文综述了以纳米药物为基础的递送系统中噬菌体包封的最新进展，包括聚合纳米颗粒、脂质体、水凝胶、纳米纤维和无机纳米颗粒。分析每个系统对噬菌体稳定性、药代动力学和宿主-病原体相互作用的影响，特别关注在噬菌体治疗的临床和临床前模型中的应用。脂质体和聚合物纳米颗粒包封增强了噬菌体在体循环中的持久性，并保护它们不被降解。水凝胶和纳米纤维改善了伤口愈合应用中噬菌体的局部递送，而无机纳米颗粒和刺激反应性纳米载体促进了细胞内和呼吸道感染的靶向递送。通过利用纳米技术驱动的封装，噬菌体疗法可以克服关键的递送挑战，扩大其治疗耐多药细菌感染的潜力。这种方法为精确抗菌治疗开辟了新的可能性，加强了噬菌体治疗作为传统抗生素的可行替代方案。

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引用次数: 0

International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗微生物化疗学会（ISAC）新闻和信息页面

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-03 DOI: 10.1016/j.ijantimicag.2025.107646

引用次数: 0

Long-acting lipoglycopeptides compared to standard-of-care for the treatment of complicated gram-positive infections: A systematic review and meta-analysis. 长效脂糖肽与标准护理治疗复杂革兰氏阳性感染的比较：系统回顾和荟萃分析。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-01 Epub Date: 2025-07-23 DOI: 10.1016/j.ijantimicag.2025.107581

Dominick Salvatore, Jaci Moore, Taylor D Steuber

Objectives: Long-acting lipoglycopeptides (LA-LGPs) are being used more frequently for the treatment of complicated Gram-positive infections, including osteomyelitis, prosthetic joint infections, bloodstream infections, and endocarditis. This systematic review and meta-analysis compared the efficacy and safety of LA-LGP to the standard of care (SOC) antibiotics for the treatment of these infections.

Methods: A systematic literature search was conducted using PubMed, Medline, Embase, Cochrane, and Clinicaltrials.gov through November 2024. Prospective and retrospective comparative studies evaluating patients being treated for complicated Gram-positive infections were included. Interventions included multi-dose LA-LGP, including dalbavancin and oritavancin, vs. SOC antibiotics. Risk of bias was assessed using Cochrane RoB 2 and ROBINS-I tools. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was clinical success.

Results: Fourteen studies (n = 1582 patients) were included. Studies included a wide array of indications and dosing schemes. LA-LGP was associated with significantly higher clinical success rates compared to SOC (RR = 1.14, 95% CI = 1.05-1.23, P < 0.01). No significant differences were observed for infection recurrence, mortality, adverse events (AEs), or serious adverse events (SAEs). LA-LGP was associated with fewer hospital readmissions. A subgroup analysis of bone and joint infections showed no significant difference in clinical success between LA-LGP and SOC.

Conclusions: LA-LGP for the treatment of complicated Gram-positive infections resulted in similar efficacy and safety to SOC antibiotics and may be a reasonable alternative for such infections. Results should be interpreted with caution given the risk of bias and heterogeneity (PROSPERO Registration ID: CRD42024532465).

目的：长效脂糖肽（LA-LGP）越来越多地被用于治疗复杂的革兰氏阳性感染，包括骨髓炎、假体关节感染、血流感染和心内膜炎。本系统综述和荟萃分析比较了LA-LGP与标准护理（SOC）抗生素治疗这些感染的疗效和安全性。方法：通过PubMed、Medline、Embase、Cochrane和Clinicaltrials.gov进行系统文献检索，检索时间截止到2024年11月。前瞻性和回顾性比较研究评估了治疗复杂革兰氏阳性感染的患者。干预措施包括多剂量LA-LGP，包括达尔巴万星和奥利塔万星，与SOC抗生素。使用Cochrane RoB 2和ROBINS-I工具评估偏倚风险。采用随机效应模型计算合并风险比（RR）和95%置信区间（CI）。主要结果是临床成功。结果：纳入14项研究（n= 1582例患者）。研究包括广泛的适应症和给药方案。与SOC相比，LA-LGP具有更高的临床成功率（RR 1.14, 95% CI 1.05-1.23）。结论：LA-LGP治疗复杂革兰氏阳性感染的疗效和安全性与SOC抗生素相似，可能是这类感染的合理替代方案。考虑到偏倚和异质性的风险，对结果的解释应谨慎。（普洛斯彼罗注册ID: CRD42024532465）。

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引用次数: 0

Enhanced immunogenicity of SARS-CoV-2 antigen with aluminum adjuvant and polysaccharide nucleic acid fraction of Bacillus Calmette Guerin. 铝佐剂和卡介苗多糖核酸片段增强SARS-CoV-2抗原的免疫原性。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-11-01 Epub Date: 2025-07-22 DOI: 10.1016/j.ijantimicag.2025.107578

Jia Ji, Miaojin Zhu, Linwei Zhu, Zhiyong Liu, Shengmei Yang, Taoming Tang, Zhigang Wu, Danrong Shi, Jiale Zhang, Xiaodi Zhang, Hangping Yao

Vaccine immunization strategies are crucial for eliciting vaccine-induced immune responses, particularly in immune compromised populations and older adults. In clinical practice in China, the polysaccharide nucleic acid fraction of Bacillus Calmette-Guérin (BCG-PSN) is extensively used as an immune modulatory agent. Herein, we describe a new immunization strategy using the SARS-CoV-2 antigen (original strain) with aluminum adjuvant and BCG-PSN. We evaluated whether BCG-PSN enhances humoral and cellular immune responses to the SARS-CoV-2 vaccine in K18-hACE2 and BALB/c mice by assessing antibody and germinal center (GC) responses, as well as the quantity and functionality of memory T cells in the spleen. At day 28 after the first immunization, the SARS-CoV-2 antigen with Alum, when combined with BCG-PSN, significantly elevated the levels of IgGantibodies. It significantly enhanced the spleen's GC structure, amplified the SARS-CoV-2 antigen-specific T cell response, and conferred protection to mice against the Delta variant challenge. This study provides a reference to evaluate immunization strategies for vaccines with high immunological efficacy, and the SARS-CoV-2 antigen combined with Alum and BCG-PSN enhances immunogenicity by significantly boosting cellular immune responses after vaccine administration. The study focuses on the impact of BCG-PSN on the SARS-CoV-2 antigen, examining its role in generating neutralizing antibodies (NAbs) and eliciting T cell responses.

疫苗免疫策略对于引起疫苗诱导的免疫反应至关重要，特别是在免疫功能低下和老年人群中。在中国的临床实践中，卡介苗-谷青孢杆菌（Bacillus calmetet - gusamrin, BCG-PSN）的多糖核酸部分被广泛用作免疫调节剂。在此，我们描述了一种新的免疫策略，使用SARS-CoV-2抗原（原始菌株）与铝佐剂和BCG-PSN。我们通过评估抗体和生生中心（GC）反应，以及脾脏记忆T细胞的数量和功能，评估BCG-PSN是否增强了K18-hACE2和BALB/c小鼠对SARS-CoV-2疫苗的体液和细胞免疫反应。第一次免疫后第28天，Alum - SARS-CoV-2抗原与bgg - psn联合使用可显著提高IgG抗体水平。它显著增强了脾脏的GC结构，增强了SARS-CoV-2抗原特异性T细胞反应，并赋予小鼠抵抗Delta变体攻击的保护作用。本研究为评价高免疫效能疫苗的免疫策略提供了参考，SARS-CoV-2抗原与Alum和BCG-PSN联合使用可显著增强疫苗给药后的细胞免疫应答，从而增强免疫原性。该研究的重点是BCG-PSN疫苗对SARS-CoV-2的影响，研究其在产生中和抗体（nab）和引发T细胞反应中的作用。

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引用次数: 0

Urinary exosome-derived microRNAs as biomarkers of tenofovir disoproxil fumarate (TDF)-induced renal toxicity in people with HIV-1 尿外泌体衍生的microrna作为富马酸替诺福韦二氧吡酯（TDF）诱导HIV-1患者肾毒性的生物标志物

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-30 DOI: 10.1016/j.ijantimicag.2025.107654

José L. Casado , Pilar Vizcarra , Francisco J. Hernández-Walias , José Manuel del Rey , Carmen Santiuste , Carmen Molano , Miriam Menacho , Alejandro Vallejo

Objectives

Tenofovir disoproxil fumarate (TDF) has been associated with proximal tubular renal toxicity, though the timing, severity, and long-term outcomes remain controversial. This study aimed to assess urinary exosome-derived microRNAs (miRNAs) as potential early biomarkers of TDF-associated renal toxicity.

Methods

In this cross-sectional study of virologically suppressed people with HIV (PWH) on TDF-based therapy (median exposure: 65 months), we isolated urinary exosomes and quantified eight pre-selected miRNAs using real-time qPCR, analysing their associations with tubular function parameters and urinary low-molecular-weight proteins.

Results

The 60 selected participants had median TDF exposure of 65 months with mean eGFR-SCr of 90.9 mL/min/1.73m² (6% with chronic kidney disease). Three miRNAs showed significant upregulation with longer TDF exposure: miR-Let-7d (P = 0.049), miR-203 (P = 0.008), and miR-29a (P = 0.02), while miR-127 negatively correlated (P = 0.009). MiR-Let-7d demonstrated strongest associations with tubular dysfunction biomarkers and highest diagnostic value (AUC 0.782; CI, 0.612–0.952). MiR-23a best identified individuals at risk for subsequent eGFR-SCr decline (AUC 0.655; CI, 0.506–0.805) after median 9-month follow-up. Multivariate analysis revealed years living with HIV, miR-Let-7d, and miR-423 were independently associated with tubular dysfunction.

Conclusions

Urinary exosome-derived miRNAs demonstrate their potential as early, non-invasive biomarkers for detecting and predicting TDF-associated renal dysfunction in PWH, potentially enabling earlier clinical intervention before irreversible damage occurs.

背景：富马酸替诺福韦二氧吡酯（TDF）与近端肾小管毒性有关，尽管时间、严重程度和长期结果仍存在争议。本研究旨在评估尿外泌体来源的microRNAs （miRNAs）作为tdf相关肾毒性的潜在早期生物标志物。方法：在这项基于tdf治疗的病毒学抑制HIV感染者（PWH）（中位暴露时间：65个月）的横断面研究中，我们分离了尿外泌体，并使用实时qPCR定量了8个预先选择的mirna，分析了它们与小管功能参数和尿低分子量蛋白的相关性。结果：60名入选的参与者中位TDF暴露为65个月，平均eGFR-SCr为90.9 mL/min/1.73m²（6%为慢性肾脏疾病）。三种mirna随着TDF暴露时间的延长而显著上调：miR-Let-7d （p=0.049）、miR-203 （p=0.008）和miR-29a (p=0.02)，而miR-127呈负相关（p=0.009）。MiR-Let-7d与小管功能障碍生物标志物的相关性最强，诊断价值最高（AUC 0.782； CI, 0.612-0.952）。中位随访9个月后，MiR-23a最能识别出eGFR-SCr随后下降的风险个体（AUC为0.655；CI为0.506-0.805）。多变量分析显示，HIV感染年限、miR-Let-7d和miR-423与小管功能障碍独立相关。结论：尿外泌体衍生的mirna显示出其作为早期、非侵入性生物标志物的潜力，可用于检测和预测PWH中tdf相关的肾功能障碍，有可能在不可逆损伤发生之前进行早期临床干预。

{"title":"Urinary exosome-derived microRNAs as biomarkers of tenofovir disoproxil fumarate (TDF)-induced renal toxicity in people with HIV-1","authors":"José L. Casado , Pilar Vizcarra , Francisco J. Hernández-Walias , José Manuel del Rey , Carmen Santiuste , Carmen Molano , Miriam Menacho , Alejandro Vallejo","doi":"10.1016/j.ijantimicag.2025.107654","DOIUrl":"10.1016/j.ijantimicag.2025.107654","url":null,"abstract":"<div><h3>Objectives</h3><div>Tenofovir disoproxil fumarate (TDF) has been associated with proximal tubular renal toxicity, though the timing, severity, and long-term outcomes remain controversial. This study aimed to assess urinary exosome-derived microRNAs (miRNAs) as potential early biomarkers of TDF-associated renal toxicity.</div></div><div><h3>Methods</h3><div>In this cross-sectional study of virologically suppressed people with HIV (PWH) on TDF-based therapy (median exposure: 65 months), we isolated urinary exosomes and quantified eight pre-selected miRNAs using real-time qPCR, analysing their associations with tubular function parameters and urinary low-molecular-weight proteins.</div></div><div><h3>Results</h3><div>The 60 selected participants had median TDF exposure of 65 months with mean eGFR-SCr of 90.9 mL/min/1.73m² (6% with chronic kidney disease). Three miRNAs showed significant upregulation with longer TDF exposure: miR-Let-7d (<em>P</em> = 0.049), miR-203 (<em>P</em> = 0.008), and miR-29a (<em>P</em> = 0.02), while miR-127 negatively correlated (<em>P</em> = 0.009). MiR-Let-7d demonstrated strongest associations with tubular dysfunction biomarkers and highest diagnostic value (AUC 0.782; CI, 0.612–0.952). MiR-23a best identified individuals at risk for subsequent eGFR-SCr decline (AUC 0.655; CI, 0.506–0.805) after median 9-month follow-up. Multivariate analysis revealed years living with HIV, miR-Let-7d, and miR-423 were independently associated with tubular dysfunction.</div></div><div><h3>Conclusions</h3><div>Urinary exosome-derived miRNAs demonstrate their potential as early, non-invasive biomarkers for detecting and predicting TDF-associated renal dysfunction in PWH, potentially enabling earlier clinical intervention before irreversible damage occurs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107654"},"PeriodicalIF":4.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of sulbactam-durlobactam disk diffusion and broth microdilution methods for Acinetobacter baumannii 舒巴坦-杜罗巴坦圆盘扩散法和微量肉汤稀释法检测鲍曼不动杆菌的评价。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-30 DOI: 10.1016/j.ijantimicag.2025.107659

Xiaolan Hong , Xinying Wang , Xin Xiang , Siquan Shen , Shaobo Zhou , Xubo Dai , Fupin Hu , Yan Guo

Objective

The broth microdilution method was used as a reference method to evaluate the accuracy of sulbactam-durlobactam disk diffusion method for A. baumannii.

Methods

In 2023, 504 nonduplicated A. baumannii isolated from 59 hospitals in China were tested by broth microdilution (M07) and disk diffusion method (M02) (10/10 µg) according to the CLSI M100 Ed34 standard. Categorical agreement (CA), minor error (mE), major error (ME), and very major error (VME) were calculated.

Results

By broth microdilution, the susceptibility, intermediate, and resistance proportions of A. baumannii against sulbactam-durlobactam were 98.4% (496/504),1% (5/504), and 0.6% (3/504), respectively. Compared to broth microdilution method, the CA and mE of all A. baumannii isolates detected by the disk diffusion method were 99.6% (502/504) and 0.4% (2/504), respectively, with no ME or VME. For carbapenem-susceptible A. baumannii, the CA of the disk diffusion method was 100% (184/184), with no mE and ME. For carbapenem-resistant A. baumannii, the CA and mE were 99.4% (318/320) and 0.6% (2/320), respectively, with no ME or VME. For difficult-to-treat resistant A. baumannii, the CA and mE were 99.2% (249/251) and 0.8% (2/251), respectively, with no ME or VME. For colistin-resistant A. baumannii, the disk diffusion method showed a CA of 100% (12/12) with no mE, ME, or VME.

Conclusions

The disk diffusion method (10/10 µg) accurately detects the susceptibility of A. baumannii to sulbactam-durlobactam. This method is characterised by its simplicity, economy, and ease of result interpretation, making it suitable for use in routine clinical microbiology laboratories.

目的：以微量肉汤稀释法为参照，评价舒巴坦-杜罗巴坦盘片扩散法检测鲍曼不动杆菌的准确性。方法：采用微量肉汤稀释法（M07）和盘片扩散法（M02）（10/10μg），按CLSI M100 Ed34标准对2023年国内59家医院分离的504株非重复鲍曼不动杆菌进行检测。计算绝对一致（CA）、轻微错误（mE）、严重错误（mE）和非常严重错误（VME）。结果：微量肉汤稀释法检测鲍曼不动杆菌对舒巴坦-杜氯巴坦的敏感率为98.4%(496/504)，中间率为1%(5/504)，耐药率为0.6%（3/504）。与微量肉汤稀释法相比，纸片扩散法检测到的鲍曼不动杆菌的CA和mE分别为99.6%（502/504）和0.4%(2/504)，无mE和VME。对于碳青霉烯类敏感鲍曼不稳定器，纸片扩散法的CA为100%(184/184)，无mE和mE。耐碳青霉烯鲍曼不动杆菌的CA和mE分别为99.4%（318/320）和0.6%(2/320)，无mE和VME。难治性耐药鲍曼不动杆菌的CA和mE分别为99.2%（249/251）和0.8%(2/251)，无mE和VME。对于耐粘菌素鲍曼不动杆菌，纸片扩散法的CA为100%(12/12)，无mE、mE和VME。结论：圆盘扩散法（10/10μg）能准确检测鲍曼不动杆菌对舒巴坦-杜氯巴坦的敏感性。该方法的特点是其简单，经济，易于结果解释，使其适用于常规临床微生物学实验室。

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引用次数: 0