Surgical site infections and the role of anesthesia and bacterial ion transporters

手术部位感染以及麻醉和细菌离子转运蛋白的作用

• 批准号: 10402288
• 负责人: Koichi Yuki
• 金额: $ 33.92万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402288
• 关键词: Adverse effects; Affect; Anesthesia procedures; Anesthetics; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Attenuated; Bacteria; Bacterial Antibiotic Resistance; Binding; Binding Sites; Biological Assay; Catheters; Cell Adhesion Molecules; Cell physiology; Cells; Clinical; Clinical Research; Communities; Complement; Data; Development; Effectiveness; Enhancers; Enterococcus faecalis; Escherichia coli; Foundations; Future; Gene Expression; General Anesthesia; Gram-Negative Bacteria; Gram-Positive Bacteria; Healthcare; Hospitals; Host Defense; Hypoxia; Immune; Impairment; In Vitro; Incubated; Infection; Intravenous Anesthetics; Ion Channel; Ions; Isoflurane; Knowledge; Lead; Learning; Microbial Biofilms; Modeling; Morbidity - disease rate; Muscle; Mutagenesis; Nosocomial Infections; Operative Surgical Procedures; Oxygen; Patients; Perioperative; Phagocytes; Phagocytosis; Procedures; Production; Propofol; Proteins; Publishing; Regimen; Reporting; Research; Resistance; Role; Staphylococcus aureus; Structure; Surface; Surgical Wound Infection; Surgical sutures; Surgical wound; TLR2 gene; Testing; Toll-like receptors; Toxin; Vancomycin Resistance; Work; clinically relevant; design; experimental study; high risk; in vitro Assay; in vivo; infection risk; macrophage; methicillin resistant Staphylococcus aureus; mortality; mutant; neutrophil; novel; pathogen; pre-clinical; prevent; screening; sevoflurane; side effect; wound

Project Summary/ Abstract The proposed research titled “Surgical site infections and the role of anesthesia and bacterial ion transporters” is to study the impact of daily used anesthetic drugs on surgical site infections (SSIs) (exposure duration and type of anesthetics) and the effectiveness of antibiotics in vivo and examine its underlying mechanism in vitro under the hypothesis that volatile anesthetics (VAs), not intravenous anesthetic (IA) increase bacteria burden in surgical wound by increasing biofilm formation via their direct interaction with bacterial ion transporters, and also by attenuating host immune cells. SSIs are the most common surgical infections in the perioperative setting, occupying 20% of in-hospital infections, and associated with significant morbidities, mortalities and healthcare expenses. Up to 80% of SSIs are due to bacteria in biofilm form, not in planktonic form. We previously reported in gram-negative bacteria Escherichia coli that 1) commonly used VAs isoflurane and sevoflurane, not IA propofol increased biofilm formation, and 2) a group of bacterial ion transporters were involved in biofilm formation, and 3) VAs enhanced the biofilm formation via affecting ion transporters. In this proposal we plan to use gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis strains, common strains for SSIs. In Aim 1, we will determine the effect of common anesthetics on biofilm formation in vitro under hypoxia to mimic oxygen level at wounds. The role of ion transporters in biofilm formation and their direct interaction with VAs will be examined. In Aim 2, we will determine the effect of common anesthetics on host defense, including phagocytosis of planktonic or biofilm bacteria cells in vitro under hypoxia and direct binding of VA to gram-positive receptor toll-like receptor 2. In Aim 3, we will determine the impact of anesthetics on biofilm-associated SSIs and the effectiveness of antibiotics in vivo. We will study the effect of anesthetics on bacterial biofilm formation and innate immune cell functions in this model. Upon the completion of the study, we expect to learn whether or not the type of anesthetics and the duration of their exposure affect bacterial loads, biofilm formation and the effectiveness of antibiotics. All the anesthetics tested are in clinical use and we expect that our study is highly clinically-relevant and readily translatable. Following the successful completion of this study, we expect to have the foundation to examine the impact of anesthetic regimens on SSIs in patients undergoing procedures with high risk of infection. The knowledge of anesthetic direct binding to bacterial ion transporters for biofilm formation and to host defense receptor toll-like receptor 2, if learned in this proposal, will not only increase our understanding of how volatile anesthetics work but also can lead us to think of developing screening assays to rule out these interactions and develop anesthetics devoid of adverse effects.

项目概要/摘要 拟议的研究题为“手术部位感染以及麻醉和细菌离子转运蛋白的作用” 旨在研究日常使用的麻醉药物对手术部位感染 (SSI) 的影响（暴露持续时间和 麻醉剂类型）和抗生素在体内的有效性，并在体外检查其潜在机制 假设挥发性麻醉剂 (VAs) 而不是静脉麻醉剂 (IA) 会增加细菌负荷 在手术伤口中，通过与细菌离子转运蛋白的直接相互作用增加生物膜的形成，以及 SSI 也是围手术期最常见的手术感染。 占院内感染的 20%，并与显着的发病率、死亡率和死亡率相关 高达 80% 的 SSI 是由生物膜形式的细菌而非浮游形式的细菌引起的。 先前报道在革兰氏阴性菌大肠杆菌中 1) 常用的 VAs 异氟烷和 七氟烷，而不是异丙酚，增加了生物膜的形成，2) 一组细菌离子转运蛋白 参与生物膜形成，3) VA 通过影响离子转运蛋白增强生物膜形成。 建议我们计划使用革兰氏阳性菌金黄色葡萄球菌和粪肠球菌菌株， 在目标 1 中，我们将确定常见麻醉剂对生物膜形成的影响。 体外缺氧条件下模拟伤口处的氧气水平离子转运蛋白在生物膜形成中的作用及其作用。 在目标 2 中，我们将检查普通麻醉剂对麻醉剂的影响。 宿主防御，包括体外缺氧和直接吞噬浮游或生物膜细菌细胞 VA 与革兰氏阳性受体 Toll 样受体 2 的结合。在目标 3 中，我们将确定 麻醉剂对生物膜相关 SSI 的影响以及抗生素在体内的有效性。 麻醉剂对该模型中细菌生物膜形成和先天免疫细胞功能的影响。 在这项研究中，我们希望了解麻醉剂的类型及其暴露时间是否会影响 细菌负荷、生物膜形成和抗生素的有效性所有麻醉剂均经过临床测试。 使用，我们希望我们的研究具有高度的临床相关性并且易于转化。 完成这项研究后，我们期望有基础来检查麻醉方案对 接受高感染风险手术的患者的 SSI。 麻醉剂直接结合的知识。 与细菌离子转运蛋白形成生物膜和宿主防御受体 Toll 样受体 2（如果在 这项建议不仅会增加我们对挥发性麻醉剂如何发挥作用的理解，而且可以引导我们 考虑开发筛选测定法来排除这些相互作用并开发没有不良反应的麻醉剂 影响。

项目成果

The Role of Anesthetic Management in Surgical Site Infections After Pediatric Intestinal Surgery.

麻醉管理在小儿肠道手术后手术部位感染中的作用。

• 发表时间: 2021
• 作者: Shibamura;Ormsby, Jennifer;Breibart, Mark;Zalieckas, Jill;Sandora, Thomas J;Priebe, Gregory P;Yuki, Koichi
• 通讯作者: Yuki, Koichi

Differential effects of dexmedetomidine on Gram-positive and Gram-negative bacterial killing and phagocytosis.

右美托咪定对革兰氏阳性和革兰氏阴性细菌杀灭和吞噬作用的不同作用。

• DOI: 10.2139/ssrn.4386906
• 发表时间: 2023-05-16
• 期刊: International immunopharmacology
• 影响因子: 5.6
• 作者: Wiriya Maisat;Xiaohui Han;S. Koutsogiannaki;S. Soriano;Koichi Yuki
• 通讯作者: Koichi Yuki

Volatile anesthetic isoflurane exposure facilitates Enterococcus biofilm infection.

挥发性麻醉剂异氟烷暴露会促进肠球菌生物膜感染。

• 发表时间: 2023-10
• 作者: Maisat, Wiriya;Yuki, Koichi
• 通讯作者: Yuki, Koichi

Surgical site infection in pediatric spinal fusion surgery revisited: outcome and risk factors after preventive bundle implementation.

重新审视小儿脊柱融合手术中的手术部位感染：预防性捆绑实施后的结果和危险因素。

• 发表时间: 2023-03
• 作者: Maisat, Wiriya;Yuki, Koichi
• 通讯作者: Yuki, Koichi

Risk factors for pediatric surgical site infection following neurosurgical procedures for hydrocephalus: a retrospective single-center cohort study.

脑积水神经外科手术后小儿手术部位感染的危险因素：一项回顾性单中心队列研究。

• 发表时间: 2021
• 影响因子: 2.2
• 作者: Shibamura;Ormsby, Jennifer;Breibart, Mark;Warf, Benjamin;Priebe, Gregory P;Soriano, Sulpicio G;Sandora, Thomas J;Yuki, Koichi
• 通讯作者: Yuki, Koichi