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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 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
Antibiotic-mediated prophage activation: Mechanisms, consequences, and therapeutic implications 抗生素介导的噬菌体激活:机制、后果和治疗意义。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-28 DOI: 10.1016/j.ijantimicag.2025.107655
Damir Gavric, Petar Knezevic

Objective

Prophages, as an integral part of bacterial genomes, play a pivotal role in regulating host virulence and shaping bacterial evolution. Exposure to antibiotics, particularly those that cause DNA damage, can trigger a shift from lysogeny to the lytic cycle, i.e., initiate prophage induction.

Methods

This review compares the effects of various antibiotic classes on prophage induction, with particular emphasis on the associated clinical consequences.

Results

This process can lead to undesirable consequences, such as increased toxin production, enhanced transduction frequency, and modulation of host phenotypes and virulence traits. Among the most potent inducers are fluoroquinolones, such as ciprofloxacin, which activate stx-harbouring prophages in enterohemorrhagic Escherichia coli (EHEC), resulting in elevated Shiga toxin production and disease exacerbation. This effect is primarily mediated through activation of the bacterial SOS response, although other mechanisms may also contribute. Similarly, subinhibitory concentrations of certain β-lactams, sulphonamides, nitrofurans, and fosfomycin can induce prophages, although the extent of induction varies depending on the antibiotic concentration, phage type, bacterial strain, and detection methodology. The antibiotics that predominantly suppress or inhibit phage induction are aminoglycosides, some macrolides, and newer generation tetracyclines.

Conclusions

Further studies on antibiotic-mediated phage induction, particularly those focusing on elucidating the underlying mechanisms of this phenomenon, are necessary to maximize its beneficial effects and minimize potential adverse outcomes during therapy.
原噬菌体作为细菌基因组的重要组成部分,在调节宿主毒力和塑造细菌进化过程中发挥着关键作用。暴露于抗生素,特别是那些引起DNA损伤的抗生素,可以触发从溶原性到溶解周期的转变,即启动前噬菌体诱导。这一过程可能导致不良后果,如毒素产生增加,转导频率增强,以及宿主表型和毒力性状的调节。这篇综述评估了不同种类的抗生素对噬菌体诱导的影响,特别强调了相关的临床后果。其中最有效的诱诱剂是氟喹诺酮类药物,如环丙沙星,可激活肠出血性大肠杆菌(EHEC)中含有stx的噬菌体,导致志贺毒素产生升高和疾病恶化。这种效应主要是通过激活细菌SOS反应介导的,尽管其他机制也可能起作用。同样,某些β-内酰胺类、磺胺类、硝基呋喃类和磷霉素的亚抑制浓度可以诱导噬菌体,尽管诱导程度取决于抗生素浓度、噬菌体类型、细菌菌株和检测方法。主要抑制或抑制噬菌体诱导的抗生素是氨基糖苷类、一些大环内酯类和新一代四环素类。对抗生素介导的噬菌体诱导的进一步研究,特别是那些专注于阐明这一现象的潜在机制的研究,对于最大限度地发挥其有益作用并最大限度地减少治疗期间潜在的不良后果是必要的。
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引用次数: 0
Antimicrobial peptide CATH-1 combats Streptococcus suis by targeting serine/threonine kinase 抗菌肽cat -1通过靶向丝氨酸/苏氨酸激酶来对抗猪链球菌。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.ijantimicag.2025.107656
Yi Lu , Xiaoying Yu , Yandi Pan, Hang Yin, Qingqing Yang, Xin Shen, Xuefeng Cao, Zhiwei Li, Lianci Peng, Rendong Fang

Objectives

With the increased bacterial resistance to conventional antibiotics, there is an urgent need for the development of novel antimicrobial agents. Cathelicidins belonging to the family of cationic host defense peptides (HDPs) are a critical component of the innate immune system with antimicrobial and immunomodulatory activities. Our previous study has shown that CATH-1 exhibits potent bactericidal activity against Streptococcus suis (S. suis), but the underlying mechanism is still unclear.

Purpose

This study investigated the effect of CATH-1 on the resistance development and antibacterial mechanisms against S. suis.

Methods

Drug resistance induction assays, time-kill curves, and Live/Dead bacterial staining were used in this study. To analyze the potential antibacterial targets of CATH-1, integrated proteomic and metabolomic analysis, scanning and transmission electron microscopy, membrane potential determination, molecular docking, GST affinity-isolation assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assays (DARTS) were employed. Furthermore, the crucial role of STK in the antibacterial activity of CATH-1 was validated through both in vitro bactericidal tests and a mouse infection model.

Results

CATH-1 did not readily induce resistance in S. suis. Multi-omics analysis revealed that CATH-1 exerts its antibacterial effects by modulating multiple pathways, including those related to the cell membrane, bacterial virulence, and energy metabolism. Mechanistically, CATH-1 exhibits dual antibacterial actions by disrupting bacterial membrane integrity and targeting the STK pathway to inhibit capsular polysaccharide (CPS) synthesis. Direct binding between CATH-1 and STK was confirmed by CETSA and DARTS. Crucially, the deletion of the stk gene significantly attenuated the anti-infective efficacy of CATH-1 both in vitro and in vivo.

Conclusion

This study reveals a novel dual anti-bacterial mechanism of action of CATH-1, inclduing membrane disruption and inhibition of STK-mediated CPS synthesis, and identifies STK as its key functional target. These findings provide a crucial theoretical foundation and new directions for developing novel anti-infective strategies based on antimicrobial peptides.
随着细菌对常规抗生素耐药性的增加,迫切需要开发新型抗菌药物。Cathelicidins属于阳离子宿主防御肽(hdp)家族,是先天免疫系统的重要组成部分,具有抗菌和免疫调节活性。我们之前的研究表明,cat -1对猪链球菌(S. suis)具有强效的杀菌活性,但其潜在的机制尚不清楚。在本研究中,我们研究了CATH-1对猪链球菌SC19耐药发展的影响及其抑菌机制。结果表明,CATH-1不诱导细菌耐药。蛋白质组学和代谢组学分析表明,CATH-1通过多种途径发挥抗菌作用,包括细胞膜、细菌毒力和能量代谢途径。在机制上,cats -1通过破坏细菌膜完整性和靶向丝氨酸/苏氨酸激酶(STK)抑制荚膜多糖(CPS)的合成来发挥双重抗菌作用。通过分子对接、GST亲和分离实验、细胞热移实验(CETSA)和药物亲和反应靶稳定性(DARTS)验证了STK与CATH-1的相互作用。此外,缺乏症使抗s基因丧失。体外抑菌试验和体内感染模型均证实了CATH-1的有效性,提示STK是CATH-1的潜在靶点。我们的研究揭示了一个新的CATH-1抗菌靶点,为抗菌肽作为抗感染药物的开发提供了新的见解。
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引用次数: 0
Helicobacter pylori eradication enters the adjunctive era: Insights from global clinical trials 幽门螺杆菌根除进入辅助时代:来自全球临床试验的见解。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.ijantimicag.2025.107653
Yang Liu , Chunyan He , Yilong Liu , Chan Lu , Jingwei Shi
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引用次数: 0
The antiarrhythmic drugs dronedarone and amiodarone exhibit potent in vitro and in vivo activity against Clostridioides difficile 抗心律失常药物雄龙酮和胺碘酮在体内和体外对难辨梭状芽胞杆菌均有较强的抑制作用。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.ijantimicag.2025.107649
Ahmed A. Abouelkhair , Nader S. Abutaleb , Mohamed N. Seleem
Clostridioides difficile (C. difficile) is the most prevalent cause of healthcare-associated diarrhea. The limited number of FDA-approved antibiotics for C. difficile infection (CDI), along with increasing rates of treatment failure and recurrence, highlight the critical need for new therapeutic options. Here, we report the anti-C. difficile activity of the antiarrhythmic drugs, dronedarone (DRO) and amiodarone (AMD). Both drugs demonstrated strong efficacy against a panel of 25 clinical isolates of C. difficile, with MIC50 values of 4 µg/mL for DRO and 8 µg/mL for AMD. In a time-kill assay, DRO outperformed the approved drugs, vancomycin (VAN) and fidaxomicin (FDX), reducing the high bacterial inoculum below the limit of detection within 2 h. Additionally, both drugs were more effective than VAN at preventing the formation and germination of C. difficile spores. Mechanistic studies indicated that these drugs exert their effects by disrupting the bacterial cell membrane. Furthermore, in the C. difficile recurrence mouse model, both drugs showed a preventive effect comparable to that of VAN. Our findings suggest that these antiarrhythmic drugs have potential as compelling lead molecule for CDI drug discovery, warranting further investigation and potentially paving the way for new anti-C. difficile therapies.
艰难梭菌(C. difficile)是医疗保健相关性腹泻的最常见原因。fda批准用于艰难梭菌感染(CDI)的抗生素数量有限,以及治疗失败率和复发率的增加,突出了对新治疗选择的迫切需求。在这里,我们报告了反c。抗心律失常药物,dronedarone (DRO)和胺碘酮(AMD)的艰难梭菌活性。这两种药物对25个临床分离的艰难梭菌均表现出很强的疗效,对DRO和AMD的MIC50值分别为4 μg/mL和8 μg/mL。在时间杀死实验中,DRO优于批准的药物万古霉素(VAN)和非达索霉素(FDX),在2小时内将高细菌接种量降低到检测极限以下。此外,这两种药物在阻止艰难梭菌孢子的形成和萌发方面都比VAN更有效。机理研究表明,这些药物通过破坏细菌细胞膜发挥作用。此外,在艰难梭菌复发小鼠模型中,两种药物均显示出与VAN相当的预防作用。我们的研究结果表明,这些抗心律失常药物有潜力成为CDI药物发现的引人注目的先导分子,值得进一步研究,并可能为新的抗c铺平道路。固执的疗法。
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引用次数: 0
Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Türkiye: A multi-centre retrospective matched-cohort study 头孢他啶-阿维巴坦与其他适当抗菌药物治疗<s:1>基耶病毒-48或产生kpc的肠杆菌感染的比较:一项多中心回顾性匹配队列研究。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.ijantimicag.2025.107650
Abdullah Tarık Aslan , Elif Seren Tanriverdi , Sibel Yıldız Kaya , Gozde Dalgan , Neşe Saltoğlu , Ezgi Yılmaz , Yeliz Çiçek , Mesut Yılmaz , Çiğdem Erol , Özlem Kurt Azap , Gülşen Hazırolan , Osman Dağ , Zeynep Türe Yüce , Pinar Sagiroglu , Damla Boztaş , Muhammed Cihan Işık , Bariş Otlu , Patrick N.A. Harris , David L. Paterson , Murat Akova

Objective

Due to underrepresentation of carbapenemase-producing Enterobacterales infections in randomized controlled trials with ceftazidime-avibactam (CZA) and high cost of CZA therapy, other appropriate antimicrobial therapies (OAAT) are still being used for OXA-48- or KPC-producing Enterobacterales infections in Türkiye.

Methods

We conducted a multicentre retrospective 1:1 matched cohort study of patients who received ≥48 h of CZA or OAAT for documented OXA-48- or KPC-producing Enterobacterales infections. Patients were matched based on (1) the number of days (± 1 d) from the infection onset to the initiation of therapy, (2) INCREMENT-CPE score (± 1), (3) source of infection, (4) year of infectious episode, and (5) type of causative microorganism.

Results

From 5 Turkish university hospitals, 180 patients were enrolled. Baseline characteristics were all similar between treatment groups. At the time of treatment initiation, 63.9% of patients were in the intensive care unit, 35.6% had septic shock and 41.1% required mechanical ventilation support. Thirty-day mortality occurred in 35.6% (32/90) of patients treated with CZA and in 56.7% (51/90) of those receiving OAAT regimens (P = 0.004). Twenty-one-day clinical response was seen in 50% (45/90) and 26.7% (24/90) of patients receiving CZA and OAAT, respectively (P = 0.002). In multivariable logistic regression analyses, CZA treatment was associated with less likelihood of mortality (aOR = 0.37; 95% CI: 0.19–0.71; P = 0.003) and higher likelihood of 21-d clinical response (aOR = 3.32; 95% CI: 1.68–6.53; P < 0·001).

Conclusions

Treatment with CZA is associated with more favourable clinical outcomes in treatment of OXA-48- or KPC-producing Enterobacterales infections. A randomized controlled trial is needed to confirm these results.
背景:由于在头孢他啶-阿维巴坦(CZA)随机对照试验中产碳青霉烯酶肠杆菌感染的代表性不足以及CZA治疗的高成本,其他适当的抗菌治疗(OAAT)仍被用于治疗基耶州产OXA-48或kpc的肠杆菌感染。方法:我们进行了一项多中心回顾性1:1匹配队列研究,这些患者接受了≥48小时的CZA或OAAT治疗,记录为产生OXA-48或kpc的肠杆菌感染。根据(1)从感染发病到开始治疗的天数(±1天),(2)INCREMENT-CPE评分(±1),(3)感染来源,(4)感染发作年份,(5)致病微生物类型对患者进行匹配。结果:来自土耳其5所大学医院的180例患者入组。治疗组间基线特征相似。在治疗开始时,63.9%的患者在重症监护病房,35.6%的患者发生感染性休克,41.1%的患者需要机械通气支持。接受CZA治疗的患者30天死亡率为35.6%(32/90),接受OAAT治疗的患者30天死亡率为56.7% (51/90)(P=0.004)。接受CZA和OAAT治疗的患者21天临床缓解率分别为50%(45/90)和26.7% (24/90)(P=0.002)。在多变量logistic回归分析中,CZA治疗与较低的死亡率(aOR=0.37; 95% CI:0.19-0.71; P=0.003)和较高的21天临床缓解可能性(aOR=3.32; 95% CI:1.68-6.53)相关。结论:在治疗OXA-48或产生kpc的肠杆菌感染时,CZA治疗与更有利的临床结果相关。需要一项随机对照试验来证实这些结果。
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引用次数: 0
Exploring the susceptome of methicillin-resistant Staphylococcus aureus to oxacillin and cefazolin using integrated transposon-directed insertion site sequencing and proteomics 综合TraDIS和蛋白质组学技术探讨耐甲氧西林金黄色葡萄球菌对肟西林和头孢唑林的敏感性。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.ijantimicag.2025.107652
Nader Abdelmalek , Sally W. Yousief , Alessandro Tanca , Martin S. Bojer , Mosaed Saleh A. Alobaidallah , John E. Olsen , Bianca Paglietti

Objective

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge to public health due to its evolving resistance to antibiotics. This study aimed to identfy the determinants that modulate MRSA susceptibility to β-lactam antibiotics.

Methods

An integrated approach combining transposon-directed insertion site sequencing (TraDIS) and proteomics was applied. TraDIS was used to identify genetic determinants influencing susceptibility to oxacillin and cefazolin while proteomics was applied to characterise the adaptive response under sub-inhibitory antibiotic concentrations.

Results

Proteomic analysis revealed significant shifts in the protein spectrum under sub-inhibitory concentrations of oxacillin and cefazolin, characterised by stringent response. This included upregulation of amino acid metabolism and oligopeptide transport pathways, and downregulation of arginine biosynthesis. Concurrently, TraDIS screening identified 50 genes whose inactivation conferred a fitness advantage in the presence of both β-lactams, implicating processes such as nucleotide second messenger signalling, DNA repair, and histidine transport. Validation with selected mutants (relA::Tn, mutY::Tn, nsaR::Tn, aroC::Tn, SAUSA300_0432::Tn, SAUSA300_0846::Tn, SAUSA300_0595::Tn) confirmed the improved fitness in the presence of β-lactams. Integrative analysis of proteomic and TraDIS datasets highlighted the implication of the stringent response in mediating MRSA adaptation to oxacillin and cefazolin.

Conclusions

These findings establish the 'susceptome' concept, a collection of genes that maintain or potentiate the vulnerability of MRSA strains to β-lactams, providing new targets for therapeutic intervention and strategies to counteract resistance evolution.
耐甲氧西林金黄色葡萄球菌(MRSA)由于其对抗生素的耐药性不断演变,对公共卫生构成了重大挑战。为了探索MRSA对β-内酰胺类抗生素敏感性的决定因素,我们采用了转座子定向插入位点测序(TraDIS)和蛋白质组学相结合的综合方法。TraDIS用于鉴定影响对oxacillin和头孢唑林易感性的遗传决定因素,而蛋白质组学用于表征亚抑制性抗生素浓度下的适应性反应。蛋白质组学分析显示,在亚抑制浓度下,oxacillin和cefazolin的蛋白质谱发生了显著变化,表现为严格的反应。这包括氨基酸代谢和寡肽运输途径的上调以及精氨酸生物合成的下调。同时,TraDIS筛选鉴定了50个基因,这些基因的失活在β-内酰胺存在的情况下具有适应性优势,涉及核苷酸第二信使信号传导、DNA修复和组氨酸运输等过程。对所选突变体(relA::Tn, mutY::Tn, nsaR::Tn, aroC::Tn, SAUSA300_0432::Tn, SAUSA300_0846::Tn, SAUSA300_0595::Tn)的验证证实,β-内酰胺的存在提高了适应度。蛋白质组学和TraDIS数据集的综合分析强调了介导MRSA对oxacillin和头孢唑林适应的严格反应的含义。这些发现建立了“易感组”概念,即维持或增强MRSA菌株对β-内酰胺易感性的基因集合,为治疗干预和对抗耐药性进化的策略提供了新的靶点。
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引用次数: 0
Development and validation of machine learning models to predict vancomycin- and teicoplanin-associated acute kidney injury: A retrospective, multicenter study 预测万古霉素和替柯普兰相关急性肾损伤的机器学习模型的开发和验证:一项回顾性、多中心研究。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-27 DOI: 10.1016/j.ijantimicag.2025.107651
Pin-Yi Lo , Fan-Ying Chan , Yi-En Ku , San-Yuan Wang , Hsiang-Yin Chen

Objective

Despite the effectiveness of vancomycin and teicoplanin in managing Gram-positive infections, their nephrotoxicity may prolong hospitalization, and increase morbidity, mortality, and healthcare costs. This study aimed to develop and validate clinically applicable prognostic machine learning models for predicting vancomycin-associated acute kidney injury (VA-AKI) and teicoplanin-associated AKI (TA-AKI).

Methods

This retrospective study in Taiwan utilized the Taipei Medical University Clinical Research Database. Patients receiving intravenous vancomycin or teicoplanin therapy between February 2010 and December 2020 were included. Features were selected from 198 variables through recursive feature elimination using feature importance (RFECV) and SHapley Additive exPlanations importance (ShapRFECV). Twelve models were constructed using XGBoost and LightGBM. Model performance was assessed by eight evaluation metrics, including the area under the receiver operating characteristic curve (AUROC). The optimal threshold was determined based on the maximum F1 score, and the SHAP analysis assisted in model interpretation.

Results

Among 9342 included patients, 19.70% (1383/7020) of patients in the training set, 18.58% (326/1755) in the internal validation set, and 20.5% (116/567) in the external validation set developed AKI. The XGBoost model, using features selected by ShapRFECV, demonstrated optimal predictive performance in both internal (AUROC 0.798, 95% confidence interval [CI] 0.791–0.804) and external (AUROC 0.779, 95% CI: 0.767–0.791) validation.

Conclusions

The XGBoost model, leveraging time-series data, accurately predicts AKI in vancomycin and teicoplanin users, supporting early risk assessment and personalized patient management. Future multicentre prospective external validation is needed to strengthen its real-world applicability and generalizability.
背景:尽管万古霉素和替柯planin在治疗革兰氏阳性感染方面有效,但它们的肾毒性可能延长住院时间,增加发病率、死亡率和医疗费用。本研究旨在开发和验证用于预测万古霉素相关急性肾损伤(VA-AKI)和替柯普兰相关AKI (TA-AKI)的临床应用预后机器学习模型。方法:利用台北医科大学临床研究数据库,在台湾进行回顾性研究。在2010年2月至2020年12月期间接受静脉万古霉素或替柯planin治疗的患者被纳入研究。通过特征重要性(RFECV)和SHapley加性解释重要性(ShapRFECV)的递归特征消去,从198个变量中选择特征。使用XGBoost和LightGBM构建了12个模型。模型的性能通过8个评价指标进行评估,包括受试者工作特征曲线下面积(AUROC)。根据F1评分最大值确定最优阈值,SHAP分析辅助模型解释。结果:9342例纳入患者中,训练组19.70%(1383/7020),内部验证组18.58%(326/1755),外部验证组20.5%(116/567)发生AKI。使用ShapRFECV选择的特征的XGBoost模型在内部(AUROC 0.798, 95%置信区间(CI) 0.791-0.804)和外部(AUROC 0.779, 95% CI 0.767-0.791)验证中均表现出最佳的预测性能。结论:利用时间序列数据的XGBoost模型可以准确预测万古霉素和替柯planin使用者的AKI,支持早期风险评估和个性化患者管理。未来的多中心前瞻性外部验证需要加强其在现实世界中的适用性和推广性。
{"title":"Development and validation of machine learning models to predict vancomycin- and teicoplanin-associated acute kidney injury: A retrospective, multicenter study","authors":"Pin-Yi Lo ,&nbsp;Fan-Ying Chan ,&nbsp;Yi-En Ku ,&nbsp;San-Yuan Wang ,&nbsp;Hsiang-Yin Chen","doi":"10.1016/j.ijantimicag.2025.107651","DOIUrl":"10.1016/j.ijantimicag.2025.107651","url":null,"abstract":"<div><h3>Objective</h3><div>Despite the effectiveness of vancomycin and teicoplanin in managing Gram-positive infections, their nephrotoxicity may prolong hospitalization, and increase morbidity, mortality, and healthcare costs. This study aimed to develop and validate clinically applicable prognostic machine learning models for predicting vancomycin-associated acute kidney injury (VA-AKI) and teicoplanin-associated AKI (TA-AKI).</div></div><div><h3>Methods</h3><div>This retrospective study in Taiwan utilized the Taipei Medical University Clinical Research Database. Patients receiving intravenous vancomycin or teicoplanin therapy between February 2010 and December 2020 were included. Features were selected from 198 variables through recursive feature elimination using feature importance (RFECV) and SHapley Additive exPlanations importance (ShapRFECV). Twelve models were constructed using XGBoost and LightGBM. Model performance was assessed by eight evaluation metrics, including the area under the receiver operating characteristic curve (AUROC). The optimal threshold was determined based on the maximum F<sub>1</sub> score, and the SHAP analysis assisted in model interpretation.</div></div><div><h3>Results</h3><div>Among 9342 included patients, 19.70% (1383/7020) of patients in the training set, 18.58% (326/1755) in the internal validation set, and 20.5% (116/567) in the external validation set developed AKI. The XGBoost model, using features selected by ShapRFECV, demonstrated optimal predictive performance in both internal (AUROC 0.798, 95% confidence interval [CI] 0.791–0.804) and external (AUROC 0.779, 95% CI: 0.767–0.791) validation.</div></div><div><h3>Conclusions</h3><div>The XGBoost model, leveraging time-series data, accurately predicts AKI in vancomycin and teicoplanin users, supporting early risk assessment and personalized patient management. Future multicentre prospective external validation is needed to strengthen its real-world applicability and generalizability.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"67 1","pages":"Article 107651"},"PeriodicalIF":4.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400702","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
Membrane-disrupting medium-chain fatty acids reduce Staphylococcus aureus persister cell survival during antibiotic treatment 在抗生素治疗期间,破坏膜的中链脂肪酸会降低金黄色葡萄球菌持久性细胞的存活率。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-22 DOI: 10.1016/j.ijantimicag.2025.107648
Yena Seo , Minjun Kim , Dae-Youn Kim , Ji-Won Park , Hyun Jung Kim , Kyun Heo , Tae-Jong Kim

Objective

Eliminating persister cells is essential to improve treatment of chronic infections and to limit the emergence of resistant strains. Medium-chain fatty acids (MCFAs) are widely used in cosmetics and antibiotic ointments where Staphylococcus aureus is a common commensal. This study evaluated the potential of MCFAs to eradicate S. aureus persister cells and investigated their mechanisms of action.

Methods

The bactericidal activity of MCFAs against S. aureus persisters was assessed after treatment with three antibiotics – ciprofloxacin, oxacillin, and tobramycin. Membrane permeability was analysed by fluorescence microscopy and ATP leakage assays.

Results

Octanoic, decanoic, and lauric acids at 10, 1, and 0.1 mM, respectively, significantly reduced antibiotic-surviving cells in persister-enriched populations, independent of antibiotic class. In contrast, myristic acid did not eliminate persisters up to 10 mM, although it was active against exponentially growing cells. The bactericidal activity of MCFAs increased with chain length from octanoic to lauric acid. Killing correlated with enhanced membrane permeability, whereas changes in membrane fluidity or transmembrane potential were not predictive.

Conclusions

MCFAs, particularly lauric acid at low concentrations, effectively eradicate S. aureus persisters and may enhance skin health when incorporated into topical products. Their activity increases with chain length and is linked to membrane permeability disruption. Myristic acid, while effective against metabolically active cells, is ineffective against persisters, highlighting physiological differences between growth states.
目的:消除持久性细胞对于改善慢性感染的治疗和限制耐药菌株的出现至关重要。中链脂肪酸(MCFAs)广泛用于化妆品和抗生素软膏中,其中金黄色葡萄球菌是常见的共生菌。本研究评估了MCFAs根除金黄色葡萄球菌持久性细胞的潜力,并研究了其作用机制。方法:采用环丙沙星、恶西林、妥布霉素3种抗生素治疗后,观察MCFAs对金黄色葡萄球菌的抑菌活性。用荧光显微镜和ATP渗漏试验分析膜的通透性。结果:辛酸、癸酸和月桂酸分别在10、1和0.1 mM时显著减少了持续富集的群体中抗生素存活细胞,与抗生素种类无关。相比之下,肉豆蔻酸虽然对呈指数增长的细胞有活性,但却不能消除10 mM以下的顽固分子。从辛烷酸到月桂酸,MCFAs的杀菌活性随链长而增加。杀伤与膜通透性增强相关,而膜流动性或跨膜电位的变化并不能预测。结论:mcfa,特别是低浓度的月桂酸,可以有效地根除金黄色葡萄球菌,并且当加入局部产品时可以改善皮肤健康。它们的活性随着链长的增加而增加,并与膜渗透性破坏有关。肉豆蔻酸虽然对代谢活跃的细胞有效,但对顽固细胞无效,突出了生长状态之间的生理差异。
{"title":"Membrane-disrupting medium-chain fatty acids reduce Staphylococcus aureus persister cell survival during antibiotic treatment","authors":"Yena Seo ,&nbsp;Minjun Kim ,&nbsp;Dae-Youn Kim ,&nbsp;Ji-Won Park ,&nbsp;Hyun Jung Kim ,&nbsp;Kyun Heo ,&nbsp;Tae-Jong Kim","doi":"10.1016/j.ijantimicag.2025.107648","DOIUrl":"10.1016/j.ijantimicag.2025.107648","url":null,"abstract":"<div><h3>Objective</h3><div>Eliminating persister cells is essential to improve treatment of chronic infections and to limit the emergence of resistant strains. Medium-chain fatty acids (MCFAs) are widely used in cosmetics and antibiotic ointments where <em>Staphylococcus aureus</em> is a common commensal. This study evaluated the potential of MCFAs to eradicate <em>S. aureus</em> persister cells and investigated their mechanisms of action.</div></div><div><h3>Methods</h3><div>The bactericidal activity of MCFAs against <em>S. aureus</em> persisters was assessed after treatment with three antibiotics – ciprofloxacin, oxacillin, and tobramycin. Membrane permeability was analysed by fluorescence microscopy and ATP leakage assays.</div></div><div><h3>Results</h3><div>Octanoic, decanoic, and lauric acids at 10, 1, and 0.1 mM, respectively, significantly reduced antibiotic-surviving cells in persister-enriched populations, independent of antibiotic class. In contrast, myristic acid did not eliminate persisters up to 10 mM, although it was active against exponentially growing cells. The bactericidal activity of MCFAs increased with chain length from octanoic to lauric acid. Killing correlated with enhanced membrane permeability, whereas changes in membrane fluidity or transmembrane potential were not predictive.</div></div><div><h3>Conclusions</h3><div>MCFAs, particularly lauric acid at low concentrations, effectively eradicate <em>S. aureus</em> persisters and may enhance skin health when incorporated into topical products. Their activity increases with chain length and is linked to membrane permeability disruption. Myristic acid, while effective against metabolically active cells, is ineffective against persisters, highlighting physiological differences between growth states.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107648"},"PeriodicalIF":4.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367917","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
One Health: Virtual Special Issue in the International Journal of Antimicrobial Agents 一个健康:国际抗菌药物杂志的虚拟特刊。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-20 DOI: 10.1016/j.ijantimicag.2025.107645
Reema Singh , Yonghong Xiao
{"title":"One Health: Virtual Special Issue in the International Journal of Antimicrobial Agents","authors":"Reema Singh ,&nbsp;Yonghong Xiao","doi":"10.1016/j.ijantimicag.2025.107645","DOIUrl":"10.1016/j.ijantimicag.2025.107645","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107645"},"PeriodicalIF":4.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336750","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
期刊
International Journal of Antimicrobial Agents
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