专题文献 人工髋关节置换：全髋、膝置换术后感染的诊治
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Evaluation and Management of the Infected Total Hip and Knee
全髋、膝置换术后感染的诊治
THOMAS F. MOYAD, MD, MPH; THOMAS THORNHILL, MD; DANIEL ESTOK, MD
Infections following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) can be a devastating complication leading to signifi cant morbidity. Multiple risk factors have been identifi ed including: 1) revision surgery, 2) rheumatoid arthritis, 3) diabetes mellitus, 4) obesity, 5) poor nutrition, 6) mmunosuppressive medications, and 7) presence of psoriatic skin lesions.1-3 Classifi cation systems devised to help guide treatment algorithms are primarily based on the duration of signs and symptoms. Therefore, early recognition and proper management of these infections is important, not only from a medicolegal standpoint, but it also has signifi cant public health implications. This review focuses on current diagnostic and management strategies, in particular with regards to single stage versus two staged resection arthroplasty for chronic hip and knee infections.
初次全髋、膝置换术后感染是可引起引起严重病废的可怕并发症。已证实的危险因素包括：1、翻修手术，2、类风湿性关节炎，3、糖尿病，4、肥胖，5、营养不良，6、使用免疫抑制剂，7、皮肤存在银屑病变。主要是依据临床表现病程的长短对感染进行分型，以指导治疗。因此，早期诊断并及时处理感染是重要的，不仅仅从医学角度是如此，而且还具有重要的公共卫生意义。本文综述目前初次全髋、膝膝置换术后感染的诊治策略，尤其是关于慢性髋、膝感染的一期和二期假体取出关节成形术。EPIDEMIOLOGY
Deep infection occurs in approximately 1% to 2 % of all primary total hip and knee arthroplasties.4 While the infection rate has remained fairly low over the past several decades, given the increasing number of total joints performed throughout the United States, total hip and knee infections create a signifi cant burden on our health care system. The institutional cost of treating an individual patient has been estimated to result in a net loss of $15,000 to $30,000. Furthermore, the cost of treating THA infections in the United States alone is approximately $200 million per year.5
Host factors such as diabetes, rheumatoid arthritis, and immune status are important considerations. However, revision surgery carries the highest risk of infection. Although the exact percent varies in the literature, revision surgery appears to carry two to three times the risk of infection versus primary THA and TKA.3
流行病学
所有初次全髋、膝置换的深部感染率约为1% 到 2 %。鉴于全美国关节置换越来越多, 近几十年来感染率其实相当低, 但全髋和膝感染给卫生系统造成沉重负担。据估计治疗一个病人所造成的净$15,000 到 $30,000。并且，每年仅仅治疗全髋置换感染的花费约2亿美元。
病人因素如糖尿病、类风湿性关节炎、免疫状态也要详细考虑。然而，翻修手术是引起感染的高危因素。虽然文献报告不一，但翻修手术的危险性是初次全髋、膝置换的2到3倍。
Prevention of infection is obviously an important consideration. A thorough history and physical examination to identify sources of potential infection, such as infected diabetic foot ulcers, is paramount prior to undergoing any arthroplasty surgery. Furthermore, a recent advisory statement provided by the American Academy of Orthopaedic Surgeons discussed routine prophylaxis with keflex, amoxicillin, or clindamycin (if penicillin allergic) for 2 years following THA or TKA prior to various procedures, such as dental cleaning.3 Routine prophylaxis after 2 years following THA or TKA may be also considered in some patients who have immune suppression due to certain medical conditions or immunosuppressive medications. Lastly, adding prophylactic antibiotics to cemented arthroplasties has been advocated, especially in revision surgery. 6 However, currently no studies conclusively demonstrate whether this technique lowers infection during primary THA and TKA surgery.
显然，预防感染是很重要的。在关节置换手术前，详细询问病史并仔细查体，确定如感染性糖尿病足溃疡可能感染源是至关重要的。最近AAOS建议在全髋、膝置换术后施行其它手术（如洁牙）前，常规预防性应用keflex、阿莫西林、或克林霉素（如果青霉素过敏）2年。在因疾病或使用免疫抑制剂而出现免疫抑制的一些病人，也可在全髋膝置换术后2年常规预防。最后，推荐在骨水泥型关节置换的骨水泥中添加预防性抗菌素，尤其在翻修手术。然而，目前没有研究能证实该技术降低初次全髋膝置换手术的感染。
ETIOLOGY
病因学
Staphylococcus epidermidis and Staphylococcus aureus are the two most common isolates found in infected total hip and knee arthroplasties. Some series point to S aureus as the most prevalent organism.7-10 Other series show that S epidermidis is the most common.11-15
表皮葡萄球菌和金黄色葡萄球菌是全髋膝置换术后感染中最多见的2类细菌。一些文献指出金黄色葡萄球菌最多见，另一些文献认为表皮葡萄球菌最多见。
Some common but less frequent organisms include Streptococcus species and gram negatives such as Pseudomonas, Klebsiella, and Escherichia coli. Occasionally, mixed infections with anaerobes like Enterococcus and Peptococcus are present. Finally, fungal infections such as Mycobacterium tuberculosis and Candida albicans are infrequent, but may be present, especially in the immune compromised host. An important consideration with regard to etiology is the virulence of the organism.
一些普通但不常见的微生物包括链球菌、革兰氏阴性菌如假单胞菌、克雷白菌、大肠杆菌。有时，存在厌氧菌如肠球菌、消化球菌等混合感染。最后，结核杆菌、白色念珠菌等真菌感染虽少见，但可能存在，尤其在免疫障碍病人。病因学需要考虑的另一重要方面是微生物的毒力。Previous investigators have cited increased diffi culty with eradication of certain bacteria. Some authors have proposed differing treatment recommendations depending on which microorganism(s) are present.16,17
In an early, often cited publication, Buchholz et al7 reported results with single staged resection and reimplantation hip arthroplasty, and found that gram negatives including Klebsiella, Proteus, and Pseudomonas groups were associated with a high rate of failure. In this study, it was found that approximately 50% of these gram negative infections failed treatment. However, these results must be viewed cautiously, since many patients in this study did not receive intravenous antibiotics postoperatively, which is the current standard of care. A few small series in the literature have shown reduced effi cacy in treating specifi c organisms such as coagulase positive Staphylococcus, and certain gram negatives.7,16-18 However, due to the lack of solid evidence based medicine, the decision to retain versus remove the implant should not be based primarily on the specifi c type of bacteria encountered, but rather on the duration of symptoms.
以前有作者报告某些细菌的根治越来越困难。一些作者建议根据微生物的种类选择治疗方案。在Buchholz早期报告I期假体取出翻修髋关节感染的有影响的一篇文章中，发现革兰氏阴性菌如克雷白菌、变形杆菌、假单胞菌与失败率高相关。该方报告约50%革兰氏阴性菌感染治疗失败。然而，由于很多病人术后未静脉应用抗菌素，该研究结果必须审慎对待。一些文献证实特异微生物如血浆凝固酶阳性葡萄球菌和某些革兰氏阴性菌疗效降低。然而，由于缺乏扎实的循症医学证据，不应该主要根据细菌的种类来决定保留或取出假体，而宁愿根据临床病程的长短来决定。
CLASSIFICATION
分型
In general, classifying total hip and knee infections relies on establishing the temporal relationship between the index procedure and the onset of symptoms, as well as the route by which the infecting organism gains access to the joint space.Acute or early infections are usually defi ned as infections presenting within approximately 1 month postoperatively or alternatively a symptom onset of _1 month duration irrespective of when the index arthroplasty was performed. Chronic or late infections are those that present after approximately a one month duration. It is extremely important to ascertain when the symptoms fi rst began, as treatment recommendations differ depending on the duration of symptoms. In general, irrigation and debridement with retention of components can be attempted if the infection is acute. Chronic infections have no chance of eradication without some form of resection arthroplasty.13,16,19 Another important consideration is the route of infection. Postoperative sources include contamination during the index procedure as well as wound colonization from prolonged drainage at the incision or drain site.
一般来说，根据手术和症状出现的空间关系以及感染性微生物进入关节腔的途径来进行全髋膝置换术后感染的分型。急性或早期感染通常定义为术后约1月或不论关节何时置换，症状出现1月内。慢性或晚期感染指病程大于1月。确定症状首次出现的时间尤其重要，因为治疗方案取决于病程。一般来说，如果是急性感染，可试行冲洗、清创并保留假体。而慢性感染如果不行某种形式的切除关节成形术，就没有治愈 的可能。感染途径是值得考虑的另一重要方面。术后感染源包括术中污染和切口或引流部位引流过长而致的伤口集群現象。Hematogenous sources may be early in the postoperative period or present late, years after the THA or TKA. Systemic seeding may occur from a variety of sources including: 1) urinary tract infections, 2) upper respiratory infections, 3) cellulitis, 4) chronic venous
stasis ulcers, 5) dental abscesses, 6) bone and joint infections at other sites, and 7) virtually any procedure that disrupts local skin and mucosal barrier immunity such as cystoscopy, colonoscopy, broncoscopy, prophylactic teeth cleaning and intra-articular joint injections. Identifying the origin of infection helps to determine when the joint became infected, as well as aids in preventing subsequent infections by eradicating the source.
血源性可在术后早期或晚期全髋、膝置换术后数年）出现，全身性来源包括：1、尿道感染，2、上呼吸道感染，3、蜂窝织炎，4、慢性静脉淤滞性溃疡，5、牙周脓肿，6、其它部位的骨与关节感染，7、破坏局部皮肤和粘膜屏障的操作，如cystoscopy，结肠镜，broncoscopy，预防性洁牙和关节内注射。确定感染源有助于确定关节何时感染，并有助于通过控制感染源来防止继发感染。
DIAGNOSIS
诊断
The fi rst step in evaluation of a total joint infection begins with a detailed history and physical examination. Specifi cally, the patient should be questioned about any wound complications following their previous surgery. In addition, prolonged drainage or extended use of antibiotics following the original surgery are possible indicators of a postoperative infection.Furthermore, the onset of symptoms such as fevers, night sweats, chills, swelling, stiffness, and pain with motion may help defi ne whether the infection is acute or chronic. Lastly, one should inspect for signs of infections such as redness, induration, callor, effusions, regional lymphadenopathy, incisional drainage, sinus tracts and pain with range of motion. Routine blood tests and radiographs should accompany every workup for total hip or knee infection. Radiographs should be inspected for progressive radiolucent regions around previous implants or areas of necrotic bone.
诊断全关节感染首先要详细询问病史和仔细查体。尤其要询问前次手术后的伤口情况。另外，较长时间渗出或初次术后滥用抗菌素也可能指示术后感染。并且，出现发热、夜间出汗、寒战、肿胀、僵硬以及活动性疼痛可能有助于确定急性或慢性感染。最后，应该检查感染体征，如发红、发硬、苍白、肿胀、局部淋巴结肿大、伤口渗出、窦道和活动性疼痛。诊断全髋、膝感染还应该常规血检和拍摄X线片。阅读X片应该观察以前假体或坏死骨周围的透亮线进展情况。While a complete blood count alone has little diagnostic value, the combination of an erythrocyte sedimentation rate and C-reactive protein is invaluable. A study from Vancouver, British Columbia prospectively analyzed 202 revision hips. The sensitivity of the C-reactive protein and erythrocyte sedimentation rate for infection was .96 and .82 respectively. Most importantly, when both the C-reactive protein and erythrocyte sedimentation rate were negative, the probability of infection was zero.5 Although, false positive results can occur, this study demonstrated that negative laboratory values are helpful in ruling out infection.
单纯全血计数的诊断价值极低，结合ESR和CRP的诊断价值无限。温哥华的British Columbia前瞻性分析了202例翻修髋。CRP和ESR诊断感染的敏感度分别为0.96和0.82. 最重要的是，当CRP和ESR 均阴性时，感染的可能性为0. 虽然可能出现假阳性，但本研究证实实验室检查阴性有助于排除感染。Most recently, Il-6 was also shown to be a sensitive as well as specifi c marker for infection.20 However, at the present time, routine clinical use of this test is limited. An aspiration of the joint should be considered if either the C-reactive protein or erythrocyte sedimentation rate is positive or if there is enough clinical suspicion to warrant its use. Although, a knee aspiration is easy to perform, a hip arthrocentesis often requires the use of fl uoroscopy and may lead to a delay in treatment unless it can be performed expediently. Furthermore, the sensitivity of aspiration varies in the literature. For example, some authors have found hip aspiration, cell count, and culture to have a sensitivity and specifi city _90%, while others have had less success.21-23 This may be related, in part, to the use of antibiotics in some patients in the days or weeks prior to the aspiration. However, a hip or knee aspiration, cell count and culture should be viewed as an adjunctive test that may provide useful information when performed in combination with a thorough clinical examination and routine blood work. The benefi t of nuclear imaging has been debated and results vary in the literature.This seems to be, at least partly due to the various techniques used. In an early study that combined technetium and gallium, the sensitivity of diagnosing a joint infection was low at 38%.25 In a latter study that used sequential technetium and indium labeled leukocyte scans, the sensitivity was found to be 64%.27 Two further studies performed by Palestro et al26 using indium labeled leukocyte scans demonstrated sensitivities of 86% in one report, while the other study had 100% sensitivity for diagnosing joint infection. Therefore, it is important to ascertain which method of radioisotope imaging is being used to account for any institutional limitations that may decrease its accuracy. It is also important to realize that nuclear imaging often remains positive for _1 year following routine THA or TKA, which limits its use in this setting. Although it may be indicated as an adjunctive test in certain situations, in general the results should not be viewed as defi nitive. Lastly, the accuracy of intraoperative tests such as frozen sections and gram stains also varies widely in the literature.
4,23,28,29
最近，已证实Il-6诊断感染的敏感性和特异性均很好。然而，目前，常规检查Il-6条件有限。如果CRP或ESR阳性或者临床高度怀疑感染，应该考虑关节穿刺。虽然膝关节穿刺非常简单，但髋关节穿刺常常需要透视，并且可能导致延误治疗，除非处理得当。文献报告穿刺的敏感度不一。例如，有人发现髋穿刺、细胞计数、和培养的敏感性和特异性高达90%，而其它学者发现其成功率并不高。这部分可能与穿刺前数周或数天使用抗菌素有关。然而，髋或膝穿刺、细胞计数和培养应该视为全面临床检查和常规血检时可提供有用信息的辅助检查。文献中核扫描的价值存在争议，效果不一。看来，这至少部分是由所用的不同技术造成的。在一项锝和铟联合应用的早期研究中，关节感染诊断的敏感性低到38%. 在其后的一项锝和铟标记白细胞连续扫描中，其敏感性为64%。Palestro等所做的另2项铟标记白细胞扫描研究中，一项个报告其关节感染诊断的敏感性为86%，另一个报告为100%。因此，确定放射同位素成像所用方法是很重要的。认识到常规全髋或全膝术后1年同位素扫描仍然阳性也是很重要的，这限制了其使用范围。虽然但某些条件下可作为辅助检查，一般情况下，其结果不作为诊断性的。最后，冰冻切片和革兰氏染色等术中检查文献报告准确性差异很大。Furthermore, the specifi city and sensitivity of frozen sections may depend on the area and number of tissue samples that are obtained, as well as the number of white blood cells visualized per high power fi eld. Lonner et al23 has recommended using 10 white blood cells/ high power fi eld for diagnosing periprosthetic infection to improve the specifi city of the frozen section. Despite their routine use, the surgeon should not rely solely on intraoperative frozen sections or gram staining to guide his or her intraoperative treatment. Rather, in the majority of situations, a complete preoperative workup including the history and physical examination, radiographs, and laboratory values should help determine the preoperative plan. Intraoperative tests are most useful as guides to postoperative management. Several tissues samples should be taken from the most infl amed areas of the joint, as well as the intramedullary canal (if component resection is performed). The excised tissue should then be sent for both anaerobic and aerobic cultures (as well as fungal cultures if clinical suspicion exists). This may be the only chance to isolate the offending microorganism and is paramount for targeting specifi c antibiotic therapy in the postoperative period. It is critical that the patient discontinue antibiotics for at least several weeks prior to obtaining cultures if possible, otherwise a false negative result may occur.并且，冰冻切片的特异性和敏感性可能取决于术中所得组织样本的取材区域和样本数量，以及每高倍镜视野观察到的白细胞数。Lonner等建议每高倍镜视野10个白细胞数来诊断假体周围感染，以提高冰冻切片的特异性。除非常规应用，术者不应该单纯依据冰冻切片或革兰氏染色来指导术中处理。多数情况下，完整的术前工作如病史、查体、X片和实验室检查应该有助于确定术前计划。术中检查对指导术后治疗最为有用。应该从关节和髓腔（如果假体已取出）内炎症最明显的区域取几个样本。切取组织应该送需氧和厌氧培养（如果临床怀疑真菌，则送真菌培养）。这可能是明确病原微生物的唯一机会，并且对于术后针对性抗菌素治疗至关重要。如果可能，培养前至少数周病人停用抗菌素，否则，可出现假阴性结果。
TREATMENT
Acute total hip and knee infections pre senting within one month of symptom onset are often initially treated with irrigation and debridement with component retention, as well as polyethylene liner exchange in implants with modular components. The success rate of this approach varies in the literature from _10% to _50%. A delay in treatment appears to be the most detrimental factor to a successful outcome.13,16,30,31 In a study performed by Crockarell et al 42 patients with an infected THA were treated with open debridement and component retention, followed by intravenous antibiotics.13 Success was demonstrated in the group treated at a mean of 6 days after symptom onset. However, patients with symptoms of infection averaging _3 weeks failed treatment. Although the success rate appeared to be high at 1-year postoperative, the re-infection rate steadily increased over time. Moreover, at 6 years mean follow up, approximately 33% of the cases were cured with _1 irrigation and debridement when performed within the fi rst 2 weeks of symptom onset versus none in those with _2 weeks of symptoms.13 Tsukayama et al had somewhat better results with irrigation and debridement and component retention in 35 acutely infected total hips (_4 weeks from symptom onset). Approximately 70% of postoperative infections and 50% of acute hematogenous infections were successfully treated in this manner.19,32 There is also some evidence to suggest that certain microorganisms are more diffi cult to eradicate and may require more aggressive forms of treatment.7,16,17,18 Deirmengian et al published his series of 31 acute total knee infections treated with irrigation, debridement, and systemic antibiotic therapy with retention of components. In this small, retrospective review the author found that S aureus was more diffi cult to eradicate.
治疗
发病1月内的急性全髋和膝置换术后感染开始常常灌注冲洗和清创，保留假体、更换组合假体的聚乙烯衬垫。文献报道该方法的成功率为10% --50%. 延误治疗看来是疗效成功的危害最大因素。Crockarell 等对42例全髋置换术后感染进行开放清创、保留假体，然后静脉应用抗菌素治疗。该组病人症状出现平均6天治疗获得成功。然而，感染症状出现平均3周的病人治疗失败。虽然术后1年成功率很高，但是随时间延长，再感染率逐步升高。并且，平均随访6年时，发病2周内行冲洗清创术的病人成功率约33%, 而发病2周后处理的病人其成功率为0。 Tsukayama 等用灌注冲洗、清创、假体保留治疗急性全髋置换术后感染（症状出现4周）35例，效果更好些。用该方法治疗术后感染的成功率约70%，急性血源性感染的成功率约50%。有证据显示某些微生物更难清除，可能需要更积极的治疗方法。Deirmengian 等用灌注清创、假体保留、全身应用抗菌素治疗急性全膝置换术后感染31例。在该小样本的回顾性研究中，作者发现金葡菌更难清除。
Patients with Streptococcus species and S epidermidis had better than a 50% chance of cure versus _10% success in individuals with positive cultures to S aureus. The average duration of symptoms in all patients before debridement was 9 days.16 These results demonstrate that prompt surgical intervention is the key to a successful outcome. However, despite early, aggressive treatment, irrigation and debridement with retention of components frequently results in persistent infection over the long run. It is well accepted that chronic total joint infections that present late are best managed with component revision and at least 6 weeks of intravenous antibiotics. Whether the best approach is a single staged revision or a two staged, delayed resection arthroplasty with interval placement of an antibiotic spacer has been a matter of debate in the literature. The trend in the United States is to perform a staged resection arthroplasty for chronically infected total hips and knees, as this has shown the highest rate of success. 8-11,14,18,31-37 However, in certain circumstances, single staged revision has been used successfully in chronic infections as well.7,11,12,15,17,38 In a large study performed in the early 1980s, direct exchange hip arthroplasty for infection demonstrated an overall success rate of 77%, even without routine postoperative intravenous antibiotics, which is the current standard of care. The results of this study may have been further skewed due to the fact that the antibiotic dose used within the bone cement was variable.7
链球菌和表皮葡萄球菌病人的治愈率大于50%，优于金葡培养阳性病人的治愈率10%。清创前所有病人的出现症状时间平均为9天。结果证实迅速手术清创是手术成功的关键。然而，从长期看，尽管早期积极处理，灌注清创、假体保留仍常常导致持续感染。普遍认为，慢性全关节置换术后感染最好采用假体翻修，并静脉应用抗菌素至少6周。不论I期翻修或II期翻修，文献中延期切除关节成形术结合抗菌素间块关节间置仍存在争议。对于慢性全髋膝关节置换术后感染，美国医生倾向于分期切除关节成形术，已证实该方法的成功率最高。然而，某种情况下，I期翻修处理慢性感染也可成功。在1980年代早期进行的一项大范围研究证实，对关节感染直接进行翻修，即使术后常规不静脉应用抗菌素（目前的标准处理方法），其总成功率为77%。由于骨水泥中抗菌素剂量不同，该研究效果可能还需要进一步解释。
Amstutz et al15 published a small series of 20 patients with infected THA. Their success rate with a single staged revision was 100% at an average 10-year follow-up. However, 5 of 20 patients were lost to follow-up, which may have biased these results. Callaghan et al12 reviewed their results in 24 infected total hips with single staged revision arthroplasty. No patients were lost to follow-up. Infection reoccurred in only 8% of patients, although the authors carefully selected their patients in this study. The majority of microorganisms were S epidermidis isolates. Furthermore, patients with a visible sinus tract, those with any immunosuppression or inadequate bone stock were viewed as contraindications and underwent resection arthroplasty instead.12 In a literature review of direct exchange arthroplasty for infected THAs, _1200 infected joints were pooled from _12 studies. Eighty-three percent of the cases were infection free with an average 5-year follow-up. Factors that were cited as positive prognostic indicators included patients with a good baseline health status and those with S epidermidis, methicillin-sensitive S aureus,and Streptococcal species. A signifi cant weakness of this review was that nearly 50% of the patients came from a single study with inherent biases. For instance, many of the patients were treated without routine systemic intravenous antibiotics postoperatively, which may have led to an underestimation of the success rate.17 A recent series of 22 infected total knees treated with single stage revision arthroplasty were reviewed at an average 10-year follow-up. The authors of this study found a _90% success rate with direct exchange arthroplasty and the use of intravenous antibiotics postoperatively. Although the average follow-up was adequate to screen for the presence of infection, individual follow-up was variable (range, 1.4-19.6 years). Therefore, it is possible that a few of the patients with short term follow up may have presented with infection at a later date, which could have led to an overestimation of the success rate in this study.11 Staged resection typically involves resection of the implant with placement of antibiotic cement in the form of beads, blocks, or articulated spacers (Figures 1, 2). In general, specifi cally targeted intravenous antibiotics are used for 6 to 8 weeks followed by oral antibiotics if necessary. A complete blood count, C-reactive protein, and erythrocyte sedimentation rate are obtained at routine intervals, and these laboratory values as well as knee or hip aspirations are often performed to guide the timing of re-implantation. There are a number of proposed advantages and disadvantages to the different types of antibiotic spacers. Antibiotic beads and blocks are relatively simple to implant and antibiotic beads have a large surface area for antibiotic elution due to the numerous spheres that are created.6 However, the main drawback for both the block and bead techniques are that joint motion is more restricted during the period between resection and re-implantation. Furthermore, the second stage surgery may be more diffi cult due to scarring, improper soft tissue tensioning and possibly bone loss.More recently, articulated spacer blocks and the PROSTALAC (prosthesis of antibiotic loaded acrylic cement) have gained popularity (Figures 3-5). Although, these are somewhat more labor intensive and are associated with increased cost, proposed advantages included ease of second stage revision and better patient function during the interval treatment period. Amstutz 等报告全髋术后感染病人20例的结果。平均随访10年时，I期翻修的成功率为100%。然而，其中5例病人失访，结果可能出现偏倚。Callaghan 等报告I期翻修治疗全髋术后感染病人24例的结果。无病人失访。仅仅8%病人复发，虽然作者仔细选择了病例。多数微生物为表皮葡萄球菌。并且，存在窦道病人、免疫抑制病人、骨量不足病人都视为禁忌症而行假体取出、关节成形术。在一项I期翻修治疗全髋术后感染的研究中，从12个单位收集了1200个感染关节。平均随访5年时，83%病人没有感染。有益预后因素包括病人健康良好，表皮葡萄球菌、甲氧西林敏感金葡菌和链球菌感染病人，该文献的缺陷在于近50%病人来自同一单位，存在固有偏倚。例如，很多病人术后常规不静脉应用抗菌素，这可能导致成功率降低。最近，有文献报告I期翻修全膝感染22例平均随访10年的结果。作者报告I期翻修并术后静脉应用抗菌素，其成功率为90%。虽然平均随访时间足够筛查感染，但病人随访时间差异很大（1.4---19.6年）。因此，随访短的病人以后可能出现感染，从而高估了本研究的成功率。典型的分期翻修包括取出假体、置入珠状、块状或关节间块状的抗菌素骨水泥（图1，2）。一般来说，如果必要，静脉应用特定抗菌素6—8周，然后再口服抗菌素。全血计数、CRP、ESR常规检测，常常进行这些实验室检查和膝、髋穿刺以指导假体再次植入时机。不同类型骨水泥间块的优缺点不同。抗菌素珠、块植入相对简单，由于圆球很多，抗菌素珠的抗菌素释放表面面积很大。然而，抗菌素珠、块的主要缺陷在于假体取出后和再植间关节活动更加受限。并且，由于瘢痕、软组织张力不当及可能骨丢失，II期手术可能更加困难。最近，关节样间块和PROSTALAC（载抗菌素的骨水泥假体）得到广泛欢迎（图3—5）。虽然增加了某种程度的工作强度和病人费用，但优点很明确：II期翻修容易，治疗期间病人功能更佳。In general, direct comparisons of antibiotic delivery systems for infected two stage revision hip and knee surgery have similar effi cacy in terms of eradication of infection.18,37 The antibiotic dosage within the cement warrants special consideration. While antibiotics are frequently added to cement during the second stage re-implantation (ie, in revision TKA and hybrid THA), the dose is limited to approximately 1 g of antibiotic powder per one packet of cement (approximately 40 g). Higher doses have been found to substantially reduce the strength of the bone cement.3,6 However, antibiotic dosages placed in temporary spacers are usually higher, which has favorable elution characteristics including increasing the amount and duration of antibiotics within the local environment of the hip or knee joint.6 The total amount of antibiotics within the cement spacers vary considerably in the literature. In some series, as low as 2 g have been used, while other authors have placed close to 20 g of antibiotics per spacer without reported systemic side effects.39 Although antibiotic spacers are often felt to be clinically safe, it is prudent to monitor patients in the postoperative period. This includes evaluating renal function when using antibiotic loaded cement and intravenous medications such as gentamicin and vancomycin. 一般来说，直接比较分期治疗全髋膝关节置换术后感染的抗菌素释放系统，其在感染治愈率方面功效相似。骨水泥内的抗菌素剂量需要特别重视。在II期翻修（如全膝或杂合髋的翻修）时，骨水泥内常常添加抗菌素，剂量限制在每包骨水泥（约40克）添加抗菌素粉约1克。已发现更高剂量将减弱骨水泥的强度。然而，临时间块内的抗菌素剂量通常更高，这有利于增高髋膝关节局部环境内的抗菌素的量和作用时间。文献中骨水泥间块内抗菌素总量变化很大。一些作者低到2克，而另一些作者每个骨水泥间块内添加高达接近20克，而据报告未出现全身负作用。虽然临床应用骨水泥间块常常感觉安全，但术后要密切监护病人。当骨水泥内添加和静脉使用庆大霉素和万古霉素时，应该评价肾功。 Numerous studies of delayed, two staged hip and knee arthroplasty have demonstrated high efficacy in terms of eradication of infection. In a study by Younger et al, 61 infected total hips were treated with staged revision using the PROSTALAC spacer.31 At fi nal follow-up, 94% of infections were eradicated. Most importantly, the authors aspirated all hip prior to re-implantation and followed intraoperative cultures obtained at the time of re-implantation, which appeared to improve their overall success rate.31 Hoffman et al8 had similar success, with a 94% eradication rate, using a two staged articulated hip spacer technique. Unfortunately, approximately 1/3rd of patients in this review were lost to followup, which may have biased the results. 多项研究证实，延期II期髋膝翻修在治愈感染的条件下，疗效很高。Younger 等用PROSTALAC 间块对全髋置换术后感染进行分期翻修。最终随访时，94%的感染病人得到治愈。最重要的是，作者对所有髋在翻修前进行穿刺培养和翻修术中取材培养，这看来提高了总成功率。Hoffman 等用II期髋关节样间块技术的成功率类似，为94%。遗憾的是，该研究约1/3病人失访，可能存在结果偏倚。
In another study comparing the use of antibiotic beads to molded articulated spacer for THA infections, success rates were similar between both groups with a 95% cure rate.37 Two recently published studies of infected TKA used a staged resection technique with articulated spacers fabricated from the original components. In both studies, the femoral component was removed, autoclaved and re-cemented with a new polyethylene insert coated with antibiotic loaded cement. The cure rate was _90% using this technique. 9,14 Meek et al10 used a PROSTALAC system for 58 total knee infections and found a 96% cure rate. They followed trends in the sedimentation rate and C-reactive protein in the interval period as well as aspirated all knees prior to fi nal re-implantation. The protocol involved discontinuing all antibiotics 4 weeks prior to aspiration and culture to reduce the number of false negative results.10
在另一项抗菌素珠与成型关节样间块治疗全髋置换感染的比较研究中，两组的治愈率类似 ，均为95%。最近有2篇文献依照原假体制备的关节样间块通过分期切除关节成形术治疗全膝置换术后感染。在2篇文献中，股骨假体都取出、消毒、用抗菌素骨水泥重新固定新的聚乙烯衬垫。该方法的治愈率为90%。Meek等使用PROSTALAC系统治疗全膝感染58例，治愈率为96%。在最终翻修前，他们研究了ESR和CRP的变化趋势，并对所有膝关节进行穿刺培养。他们在穿刺和培养前停用抗菌素4周，以减少假阴性结果。
SUMMARY
小结
Infection should be in the differential for any painful total hip or knee. A thorough history and physical, complete set of radiographs and appropriate labs including C-reactive protein and erythrocyte sedimentation rate are essential in the initial evaluation. Ancillary tests such as aspiration and nuclear imaging may be helpful in unclear cases or when labs are concerning for infection. It is essential that all antibiotics are discontinued several weeks prior to gram stain and culture, if possible, to reduce the number of false negative test results.
对任何疼痛性全髋膝关节置换，都应该鉴别诊断感染。详细病史、仔细查体、完整的X片和合适的实验室检查如CRP、ESR是初步诊断的基础。辅助检查如穿刺和核素扫描在不明确病例或当实验室检查怀疑感染时可有帮助。如果可能，为减少假阴性检查结果数量，在革兰氏染色和细菌培养前几周，停用所有抗菌素是必要的。
Classifying infection into acute versus late infection aids in the treatment plan. For acute infections presenting within 2 to 4 weeks of symptom onset, irrigation and debridement with polyethylene liner exchange and retention of components may be possible. When attempting component retention, thorough debridement and rapid treatment of the infection prior to the accumulation of any biofi lm is paramount for a successful outcome. Other important prognostic factors to consider include the virulence of the microorganism as well as the immune status of the host. Despite expeditious management, irrigation and debridement of acute total hip and knee infections frequently leads to recurrent infection. Thus, patients should be counseled accordingly. Further management may be needed following an initial attempt at component retention. These options include resection arthroplasty with or without re-implantation, long term antibiotic suppressive therapy, arthrodesis and even above the knee amputation in rare circumstances. For chronic infections, a successful outcome depends on several factors including the baseline health status of the patient, implant removal with a thorough debridement followed by culture specific antibiotic treatment. Furthermore, methods of monitoring for persistent infection include following laboratory values such as the C-reactive protein, erythrocyte sedimentation rate, and cultures from joint aspirations. Whether to perform a direct exchange versus a delayed revision arthroplasty for chronic total hip and knee infections can be debated. Several published series have reported successful outcomes with single stage procedures when patients are carefully selected. However, the majority of chronic infections in the United States are treated with two stage resection, since this method has consistently provided the highest cure rates, with many current studies demonstrating _90% success.
感染分为急性和慢性有助于制定治疗方案。对于症状出现2—4周内的急性感染，冲洗、清创、更换聚乙烯垫，保留假体是可能的。当试图保留假体时，在生物膜形成前彻底清创、迅速治疗感染对于成功治愈是至关重要的。需要考虑的另一重要预后因素包括微生物的毒力和机体的免疫状态。尽管积极处理，对全髋膝急性感染进行冲洗和清创仍常常复发。因此，应该对病人进行相应告知。在最初试图保留假体后，可能需要更进一步处理。包括进行或不进行假体再次植入的切除成形术、长期应用抗菌素、关节融合术以及极少情况下需要膝上截肢。对于慢性感染，治愈的因素包括病人的健康状况、假体取出、彻底清创，然后细菌培养，针对性抗菌素治疗。并且，监测持续感染的方法包括CRP、ESR等实验室检查和关节穿刺培养。慢性髋膝感染直接翻修或延期翻修存在争议。几篇文献报告对仔细选择的病例进行I期翻修获得成功。然而，在美国，大多数慢性感染分期翻修，该方法治愈率高，目前很多研究证实成功率为90%。
全髋、膝置换术后感染的诊治
THOMAS F. MOYAD, MD, MPH; THOMAS THORNHILL, MD; DANIEL ESTOK, MD
Infections following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) can be a devastating complication leading to signifi cant morbidity. Multiple risk factors have been identifi ed including: 1) revision surgery, 2) rheumatoid arthritis, 3) diabetes mellitus, 4) obesity, 5) poor nutrition, 6) mmunosuppressive medications, and 7) presence of psoriatic skin lesions.1-3 Classifi cation systems devised to help guide treatment algorithms are primarily based on the duration of signs and symptoms. Therefore, early recognition and proper management of these infections is important, not only from a medicolegal standpoint, but it also has signifi cant public health implications. This review focuses on current diagnostic and management strategies, in particular with regards to single stage versus two staged resection arthroplasty for chronic hip and knee infections.
初次全髋、膝置换术后感染是可引起引起严重病废的可怕并发症。已证实的危险因素包括：1、翻修手术，2、类风湿性关节炎，3、糖尿病，4、肥胖，5、营养不良，6、使用免疫抑制剂，7、皮肤存在银屑病变。主要是依据临床表现病程的长短对感染进行分型，以指导治疗。因此，早期诊断并及时处理感染是重要的，不仅仅从医学角度是如此，而且还具有重要的公共卫生意义。本文综述目前初次全髋、膝膝置换术后感染的诊治策略，尤其是关于慢性髋、膝感染的一期和二期假体取出关节成形术。EPIDEMIOLOGY
Deep infection occurs in approximately 1% to 2 % of all primary total hip and knee arthroplasties.4 While the infection rate has remained fairly low over the past several decades, given the increasing number of total joints performed throughout the United States, total hip and knee infections create a signifi cant burden on our health care system. The institutional cost of treating an individual patient has been estimated to result in a net loss of $15,000 to $30,000. Furthermore, the cost of treating THA infections in the United States alone is approximately $200 million per year.5
Host factors such as diabetes, rheumatoid arthritis, and immune status are important considerations. However, revision surgery carries the highest risk of infection. Although the exact percent varies in the literature, revision surgery appears to carry two to three times the risk of infection versus primary THA and TKA.3
流行病学
所有初次全髋、膝置换的深部感染率约为1% 到 2 %。鉴于全美国关节置换越来越多, 近几十年来感染率其实相当低, 但全髋和膝感染给卫生系统造成沉重负担。据估计治疗一个病人所造成的净$15,000 到 $30,000。并且，每年仅仅治疗全髋置换感染的花费约2亿美元。
病人因素如糖尿病、类风湿性关节炎、免疫状态也要详细考虑。然而，翻修手术是引起感染的高危因素。虽然文献报告不一，但翻修手术的危险性是初次全髋、膝置换的2到3倍。
Prevention of infection is obviously an important consideration. A thorough history and physical examination to identify sources of potential infection, such as infected diabetic foot ulcers, is paramount prior to undergoing any arthroplasty surgery. Furthermore, a recent advisory statement provided by the American Academy of Orthopaedic Surgeons discussed routine prophylaxis with keflex, amoxicillin, or clindamycin (if penicillin allergic) for 2 years following THA or TKA prior to various procedures, such as dental cleaning.3 Routine prophylaxis after 2 years following THA or TKA may be also considered in some patients who have immune suppression due to certain medical conditions or immunosuppressive medications. Lastly, adding prophylactic antibiotics to cemented arthroplasties has been advocated, especially in revision surgery. 6 However, currently no studies conclusively demonstrate whether this technique lowers infection during primary THA and TKA surgery.
显然，预防感染是很重要的。在关节置换手术前，详细询问病史并仔细查体，确定如感染性糖尿病足溃疡可能感染源是至关重要的。最近AAOS建议在全髋、膝置换术后施行其它手术（如洁牙）前，常规预防性应用keflex、阿莫西林、或克林霉素（如果青霉素过敏）2年。在因疾病或使用免疫抑制剂而出现免疫抑制的一些病人，也可在全髋膝置换术后2年常规预防。最后，推荐在骨水泥型关节置换的骨水泥中添加预防性抗菌素，尤其在翻修手术。然而，目前没有研究能证实该技术降低初次全髋膝置换手术的感染。
ETIOLOGY
病因学
Staphylococcus epidermidis and Staphylococcus aureus are the two most common isolates found in infected total hip and knee arthroplasties. Some series point to S aureus as the most prevalent organism.7-10 Other series show that S epidermidis is the most common.11-15
表皮葡萄球菌和金黄色葡萄球菌是全髋膝置换术后感染中最多见的2类细菌。一些文献指出金黄色葡萄球菌最多见，另一些文献认为表皮葡萄球菌最多见。
Some common but less frequent organisms include Streptococcus species and gram negatives such as Pseudomonas, Klebsiella, and Escherichia coli. Occasionally, mixed infections with anaerobes like Enterococcus and Peptococcus are present. Finally, fungal infections such as Mycobacterium tuberculosis and Candida albicans are infrequent, but may be present, especially in the immune compromised host. An important consideration with regard to etiology is the virulence of the organism.
一些普通但不常见的微生物包括链球菌、革兰氏阴性菌如假单胞菌、克雷白菌、大肠杆菌。有时，存在厌氧菌如肠球菌、消化球菌等混合感染。最后，结核杆菌、白色念珠菌等真菌感染虽少见，但可能存在，尤其在免疫障碍病人。病因学需要考虑的另一重要方面是微生物的毒力。Previous investigators have cited increased diffi culty with eradication of certain bacteria. Some authors have proposed differing treatment recommendations depending on which microorganism(s) are present.16,17
In an early, often cited publication, Buchholz et al7 reported results with single staged resection and reimplantation hip arthroplasty, and found that gram negatives including Klebsiella, Proteus, and Pseudomonas groups were associated with a high rate of failure. In this study, it was found that approximately 50% of these gram negative infections failed treatment. However, these results must be viewed cautiously, since many patients in this study did not receive intravenous antibiotics postoperatively, which is the current standard of care. A few small series in the literature have shown reduced effi cacy in treating specifi c organisms such as coagulase positive Staphylococcus, and certain gram negatives.7,16-18 However, due to the lack of solid evidence based medicine, the decision to retain versus remove the implant should not be based primarily on the specifi c type of bacteria encountered, but rather on the duration of symptoms.
以前有作者报告某些细菌的根治越来越困难。一些作者建议根据微生物的种类选择治疗方案。在Buchholz早期报告I期假体取出翻修髋关节感染的有影响的一篇文章中，发现革兰氏阴性菌如克雷白菌、变形杆菌、假单胞菌与失败率高相关。该方报告约50%革兰氏阴性菌感染治疗失败。然而，由于很多病人术后未静脉应用抗菌素，该研究结果必须审慎对待。一些文献证实特异微生物如血浆凝固酶阳性葡萄球菌和某些革兰氏阴性菌疗效降低。然而，由于缺乏扎实的循症医学证据，不应该主要根据细菌的种类来决定保留或取出假体，而宁愿根据临床病程的长短来决定。
CLASSIFICATION
分型
In general, classifying total hip and knee infections relies on establishing the temporal relationship between the index procedure and the onset of symptoms, as well as the route by which the infecting organism gains access to the joint space.Acute or early infections are usually defi ned as infections presenting within approximately 1 month postoperatively or alternatively a symptom onset of _1 month duration irrespective of when the index arthroplasty was performed. Chronic or late infections are those that present after approximately a one month duration. It is extremely important to ascertain when the symptoms fi rst began, as treatment recommendations differ depending on the duration of symptoms. In general, irrigation and debridement with retention of components can be attempted if the infection is acute. Chronic infections have no chance of eradication without some form of resection arthroplasty.13,16,19 Another important consideration is the route of infection. Postoperative sources include contamination during the index procedure as well as wound colonization from prolonged drainage at the incision or drain site.
一般来说，根据手术和症状出现的空间关系以及感染性微生物进入关节腔的途径来进行全髋膝置换术后感染的分型。急性或早期感染通常定义为术后约1月或不论关节何时置换，症状出现1月内。慢性或晚期感染指病程大于1月。确定症状首次出现的时间尤其重要，因为治疗方案取决于病程。一般来说，如果是急性感染，可试行冲洗、清创并保留假体。而慢性感染如果不行某种形式的切除关节成形术，就没有治愈 的可能。感染途径是值得考虑的另一重要方面。术后感染源包括术中污染和切口或引流部位引流过长而致的伤口集群現象。Hematogenous sources may be early in the postoperative period or present late, years after the THA or TKA. Systemic seeding may occur from a variety of sources including: 1) urinary tract infections, 2) upper respiratory infections, 3) cellulitis, 4) chronic venous
stasis ulcers, 5) dental abscesses, 6) bone and joint infections at other sites, and 7) virtually any procedure that disrupts local skin and mucosal barrier immunity such as cystoscopy, colonoscopy, broncoscopy, prophylactic teeth cleaning and intra-articular joint injections. Identifying the origin of infection helps to determine when the joint became infected, as well as aids in preventing subsequent infections by eradicating the source.
血源性可在术后早期或晚期全髋、膝置换术后数年）出现，全身性来源包括：1、尿道感染，2、上呼吸道感染，3、蜂窝织炎，4、慢性静脉淤滞性溃疡，5、牙周脓肿，6、其它部位的骨与关节感染，7、破坏局部皮肤和粘膜屏障的操作，如cystoscopy，结肠镜，broncoscopy，预防性洁牙和关节内注射。确定感染源有助于确定关节何时感染，并有助于通过控制感染源来防止继发感染。
DIAGNOSIS
诊断
The fi rst step in evaluation of a total joint infection begins with a detailed history and physical examination. Specifi cally, the patient should be questioned about any wound complications following their previous surgery. In addition, prolonged drainage or extended use of antibiotics following the original surgery are possible indicators of a postoperative infection.Furthermore, the onset of symptoms such as fevers, night sweats, chills, swelling, stiffness, and pain with motion may help defi ne whether the infection is acute or chronic. Lastly, one should inspect for signs of infections such as redness, induration, callor, effusions, regional lymphadenopathy, incisional drainage, sinus tracts and pain with range of motion. Routine blood tests and radiographs should accompany every workup for total hip or knee infection. Radiographs should be inspected for progressive radiolucent regions around previous implants or areas of necrotic bone.
诊断全关节感染首先要详细询问病史和仔细查体。尤其要询问前次手术后的伤口情况。另外，较长时间渗出或初次术后滥用抗菌素也可能指示术后感染。并且，出现发热、夜间出汗、寒战、肿胀、僵硬以及活动性疼痛可能有助于确定急性或慢性感染。最后，应该检查感染体征，如发红、发硬、苍白、肿胀、局部淋巴结肿大、伤口渗出、窦道和活动性疼痛。诊断全髋、膝感染还应该常规血检和拍摄X线片。阅读X片应该观察以前假体或坏死骨周围的透亮线进展情况。While a complete blood count alone has little diagnostic value, the combination of an erythrocyte sedimentation rate and C-reactive protein is invaluable. A study from Vancouver, British Columbia prospectively analyzed 202 revision hips. The sensitivity of the C-reactive protein and erythrocyte sedimentation rate for infection was .96 and .82 respectively. Most importantly, when both the C-reactive protein and erythrocyte sedimentation rate were negative, the probability of infection was zero.5 Although, false positive results can occur, this study demonstrated that negative laboratory values are helpful in ruling out infection.
单纯全血计数的诊断价值极低，结合ESR和CRP的诊断价值无限。温哥华的British Columbia前瞻性分析了202例翻修髋。CRP和ESR诊断感染的敏感度分别为0.96和0.82. 最重要的是，当CRP和ESR 均阴性时，感染的可能性为0. 虽然可能出现假阳性，但本研究证实实验室检查阴性有助于排除感染。Most recently, Il-6 was also shown to be a sensitive as well as specifi c marker for infection.20 However, at the present time, routine clinical use of this test is limited. An aspiration of the joint should be considered if either the C-reactive protein or erythrocyte sedimentation rate is positive or if there is enough clinical suspicion to warrant its use. Although, a knee aspiration is easy to perform, a hip arthrocentesis often requires the use of fl uoroscopy and may lead to a delay in treatment unless it can be performed expediently. Furthermore, the sensitivity of aspiration varies in the literature. For example, some authors have found hip aspiration, cell count, and culture to have a sensitivity and specifi city _90%, while others have had less success.21-23 This may be related, in part, to the use of antibiotics in some patients in the days or weeks prior to the aspiration. However, a hip or knee aspiration, cell count and culture should be viewed as an adjunctive test that may provide useful information when performed in combination with a thorough clinical examination and routine blood work. The benefi t of nuclear imaging has been debated and results vary in the literature.This seems to be, at least partly due to the various techniques used. In an early study that combined technetium and gallium, the sensitivity of diagnosing a joint infection was low at 38%.25 In a latter study that used sequential technetium and indium labeled leukocyte scans, the sensitivity was found to be 64%.27 Two further studies performed by Palestro et al26 using indium labeled leukocyte scans demonstrated sensitivities of 86% in one report, while the other study had 100% sensitivity for diagnosing joint infection. Therefore, it is important to ascertain which method of radioisotope imaging is being used to account for any institutional limitations that may decrease its accuracy. It is also important to realize that nuclear imaging often remains positive for _1 year following routine THA or TKA, which limits its use in this setting. Although it may be indicated as an adjunctive test in certain situations, in general the results should not be viewed as defi nitive. Lastly, the accuracy of intraoperative tests such as frozen sections and gram stains also varies widely in the literature.
4,23,28,29
最近，已证实Il-6诊断感染的敏感性和特异性均很好。然而，目前，常规检查Il-6条件有限。如果CRP或ESR阳性或者临床高度怀疑感染，应该考虑关节穿刺。虽然膝关节穿刺非常简单，但髋关节穿刺常常需要透视，并且可能导致延误治疗，除非处理得当。文献报告穿刺的敏感度不一。例如，有人发现髋穿刺、细胞计数、和培养的敏感性和特异性高达90%，而其它学者发现其成功率并不高。这部分可能与穿刺前数周或数天使用抗菌素有关。然而，髋或膝穿刺、细胞计数和培养应该视为全面临床检查和常规血检时可提供有用信息的辅助检查。文献中核扫描的价值存在争议，效果不一。看来，这至少部分是由所用的不同技术造成的。在一项锝和铟联合应用的早期研究中，关节感染诊断的敏感性低到38%. 在其后的一项锝和铟标记白细胞连续扫描中，其敏感性为64%。Palestro等所做的另2项铟标记白细胞扫描研究中，一项个报告其关节感染诊断的敏感性为86%，另一个报告为100%。因此，确定放射同位素成像所用方法是很重要的。认识到常规全髋或全膝术后1年同位素扫描仍然阳性也是很重要的，这限制了其使用范围。虽然但某些条件下可作为辅助检查，一般情况下，其结果不作为诊断性的。最后，冰冻切片和革兰氏染色等术中检查文献报告准确性差异很大。Furthermore, the specifi city and sensitivity of frozen sections may depend on the area and number of tissue samples that are obtained, as well as the number of white blood cells visualized per high power fi eld. Lonner et al23 has recommended using 10 white blood cells/ high power fi eld for diagnosing periprosthetic infection to improve the specifi city of the frozen section. Despite their routine use, the surgeon should not rely solely on intraoperative frozen sections or gram staining to guide his or her intraoperative treatment. Rather, in the majority of situations, a complete preoperative workup including the history and physical examination, radiographs, and laboratory values should help determine the preoperative plan. Intraoperative tests are most useful as guides to postoperative management. Several tissues samples should be taken from the most infl amed areas of the joint, as well as the intramedullary canal (if component resection is performed). The excised tissue should then be sent for both anaerobic and aerobic cultures (as well as fungal cultures if clinical suspicion exists). This may be the only chance to isolate the offending microorganism and is paramount for targeting specifi c antibiotic therapy in the postoperative period. It is critical that the patient discontinue antibiotics for at least several weeks prior to obtaining cultures if possible, otherwise a false negative result may occur.并且，冰冻切片的特异性和敏感性可能取决于术中所得组织样本的取材区域和样本数量，以及每高倍镜视野观察到的白细胞数。Lonner等建议每高倍镜视野10个白细胞数来诊断假体周围感染，以提高冰冻切片的特异性。除非常规应用，术者不应该单纯依据冰冻切片或革兰氏染色来指导术中处理。多数情况下，完整的术前工作如病史、查体、X片和实验室检查应该有助于确定术前计划。术中检查对指导术后治疗最为有用。应该从关节和髓腔（如果假体已取出）内炎症最明显的区域取几个样本。切取组织应该送需氧和厌氧培养（如果临床怀疑真菌，则送真菌培养）。这可能是明确病原微生物的唯一机会，并且对于术后针对性抗菌素治疗至关重要。如果可能，培养前至少数周病人停用抗菌素，否则，可出现假阴性结果。
TREATMENT
Acute total hip and knee infections pre senting within one month of symptom onset are often initially treated with irrigation and debridement with component retention, as well as polyethylene liner exchange in implants with modular components. The success rate of this approach varies in the literature from _10% to _50%. A delay in treatment appears to be the most detrimental factor to a successful outcome.13,16,30,31 In a study performed by Crockarell et al 42 patients with an infected THA were treated with open debridement and component retention, followed by intravenous antibiotics.13 Success was demonstrated in the group treated at a mean of 6 days after symptom onset. However, patients with symptoms of infection averaging _3 weeks failed treatment. Although the success rate appeared to be high at 1-year postoperative, the re-infection rate steadily increased over time. Moreover, at 6 years mean follow up, approximately 33% of the cases were cured with _1 irrigation and debridement when performed within the fi rst 2 weeks of symptom onset versus none in those with _2 weeks of symptoms.13 Tsukayama et al had somewhat better results with irrigation and debridement and component retention in 35 acutely infected total hips (_4 weeks from symptom onset). Approximately 70% of postoperative infections and 50% of acute hematogenous infections were successfully treated in this manner.19,32 There is also some evidence to suggest that certain microorganisms are more diffi cult to eradicate and may require more aggressive forms of treatment.7,16,17,18 Deirmengian et al published his series of 31 acute total knee infections treated with irrigation, debridement, and systemic antibiotic therapy with retention of components. In this small, retrospective review the author found that S aureus was more diffi cult to eradicate.
治疗
发病1月内的急性全髋和膝置换术后感染开始常常灌注冲洗和清创，保留假体、更换组合假体的聚乙烯衬垫。文献报道该方法的成功率为10% --50%. 延误治疗看来是疗效成功的危害最大因素。Crockarell 等对42例全髋置换术后感染进行开放清创、保留假体，然后静脉应用抗菌素治疗。该组病人症状出现平均6天治疗获得成功。然而，感染症状出现平均3周的病人治疗失败。虽然术后1年成功率很高，但是随时间延长，再感染率逐步升高。并且，平均随访6年时，发病2周内行冲洗清创术的病人成功率约33%, 而发病2周后处理的病人其成功率为0。 Tsukayama 等用灌注冲洗、清创、假体保留治疗急性全髋置换术后感染（症状出现4周）35例，效果更好些。用该方法治疗术后感染的成功率约70%，急性血源性感染的成功率约50%。有证据显示某些微生物更难清除，可能需要更积极的治疗方法。Deirmengian 等用灌注清创、假体保留、全身应用抗菌素治疗急性全膝置换术后感染31例。在该小样本的回顾性研究中，作者发现金葡菌更难清除。
Patients with Streptococcus species and S epidermidis had better than a 50% chance of cure versus _10% success in individuals with positive cultures to S aureus. The average duration of symptoms in all patients before debridement was 9 days.16 These results demonstrate that prompt surgical intervention is the key to a successful outcome. However, despite early, aggressive treatment, irrigation and debridement with retention of components frequently results in persistent infection over the long run. It is well accepted that chronic total joint infections that present late are best managed with component revision and at least 6 weeks of intravenous antibiotics. Whether the best approach is a single staged revision or a two staged, delayed resection arthroplasty with interval placement of an antibiotic spacer has been a matter of debate in the literature. The trend in the United States is to perform a staged resection arthroplasty for chronically infected total hips and knees, as this has shown the highest rate of success. 8-11,14,18,31-37 However, in certain circumstances, single staged revision has been used successfully in chronic infections as well.7,11,12,15,17,38 In a large study performed in the early 1980s, direct exchange hip arthroplasty for infection demonstrated an overall success rate of 77%, even without routine postoperative intravenous antibiotics, which is the current standard of care. The results of this study may have been further skewed due to the fact that the antibiotic dose used within the bone cement was variable.7
链球菌和表皮葡萄球菌病人的治愈率大于50%，优于金葡培养阳性病人的治愈率10%。清创前所有病人的出现症状时间平均为9天。结果证实迅速手术清创是手术成功的关键。然而，从长期看，尽管早期积极处理，灌注清创、假体保留仍常常导致持续感染。普遍认为，慢性全关节置换术后感染最好采用假体翻修，并静脉应用抗菌素至少6周。不论I期翻修或II期翻修，文献中延期切除关节成形术结合抗菌素间块关节间置仍存在争议。对于慢性全髋膝关节置换术后感染，美国医生倾向于分期切除关节成形术，已证实该方法的成功率最高。然而，某种情况下，I期翻修处理慢性感染也可成功。在1980年代早期进行的一项大范围研究证实，对关节感染直接进行翻修，即使术后常规不静脉应用抗菌素（目前的标准处理方法），其总成功率为77%。由于骨水泥中抗菌素剂量不同，该研究效果可能还需要进一步解释。
Amstutz et al15 published a small series of 20 patients with infected THA. Their success rate with a single staged revision was 100% at an average 10-year follow-up. However, 5 of 20 patients were lost to follow-up, which may have biased these results. Callaghan et al12 reviewed their results in 24 infected total hips with single staged revision arthroplasty. No patients were lost to follow-up. Infection reoccurred in only 8% of patients, although the authors carefully selected their patients in this study. The majority of microorganisms were S epidermidis isolates. Furthermore, patients with a visible sinus tract, those with any immunosuppression or inadequate bone stock were viewed as contraindications and underwent resection arthroplasty instead.12 In a literature review of direct exchange arthroplasty for infected THAs, _1200 infected joints were pooled from _12 studies. Eighty-three percent of the cases were infection free with an average 5-year follow-up. Factors that were cited as positive prognostic indicators included patients with a good baseline health status and those with S epidermidis, methicillin-sensitive S aureus,and Streptococcal species. A signifi cant weakness of this review was that nearly 50% of the patients came from a single study with inherent biases. For instance, many of the patients were treated without routine systemic intravenous antibiotics postoperatively, which may have led to an underestimation of the success rate.17 A recent series of 22 infected total knees treated with single stage revision arthroplasty were reviewed at an average 10-year follow-up. The authors of this study found a _90% success rate with direct exchange arthroplasty and the use of intravenous antibiotics postoperatively. Although the average follow-up was adequate to screen for the presence of infection, individual follow-up was variable (range, 1.4-19.6 years). Therefore, it is possible that a few of the patients with short term follow up may have presented with infection at a later date, which could have led to an overestimation of the success rate in this study.11 Staged resection typically involves resection of the implant with placement of antibiotic cement in the form of beads, blocks, or articulated spacers (Figures 1, 2). In general, specifi cally targeted intravenous antibiotics are used for 6 to 8 weeks followed by oral antibiotics if necessary. A complete blood count, C-reactive protein, and erythrocyte sedimentation rate are obtained at routine intervals, and these laboratory values as well as knee or hip aspirations are often performed to guide the timing of re-implantation. There are a number of proposed advantages and disadvantages to the different types of antibiotic spacers. Antibiotic beads and blocks are relatively simple to implant and antibiotic beads have a large surface area for antibiotic elution due to the numerous spheres that are created.6 However, the main drawback for both the block and bead techniques are that joint motion is more restricted during the period between resection and re-implantation. Furthermore, the second stage surgery may be more diffi cult due to scarring, improper soft tissue tensioning and possibly bone loss.More recently, articulated spacer blocks and the PROSTALAC (prosthesis of antibiotic loaded acrylic cement) have gained popularity (Figures 3-5). Although, these are somewhat more labor intensive and are associated with increased cost, proposed advantages included ease of second stage revision and better patient function during the interval treatment period. Amstutz 等报告全髋术后感染病人20例的结果。平均随访10年时，I期翻修的成功率为100%。然而，其中5例病人失访，结果可能出现偏倚。Callaghan 等报告I期翻修治疗全髋术后感染病人24例的结果。无病人失访。仅仅8%病人复发，虽然作者仔细选择了病例。多数微生物为表皮葡萄球菌。并且，存在窦道病人、免疫抑制病人、骨量不足病人都视为禁忌症而行假体取出、关节成形术。在一项I期翻修治疗全髋术后感染的研究中，从12个单位收集了1200个感染关节。平均随访5年时，83%病人没有感染。有益预后因素包括病人健康良好，表皮葡萄球菌、甲氧西林敏感金葡菌和链球菌感染病人，该文献的缺陷在于近50%病人来自同一单位，存在固有偏倚。例如，很多病人术后常规不静脉应用抗菌素，这可能导致成功率降低。最近，有文献报告I期翻修全膝感染22例平均随访10年的结果。作者报告I期翻修并术后静脉应用抗菌素，其成功率为90%。虽然平均随访时间足够筛查感染，但病人随访时间差异很大（1.4---19.6年）。因此，随访短的病人以后可能出现感染，从而高估了本研究的成功率。典型的分期翻修包括取出假体、置入珠状、块状或关节间块状的抗菌素骨水泥（图1，2）。一般来说，如果必要，静脉应用特定抗菌素6—8周，然后再口服抗菌素。全血计数、CRP、ESR常规检测，常常进行这些实验室检查和膝、髋穿刺以指导假体再次植入时机。不同类型骨水泥间块的优缺点不同。抗菌素珠、块植入相对简单，由于圆球很多，抗菌素珠的抗菌素释放表面面积很大。然而，抗菌素珠、块的主要缺陷在于假体取出后和再植间关节活动更加受限。并且，由于瘢痕、软组织张力不当及可能骨丢失，II期手术可能更加困难。最近，关节样间块和PROSTALAC（载抗菌素的骨水泥假体）得到广泛欢迎（图3—5）。虽然增加了某种程度的工作强度和病人费用，但优点很明确：II期翻修容易，治疗期间病人功能更佳。In general, direct comparisons of antibiotic delivery systems for infected two stage revision hip and knee surgery have similar effi cacy in terms of eradication of infection.18,37 The antibiotic dosage within the cement warrants special consideration. While antibiotics are frequently added to cement during the second stage re-implantation (ie, in revision TKA and hybrid THA), the dose is limited to approximately 1 g of antibiotic powder per one packet of cement (approximately 40 g). Higher doses have been found to substantially reduce the strength of the bone cement.3,6 However, antibiotic dosages placed in temporary spacers are usually higher, which has favorable elution characteristics including increasing the amount and duration of antibiotics within the local environment of the hip or knee joint.6 The total amount of antibiotics within the cement spacers vary considerably in the literature. In some series, as low as 2 g have been used, while other authors have placed close to 20 g of antibiotics per spacer without reported systemic side effects.39 Although antibiotic spacers are often felt to be clinically safe, it is prudent to monitor patients in the postoperative period. This includes evaluating renal function when using antibiotic loaded cement and intravenous medications such as gentamicin and vancomycin. 一般来说，直接比较分期治疗全髋膝关节置换术后感染的抗菌素释放系统，其在感染治愈率方面功效相似。骨水泥内的抗菌素剂量需要特别重视。在II期翻修（如全膝或杂合髋的翻修）时，骨水泥内常常添加抗菌素，剂量限制在每包骨水泥（约40克）添加抗菌素粉约1克。已发现更高剂量将减弱骨水泥的强度。然而，临时间块内的抗菌素剂量通常更高，这有利于增高髋膝关节局部环境内的抗菌素的量和作用时间。文献中骨水泥间块内抗菌素总量变化很大。一些作者低到2克，而另一些作者每个骨水泥间块内添加高达接近20克，而据报告未出现全身负作用。虽然临床应用骨水泥间块常常感觉安全，但术后要密切监护病人。当骨水泥内添加和静脉使用庆大霉素和万古霉素时，应该评价肾功。 Numerous studies of delayed, two staged hip and knee arthroplasty have demonstrated high efficacy in terms of eradication of infection. In a study by Younger et al, 61 infected total hips were treated with staged revision using the PROSTALAC spacer.31 At fi nal follow-up, 94% of infections were eradicated. Most importantly, the authors aspirated all hip prior to re-implantation and followed intraoperative cultures obtained at the time of re-implantation, which appeared to improve their overall success rate.31 Hoffman et al8 had similar success, with a 94% eradication rate, using a two staged articulated hip spacer technique. Unfortunately, approximately 1/3rd of patients in this review were lost to followup, which may have biased the results. 多项研究证实，延期II期髋膝翻修在治愈感染的条件下，疗效很高。Younger 等用PROSTALAC 间块对全髋置换术后感染进行分期翻修。最终随访时，94%的感染病人得到治愈。最重要的是，作者对所有髋在翻修前进行穿刺培养和翻修术中取材培养，这看来提高了总成功率。Hoffman 等用II期髋关节样间块技术的成功率类似，为94%。遗憾的是，该研究约1/3病人失访，可能存在结果偏倚。
In another study comparing the use of antibiotic beads to molded articulated spacer for THA infections, success rates were similar between both groups with a 95% cure rate.37 Two recently published studies of infected TKA used a staged resection technique with articulated spacers fabricated from the original components. In both studies, the femoral component was removed, autoclaved and re-cemented with a new polyethylene insert coated with antibiotic loaded cement. The cure rate was _90% using this technique. 9,14 Meek et al10 used a PROSTALAC system for 58 total knee infections and found a 96% cure rate. They followed trends in the sedimentation rate and C-reactive protein in the interval period as well as aspirated all knees prior to fi nal re-implantation. The protocol involved discontinuing all antibiotics 4 weeks prior to aspiration and culture to reduce the number of false negative results.10
在另一项抗菌素珠与成型关节样间块治疗全髋置换感染的比较研究中，两组的治愈率类似 ，均为95%。最近有2篇文献依照原假体制备的关节样间块通过分期切除关节成形术治疗全膝置换术后感染。在2篇文献中，股骨假体都取出、消毒、用抗菌素骨水泥重新固定新的聚乙烯衬垫。该方法的治愈率为90%。Meek等使用PROSTALAC系统治疗全膝感染58例，治愈率为96%。在最终翻修前，他们研究了ESR和CRP的变化趋势，并对所有膝关节进行穿刺培养。他们在穿刺和培养前停用抗菌素4周，以减少假阴性结果。
SUMMARY
小结
Infection should be in the differential for any painful total hip or knee. A thorough history and physical, complete set of radiographs and appropriate labs including C-reactive protein and erythrocyte sedimentation rate are essential in the initial evaluation. Ancillary tests such as aspiration and nuclear imaging may be helpful in unclear cases or when labs are concerning for infection. It is essential that all antibiotics are discontinued several weeks prior to gram stain and culture, if possible, to reduce the number of false negative test results.
对任何疼痛性全髋膝关节置换，都应该鉴别诊断感染。详细病史、仔细查体、完整的X片和合适的实验室检查如CRP、ESR是初步诊断的基础。辅助检查如穿刺和核素扫描在不明确病例或当实验室检查怀疑感染时可有帮助。如果可能，为减少假阴性检查结果数量，在革兰氏染色和细菌培养前几周，停用所有抗菌素是必要的。
Classifying infection into acute versus late infection aids in the treatment plan. For acute infections presenting within 2 to 4 weeks of symptom onset, irrigation and debridement with polyethylene liner exchange and retention of components may be possible. When attempting component retention, thorough debridement and rapid treatment of the infection prior to the accumulation of any biofi lm is paramount for a successful outcome. Other important prognostic factors to consider include the virulence of the microorganism as well as the immune status of the host. Despite expeditious management, irrigation and debridement of acute total hip and knee infections frequently leads to recurrent infection. Thus, patients should be counseled accordingly. Further management may be needed following an initial attempt at component retention. These options include resection arthroplasty with or without re-implantation, long term antibiotic suppressive therapy, arthrodesis and even above the knee amputation in rare circumstances. For chronic infections, a successful outcome depends on several factors including the baseline health status of the patient, implant removal with a thorough debridement followed by culture specific antibiotic treatment. Furthermore, methods of monitoring for persistent infection include following laboratory values such as the C-reactive protein, erythrocyte sedimentation rate, and cultures from joint aspirations. Whether to perform a direct exchange versus a delayed revision arthroplasty for chronic total hip and knee infections can be debated. Several published series have reported successful outcomes with single stage procedures when patients are carefully selected. However, the majority of chronic infections in the United States are treated with two stage resection, since this method has consistently provided the highest cure rates, with many current studies demonstrating _90% success.
感染分为急性和慢性有助于制定治疗方案。对于症状出现2—4周内的急性感染，冲洗、清创、更换聚乙烯垫，保留假体是可能的。当试图保留假体时，在生物膜形成前彻底清创、迅速治疗感染对于成功治愈是至关重要的。需要考虑的另一重要预后因素包括微生物的毒力和机体的免疫状态。尽管积极处理，对全髋膝急性感染进行冲洗和清创仍常常复发。因此，应该对病人进行相应告知。在最初试图保留假体后，可能需要更进一步处理。包括进行或不进行假体再次植入的切除成形术、长期应用抗菌素、关节融合术以及极少情况下需要膝上截肢。对于慢性感染，治愈的因素包括病人的健康状况、假体取出、彻底清创，然后细菌培养，针对性抗菌素治疗。并且，监测持续感染的方法包括CRP、ESR等实验室检查和关节穿刺培养。慢性髋膝感染直接翻修或延期翻修存在争议。几篇文献报告对仔细选择的病例进行I期翻修获得成功。然而，在美国，大多数慢性感染分期翻修，该方法治愈率高，目前很多研究证实成功率为90%。
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