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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

基本信息

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
项目类别：
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

项目摘要

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，以及还通过减弱宿主免疫细胞。 SSI 是围手术期最常见的外科感染占院内感染的 20%，并与显着的发病率、死亡率和死亡率相关医疗费用。高达 80% 的 SSI 是由生物膜形式的细菌引起的，而不是浮游形式的细菌。我们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。在这个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， SSI 的常见菌株。在目标 1 中，我们将确定普通麻醉剂对生物膜形成的影响在缺氧条件下体外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将检查与 VA 的直接相互作用。在目标 2 中，我们将确定普通麻醉剂对宿主防御，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 的影响以及体内抗生素的有效性。我们将研究效果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。完成后在这项研究中，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。所有麻醉药均在临床测试使用，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。继成功完成这项研究后，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出现 SSI。麻醉直接结合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利影响的麻醉剂影响。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

DOI：
10.1016/j.jss.2020.10.015
发表时间：
2021-03
期刊：
The Journal of surgical research
影响因子：
0
作者：
Shibamura-Fujiogi M;Ormsby J;Breibart M;Zalieckas J;Sandora TJ;Priebe GP;Yuki K
通讯作者：
Yuki K

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

DOI：
10.1186/s12871-021-01342-5
发表时间：
2021-04-21
期刊：
BMC anesthesiology
影响因子：
2.2
作者：
Shibamura-Fujiogi M;Ormsby J;Breibart M;Warf B;Priebe GP;Soriano SG;Sandora TJ;Yuki K
通讯作者：
Yuki K

GltS regulates biofilm formation in methicillin-resistant Staphylococcus aureus.