International Journal of Antimicrobial Agents最新文献_第8页

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

International Journal of Antimicrobial Agents

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。

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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

International Journal of Antimicrobial Agents

Pub Date : 2025-10-20 DOI: 10.1016/j.ijantimicag.2025.107645

Reema Singh , Yonghong Xiao

引用次数: 0

Fluconazole exposure during mechanical circulatory support (MCS) device insertion 机械循环支持（MCS）装置插入期间氟康唑暴露。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-19 DOI: 10.1016/j.ijantimicag.2025.107647

Kelly A. Cairns , Kate Morton , Trisha N. Peel , Iain J. Abbott , David M. Kaye , Silvana Marasco , Andrew A. Udy , David Daly , Victoria Warner , Anna Coldham , Jeffrey D. Pope , Hans G. Schneider , Michael J. Dooley

Objective

Mechanical circulatory support (MCS) devices are an important intervention for patients with advanced heart failure. Invasive Candida spp. infections following MCS device insertion have been reported. The addition of fluconazole to surgical prophylaxis regimens is controversial, and there is a lack of data describing exposures achieved during MCS device insertion.

Methods

A pilot pharmacokinetic study was undertaken to determine the plasma fluconazole exposure achieved during MCS device insertion. Perioperative fluconazole levels were drawn at four time points during the MCS device insertion surgery: knife to skin, start of cardiac bypass, end of cardiac bypass, and at the time of skin closure. A secondary outcome was to determine the Candida spp. colonization patterns in this patient cohort.

Results

Forty perioperative plasma fluconazole concentrations (from 10 patients) were available for analysis. One patient received 400 mg IV fluconazole preoperatively, and the remainder received 200 mg IV. The median measured concentration at knife to skin, start of cardiac bypass, end of cardiac bypass, and skin closure, was 3.85 mg/L (IQR: 3.53–4.48 mg/L), 3.75 mg/L (IQR: 3.45–4.23 mg/L), 3.45 mg/L (IQR: 3.08–3.75 mg/L), and 3.35 mg/L (IQR: 2.93–3.55 mg/L), respectively. Preoperative Candida colonization swabs isolated Candida parapsilosis (n = 2), Candida glabrata (n = 2), and Candida albicans (n = 1). A single postoperative swab was positive for C. glabrata.

Conclusion

In 10 patients undergoing MCS device insertion, fluconazole 200 to 400 mg IV achieved median plasma levels of between 3 and 4 mg/L throughout the surgical procedure but may not adequately cover for C. glabrata.

背景：机械循环支持装置（MCS）是晚期心力衰竭患者的重要干预手段。侵袭性念珠菌感染后，MCS装置插入有报道。在手术预防方案中添加氟康唑是有争议的，并且缺乏描述MCS装置插入期间达到的暴露的数据。方法：进行初步药代动力学研究，以确定MCS装置插入期间血浆氟康唑暴露情况。在MCS装置插入手术期间的四个时间点——刀到皮肤（KTS）、心脏搭桥开始（SOB）、心脏搭桥停止（EOB）和皮肤闭合（SC）时，绘制围术期氟康唑水平。次要结果是确定该患者队列中念珠菌的定植模式。结果：40例围手术期血浆氟康唑浓度（来自10例患者）可供分析。1例患者术前静脉注射氟康唑400 mg，其余患者静脉注射氟康唑200 mg。KTS、SOB、EOB和SC的中位测量浓度分别为3.85 mg/L （IQR: 3.53 ~ 4.48 mg/L）、3.75 mg/L （IQR: 3.45 ~ 4.23 mg/L）、3.45 mg/L （IQR: 3.08 ~ 3.75 mg/L）和3.35 mg/L （IQR: 2.93 ~ 3.55 mg/L）。术前念珠菌定植拭子分离出假丝酵母菌（n = 2）、光丝酵母菌（n = 2）和白色念珠菌（n = 1）。单次术后拭子检出光滑棘球蚴阳性。结论：在10例接受MCS装置插入的患者中，氟康唑200至400mg IV在整个手术过程中达到了3至4mg /L的中位血浆水平，可能无法充分覆盖光滑锥体。

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引用次数: 0

Comment on “Human serum lipids affect Staphylococcus aureus sensitivity to phage infection” 评“人血脂影响金黄色葡萄球菌对噬菌体感染的敏感性”。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-14 DOI: 10.1016/j.ijantimicag.2025.107644

Nathkapach K. Rattanapitoon , Nav La , Patpicha Arunsan , Schawanya K. Rattanapitoon

引用次数: 0

Retrospective evaluation of a vancomycin dosing bundle in paediatric intensive care 儿科重症监护中万古霉素剂量束的回顾性评价。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-08 DOI: 10.1016/j.ijantimicag.2025.107638

Michael A. Stokes , Tony Lai , Lana Reiter , Bradley Rockliff , Deirdre Hahn , Marino S. Festa , Indy Sandaradura

Objective

To describe the impact of a real-world, vancomycin dosing bundle (‘the bundle’), on vancomycin-associated nephrotoxicity (VAN) rates in critically ill children in a single paediatric intensive care unit (PICU).

Methods

A retrospective observational study was conducted in an Australian tertiary PICU from January 2020 to December 2022. The study included all patients who received vancomycin for two or more doses with an associated vancomycin level. During the study period, a staggered implementation was undertaken entailing three interventions on vancomycin prescribing (the bundle): (1) employment of a pharmacist to the PICU, (2) model-informed precision dosing (MIPD), and (2) a reduction in initial vancomycin dosing (15 mg/kg 6 hourly, to 15 mg/kg for the first dose then 10 mg/kg 6 hourly thereafter) alongside a reduction in target trough concentrations from 10–20 to 7–15 mg/L. Data on dosing, vancomycin concentrations, and patient characteristics were collected, and AUC₂₄ was calculated using MIPD software. VAN was defined as a creatinine increase of 0.5 mg/dL or 50% from baseline on two consecutive measurements. Statistical analysis explored associations between time and VAN outcomes.

Results

A total of 648 vancomycin courses were analysed, across 477 unique patients, with a median treatment length of 44.59 h. MIPD represented 18% of the total courses, increasing from 2% to 37% over the study period. VAN occurred in 11.3% of courses, with a consistent rate over the years (13% in 2020, 12% in 2021, and 9% in 2022). Severe VAN rates decreased from 8.6% in 2020 to 3.9% in 2022. The reduction in both severe (P = 0.16) and total (P = 0.4) VAN did not achieve statistical significance.

Conclusions

Implementation of a staggered pharmacist-led vancomycin dosing bundle did not result in a statistically significant reduction in VAN rates over time. However, the observed reduction in severe VAN and associated reduction in AUC₂₄ warrant further investigation with a prospective study design in the high-risk PICU cohort.

目的：描述现实世界中万古霉素剂量束（“该束”）对单一儿科重症监护病房危重儿童万古霉素相关肾毒性（VAN）率的影响。方法：2020年1月至2022年12月在澳大利亚一家三级儿科重症监护病房（PICU）进行回顾性观察研究。该研究包括所有接受万古霉素两次或两次以上剂量并伴有相关万古霉素水平的患者。在研究期间，对万古霉素处方进行了交错实施，包括三种干预措施：(i) PICU雇用药剂师，（ii）模型知情个性化给药（MIPD），以及（iii）减少万古霉素初始剂量（15mg /kg 6小时，第一次剂量为15mg /kg，之后6小时为10mg /kg），同时将目标谷浓度从10 - 20mg /L降低到7 - 15mg /L。收集剂量、万古霉素浓度和患者特征数据，并使用MIPD软件计算AUC24。VAN定义为连续两次测量肌酐比基线增加0.5 mg/dL或50%。统计分析探讨了时间与VAN结果之间的关系。结果：共分析了648个万古霉素疗程，涉及477例独特患者，中位治疗时间为44.59小时。MIPD占总课程的18%，在研究期间从2%增加到37%。11.3%的课程发生了VAN，多年来的比例保持一致（2020年为13%，2021年为12%，2022年为9%）。严重VAN率从2020年的8.6%下降到2022年的3.9%。严重VAN （p = 0.16）和总VAN （p = 0.4）的减少均无统计学意义。结论：实施交错药师主导的万古霉素给药束并没有导致VAN率随时间的统计学显著降低。然而，观察到的严重VAN的减少和相关的AUC24的减少值得在高危PICU队列中进行进一步的前瞻性研究设计。

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引用次数: 0

Expanded applications of omeprazole: Synergistic reversal of colistin resistance in Acinetobacter baumannii 奥美拉唑的扩展应用：协同逆转鲍曼不动杆菌粘菌素耐药性。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-08 DOI: 10.1016/j.ijantimicag.2025.107639

Xiaowei Lv, Fan Ye, Juan Pan, Panjie Hu, Endian Sun, Hong Wen, Ziyue Zeng, Mengjie Wei, Jianzhong Ye , Tieli Zhou

Objectives

Acinetobacter baumannii (A. baumannii) is an opportunistic microorganism capable of triggering life-threatening infections. The rising prevalence of multidrug-resistant A. baumannii in clinical settings has complicated treatment efforts. Colistin serves as the last-line therapy against multidrug-resistant A. baumannii. However, its resurgence has accelerated antimicrobial resistance. To address escalating resistance and stagnant drug development, repurposing clinical drugs for antibacterial applications shows significant promise. Omeprazole, a proton pump inhibitor, is widely used to treat digestive system disorders.

Methods

This study demonstrated that the combination of omeprazole and colistin exhibits considerable antibacterial activity through checkerboard susceptibility assays, time-killing experiments, and live/dead bacterial cell viability tests.

Results

In vivo experiments using a mouse leg infection model confirmed the synergistic antibacterial effect. Further mechanistic investigations have disclosed that this combined medication exerts its antibacterial effect by inducing bacterial death through the accumulation of reactive oxygen species and subsequent oxidative stress, by inhibiting the formation of biofilms, and by suppressing the expression of drug efflux pumps.

Conclusions

Overall, this study discovered that the clinical drug omeprazole has the potential to act as an adjuvant to colistin, synergistically reversing colistin resistance in A. baumannii and providing a novel therapeutic strategy for the treatment of infections caused by this pathogen.

鲍曼不动杆菌（鲍曼不动杆菌）是一种机会性微生物，能够引发危及生命的感染。临床环境中耐多药鲍曼不动杆菌的流行率不断上升，使治疗工作复杂化。粘菌素是对抗多重耐药鲍曼杆菌的最后一线疗法。然而，它的死灰复燃加速了抗菌素耐药性。为了解决不断升级的耐药性和停滞不前的药物开发，将临床药物重新用于抗菌应用显示出巨大的希望。奥美拉唑是一种质子泵抑制剂，广泛用于治疗消化系统疾病。本研究通过棋盘药敏试验、时间杀伤实验和活/死细菌细胞活力试验证明，奥美拉唑和粘菌素联合使用具有相当的抗菌活性。小鼠腿部感染模型的体内实验证实了其协同抗菌作用。进一步的机制研究表明，这种联合用药通过活性氧（ROS）的积累和随后的氧化应激诱导细菌死亡、抑制生物膜的形成和抑制药物外排泵的表达来发挥其抗菌作用。总的来说，本研究发现临床药物奥美拉唑有可能作为粘菌素的佐剂，协同逆转鲍曼不动杆菌对粘菌素的耐药性，为治疗该病原体引起的感染提供了一种新的治疗策略。

{"title":"Expanded applications of omeprazole: Synergistic reversal of colistin resistance in Acinetobacter baumannii","authors":"Xiaowei Lv, Fan Ye, Juan Pan, Panjie Hu, Endian Sun, Hong Wen, Ziyue Zeng, Mengjie Wei, Jianzhong Ye , Tieli Zhou","doi":"10.1016/j.ijantimicag.2025.107639","DOIUrl":"10.1016/j.ijantimicag.2025.107639","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Acinetobacter baumannii</em> (<em>A. baumannii</em>) is an opportunistic microorganism capable of triggering life-threatening infections. The rising prevalence of multidrug-resistant <em>A. baumannii</em> in clinical settings has complicated treatment efforts. Colistin serves as the last-line therapy against multidrug-resistant <em>A. baumannii</em>. However, its resurgence has accelerated antimicrobial resistance. To address escalating resistance and stagnant drug development, repurposing clinical drugs for antibacterial applications shows significant promise. Omeprazole, a proton pump inhibitor, is widely used to treat digestive system disorders.</div></div><div><h3>Methods</h3><div>This study demonstrated that the combination of omeprazole and colistin exhibits considerable antibacterial activity through checkerboard susceptibility assays, time-killing experiments, and live/dead bacterial cell viability tests.</div></div><div><h3>Results</h3><div><em>In vivo</em> experiments using a mouse leg infection model confirmed the synergistic antibacterial effect. Further mechanistic investigations have disclosed that this combined medication exerts its antibacterial effect by inducing bacterial death through the accumulation of reactive oxygen species and subsequent oxidative stress, by inhibiting the formation of biofilms, and by suppressing the expression of drug efflux pumps.</div></div><div><h3>Conclusions</h3><div>Overall, this study discovered that the clinical drug omeprazole has the potential to act as an adjuvant to colistin, synergistically reversing colistin resistance in <em>A. baumannii</em> and providing a novel therapeutic strategy for the treatment of infections caused by this pathogen.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107639"},"PeriodicalIF":4.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274461","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

Molecular characterisation of two novel KPC variants mediating ceftazidime-avibactam resistance in ST11 Klebsiella pneumoniae 介导ST11肺炎克雷伯菌对头孢他啶-阿维巴坦耐药的两种新型KPC变异的分子特征

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-08 DOI: 10.1016/j.ijantimicag.2025.107642

Tengfei Guo , Li Ding , Siquan Shen , Chengkang Tang , Tao Jiang , Fupin Hu

Objective

Mutations in bla_KPC that confer resistance to ceftazidime-avibactam pose a new clinical challenge. This study reports the molecular characterisation of two novel KPC variants mediating ceftazidime-avibactam resistance in Klebsiella. pneumoniae.

Methods

Six K. pneumoniae strains were isolated from the endotracheal aspirate of a single patient. Antimicrobial susceptibility testing, whole genome sequencing, conjugation and cloning assays, enzyme kinetic and growth assays were performed to explore the molecular characterisation and antimicrobial resistance mechanisms.

Results

Two novel KPC variants, KPC-207 (L169Q and 274-275S ins) and KPC-208 (L169Q and D179Y), produced by a patient infected with KPC-producing ST11-KL19 K. pneumoniae which underwent a drug-resistant mutation during treatment. The mutation process encompassed a sequential transition from KPC-2 to KPC-207, then KPC-208, a reversion to KPC-207, and ultimately a return to KPC-208. Both KPC-207-and KPC-208-producing strains were resistant to ceftazidime-avibactam, but showed restored susceptibility to carbapenems. Cloning assays showed a 128- and 64-fold increase in the MIC of ceftazidime-avibactam for clonal strains carrying bla_KPC-207 and bla_KPC-208 compared to bla_KPC-2 carrier. Enzyme kinetic assays revealed diminished hydrolysis of imipenem and meropenem by KPC-207 and KPC-208, along with reduced inhibitory effect of avibactam on both proteins. The core structure of the plasmid harboring the bla_KPC-207 and bla_KPC-208 genes was Tn1721-ISkpn6-bla_KPC-ISkpn27-IS26, which belonged to the A2-type Tn1721. Compared with the bla_KPC-2, the bla_KPC-207 and bla_KPC-208 genes had essentially no effect on the cost of adaptation to K. pneumoniae.

Conclusions

The antimicrobial susceptibility and the bla_KPC should be continuously monitored during clinical treatment of carbapenem-resistant K. pneumoniae with ceftazidime-avibactam.

导致肺炎克雷伯菌对头孢他啶-阿维巴坦耐药的blaKPC突变对全球临床抗感染治疗提出了新的挑战。尽管近年来关于KPC变异机制的报道越来越多，但在同一患者中同时发生两种新的KPC变异的报道仍然很少。在这项研究中，我们报道了两种新的KPC变体，KPC-207 （L169Q和274-275S ins）和KPC-208 (L169Q和D179Y)，它们是由感染产KPC的ST11-KL19肺炎克雷伯菌的患者在治疗期间产生的耐药突变。突变过程包括从KPC-2到KPC-207，然后是KPC-208，再到KPC-207，最后回到KPC-208。产kpc -207和产kpc -208的肺炎克雷伯菌均对头孢他啶-阿维巴坦耐药，但对碳青霉烯类恢复了敏感性。克隆实验显示，携带blaKPC-207和blaKPC-208的克隆菌株与携带blaKPC-2的克隆菌株相比，头孢他啶-阿维巴坦的MIC分别增加了128倍和64倍。酶动力学分析显示KPC-207和KPC-208对亚胺培南和美罗培南的水解作用减弱，同时阿维巴坦对这两种蛋白的抑制作用减弱。序列分析显示，所有临床菌株均具有较高的同源性，携带blaKPC-207和blaKPC-208基因的质粒核心结构为Tn1721- iskpn6 - blakpc - iskpn27 - is26，属于a2型Tn1721。与野生型blaKPC-2基因相比，blaKPC-207和blaKPC-208基因对肺炎克雷伯菌的适应成本基本没有影响。临床应用头孢他啶-阿维巴坦治疗耐碳青霉烯类肺炎克雷伯菌时应持续监测抗菌药物敏感性和blaKPC。

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引用次数: 0

Overcoming antimicrobial resistance: Phage therapy as a promising solution to combat ESKAPE pathogens 克服抗菌素耐药性：噬菌体治疗作为对抗ESKAPE病原体的有希望的解决方案。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-08 DOI: 10.1016/j.ijantimicag.2025.107640

Ritu Raj Patel , Pandey Priya Arun , Sudhir Kumar Singh , Meenakshi Singh

Objective

The global escalation of antimicrobial resistance (AMR) has intensified the search for alternative therapies, with bacteriophage (phage) therapy re-emerging as a promising solution. This review aims to critically evaluate the therapeutic potential of phage therapy against multidrug-resistant (MDR) ESKAPE pathogens, which are major contributors to hospital-acquired infections. The review discusses the distinct antibacterial strategies of phage namely, targeted lysis, enzymatic biofilm disruption, and synergy with antibiotics.

Methods

A comprehensive literature review was conducted focusing on the mechanisms of phage antibacterial activity and the molecular regulation of lytic and lysogenic life cycles, highlighting the therapeutic importance of the lytic-lysogenic switch. It also explores the integration of nanotechnology-based delivery systems that enhances therapeutic efficacy. Recent advances in phage engineering, including CRISPR-Cas technologies and synthetic biology approaches, were also analyzed to understand their contribution to optimizing phage efficacy.

Results

Phage therapy demonstrates multiple antibacterial mechanisms, including targeted bacterial lysis, enzymatic biofilm disruption, and synergistic interactions with antibiotics. Advanced delivery systems such as liposomes, hydrogels, nanofibers, and nanoemulsions enhance phage stability and retention by overcoming physiological barriers like gastric acidity, enzymatic degradation, and immune clearance. Clinical evidence from compassionate use cases and early-phase trials highlights the safety and therapeutic promise of phage therapy.

Conclusions

Phage therapy represents a versatile and sustainable approach to combat multidrug-resistant infections. While regulatory, resistance, and scalability challenges remain, continued integration of microbiology, nanotechnology, and clinical research may enable its transition from experimental to mainstream therapeutic application in the post-antibiotic era.

全球抗菌素耐药性（AMR）的升级加强了对替代疗法的探索，噬菌体（噬菌体）疗法再次成为一种有希望的解决方案。这篇综述严格审查了噬菌体治疗多药耐药（MDR） ESKAPE病原体的治疗潜力，这些病原体是医院获得性感染的主要原因之一。本文讨论了噬菌体不同的抗菌策略，即靶向裂解、酶促生物膜破坏和与抗生素的协同作用。它还探讨了噬菌体生命周期的分子调控，强调了溶菌-溶原开关的治疗重要性。中心焦点是脂质体、水凝胶、纳米纤维和纳米乳液等先进给药系统与特定给药途径（包括口服、局部、静脉、鼻内和膀胱内给药途径）之间的相互作用。这些递送策略对于克服胃酸、酶降解和免疫清除等关键生理障碍至关重要，从而增强噬菌体的稳定性、滞留性和治疗效果。还探讨了噬菌体工程的最新创新，特别是使用CRISPR-Cas系统，合成生物学和持续进化平台来扩大宿主范围和优化裂解功能。该综述进一步评估了新出现的临床证据，包括来自富有同情心的用例和早期试验的结果，这些结果强调了噬菌体治疗在现实环境中的安全性和治疗潜力。尽管取得了这些进展，但仍存在重大挑战，包括细菌对噬菌体的耐药性、监管清晰度的需求以及个性化治疗的可扩展性。随着微生物学、纳米技术和临床实践的整合，噬菌体治疗弥合了生态解决方案和现代医学之间的差距，将自己定位为后抗生素时代的多功能、可持续支柱。

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引用次数: 0

Efficacy and safety of selective decontamination of the digestive tract in oesophageal surgery: A systematic review and meta-analysis 食道手术中选择性消化道去污的有效性和安全性：一项系统综述和荟萃分析。

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-08 DOI: 10.1016/j.ijantimicag.2025.107637

Justin G.A. Grootenhuis , Ward Seurs , Nynke G.L. Jager , Jaap Ten Oever , Hans Van Veer , Bastiaan R. Klarenbeek , Jeroen A. Schouten

Objectives

Oesophagectomy is a complex surgery with high mortality and morbidity caused by postoperative infectious complications such as pneumonia and anastomotic leakage. Selective decontamination of the digestive tract (SDD) with non-absorbable antimicrobial agents may lower the density of pathogenic organisms in the oropharynx and oesophagus, thereby providing a perioperative prophylactic strategy. While SDD has shown benefits in intensive care units and lower gastrointestinal surgery, its efficacy and safety in oesophagectomy remains unclear. This study aimed to evaluate the efficacy and safety of perioperative SDD in patients undergoing oesophagectomy.

Methods

A systematic review and meta-analysis were conducted, including all relevant studies published up to April 3, 2025. The primary outcome was the efficacy, defined as reduced incidence of pneumonia, anastomotic leakage, surgical site infection and mortality. Safety, measured by reported side effects, was the secondary outcome.

Results

Of 628 articles screened, six studies comprising 1074 patients were included. Of these, 487 (45.3%) received SDD and 587 (54.7%) received placebo or standard care. None of the studies focused primarily on the safety of SDD, and side effects were not systematically reported. SDD was significantly associated with a lower incidence of pneumonia (OR: 0.42, 95% CI: 0.30–0.58, P < 0.01), anastomotic leakage (OR: 0.43, 95% CI: 0.29–0.65, P < 0.01) and 30-day mortality (OR: 0.25, 95% CI: 0.07–0.94; P = 0.04). Although significant, 30-day mortality should be interpreted with caution due to the limited number of studies and the high risk of bias among them. No significant reduction was observed for in-hospital mortality or surgical site infections.

Conclusions

The meta-analysis indicates that perioperative SDD may reduce pneumonia and anastomotic leakage after oesophagectomy. However, the large heterogeneity, risk of bias and the lack of adequate safety assessment make the available studies insufficient to advance a qualitative recommendation on the topic. For this, a large randomised controlled trial is imperative.

食管切除术是一项复杂的手术，术后感染并发症如肺炎、吻合口漏等死亡率和发病率高。用不可吸收的抗菌药物选择性地净化消化道（SDD）可能降低口咽部和食道中致病菌的密度，从而提供围手术期预防策略。虽然SDD在重症监护病房和下消化道手术中显示出益处，但其在食管切除术中的有效性和安全性仍不清楚。本研究旨在评价食管切除术患者围手术期SDD的疗效和安全性。系统回顾和荟萃分析纳入截至2025年4月3日发表的所有相关研究。主要终点是疗效，定义为肺炎、吻合口漏、手术部位感染和死亡率的降低。安全性，通过报告的副作用来衡量，是次要的结果。在筛选的628篇文章中，包括1074名患者的6项研究被纳入。其中，487例（45.3%）接受了SDD治疗，587例（54.7%）接受了安慰剂或标准治疗。没有一项研究主要关注SDD的安全性，副作用也没有系统的报道。SDD与较低的肺炎发生率（OR 0.42, 95% CI: 0.30-0.58， P< 0.01）、吻合口漏发生率（OR 0.43, 95% CI: 0.29-0.65， P< 0.01）和30天死亡率（OR 0.25, 95% CI: 0.07-0.94， P= 0.04）显著相关。尽管具有重要意义，但由于研究数量有限且其中存在高偏倚风险，因此应谨慎解释30天死亡率。住院死亡率或手术部位感染未见显著降低。荟萃分析表明围手术期SDD可减少食管切除术后肺炎和吻合口漏。然而，巨大的异质性、偏倚风险和缺乏足够的安全性评估使得现有的研究不足以提出关于该主题的定性建议。为此，必须进行大规模的随机对照试验。

{"title":"Efficacy and safety of selective decontamination of the digestive tract in oesophageal surgery: A systematic review and meta-analysis","authors":"Justin G.A. Grootenhuis , Ward Seurs , Nynke G.L. Jager , Jaap Ten Oever , Hans Van Veer , Bastiaan R. Klarenbeek , Jeroen A. Schouten","doi":"10.1016/j.ijantimicag.2025.107637","DOIUrl":"10.1016/j.ijantimicag.2025.107637","url":null,"abstract":"<div><h3>Objectives</h3><div>Oesophagectomy is a complex surgery with high mortality and morbidity caused by postoperative infectious complications such as pneumonia and anastomotic leakage. Selective decontamination of the digestive tract (SDD) with non-absorbable antimicrobial agents may lower the density of pathogenic organisms in the oropharynx and oesophagus, thereby providing a perioperative prophylactic strategy. While SDD has shown benefits in intensive care units and lower gastrointestinal surgery, its efficacy and safety in oesophagectomy remains unclear. This study aimed to evaluate the efficacy and safety of perioperative SDD in patients undergoing oesophagectomy.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis were conducted, including all relevant studies published up to April 3, 2025. The primary outcome was the efficacy, defined as reduced incidence of pneumonia, anastomotic leakage, surgical site infection and mortality. Safety, measured by reported side effects, was the secondary outcome.</div></div><div><h3>Results</h3><div>Of 628 articles screened, six studies comprising 1074 patients were included. Of these, 487 (45.3%) received SDD and 587 (54.7%) received placebo or standard care. None of the studies focused primarily on the safety of SDD, and side effects were not systematically reported. SDD was significantly associated with a lower incidence of pneumonia (OR: 0.42, 95% CI: 0.30–0.58, P < 0.01), anastomotic leakage (OR: 0.43, 95% CI: 0.29–0.65, P < 0.01) and 30-day mortality (OR: 0.25, 95% CI: 0.07–0.94; P = 0.04). Although significant, 30-day mortality should be interpreted with caution due to the limited number of studies and the high risk of bias among them. No significant reduction was observed for in-hospital mortality or surgical site infections.</div></div><div><h3>Conclusions</h3><div>The meta-analysis indicates that perioperative SDD may reduce pneumonia and anastomotic leakage after oesophagectomy. However, the large heterogeneity, risk of bias and the lack of adequate safety assessment make the available studies insufficient to advance a qualitative recommendation on the topic. For this, a large randomised controlled trial is imperative.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 6","pages":"Article 107637"},"PeriodicalIF":4.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274479","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

Global, Regional, and National Burden of Bacterial Carbapenem Resistance from 1990 to 2021 and predictions up to 2035 1990年至2021年全球、地区和国家细菌碳青霉烯耐药负担及2035年预测

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents

Pub Date : 2025-10-08 DOI: 10.1016/j.ijantimicag.2025.107636

Jie-Hao Tai , Yi-Yu Lyu , Yu-Shan Zhang , Wen-Wen Chu , Min Yang , Qiang Zhou , Yi-Le Wu

Background

Carbapenem resistance (CR) critically endangers global health. This study aims to report global burden of bacterial CR and forecast future trends.

Methods

Using MICROBE database data (1990–2021) from 204 countries/territories, we analysed CR-attributable and -associated deaths and disability-adjusted life years by age, regions, and pathogens. Joinpoint regression analysed CR burden trends using average annual percent change (AAPC). A Bayesian age-period-cohort model projected burden through 2035.

Results

Globally, CR-attributable deaths rose from 0.23 million (95% uncertainty interval, UI 0.15–0.32) in 1990 to 0.29 million (0.22–0.35) in 2021, yet age-standardised mortality rates (ASMRs) declined from 5.1 (3.2–7.0) to 3.6 (2.8–4.5) per 100 000. Pathogen-specific CR-attributable mortality diverged during 1990–2021: Klebsiella pneumoniae markedly surged (AAPC=3.09% [95% confidence interval, CI 2.55–3.62]), while Streptococcus pneumoniae declined (−1.28% [−1.60 to −0.97]). By age, deaths fell 56% in children <5 years but rose 112% in adults ≥70 years (2021 vs 1990). Thirteen GBD regions saw increased CR-attributable deaths in 2021 compared with 1990, while eight declined. Projections estimate 3.76 million (95% CI 3.70–3.83) global cumulative deaths from 2025 to 2035. Six super-regions will experience rising CR-attributable deaths by 2035; only the High-income super-region will decline.

Conclusion

This study reveals a complex epidemiological landscape of CR, marked by rising global deaths alongside declining ASMRs. The CR death burden is projected to escalate severely by 2035. These findings on high-risk regions, populations, and pathogens underscore the imperative for tailored mitigation strategies aligning with global antimicrobial resistance containment goals.

背景：碳青霉烯耐药性（CR）严重危及全球健康。本研究旨在报告细菌CR的全球负担并预测未来趋势。方法：使用来自204个国家/地区的微生物数据库数据（1990-2021年），我们按年龄、地区和病原体分析了cr归因于和相关的死亡和残疾调整寿命年。结合点回归使用平均年变化百分比（AAPC）分析企业责任负担趋势。贝叶斯年龄时期队列模型预测了到2035年的负担。结果：在全球范围内，cr导致的死亡人数从1990年的23万（95%不确定区间，UI为0.15至0.32）上升到2021年的29万（0.22至0.35），但年龄标准化死亡率（ASMRs）从每10万人5.1（3.2至7.0）下降到3.6（2.8至4.5）。1990-2021年间，病原体特异性cr归因死亡率出现分化：肺炎克雷伯菌显著上升（AAPC=3.09%[95%置信区间，CI 2.55 ~ 3.62]），而肺炎链球菌下降（-1.28%[-1.60 ~ -0.97]）。结论：本研究揭示了CR复杂的流行病学格局，其特征是全球死亡人数上升，而asmr下降。预计到2035年，慢性阻塞性肺病的死亡负担将严重加剧。这些关于高风险地区、人群和病原体的发现强调了制定符合全球抗微生物药物耐药性控制目标的量身定制缓解战略的必要性。

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引用次数: 0