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N-乙酰半胱氨酸作为骨水泥佐剂防治人工关节周围感染的体外疗效和生物相容性初步研究。

N-acetylcysteine use as an adjuvant to bone cement to fight periprosthetic joint infections: A preliminary in vitro efficacy and biocompatibility study.

机构信息

Rothman Orthopaedic Institute, Philadelphia, Pennsylvania, USA.

出版信息

J Orthop Res. 2021 Feb;39(2):356-364. doi: 10.1002/jor.24910. Epub 2020 Nov 25.

Abstract

When antibiotic laden bone cement is used to manage periprosthetic joint infection (PJI), failure still occurs with its use in up to 30% of cases. Therefore, we designed an in vitro study to assess the bactericidal effect of N-acetylcysteine (NAC), an antibacterial adjuvant, in cement against planktonic and biofilm forms of common PJI pathogens. NAC (10%, 20%, 30%, 40%, and 50% w/v) added to polymethyl methacrylate (PMMA) and incubated in broth at 36°C. PMMA-alone and/or culture bacteria alone were used as a negative control. Aliquots of cement elution from each group were taken at 1 day and 1 week and then were investigated for antimicrobial efficacy against the planktonic-form and the biofilm-form of Staphylococcus aureus and Escherichia coli. The primary outcome was the residual colony-forming unit count. The cytotoxicity and mechanical properties of the NAC-PMMA cement-blocks were also assessed. NAC-PMMA efficacy against the planktonic bacteria was demonstrated at a minimum of 30% at Day 1 and a minimum of 20% at 1 week after (p < .001). NAC-PMMA cement was effective against biofilm at a minimum of 30% of NAC at 1 day and 1 week of cement immersion (p < .001). The PMMA alone group was identified as having the highest cytotoxicity (p < .001). NAC decreased the stiffness (p = .004) and maximum load breaking point of the cement (p = .029). NAC is an effective and biocompatible adjuvant to PMMA in terms of antibacterial activity against Staphylococcus aureus and Escherichia coli. The broad antibacterial spectrum of NAC, its low expense, and minimal cytotoxicity makes it an ideal agent for addition to PMMA cement.

摘要

当使用含抗生素的骨水泥来治疗假体周围关节感染(PJI)时,即使使用这种方法,仍有高达 30%的病例会出现治疗失败。因此,我们设计了一项体外研究,以评估 N-乙酰半胱氨酸(NAC)作为一种抗菌佐剂在对抗常见 PJI 病原体的浮游生物和生物膜形式方面对抗生素骨水泥的杀菌效果。将 NAC(10%、20%、30%、40%和 50%w/v)添加到聚甲基丙烯酸甲酯(PMMA)中,并在 36°C 的肉汤中孵育。PMMA 单独和/或单独培养细菌作为阴性对照。从每组水泥洗脱的等分试样在第 1 天和第 1 周进行采集,并用于研究其对金黄色葡萄球菌和大肠杆菌浮游生物形式和生物膜形式的抗菌功效。主要结果是残留的菌落形成单位计数。还评估了 NAC-PMMA 水泥块的细胞毒性和机械性能。在第 1 天,NAC-PMMA 对浮游细菌的疗效至少为 30%,在第 1 周时至少为 20%(p<0.001)。在第 1 天和第 1 周的水泥浸泡时,NAC-PMMA 水泥对生物膜的疗效至少为 30%的 NAC(p<0.001)。单独的 PMMA 组被确定为具有最高的细胞毒性(p<0.001)。NAC 降低了水泥的刚度(p=0.004)和最大负荷破坏点(p=0.029)。NAC 是 PMMA 的有效且具有生物相容性的佐剂,在针对金黄色葡萄球菌和大肠杆菌的抗菌活性方面。NAC 的广谱抗菌谱、低廉的费用和最小的细胞毒性使其成为 PMMA 水泥的理想添加物。

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