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退变椎间盘感染的对照研究(DISC):一项多中心前瞻性病例对照研究。

Degenerate-disc infection study with contaminant control (DISC): a multicenter prospective case-control trial.

机构信息

School of Medical Sciences, University of New South Wales, Sydney, Australia; Neurosurgical Research Group (NSURG), Sydney, Australia.

School of Medical Sciences, University of New South Wales, Sydney, Australia; Neurosurgical Research Group (NSURG), Sydney, Australia; Department of Neurosurgery, Prince of Wales Public and Private Hospitals, Suite 7, Level 7, Randwick 2031, Australia.

出版信息

Spine J. 2020 Oct;20(10):1544-1553. doi: 10.1016/j.spinee.2020.03.013. Epub 2020 Apr 25.

DOI:10.1016/j.spinee.2020.03.013
PMID:32339766
Abstract

BACKGROUND

A bacterial cause of disc degeneration has evoked several controversies and, if true, would lead to a major shift in treatment paradigm. Earlier studies analyzing the relationship of bacterial disc infection within a degenerative cohort featured prolonged cultures susceptible to contamination. The degenerate-disc infection study with contaminant control (DISC) trial aims to investigate this theory further by examining infection rates using a non-degenerative control cohort in comparison to a degenerative internal control cohort and a sham cohort (sampling only sterile paraspinal tissue). To our knowledge, the current study is the largest evaluating the growth of organisms (or possible contamination rate) in paraspinal tissue if prolonged cultures are performed. Protocols on methodology have been previously published.

PURPOSE

(1) To investigate the infection rates across cohorts (degenerative vs. nondegenerative control; paraspinal and/or disc controls vs. combined sampling cohorts) using stringent standardized aseptic surgical technique and laboratory processing. (2) To compare our findings to that of the literature and make a statement in support and/or against a possible contamination theory to positive cultures.

STUDY DESIGN

Multicenter, multisurgeon case-control trial.

PATIENT SAMPLE

In all, 812 surgical samples were retrieved across a 3.5-year period (2013-2016) including 25 trauma controls (nondegenerative), 550 "disc and paraspinal" samples (degenerative cases with internal control), 190 disc-only samples (degenerative cases without internal control), and 46 paraspinal only controls (sham group).

OUTCOME MEASURES

Growth and/or Contamination rate (%) per cohort. Chi-square of growth in disc versus paraspinal samples as a means of examining the distribution of false positive and contaminant growth. The impact of previous injections and/or surgery on positive disc or paraspinal growth. Correlation of Modic changes with positive growth rates analyzed with the Kruskal-Wallis Test. The distribution of species in positive samples were also analyzed.

METHODS

The DISC trial is registered under Australian and New Zealand clinical trials registry-ACTRN12616000541404. Institutional ethics review was obtained (HREC northern sector 13/218) at the primary center and further centers (n=6) were recruited. Patients undergoing spinal surgery with discectomy were eligible for trial entry with tissue specimens obtained using strict aseptic technique for microbiological examination. All specimens were handled with sterile instruments only and by a fresh instrument to a sterile pot that was closed immediately. Separate pots were used for the disc and paraspinal tissue respectively with similar stringent processing during microbiological assessment. A cohort of the degenerative cases at one single institution also underwent an additional histopathological examination.

RESULTS

There was an expected significant difference in gender and age associated with the non-degenerative control group (due to trauma patients) compared with other cohorts. There was a higher percentage of positive-growth in the control group in comparison to the disc and paraspinal and disc only groups across positive disc growth (48% vs. 27% vs. 17%, p<.001). A similar infection rate was observed in the paraspinal samples across the equivalent controls (44% vs. 36% vs. 37%, p=.739). There was a significant difference in the proportions of positive growth with a large proportion of false positives (growth in both disc and paraspinal samples; p<.001). There was no difference in true positive growth between the case and control groups (16.0 vs. 7.7%, p=.112). These trends were preserved across all cohorts and when stratifying by spinal segment (cervical or lumbar). There was no correlation between Modic changes and positive disc culture growth (p=.398, n=144 samples). Cutibacterium (formerly Propionibacterium) acnes was the most dominant pathogen isolated, representing between 50% and 70% of positive disc and paraspinal specimens, followed by staphylococcal species.

CONCLUSIONS

Our study failed to find a difference in true infection rates between the nondegenerative and degenerative disc populations. These findings are suggestive of a contamination theory and against a common infective etiology in the setting of discogenic back and neck pain. We believe the rationale for antibiotic therapy in the management of discogenic back pain warrants further evidence to establish efficacy.

摘要

背景

椎间盘退变的细菌病因引起了一些争议,如果这是真的,将会导致治疗模式的重大转变。早期分析退变人群椎间盘感染关系的研究,其特征是延长了易受污染的培养时间。退变椎间盘感染研究与污染物控制(DISC)试验旨在通过比较非退变对照组、退变内部对照组和假对照组(仅采样无菌脊柱旁组织),进一步研究这一理论。据我们所知,目前的研究是评估脊柱旁组织中是否存在(或可能的污染率)生物体生长的最大研究,如果进行延长培养。之前已经发表了关于方法学的协议。

目的

(1)使用严格的无菌外科技术和实验室处理,调查各队列(退变与非退变对照组;脊柱旁和/或椎间盘对照与联合采样队列)的感染率。(2)将我们的发现与文献进行比较,并对阳性培养物支持和/或反对可能的污染理论做出陈述。

研究设计

多中心、多外科医生病例对照试验。

患者样本

共检索了 812 个手术样本,时间跨度为 3.5 年(2013-2016 年),包括 25 例创伤对照组(非退变)、550 例“椎间盘和脊柱旁”样本(退变病例的内部对照组)、190 例椎间盘样本(退变病例无内部对照组)和 46 例脊柱旁对照组(假对照组)。

结果

每个队列的生长和/或污染率(%)。分析椎间盘与脊柱旁样本生长差异的卡方检验,以检验假阳性和污染物生长的分布。先前的注射和/或手术对阳性椎间盘或脊柱旁生长的影响。用 Kruskal-Wallis 检验分析 Modic 变化与阳性生长率的相关性。对阳性样本中的物种分布也进行了分析。

方法

DISC 试验在澳大利亚和新西兰临床试验注册处(ACTRN12616000541404)注册。在主要中心和其他中心(n=6)获得了机构伦理审查。符合试验纳入标准的患者为接受椎间盘切除术的脊柱手术患者,采集组织标本进行微生物学检查。所有标本均使用无菌器械处理,用无菌器械将标本从一个无菌容器转移到另一个无菌容器,立即关闭容器。椎间盘和脊柱旁组织分别使用类似的严格处理方法进行微生物学评估。一个退变病例的单独队列还接受了额外的组织病理学检查。

结论

我们的研究未能发现非退变和退变椎间盘人群之间的真正感染率有差异。这些发现提示存在污染理论,而不是椎间盘源性颈腰痛的共同感染病因。我们认为,在管理椎间盘源性颈腰痛时,抗生素治疗的合理性需要进一步的证据来证实其疗效。

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