表皮葡萄球菌引起假体周围感染的生物膜形成机制

关节假体周围感染是人工关节置换术后严重的并发症之一。流行病学研究发现,表皮葡萄球菌是导致假体周围感染的最主要致病菌之一。感染过程中,细菌通过在植入物表面定植形成生物膜,从而有效逃避抗生素和宿主免疫反应,并通过群体感应系统调节生物膜的成长过程。该文就表皮葡萄球菌引起假体周围感染的生物膜形成机制作一综述。     

血清炎症指标在髋关节置换术后慢性假体周围感染中的诊断作用

目的 验证髋关节置换患者术后血清炎症指标在慢性假体周围感染早期诊断中的价值。方法 选取2020年1月至2022年1月期间于医院行髋关节置换术者148例进行研究,其中慢性假体周围感染者9例（对照组）、无菌性松动7例（观察组）。检测两组患者术前血清炎症学指标,并评价各项指标对慢性假体周围感染的诊断价值。结果 对照组患者术前D-二聚体、C-反应蛋白（CRP）以及红细胞沉降率（ESR）水平,明显高于观察组各项对应指标水平,P<0.05。D二聚体、CRP、ESR诊断慢性假体周围感染的AUC值分别为,P<0.05。结论 检测患者D-二聚体对诊断慢性假体周围感染有较高价值,且CRP、ESR在慢性假体周围感染诊断中也具有一定价值,但特异度较低,因此不能作为诊断依据,但可为临床诊治提供可靠依据。     

人工关节周围感染性生物膜的组织学观察

目的通过动物实验探索人工关节假体周围感染性生物膜的组成及生物膜在假体感染中的机制。方法以健康成年ＳＤ大鼠为研究对象,在置入假体的关节内注入ＳＬ－７６或Ｇ２亚型的表皮葡萄球菌,一周后以其表面的生物膜做细菌培养以断定是否存在感染。并利用ＨＥ、革兰氏。甲苯胺蓝。奥辛蓝－ＰＡＳ染色等方法观察所有生物膜的组织切片。结果所有的假体表面均有生物膜形成,感染性生物膜中有大量的成纤维细胞、炎性细胞、纤维蛋白以及葡萄球菌,在表皮葡萄球菌ＳＬ－７６组中尚有大量奥辛蓝染色呈蓝染的细胞外多粘质物质（ＥＳＳ）,而表皮葡萄球菌Ｇ２组则缺乏这种物质。结论ＥＳＳ可能是促进假体相关感染的关键性物质。     

血清学炎性因子在假体周围感染中的应用

目的通过检测由于各种原因接受关节翻修手术患者血清中C-反应蛋白(CRP)、动态红细胞沉降率(ESR)、超敏C-反应蛋白(hs-CRP)及白细胞介素-6(IL-6),探讨其在诊断假体周围感染中的临床意义与诊断价值。方法选取2013年8月至2016年8月于北京大学人民医院骨关节科接受关节翻修手术的患者160例,符合美国肌肉与骨骼肌感染协会(MSIS)制定的假体周围感染诊断标准的患者为感染组,不符合者为非感染组,测量患者的血清中CRP、ESR、hs-CRP及IL-6水平,并通过受试者工作特征曲线-曲线下面积(ROC-AUC)分析评估各指标诊断假体周围感染的临床意义与价值。结果血清学炎性指标CRP、ESR、hs-CRP及IL-6水平感染组较非感染组高(P0.01),其AUC值为0.89(95%CI:0.83,0.94)、0.88(95%CI:0.82,0.93)、0.90(95%CI:0.84,0.95)及0.92(95%CI:0.89,0.96)。各指标之间无明显统计学差异。IL-6与CRP或hs-CRP平行试验联合诊断PJI敏感性高(敏感性分别为100.0%(93.9%,100.0%)和98.3%(90.9%,100.0%)),具有很好的应用价值。结论 CRP、ESR、hs-CRP和IL-6对于假体周围感染具有明确的诊断意义,其中IL-6的诊断价值可能更高。联合诊断能提高假体周围感染诊断的敏感性或者特异性。CRP与IL-6联合或者hs-CRP与IL-6联合对于排除假体周围感染临床意义更大。     

超声裂解法诊断关节置换术后假体周围感染研究进展

假体周围感染是关节置换术后最具破坏性的并发症之一。及时准确地作出临床诊断, 是治疗假体周围感染的重要环节。然而, 生物膜的形成限制了一些常规检测方法的应用, 大大降低了传统关节滑液培养和假体周围组织培养等方法的检出率。超声裂解法可通过空化作用的驱动, 在不破坏病原体活性的情况下破裂和剥离假体周围的生物膜释放出微生物, 极大地提高了培养检出率。本文就近年来假体周围感染、生物膜和超声裂解法相关文献进行综述, 旨在指导临床医生将超声裂解法用于假体周围感染的诊断。     

关节假体多重感染对金葡菌致病特性的影响

假体周围感染是关节置换术后严重的并发症，其中最常见的是金黄色葡萄球菌感染。然而，金葡菌经常与其他微生物在假体周围感染灶共存，迄今已有多篇文献报道金葡菌与其他微生物之间存在相互作用，包括凝固酶阴性葡萄球菌、铜绿假单胞菌以及白色念珠菌等。这些相互作用涉及影响生物膜形成能力、增加耐药性、改变毒力因子表达水平等。本文拟对关节假体多重感染对金葡菌致病特性的影响作简要综述。     

白介素-6对于早期诊断关节置换术后假体周围感染的意义

随着关节置换手术的开展,关节置换术后假体感染的患者数量不在少数,而关节置换术后假体周围感染无论对于患者还是医生都是一场灾难,如何能对关节置换术后假体感染进行早期诊断显得尤为重要。目前,C反应蛋白（CRP）和血沉（ESR）被认为是早期诊断假体周围感染的重要血清学手段,本文汇总分析国内外文献,通过C反应蛋白,血沉与白介素-6（IL-6）的对比,发现白介素-6具有较高的特异性,敏感性和准确性,是早期诊断假体周围感染血清学检查的一个有价值的补充。通过对关节置换术后假体周围感染早期诊断的研究进展作出综述,旨在为临床工作提供参考。     

血清HBd-3、TNFα表达水平在全膝关节置换术后早期假体周围感染诊断中的意义

目的研究血清β-防御素-3(HBd-3)、肿瘤坏死因子α(TNFα)表达水平在全膝关节置换术后早期假体周围感染诊断中的意义。方法感染组纳入自2011-02—2018-11全膝关节置换术后早期假体周围感染92例,选取同期全膝关节置换术后未感染92例作为对照组。比较组内术前、术后1 d、术后3 d、术后7 d血清HBd-3蛋白与TNFα水平,比较组间术后1 d、术后3 d、术后7 d血清HBd-3蛋白与TNFα水平,比较组间术后3 d血清CRP、ESR、WBC。结果感染组与对照组术后1 d血清HBd-3蛋白、TNFα水平较术前明显升高,感染组术后3 d、术后7 d持续升高,而对照组术后3 d恢复到术前水平。感染组术后1 d血清HBd-3水平低于对照组,但术后3 d、术后7 d血清HBd-3水平明显高于对照组;感染组术后1 d、术后3 d、术后7 d血清TNFα水平明显高于对照组;感染组术后3 d血清CRP、ESR、WBC水平明显高于对照组,差异有统计学意义(P 0.05)。全膝关节置换术后早期假体周围感染患者术后3 d血清HBd-3蛋白、TNFα水平与CRP、ESR、WBC呈正相关(P 0.05)。结论血清HBd-3、TNFα在全膝关节置换术后早期假体周围感染患者中表达水平较高,且与CRP、ESR、WBC水平呈正相关,可能对早期假体周围感染有一定的预测和诊断价值。     

关节液CRP对假体周围感染诊断价值的系统评价

目的系统评价关节液C反应蛋白(CRP)对于人工关节置换术后假体周围感染的诊断价值,并与血清CRP的诊断价值进行比较,为临床诊断和治疗提供依据。方法计算机检索PubMed、EMBase、Oivd、Scopus数据库关于关节液CRP诊断假体周围感染的文献,提取数据进行系统评价,合并灵敏度、特异度、阳性似然比、阴性似然比、诊断比值比,绘制综合受试者工作特征曲线(SROC),计算曲线下面积(AUC)、Q指数,比较关节液CRP组与血清CRP组诊断价值合并值的差异。结果纳入7篇文献,共469例,合并的灵敏度、特异度、阳性似然比、阴性似然比和诊断比值比分别为0.89、0.91、10.52、0.13、91.22,SROCAUC为0.957,Q指数为0.901。关节液CRP组诊断假体周围感染的敏感度、特异度、SROCAUC高于血清CRP组,差异有统计学意义(P 0.05)。结论关节液CRP诊断假体周围感染的临床价值较高,与检测血清CRP比较,关节液CRP诊断假体周围感染的敏感度、特异度更高。     

人工关节置换术后假体周围感染的生物膜研究进展

目的综述人工关节置换术后假体周围感染生物膜研究的最新进展。方法查阅近年有关人工关节术后感染及生物膜研究方面的最新文献,对于生物膜的形成、生物膜的耐药性、人工关节假体感染的诊断、治疗、预防的最新进展进行回顾,综合分析。结果生物膜是细菌在生物医学材料表面形成的特殊膜样结构,是假体周围感染诊断和治疗的焦点。生物膜可通过其中细菌的变异提高耐药性并不易检测诊断。目前已有声波降解基因检测等手段进行诊断。而假体涂层的载药设计是预防生物膜形成的有效方法。结论针对生物膜的生物学特性进行积极的预防,早期的诊断和恰当的治疗,是假体周围感染诊治的关键所在。应用新技术检测辅助诊断和将“自清洁表面”预防生物膜形成,可能是诊治假体周围感染的突破点。     

Pulse Lavage is Inadequate at Removal of Biofilm from the Surface of Total Knee Arthroplasty Materials

In acute periprosthetic infection, irrigation and debridement with component retention has a high failure rate in some studies. We hypothesize that pulse lavage irrigation is ineffective at removing biofilm from total knee arthroplasty (TKA) components. Staphylococcus aureus biofilm mass and location was directly visualized on arthroplasty materials with a photon collection camera and laser scanning confocal microscopy. There was a substantial reduction in biofilm signal intensity, but the reduction was less than a ten-fold decrease. This suggests that irrigation needs to be further improved for the removal of biofilm mass below the necessary bioburden level to prevent recurrence of acute infection in total knee arthroplasty.     

Treatment of stage III-A-1 and III-B-1 periprosthetic knee infection with two-stage exchange arthroplasty and articulating spacer

The incidence of periprosthetic knee infection is generally low, but the economic impact is great. Treatment should take into account the acuteness of the infection, the overall immune/medical status of the patient, and the local factors at the site of the infection. The aim of this study was to evaluate the two-phase exchange arthroplasty with the use of antibiotic-impregnated articulating spacer, as an alternative treatment of chronic periprosthetic knee infection in patients with minimum systemic and no local compromising factors. Staphylococcus aureus was the most common pathogen followed by Staphylococcus epidermidis and Pseudomonas aeruginosa. Twenty-four patients were treated with this regiment. All of them returned to normal everyday activity and no infection recurrence was noted over a 2- to 10-year follow-up. Excellent long-term results can be achieved for patients staged as III-A-1 and III-B-1 according to the Musculoskeletal Infection Society staging system, when treated with the aforementioned protocol and intravenous antibiotics.     

Detection of bacteria with molecular methods in prosthetic joint infection: sonication fluid better than periprosthetic tissue

Background and purpose — The correct diagnosis of prosthetic joint infection (PJI) can be difficult because bacteria form a biofilm on the surface of the implant. The sensitivity of culture from sonication fluid is better than that from periprosthetic tissue, but no comparison studies using molecular methods on a large scale have been performed. We assessed whether periprosthetic tissue or sonication fluid should be used for molecular analysis. Patients and methods — Implant and tissue samples were retrieved from 87 patients who underwent revision operation of total knee or total hip arthroplasty. Both sample types were analyzed using broad-range (BR-) PCR targeting the 16S rRNA gene. The results were evaluated based on the definition of periprosthetic joint infection from the Workgroup of the Musculoskeletal Infection Society. Results — PJI was diagnosed in 29 patients, whereas aseptic failure was diagnosed in 58 patients. Analysis of sonication fluid using BR-PCR detected bacteria in 27 patients, whereas analysis of periprosthetic tissue by BR-PCR detected bacteria in 22 patients. In 6 of 7 patients in whom BR-PCR analysis of periprosthetic tissue was negative, low-virulence bacteria were present. The sensitivity and specificity values for periprosthetic tissue were 76% and 93%, respectively, and the sensitivity and specificity values for sonication fluid were 95% and 97%. Interpretation — Our results suggest that sonication fluid may be a more appropriate sample than periprosthetic tissue for BR-PCR analysis in patients with PJI. However, further investigation is required to improve detection of bacteria in patients with so-called aseptic failure.     

Results of one-stage endoprosthesis revision in periprosthetic infection cause by methicillin-resistant Staphylococcus aureus

OBJECTIVE: Are the results of one-stage exchange arthroplasties to treat periprosthetic infection caused by methicillin-resistant Staphylococcus aureus (MRSA) comparable to bacteriologically unselected studies of one-stage exchange operations? METHOD: From 1996 to 1997 twenty patients with a periprosthetic infection caused by methicillin-resistant Staphylococcus aureus (MRSA) were treated at the ENDO-Klinik by an one-stage exchange arthroplasty. Mean follow-up of fifteen one-stage exchange total hip replacements and 5 one-stage exchange total knee replacements was 16 months. The patients were examined by means of clinical, laboratory-chemical and radiological tests. In addition, postoperative joint aspiration was performed on 14 patients. RESULTS: In 11 cases (61%) the periprosthetic infection was treated successfully with only one one-stage exchange operation. In cases with persisting infection the period between the first exchange arthroplasty and the repeated clinical manifestation of the infection (second exchange operation) was 2 months on average. 93% of the joint aspirations (n = 14), performed on average 4 weeks postoperatively, correlated with the result of the follow-up tests. CONCLUSION: Periprosthetic infection with MRSA is a problematic infection. Because of the reduced therapeutic possibilities it is associated with a higher rate of recurrence than the unselected group of patients as a whole [6, 11, 16, 17, 19, 20]. The authors recommend one-stage exchange arthroplasty using a combination of vancomycin and ofloxacin as admixture to polymethylmethacrylat (Refobacin Palacos R). This procedure does, however, need further development. Intraoperative use of an antiseptic and systemic administration of rifampicin, as recommended by Zimmerli [23] is a further possibility.     

Complete Eradication of Biofilm From Orthopedic Materials

Background

Interest exists in finding alternatives to current management strategies in periprosthetic joint infections, which typically include a 2-stage revision with placement of an antibiotic spacer and delayed placement of a new implant. We studied the efficacy of autoclaving, ultrasonication, and mechanical scrubbing for sterilization and biofilm eradication on infected cobalt-chrome discs.

Removed Antibiotic-Impregnated Cement Spacers in Two-Stage Revision Joint Arthroplasty Do Not Show Biofilm Formation In Vivo

Use of antibiotic-impregnated spacers is common in the two-stage approach to treatment of periprosthetic joint infection despite the lack of information regarding in vivo performance of these implants. Antibiotic elution levels likely often fall below the minimal inhibitory concentration need to inhibit bacterial growth, raising concern that the spacers themselves may provide a potential attachment site for biofilm formation. Advanced microscopy was used in this study to evaluate the surface characteristics of antibiotic-eluting spacers collected at the time of prosthesis reimplantation from 6 patients undergoing two-stage treatment for an infected total joint arthroplasty. Scanning electron microscopy and confocal scanning microscopy of the removed spacers revealed modest fibrous matrix formation and inflammatory cells with no biofilm or bacteria detected. This study supports the continued use of antibiotic spacers in the treatment of periprosthetic joint infection.     

Berberine inhibits Staphylococcus Epidermidis adhesion and biofilm formation on the surface of titanium alloy

Biofilm formed by Staphylococcus epidermidis (S. epidermidis) is a common cause of periprosthetic infection. Recently, we have discovered that berberine is bacteriostatic for S. epidermidis. The purpose of the present study was to examine the effect of berberine on S. epidermidis adhesion and biofilm formation on the surface of titanium alloy, which is a popular material for orthopedic joint prostheses. Three strains of S. epidermidis (ATCC 35984, ATCC 12228, and SE 243) were used for in vitro experiment. Direct colony counting showed that berberine significantly inhibited S. epidermidis adhesion on the titanium alloy disk in 2 h at the concentration of 45 µg/mL. When examined with crystal violet staining, confocal laser scanning microscopy, and scanning electron microscopy, we found that higher concentrations (>30 µg/mL) of berberine effectively prevented the formation of S. epidermidis biofilm on the surface of the titanium disk in 24 h. These findings suggest that berberine is a potential agent for the treatment of periprosthetic infection. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1487–1492, 2009     

假体周围高糖环境对葡萄球菌感染影响的实验研究

目的 探讨假体周围高糖环境对葡萄球菌生长和细菌生物膜形成的影响.方法 利用新西兰大白兔建立假体感染的动物模型,分为金黄色葡萄球菌组(金葡菌组,n=40)和表皮葡萄球菌组(表葡菌组,n=60),每组再随机分为实验组和对照组,实验组注入细菌的同时加入0.1ml质量浓度为1%的葡萄糖溶液,对照组加入0.1 ml生理盐水.金葡菌组分别于第2、4、6和8天观察;表葡菌组分别于2、4、6、8、12和16天观察.对不同时间点的膝关节假体感染动物行细菌计数、扫描电镜和组织学观察.结果 金葡菌组第2天实验组和对照组关节液细菌计数差异无统计学意义(P=0.426),注入细菌后第4、6和8天实验组较对照组细菌生长明显增强,差异均有统计学意义(P<0.05).扫描电镜观察第2、4、6天实验组较对照组假体表面黏附细菌明显增多(P<0.05),细菌生物膜生成明显.组织学观察第2天实验组假体周围组织发现细菌,而对照组未发现细菌.表葡菌组第2、4、6、8、12和16天实验组与对照组细菌计数差异均无统计学意义(P>0.05),假体表面黏附细菌没有明显区别(P>0.05).组织学观察第2天实验组和对照组假体周围组织均未发现细菌.结论 假体周围高糖环境对金葡菌感染影响明显,而对表葡菌感染影响不明显.     

Periprosthetic infections after shoulder hemiarthroplasty

BACKGROUND: To examine the rates and predictors of deep periprosthetic infections after shoulder hemiarthroplasty. METHODS: We used prospectively collected institutional registry data on all primary shoulder hemiarthroplasty patients from 1976-2008. We estimated survival free of deep periprosthetic infections using Kaplan-Meier survival curves. Using univariate Cox regression analyses, we examined the association of patient-related factors (age, sex, body mass index), comorbidity (Deyo-Charlson index), American Society of Anesthesiologists grade, underlying diagnosis, and implant fixation with the risk of infection. RESULTS: A total of 1,349 patients, with a mean age of 63 years (SD, 16 years), 63% of whom were women, underwent 1,431 primary shoulder hemiarthroplasties. Mean follow-up was 8 years (SD, 7 years). Fourteen deep periprosthetic infections occurred during the follow-up, confirmed by medical record review. The most common organisms were Staphylococcus aureus, coagulase-negative Staphylococcus, and Propionibacterium acnes, each accounting for 3 cases (21% each). The 5-, 10-, and 20-year prosthetic infection-free rates were 98.9% (95% confidence interval [CI], 98.3%-99.5%), 98.7% (95% CI, 98.1%-99.4%), and 98.7% (95% CI, 98.1%-99.4%), respectively. None of the factors evaluated were significantly associated with risk of prosthetic infection after primary shoulder hemiarthroplasty, except that an underlying diagnosis of trauma was associated with a significantly higher hazard ratio of 3.18 (95% CI, 1.06-9.56) for infection compared with all other diagnoses (P = .04). A higher body mass index showed a non-statistically significant trend toward an association with higher hazard (P = .13). CONCLUSION: The periprosthetic infection rate after shoulder hemiarthroplasty was low, estimated at 1.3% at 20-year follow-up. An underlying diagnosis of trauma was associated with a higher risk of periprosthetic infection. These patients should be observed closely for development of infection.