Department of Biomedical Engineering, University at Buffalo, Buffalo, New York, USA.
Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
mSphere. 2019 May 1;4(3):e00178-19. doi: 10.1128/mSphere.00178-19.
Periprosthetic joint infection (PJI) develops clinically, even with antibiotic treatment, and methicillin-resistant (MRSA) and are predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can perpetuate resistance, further complicating the use of noninvasive treatments. This study evaluated cathodic-voltage-controlled electrical stimulation (CVCES) of titanium, in combination with a clinically relevant antibiotic, to synergistically prevent MRSA and PJIs by inhibiting bacterial adherence or as a treatment for eradicating established biofilms. CVCES of -1.0 V, -1.5 V, or -1.8 V (versus Ag/AgCl), with or without vancomycin for MRSA or gentamicin for , was applied to sterile titanium incubated with cultures to evaluate prevention of attachment or eradication of preestablished biofilms. Treatments were 24 h long and included open-circuit potential controls, antibiotic alone, CVCES, and CVCES plus antibiotic. Biofilm-associated and planktonic CFU were enumerated. In general, CVCES at -1.8 V alone or with antibiotic completely eradicated biofilm-associated CFU for both strains, and these parameters were also highly effective against planktonic bacteria, resulting in a >6-log reduction in MRSA and no detectable planktonic All CFU were reduced ∼3 to 5 logs from controls for prevention CVCES plus antibiotics at -1.0 V and -1.5 V against MRSA. Remarkably, there were no detectable CFU following prevention CVCES at -1.0 V or -1.5 V with gentamicin. Our results suggest that CVCES in combination with antibiotics may be an effective approach for prevention and treatment of PJI. Periprosthetic joint infections (PJIs) develop clinically in the presence of antibiotic therapies and are responsible for increased patient morbidity and rising health care costs. Many of these infections involve bacterial biofilm formation on orthopedic hardware, and it has been well established that these biofilms are refractory to most antibiotic treatments. Recent studies have focused on novel methods to prevent and eradicate infection. Cathodic-voltage-controlled electrical stimulation (CVCES) has previously been shown to be effective as a method for prevention and eradication of Gram-positive and Gram-negative infections. The present study revealed that the utility of CVCES for prevention and eradication of methicillin-resistant and is enhanced in the presence of clinically relevant antibiotics. The synergistic effects of CVCES and antibiotics are effective in a magnitude-dependent manner. The results of this study indicate a promising alternative method to current PJI mitigation techniques.
假体周围关节感染(PJI)即使在抗生素治疗下也会在临床上发展,耐甲氧西林金黄色葡萄球菌(MRSA)和 是这些感染的主要原因。由于生物膜的形成,PJI 患者的抗生素治疗会导致耐药性持续存在,进一步使非侵入性治疗复杂化。本研究评估了钛的阴极电压控制电刺激(CVCES)与临床相关抗生素联合使用,通过抑制细菌黏附或作为根除已建立生物膜的治疗方法,协同预防 MRSA 和 。CVCES 为 -1.0 V、-1.5 V 或-1.8 V(相对于 Ag/AgCl),联合或不联合万古霉素用于 MRSA 或庆大霉素用于 ,用于孵育有培养物的无菌钛,以评估预防附着或根除预先建立的生物膜。治疗时间为 24 小时,包括开路电位对照、单独使用抗生素、CVCES 和 CVCES 加抗生素。对生物膜相关和浮游 CFU 进行计数。一般来说,CVCES 单独在 -1.8 V 或与抗生素一起可完全根除两种菌株的生物膜相关 CFU,并且这些参数对浮游细菌也非常有效,导致 MRSA 减少 6 个对数级以上,浮游菌无法检测到 所有 CFU 与对照相比,预防 CVCES 加抗生素在 -1.0 V 和 -1.5 V 下针对 MRSA 减少了 3 至 5 个对数级。值得注意的是,在用庆大霉素进行预防 CVCES 时,-1.0 V 或 -1.5 V 时没有检测到 存活 CFU。我们的结果表明,CVCES 联合抗生素可能是预防和治疗 PJI 的有效方法。假体周围关节感染(PJIs)在抗生素治疗的情况下临床上会发展,导致患者发病率增加和医疗保健成本上升。这些感染中有许多涉及骨科硬件上的细菌生物膜形成,并且已经证实这些生物膜对大多数抗生素治疗具有抗药性。最近的研究集中在预防和消除感染的新方法上。阴极电压控制电刺激(CVCES)先前已被证明是预防和消除革兰氏阳性和革兰氏阴性感染的有效方法。本研究表明,在存在临床相关抗生素的情况下,CVCES 预防和消除耐甲氧西林金黄色葡萄球菌和 的效果得到增强。CVCES 和抗生素的协同作用以剂量依赖性方式有效。本研究的结果表明,这是一种有前途的替代当前 PJI 缓解技术的方法。