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静态与活动间隔物:感染病原体类型是否影响治疗成功率?

Static Versus Articulating Spacer: Does Infectious Pathogen Type Affect Treatment Success?

机构信息

Duke University School of Medicine, Durham, NC, USA.

Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.

出版信息

Clin Orthop Relat Res. 2024 Oct 1;482(10):1850-1855. doi: 10.1097/CORR.0000000000003075. Epub 2024 Apr 25.

Abstract

BACKGROUND

Treatment with a static or an articulating antibiotic-containing spacer is a common strategy for treating periprosthetic joint infection (PJI), yet many patients have persistent infections after spacer treatment. Although previous studies have compared the efficacy of a static and articulating spacer for treating PJI, few studies have assessed infection control from the time of spacer implantation, or they defined treatment failure as including reinfection, reoperation, or chronic suppressive therapy. Additionally, few studies have examined whether there is an interaction between spacer and pathogen type with respect to treatment success.

QUESTIONS/PURPOSES: (1) Is there a difference in failure-free survival (defined as no reoperation, reinfection, or suppressive antibiotic therapy) between static and articulating spacers after spacer implantation for PJI? (2) Did the relationship between spacer type and failure-free survival differ by pathogen type (staphylococcal versus nonstaphylococcal and difficult-to-treat [including methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus , Corynebacterium, Mycobacterium, Enterococcus spp , and other gram-negative bacterium] versus not-difficult-to-treat organisms)?

METHODS

Between January 2014 and January 2022, a convenience sample of 277 patients was identified as having knee PJIs treated with an articulating (75% [208 of 277]) or static (25% [69 of 277]) antibiotic spacer and potentially eligible for this study. During that time, providers at our institution generally used spacers for later-presenting or chronic infections. Spacer choice was determined by surgeon preference, with static spacers used more often in instances of higher bone loss and poor soft tissue coverage. Thirty-one patients (8 static and 23 articulating spacers) were considered lost to follow-up or had incomplete datasets and were excluded from the analysis, resulting in a final analysis cohort of 246 patients: 25% (61 of 246) received a static spacer and 75% (185 of 246) received an articulating spacer. The mean ± standard deviation age of patients was 66 ± 9.9 years, BMI was 33.3 ± 6.9 kg/m 2 , and Elixhauser score was 18.1 ± 16.9. Demographic and clinical characteristics were similar between the two groups. Pathogen type was collected and categorized as staphylococcal versus nonstaphylococcal , and difficult-to-treat (including methicillin-resistant Staphylococcus aureus , methicillin-susceptible S. aureus , Corynebacterium, Mycobacterium, Enterococcus spp , and other gram-negative bacterium) versus not-difficult-to-treat, as defined by an infectious disease physician. Other variables we collected included sex, age, American Society of Anesthesiologists classification, BMI, and Elixhauser score. The primary outcome of interest was failure-free survival, which was a composite time-to-event outcome, with failure defined as reoperation, reinfection, death owing to infection, or chronic antibiotic use at a minimum of 1 year after the completion of the patient's Stage 1 postoperative antibiotic course, whichever came first. Reinfection was determined by the treating physicians in accordance with the Musculoskeletal Infection Society guidelines and included an evaluation of infectious laboratory values, cultures, and clinical signs of infection. We compared static and articulating spacers using a Cox proportional hazards model, with spacer type as the primary predictor variable. We compared staphylococcal versus nonstaphylococcal and difficult-to-treat versus not-difficult-to-treat infections by running additional models with interaction terms between spacer type and pathogen type.

RESULTS

No difference was observed in the cause-specific hazard ratio for static versus articulating (reference) spacers (HR 1.45 [95% confidence interval 0.94 to 2.22]; p = 0.09), after adjusting for covariates. Additionally, no difference in the association between spacer type and failure-free survival was found between pathogen types or treatment difficulty after evaluating interactions (staphylococcal HR 0.37 [95% CI 0.15 to 0.91], nonstaphylococcal HR 0.79 [95% CI 0.49 to 1.28]; p value for interaction = 0.14; difficult-to-treat HR 0.37 [95% CI 0.14 to 0.99], not-difficult-to-treat HR 0.75 [95% CI 0.47 to 1.20]; p value for interaction = 0.20).

CONCLUSION

The lack of a difference in failure-free survival and insufficient evidence of a difference in the association between spacer type and treatment failure by pathogen type suggests that infectious organism may not be an important consideration in the decision about spacer treatment type. Further studies should aim to elucidate which patient factors are the most influential in surgeon decision-making when choosing a spacer type in patients with PJI of the knee.Level of Evidence Level III, therapeutic study.

摘要

背景

使用含抗生素的静态或可活动间隔物治疗假体周围关节感染(PJI)是一种常见策略,但许多患者在间隔物治疗后仍存在持续性感染。尽管以前的研究比较了静态和可活动间隔物治疗 PJI 的疗效,但很少有研究评估从间隔物植入时起的感染控制情况,或者将治疗失败定义为包括再感染、再手术或慢性抑制性治疗。此外,很少有研究检查间隔物和病原体类型之间是否存在与治疗成功相关的相互作用。

问题/目的:(1)在 PJI 患者中植入静态和可活动间隔物后,在没有再手术、再感染或抑制性抗生素治疗的情况下,失败无生存(定义为无再手术、再感染或抑制性抗生素治疗)之间是否存在差异?(2)病原体类型(葡萄球菌与非葡萄球菌和难治疗[包括耐甲氧西林金黄色葡萄球菌、甲氧西林敏感金黄色葡萄球菌、棒状杆菌、分枝杆菌、肠球菌属和其他革兰氏阴性菌]与非难治疗生物体)与失败无生存之间的关系是否因间隔物类型而异?

方法

在 2014 年 1 月至 2022 年 1 月期间,我们方便地确定了 277 名患有膝关节 PJI 的患者,他们接受了可活动(75%[208/277])或静态(25%[69/277])抗生素间隔物治疗,并且可能符合本研究的条件。在此期间,我们机构的提供者通常在出现较晚或慢性感染时使用间隔物。间隔物的选择取决于外科医生的偏好,在存在更高的骨丢失和软组织覆盖不良的情况下,更常使用静态间隔物。31 名患者(8 名静态和 23 名可活动间隔物)被认为随访丢失或数据集不完整,并从分析中排除,最终分析队列包括 246 名患者:25%(61/246)接受静态间隔物,75%(185/246)接受可活动间隔物。患者的平均年龄为 66±9.9 岁,BMI 为 33.3±6.9kg/m2,Elixhauser 评分是 18.1±16.9。两组之间的人口统计学和临床特征相似。病原体类型分为葡萄球菌和非葡萄球菌,难治疗(包括耐甲氧西林金黄色葡萄球菌、甲氧西林敏感金黄色葡萄球菌、棒状杆菌、分枝杆菌、肠球菌属和其他革兰氏阴性菌)和非难治疗,由传染病医生定义。我们收集的其他变量包括性别、年龄、美国麻醉师协会分类、BMI 和 Elixhauser 评分。主要观察结果是失败无生存,这是一个复合时间事件结局,失败定义为再手术、再感染、因感染而死亡或在完成患者第 1 期术后抗生素疗程后至少 1 年内慢性使用抗生素,以先发生者为准。再感染由治疗医生根据肌肉骨骼感染协会指南确定,并包括评估感染性实验室值、培养物和感染的临床体征。我们使用 Cox 比例风险模型比较了静态和可活动间隔物,间隔物类型是主要预测变量。我们通过运行具有间隔物类型和病原体类型之间交互项的附加模型,比较了葡萄球菌与非葡萄球菌和难治疗与非难治疗感染。

结果

在调整了协变量后,静态与可活动(参考)间隔物之间的原因特异性风险比没有差异(HR 1.45[95%置信区间 0.94 至 2.22];p=0.09)。在评估相互作用后,我们也没有发现间隔物类型和失败无生存之间的关联在病原体类型或治疗难度方面存在差异(葡萄球菌 HR 0.37[95%置信区间 0.15 至 0.91],非葡萄球菌 HR 0.79[95%置信区间 0.49 至 1.28];p 值交互作用=0.14;难治疗 HR 0.37[95%置信区间 0.14 至 0.99],非难治疗 HR 0.75[95%置信区间 0.47 至 1.20];p 值交互作用=0.20)。

结论

失败无生存无差异,且间隔物类型与治疗失败之间的关联证据不足,提示病原体可能不是膝关节 PJI 患者间隔物治疗类型决策中的重要考虑因素。进一步的研究应旨在阐明在膝关节 PJI 患者中,哪些患者因素对外科医生选择间隔物类型的决策最有影响。

水平的证据

III 级,治疗性研究。

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