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钛的阴极电压控制电刺激预防耐甲氧西林金黄色葡萄球菌和鲍曼不动杆菌生物膜感染

Cathodic voltage-controlled electrical stimulation of titanium for prevention of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii biofilm infections.

作者信息

Canty Mary, Luke-Marshall Nicole, Campagnari Anthony, Ehrensberger Mark

机构信息

Department of Biomedical Engineering, University at Buffalo, 445 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA.

Department of Microbiology and Immunology, University at Buffalo, 140 Biomedical Research Building, 3435 Main Street, Buffalo, NY 14214, USA.

出版信息

Acta Biomater. 2017 Jan 15;48:451-460. doi: 10.1016/j.actbio.2016.11.056. Epub 2016 Nov 24.

DOI:10.1016/j.actbio.2016.11.056
PMID:27890730
Abstract

UNLABELLED

Antibiotic resistance of bacterial biofilms limits available treatment methods for implant-associated orthopaedic infections. This study evaluated the effects of applying cathodic voltage-controlled electrical stimulations (CVCES) of -1.5V and -1.8V (vs. Ag/AgCl) to coupons of commercially pure titanium (cpTi) incubated in cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii (A. baumannii) as a method of preventing bacterial attachment. Stimulations were applied for 2, 4, and 8h and coupon-associated and planktonic colony-forming units (CFU) were enumerated following stimulation. Compared to open circuit potential (OCP) controls, CVCES for 4h at -1.8V significantly reduced coupon-associated MRSA CFU by 99.9% (1.30×10vs. 4.45×10, p=0.047) and A. baumannii coupon-associated CFU by 99.9% (1.64×10vs. 5.93×10, p=0.001) and reduced planktonic CFU below detectable levels for both strains. CVCES at -1.8V for 8h also reduced coupon-associated and planktonic CFU below detectable levels for each strain. CVCES at -1.5V for 4 and 8h, and -1.8V for 2h did not result in clinically relevant reductions. For 4 and 8h stimulations, the current density was significantly higher for -1.8V than -1.5V, an effect directly related to the rate of water and oxygen reduction on the cpTi surface. This significantly increased the pH, a suspected influence in decreased CFU viability. The voltage-dependent electrochemical properties of cpTi likely contribute to the observed antimicrobial effects of CVCES. This study revealed that CVCES of titanium could prevent coupon-associated and planktonic CFU of Gram-positive MRSA and Gram-negative A. baumannii from reaching detectable levels in a magnitude-dependent and time-dependent manner.

STATEMENT OF SIGNIFICANCE

Periprosthetic joint infection is a devastating outcome of total joint arthroplasty and has led to increased patient morbidity and rising healthcare costs. Current treatments are limited by the growing prevalence of antimicrobial resistant biofilms. Therefore, there is a growing interest in the prevention of bacterial colonization of implants. Previous work has shown that cathodic voltage-controlled electrical stimulation (CVCES) of titanium is effective both in vitro and in vivo as an antimicrobial strategy to eradicate established implant-associated biofilm infections. The present study revealed that CVCES of titanium coupons also has utility in preventing coupon-associated and planktonic colony-forming units of Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Acinetobacter baumannii from reaching detectable levels in a magnitude-dependent and time-dependent manner.

摘要

未标注

细菌生物膜的抗生素耐药性限制了植入相关骨科感染的可用治疗方法。本研究评估了施加-1.5V和-1.8V(相对于Ag/AgCl)的阴极电压控制电刺激(CVCES)对在耐甲氧西林金黄色葡萄球菌(MRSA)和鲍曼不动杆菌(鲍曼不动杆菌)培养物中孵育的商业纯钛(cpTi)试样的影响,以此作为一种防止细菌附着的方法。刺激施加2、4和8小时,刺激后对试样相关和浮游菌落形成单位(CFU)进行计数。与开路电位(OCP)对照相比,在-1.8V下进行4小时的CVCES可使试样相关的MRSA CFU显著降低99.9%(1.30×10对4.45×10,p = 0.047),使鲍曼不动杆菌试样相关CFU降低99.9%(1.64×10对5.93×10,p = 0.001),并使两种菌株的浮游CFU降低到检测水平以下。在-1.8V下进行8小时的CVCES也使每种菌株的试样相关和浮游CFU降低到检测水平以下。在-1.5V下进行4小时和8小时以及在-1.8V下进行2小时的CVCES未导致临床上相关的降低。对于4小时和8小时的刺激,-1.8V的电流密度显著高于-1.5V,这一效应与cpTi表面水和氧还原速率直接相关。这显著提高了pH值,这可能是CFU活力降低的一个影响因素。cpTi的电压依赖性电化学性质可能有助于观察到的CVCES的抗菌作用。本研究表明,钛的CVCES可以以剂量和时间依赖性方式防止革兰氏阳性MRSA和革兰氏阴性鲍曼不动杆菌的试样相关和浮游CFU达到可检测水平。

意义声明

假体周围关节感染是全关节置换术的一个毁灭性后果,导致患者发病率增加和医疗成本上升。当前的治疗方法受到抗菌耐药生物膜日益普遍的限制。因此,人们对预防植入物细菌定植的兴趣日益浓厚。先前的研究表明,钛的阴极电压控制电刺激(CVCES)作为一种根除已建立的植入相关生物膜感染的抗菌策略,在体外和体内均有效。本研究表明,钛试样的CVCES在以剂量和时间依赖性方式防止革兰氏阳性耐甲氧西林金黄色葡萄球菌和革兰氏阴性鲍曼不动杆菌的试样相关和浮游菌落形成单位达到可检测水平方面也具有作用。

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