【专题文献】之人工髋关节置换－－<<全髋关节置换术假体周围感染的处理>>

【专题文献】之人工髋关节置换

全髋翻修讲座之一：全髋关节置换疼痛的评估 By: 宋兵乙
全髋翻修讲座之二：髋关节翻修术中内植物的取出 By: 宋兵乙
全髋翻修讲座之三：髋关节翻修术中髋臼失败的重建和翻修 By: 宋兵乙
全髋翻修讲座之四：髋关节翻修术中股骨失败的重建和翻修 By: 宋兵乙
全髋翻修讲座之五：全髋关节置换术后髋关节脱位的处理 By: 飘洋过海
全髋翻修讲座之六：全髋关节置换术假体周围感染的处理 By: shiitake
全髋翻修讲座之七：下肢假体周围骨折的处理 By：宋兵乙

MINI-SYMPOSIUM: REVISION HIP SURGERY
小讲座：髋关节翻修术之六

Management of periprosthetic infection in total hip arthroplasty
全髋关节置换术假体周围感染的处理

M.T.S. Sukeik and F.S. Haddad
Abstract
Total hip arthroplasty (THA) is one of the most commonly preferred orthopaedic procedures. Although the rate of deep infection after primary hip arthroplasty is relatively low, the economic burden, associated morbidity and mortality make it potentially devastating. Because of an ageing population will need an increasing number of arthroplasties, prevention, diagnosis and treatment of infection must be optimised in order to reduce both direct and indirect costs to patients and healthcare systems.
摘要
全髋关节置换术（THA）是目前开展最多的骨科手术之一。尽管初次髋关节置换术后深部发生率相对较低，但一旦感染发生，于此相关的经济花费负担、相关合并症和死亡危险都使深部感染成为最令人担忧的手术并发症。随着人口老龄化，需要接受关节成形术的患者逐渐增多，因此，对于手术相关感染的预防、诊断和治疗都应成为我们主要关注并完善的目标，这样才能减少对患者和医疗系统的直接或间接经济损失。

Keywords: infection ; management; presentation; revision; total hip arthroplasty
关键词：感染，处理，表现，翻修，全髋关节置换
Introduction
Periprosthetic infection in THA was one of its most common and dangerous complications in the early years of total hip replacement, with a rate as high as 9.5% reported by Charnley.1 More recently, the incidence has decreased significantly due to improvements in operating room discipline, surgical technique, more assiduous preoperative assessment of the patient, and the prophylactic administration of antimicrobial agents.2 Although rates now are around one to two percent of all primary hip replacements and five percent of revision hip arthroplasties, 3 their management, for both patient and surgeon is challenging, often requiring prolonged treatment. It is also expensive; estimated at four times the cost of a primary hip replacement without infection. 4 Additionally the infection may recur with septic loosening of the prosthesis.
Multiple risk factors for developing infection after THA have been identified including
• length of the procedure
• number of previous operative interventions
• rheumatoid arthritis
• diabetes mellitus
• sickle cell disease
• obesity
• poor nutrition
• immunosuppressive medications including systemic steroids
• history of osteomyelitis or septic arthritis
• presence of open skin lesions on the affected extremity.6
Infection following THA can be a diagnostic challenge, there is no gold standard for determining whether an infection is present and none of the tests available are 100% sensitive and 100% specific.7 The treatment of an infected THA leads to a long and difficult course for the patient, and frequently leads to a suboptimal functional outcome. An infected THA should be approached with careful preoperative assessment and a well defined treatment plan, which depends on many factors including:
• acute or chronic infection
• infecting organism, its antibiotic sensitivity and its ability to manufacture glycocalyx
• the health of the patient
• fixity of the prosthesis
• bone stock
• the particular philosophy and training of the surgeon
简介
在全髋关节置换术开展的早期，假体周围感染是最常见且最为严重的并发症。据Charnley报道，假体周围感染的发生率高达9.5%。近来，随着手术室规章制度、手术技术、患者术前评估的完善及预防性抗生素的使用，感染的发生率已经显著降低。尽管目前初次THA手术感染的发生率仅为1-2%，THA翻修中为5%，其对患者和术者来说仍是很大的威胁和挑战，并且患者往往需要接受冗长的治疗。同时，治疗的费用也十分昂贵，约为未发生感染的初次髋关节置换术花费的4倍。此外，随着感染导致假体松动的发生，感染可能还会复发。以下为THA术后感染发生的危险因素：
• 手术耗时
• 术前接受治疗的次数
• 风湿性关节炎
• 糖尿病
• 镰状红细胞贫血
• 肥胖
• 营养不良
• 免疫抑制药物，包括全身使用激素
• 既往骨髓炎或感染性关节炎的病史
• 患肢存在开放性皮肤损伤病灶
THA术后发生的感染有时难以进行诊断，目前尚无诊断的金标准，并且现有检查手段均难以达到100%的特异性和敏感性，其治疗对于患者来说是极其艰难的过程，且往往导致患者功能恢复不良。为防止THA术后感染的发生，应该进行仔细的术前评估，并制定完善的治疗方案，重点关注以下因素：
• 急、慢性感染
• 致病菌及其对抗生素的敏感性和产生蛋白多糖的能力
• 患者的健康状态
• 假体固定的稳定性
• 骨存量
• 术者的训练水平和独到见解


















Prevention of infection and microbiologic considerations
While infection after THA may be caused by haematogenous seeding, it is more commonly due to bacteria entering the wound at the time of surgery, either from the patients skin flora or airborne bacteria from the operating theatre environment including from theatre staff. Many studies have demonstrated that individuals moving around the operating theatre contribute the largest proportion of pathogenic bacteria to the wound. This led to the introduction of a controlled operating environment, such as laminar air flow and Charnley's ultraclean air system with sterile hoods and a body-exhaust system. Together with prophylactic antibiotics, these have reduced rates of infection from 9% to 1.3%.
To use the appropriate antibiotics for prophylaxis and treatment, a good understanding of potential pathogens contaminating surgical wounds is essential. Staphylococcus aureus and Staphylococcus epidermidis are the most common infecting organisms in periprosthetic hip infections, accounting for approximately 85%–90% of cases. Some common but less frequent organisms include Streptococcus species and gram negatives such as Pseudomonas, Klebsiella, and Escherichia coli. These are usually secondary invaders of open, draining wounds in patients with deep sepsis of a hip arthroplasty. Anaerobic microorganisms are isolated in 10% of such patients.11 Occasionally, the treatment of the infected arthroplasty is complicated by polymicrobial infections with particularly virulent organisms such as Group D Streptococci, Pseudomonas, fungal or mycobacterial infections which can be difficult to both diagnose and treat due to recurrent sepsis.12 Increasing infection involving methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis has also emerged.
Resistance has been attributed to the ability of the organism to produce a slime layer, or a biofilm of glycocalyx. This layer is made up of a variety of polysaccharides synthesised by the bacteria, as well as a range of host molecules which enables the organism to adhere to and survive on synthetic surfaces. Bacteria that exist within a biofilm are at least 500 times more resistant to antibiotics than bacteria which exist as individual free-floating cells.
Antimicrobial prophylaxis has been established as the single most significant factor in the prevention of deep wound infection following total hip arthroplasty. 14 The classes of antibiotics used include the β-lactams such as cephalosporins, penicillin and its derivatives, glycopeptides such as teicoplanin, and aminoglycosides such as gentamicin. Al-Maiyah et al.15 reported an increased resistance of coagulase negative staphylococci to cephalosporins and recommended a revised prophylaxis strategy avoiding cephalosporins, but Al Buhairan et al.16 showed in a systematic review of antibiotic prophylaxis in joint arthroplasty that there is no evidence that any type of antibiotic prophylaxis has better results than any other and that selection should be on the basis of cost and local availability. There is insufficient evidence to determine if there is a threshold prevalence of MRSA at which switching from non-glycopeptide to glycopeptide antibiotic prophylaxis might be clinically effective and cost-effective.17 Furthermore, the American Academy of Orthopaedic Surgeons has suggested routine antibiotic prophylaxis for 2 years after THA prior to various procedures associated with significant risk of bacteraemia such as dental cleaning and extraction.
The role of antibiotic loaded cement (ALC) in primary hip arthroplasties has also been assessed in prospective studies in over 1600 cases. In data from the Scandinavian arthroplasty registers, with an exhaustive follow-up of more than 2,400,000 hip replacements, infection rate was reduced by 50%. Human pharmacokinetics during total hip replacement showed antibiotic concentrations 20 times the minimal inhibitory concentration (MIC) in drainage fluids. No toxic concentrations have been detected in blood or urine, and no allergies, toxic effects, mechanical failures or selection of resistant microorganisms have been observed. Therefore, ALC prophylaxis is now widely used in countries with prostheses registers. The most commonly used antibiotics in ALC include tobramycin, gentamicin and vancomycin.21 The combination of vancomycin and one of the aminoglycosides provides a broad spectrum of coverage for organisms commonly encountered with deep periprosthetic infections. The presence of tobramycin has a synergistic like effect on the bactericidal activity of vancomycin. A low dose of ALC (≤ 1 g of antibiotic per batch of cement) should be used for prophylaxis. However, when used in treatment of infected THA, ALC is used in higher doses as an adjuvant to excision of infected and devascularised tissues and systemic antibiotic treatment.22 Antibiotics leach from Palacos bone cement in higher concentrations and for longer periods than from Simplex-P, CMW, and Sulfix acrylic bone cements.19 Furthermore, Palacos with gentamicin is more resistant to fracture than Zimmer or Simplex-P cement mixed with gentamicin.
Other general measures to prevent infection include stopping smoking, weight loss in the obese and control of co-morbid diseases, such as diabetes, sickle cell disease and rheumatoid arthritis. Temporary cessation of medications such as methotrexate also decreases infection risk23 although this needs to be balanced against the risk of a rheumatoid flare. In theatre, staff should be kept to a minimum, appropriate use of gowns, face masks, double gloving and hand-washing should always be implemented and duration of surgery should be kept as short as possible. The use of pulsatile lavage has also been reported to remove up to 87% of all organisms from wounds.In the perioperative period, periodontal and urinary tract sepsis must be eradicated early to prevent haematogenous seeding of the prosthesis.
感染的预防和微生物学基础
THA术后感染可能由血源性种植引起，通常因术中细菌直接进入术口。其可以来源于患者皮肤的定植菌群或手术室环境（空气和手术人员）的细菌。很多研究都证实手术人员在手术室的走动是导致致病菌进入术口的最大原因。由此，各国逐渐将层流系统和Charnley的超洁净空气系统（包括消毒面罩和隔离系统）引入对手术室环境的控制中。通过使用以上方法，并预防性使用抗生素，感染率已经从9%下降到了1.3%。
为了恰当地使用合适的抗生素进行预防性治疗，我们应当很好地了解污染术口的潜在病原菌。金黄色葡萄球菌和表皮葡萄球菌是髋关节假体周围感染最常见的病原菌，占所有病例的近85%–90%。另外还有一些常见但出现率不高的病原菌，包括葡萄球菌属和葛兰阴性菌，如假单胞菌、克雷白菌核和大肠埃希菌。上述细菌通常继发于髋关节成形术后深部感染的开放引流操作。在10%的患者体内分离出了厌氧菌。偶尔，对关节成形术后感染的治疗可能并发多重细菌性感染，通常由具有特定毒力的细菌引起，如D族葡萄球菌、假单胞菌、真菌或分支杆菌，这些细菌往往导致感染反复发作，在诊断和治疗上均较为困难。此外，耐甲氧西林金葡菌和表皮葡萄球菌所致感染的发生也有所增加。
耐药性的产生是由于细菌能够分泌层粘液或产生蛋白多糖生物膜。这一保护层由细菌合成的多种多糖及宿主的一系列分子所共同构成。这一保护层使细菌得以粘附与其上并且在合成魔膜上继续生存。处于生物膜内的细菌，其耐药性至少是处于个体自由细胞内细菌的500倍。预防THA术后深部感染最重要的措施就是预防性抗感染。可以使用的抗生素有β内酰胺类，如头孢菌素、青霉素及其衍生物；糖肽类，如替考拉宁和氨基糖苷类（如庆大霉素）。Al-Maiyah等发现凝固酶阴性葡萄球菌对头孢菌素的耐药性不断增高，并推荐术者使用其他种类的抗生素。但他们同时还对关节成形术中抗生素的预防性使用做了系统评价，结果表明尚无证据显示某种抗生素的效果更加明显，因此，抗生素的选择应基于局部适应证和经济考虑。目前尚无充足的证据表明，当从非糖肽类抗生素转而使用糖肽类抗生素（效果可能更好，且效价比更高）时，是否存在MRSA感染发生的阈限。此外，美国矫形外科医师学院建议，在THA术后的两年内，当患者接受可能引发感染的相关治疗时（洗牙或拔牙），均应常规预防使用抗生素。
已经有研究评估了在超过1600例初次接受髋关节成形术患者中，抗生素骨水泥（ALC）的作用。斯堪的纳维亚关节成形注册中心的数据表明，在对超过2400000例髋关节置换术的随访中，感染的发生率降低了50%。在人体药代动力学的研究表明，在全髋关节置换术中引流液内的抗生素浓度是最小抑菌浓度的20倍。尿液和血液中抗生素浓度未达其毒性剂量，并且患者未出现过敏、毒副作用或对细菌的选择性耐药等表现。因此，ALC目前已经在各国得到广泛使用。ALC中最常使用的抗生素包括妥布霉素、庆大霉素和万古霉素。联合使用万古霉素和另一种氨基糖苷类抗生素可以扩大抗菌谱，基本能够覆盖目前在深部假体周围感染的常见细菌。妥布霉素与万古霉素一同使用，对其抑制细菌活性的作用具有协同效应。混合较低剂量抗生素的骨水泥(每份骨水泥中抗生素≤ 1g)可用于预防性抗感染治疗。当ALC用于治疗THA感染时，需要加入较高剂量的抗生素。此时，抗生素的用途是辅助去除感染和缺血组织，并达到全身性治疗的目的。对比Simplex-P、CMW和磺胺异噁唑丙烯酸骨水泥，Palacos骨水泥中的抗生素释放的浓度较高，且持续作用时间更长。此外，相比加入庆大霉素的Zimmer或Simplex-P骨水泥，Palacos骨水泥（加入庆大霉素）能够更好地预防骨折的发生。
戒烟、肥胖患者减轻体重和控制合并症（如糖尿病、镰状红细胞病和风湿性关节炎）也能够预防感染的发生。暂时停用药物（如甲氨喋呤），也能够降低感染发生的风险，当然，应该充分权衡控制风湿疾病和预防感染的利弊。对于手术室人员，应该注意以下几方面：尽量减少手术室内人数、恰当地穿着手术服、穿戴口罩、戴双层手套和注意刷手，并尽量缩短手术时间。据报道，使用脉冲灌洗也能够去除术口近87%的细菌。在围手术期，患者如存在牙周病和尿路感染，应该尽早接受治疗以防止假体处细菌通过血源性种植。





Classification
Classification systems are based on the time of onset of symptoms after surgery and the route by which the infecting organism gained access to the joint space. Coventry26 in 1975, classified infections after THA into three stages:
• Stage I acute infections developing within three months of surgery caused by contamination at the time of operation
• Stage II delayed infections which are more indolent and may not become apparent until several months after the hip replacement but are also related to contamination at the time of surgery
• Stage III haematogenous infections associated with an infection remote from the hip joint e.g. respiratory, dental and urinary tract infection, which may develop soon after the remote infection or as late as two or even several years after the hip replacement.
Tsukayama et al.27 D.T. Tsukayama, R. Estrada and R.B. Gustilo, Infection after total hip arthroplasty: a study of the treatment of one hundred and six infections, J Bone Joint Surg 78A (1996), pp. 512–523. View Record in Scopus | Cited By in Scopus (241)27 expanded the classification into four categories to aid the management of these patients:
• positive intra-operative cultures found when undertaking a revision THA. The infection should be treated with six weeks of intravenous antibiotics and no additional operative intervention
• early postoperative infections (occurring less than 1 month postoperatively) when treatment should include debridement, retention of the prosthesis, and intravenous antibiotics
• late chronic infections (occurring more than 1 month postoperatively with an insidious onset) requiring removal of the prosthesis and a staged revision
• acute haematogenous infections. If the prosthesis is well fixed debridement is sufficient. If the prosthesis is loose, treatment should be the same as for a late chronic infection.
分型
对于假体周围感染的分型主要基于术后症状出现的时间和致病菌进入关节间隙的途径。1975年，Coventry将THA术后感染分为3个阶段：
• 第一阶段:由于术中感染导致的术后3个月内发生的急性感染
• 第二阶段：与书中污染有关，但在术后数月可能无明显临床症状的迟发型感染
• 第三阶段：与髋关节感染有关的远隔部位血源性感染，如呼吸、口腔和泌尿系感染。感染可以发生在任何时间。
为更好地治疗假体周围感染的患者，Tsukayama等将分型系统进一步分为四个组别：
•THA翻修术中细菌培养阳性组。应至少静脉用抗生素治疗6周，且不能再进行手术干预。
•早期术后感染 (术后1周内)组。治疗方法包括清创、保留假体和静脉应用抗菌药物。
•晚期慢性感染（术后1月以后隐匿发病的）组。治疗上应取出假体，二期实施翻修手术。
•急性血源性感染组。应保证假体固定的牢固，患处得到彻底的清创。如果假体出现松动，治疗方法应与晚期慢性感染相同。









Clinical presentation
History and examination
A thorough history and physical examination are essential. Acute prosthetic infections are caused by infected haematomas or superficial wound infections spreading into the deep periprosthetic space and present in the immediate postoperative period with continuous pain. The patient may have an erythematous, swollen and fluctuant wound with purulent discharge and systemic signs of infection including fever, chills and sweating.
Chronic infections are characterised by gradual deterioration of function and persistent pain from the time of the operation, classically presenting after a few months from the index procedure. A history of prolonged hospital stay after the surgery, a prolonged course of antibiotics and continuous wound discharge are important in the diagnosis, as symptoms and signs may be nonspecific.28
Haematogenous infections can occur early or late in relation to joint surgery. However, the typical case is of a prosthesis that has been functioning well for months or years that suddenly becomes painful and swollen associated with systemic manifestations, such as fever and chills. This type of infection is more likely to occur in immunocompromised patients. Early diagnosis may allow salvage of the prosthesis by means of a thorough debridement, whereas a delay in diagnosis may necessitate a staged exchange procedure in order to eradicate the infection.
临床表现
病史和检查
彻底地询问病史和物理检查是非常必要的。急性假体感染通常由污染的血液或表浅创口感染扩散至深部的假体周围，可在术后即可表现为持续性关节疼痛。患者可出现红斑、肿胀和反复排出的术口化脓性液体，并可伴有全身性感染症状，包括发热、寒战和发汗。
慢性感染主要表现为逐渐严重的功能障碍和术后持续性疼痛，上述症状通常在术后几个月内出现。由于患者的症状通常不典型，术后住院时间延长、应用抗生素时间延长和持续的术口渗出都有助于诊断。
血源性感染可以在关节术后早期或晚期发生。有时，患者在术后功能恢复良好，但数月或数年后突然出现疼痛和肿胀，并伴有发热和寒战等全身表现。此类型感染更多见于免疫缺陷的患者。早期的诊断可能有助于保留假体，但需要在诊断后进行彻底清创。因此，如未能早期进行诊断，患者可能需要接受择期手术，以彻底清除感染。




Investigations
It is essential that the relative utility of preoperative and intra-operative tests used to diagnose periprosthetic sepsis are thoroughly understood.7
Helpful laboratory investigations include the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The white blood cell count is usually unhelpful and is often normal even in patients with an actively infected hip and cannot relied upon to exclude infection. 29 CRP level is a sensitive indicator of postoperative infection; it reaches maximum values within 48 hours from surgery, returning to normal levels within 2 to 3 weeks. However the ESR may remain elevated for months after an uncomplicated THA. Therefore, a persistently elevated CRP is more accurate in identifying patients with a deep infection. 30 In a study of 202 hip replacements, Spangehl et al.29 demonstrated that all thirty-five cases complicated by deep infection were in patients who had an ESR of >30 mm/hr (sensitivity 0.82, specificity 0.85) or a CRP of >10 mg/L (sensitivity 0.96, specificity 0.92). They suggested that a normal ESR and CRP effectively excludes the possibility of infection at the site of a THA and that combining both tests should improve the accuracy of diagnosis. It is essential though to recognise that both ESR and CRP are nonspecific markers of inflammation that may be elevated in other conditions such as rheumatoid arthritis, neoplasia, collagen vascular disease, other inflammatory conditions and after a recent operation.
Plain radiographs should be taken of all failed arthroplasties and can occasionally provide clues to infection, but they are neither sensitive nor specific for detection of infection. Radiographic findings including loosening, osteolysis and endosteal scalloping are common to both septic and aseptic failures. Periosteal new bone formation has been considered by some to be suggestive of infection. 29
Hip joint aspiration is used to evaluate patients with non-inflammatory arthritis with a painful total hip arthroplasty and an elevated ESR or CRP levels. It is also useful when ESR and CRP levels are elevated in chronic inflammatory conditions. However, the reported rates of sensitivity and specificity have varied widely in the literature, with the sensitivity ranging from 0.50 to 0.93 and the specificity ranging from 0.82 to 0.97. Therefore, a strict aseptic technique is imperative to reduce false positive results as well as preventing iatrogenic periprosthetic infection. It is also essential that all antibiotics are discontinued several weeks prior to joint aspiration to reduce the number of false negative test results.
Nuclear medicine studies are second-line investigations of patients with infected THA when serologic tests may be falsely elevated and aspiration cultures from the hip joint unreliable because of the administration of antibiotics. However, its use is limited by cost, the time to undertake the procedure and because scans can remain positive for as long as one year after a hip replacement due the surgery itself or complications such as heterotopic ossification. Various isotopes including Technetium-99 m, Gallium-67 citrate, and Indium-111-labeled white blood cells have been used, resulting in a wide range of sensitivities and specificities in detecting periprosthetic infection. Pakos et al.33 reported in a recent meta-analysis of antigranulocyte scintigraphy with monoclonal antibodies a reasonably high discriminating ability to identify prosthesis infection in patients who underwent THA (sensitivity 90%, specificity 80%).
Intra-operative evaluation at revision THA, including tissue appearance combined with intra-operative gram stains, are unreliable for detecting periprosthetic sepsis, and neither is adequate alone for ruling out infection. 7 Intra-operative frozen section has been shown to be a useful tool for identifying infection during the revision procedure, depending on the area and number of tissue samples obtained, the availability of an experienced pathologist to interpret the results and the number of white blood cells visualised per high power field. Lonner et al.34 in a prospective study of 175 revision arthroplasties recommended using 10 white blood cells/high power field for diagnosing periprosthetic infection (sensitivity 0.84 specificity 0.99). Intra-operative culture, although assumed to be the gold standard for identifying periprosthetic infection, is subject to false-negative and false-positive results. As with joint aspiration, careful technique and withholding antibiotics for a few weeks preoperatively are essential in reducing false results. A minimum of five tissue samples should be sent to the laboratory for processing to rule out infection.
实验室检查
在术前术后使用相应的实验诊断方法对假体周围感染的诊断同样重要。
对诊断有帮助的实验室检查包括血沉（ESR）和C反应蛋白（CRP）。白细胞计数通常对诊断没有价值，并且在活动性髋部感染的患者中仍为正常水平，因此，不能依靠该指标排除感染的可能。CRP水平是预测术后感染的敏感指标，其在术后48小时内达到最高值，在术后2-3周后恢复正常。在复杂的THA术后，ESR的水平可能会持续升高数月。因此，持续性升高的CRP水平，对于患者深部感染的诊断较为准确。Spangehl等对202例髋关节置管的患者进行了研究，所有伴发深部感染的34例患者，ESR均>30 mm/hr (敏感性为 0.82, 特异性为 0.85)，或 CRP >10 mg/L (敏感性 0.96,特异性 0.92)。据此，Spangehl等认为ESR和CRP水平的正常能够有效地排除THA手术感染的可能性，并且可以增加诊断的准确性。但应注意ESR和CRP都不是反映炎症的特异性指标，可能在类风湿关节炎、肿瘤、血管胶原病、其他炎症反应或大手术后均表现异常。
应对所有关节成形术失败的患者进行平片检查，有时能够发现感染的证据，但特异性和敏感性均较差。平片的表现主要有假体松动、溶骨显像和骨膜扇状征，但在非感染性并发症中也均可能出现。骨膜周围新骨形成被认为是提示感染的有力证据。
对伴有THA术后疼痛和ESR或CRP水平增高的非炎性关节炎患者，可使用髋关节穿刺进行评价，并且髋关节穿刺对慢性炎症伴ESR和CRP水平增高的情况也具有诊断价值。 但其该检查的特异性和敏感性各项研究结论不一，其中敏感性（0.50-0.93），特异性（0.82-0.97）。因此，需要在穿刺过程中严格注意无菌技术，以降低诊断的假阳性率，并且可以预防医源性假体周围感染的发生。此外，在进行穿刺检查前，应至少停用抗生素数周，以降低结果的假阴性率。
当血清学检查和穿刺检查均无法确定是否存在THA感染时，可以选择核医学的相关检查方法。核医学检查费用高、耗时长，且在髋关节置换术后1年，由于手术本身或并发症（如异位骨化）的原因，检查结果也有可能为阳性。尽管目前核医学检查所可供选择的同位素种类很多，如锝99m，镓67枸橼酸盐和铟111标记的白细胞，但各种方法对假体周围感染诊断的敏感性和特异性不一。Pakos等所报道的有关使用单克隆抗体-抗粒细胞闪烁现象技术的荟萃分析显示，该技术能够较好地诊断THA术后患者是否发生假体周围感染(敏感性90%,特异性 80%)。
在THA翻修术中，通过格兰染色观察的方法以确定是否存在假体周围感染，其结果不甚可靠，因此，不能够依据该检查结果排除感染的诊断。在翻修术中进行冰冻切片检查，对诊断是否存在感染较有价值，但其结果取决于组织标本的切取部位和数量，并且需要由经验丰富的病理科医生对其结果进行判读（包括计数每个高倍镜视野下的白细胞数量）。Lonner等进行了一项对175例返修手术患者的前瞻性研究。他们推荐使用白细胞计数（10/HPF）作为诊断假体周围感染的标准 (敏感性0.84，特异性0.99)。术中进行细菌培养，尽管被认为是诊断假体周围感染的金标准，但易受到假阴性或假阳性结果的影响。在关节穿刺检查中，应在操作中注意无菌技术并在操作前停用抗生素一段时间，以降低假阴性率。此外，在操作中，应至少取得5块组织样本。






Management
The goals of treatment are the eradication of infection and the restoration of function of the affected limb. Treatment options include
• debridement with retention of components
• single-stage revision
• two-stage revision
• multi-stage revision and long term suppressive antibiotics
• salvage procedures.
The extent of infection and the length of time it has been present affect the choice of the revision procedure and the success rate following revision.3 Classifying infection into acute or late infection aids in the treatment plan. Treatment of mycobacterial infections follows the same guidelines.
处理
治疗目标是去除感染病恢复患肢功能。治疗方案包括：
• 保留假体等植入物的清创术
• 单次翻修手术
• 分期进行两次翻修手术
• 分期多次翻修手术，并长期使用抗生素
• 挽救手术
感染的程度和感染的持续时间都会影响翻修手术方法的选择和手术成功率。因此，可以在指定治疗计划时，将感染分为急性和慢性感染两类。抗菌治疗应统一按照指南进行。







Acute infection
Debridement with component retention
For early or late infections with a short duration of symptoms, stable components, no significant immunosuppression and overlying soft tissue and skin of good condition, irrigation and debridement with exchange of mobile parts (femoral heads and acetabular inserts) but retention of the infected implant has been advocated.[38] and 39 W. Zimmerli, A. Trampuz and P.E. Ochsner, Prosthetic-joint infections, N Engl J Med 351 (2004), pp. 1645–1654. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (33)[39] The aim of rapid intervention with thorough debridement is the prevention of the production of a biofilm by the infecting organism which is essential for a successful outcome.40 Difficulties include determination of the time of onset of infection and the establishment of a point beyond which it is no longer reasonable to retain the implant. Davis et al.38 suggested up to two weeks for early infection and up to 72 hours for acute haematogenous, late infection whereas Zimmerli et al.39 recommended a period of three weeks for both early and late infections. Despite expeditious management with irrigation and debridement, acute total hip infections may lead to recurrent infections. Success rates in the literature range between less than 10% and more than 50%.[41] and [42] Thus patients should be advised that further treatment may be necessary if the attempt to retain the prosthesis is unsuccessful including a staged revision or salvage procedures.
Debridement with single-stage revision
At our institution, for acutely infected uncemented prosthesis following aggressive debridement, we then proceed to a single-stage revision with ALC. This is an ideal opportunity to remove both the implant and biofilm, prior to in-growth. Over the past 7 years, in a series of 28 patients with acutely infected hip prostheses, 21 patients (75%) are now infection free at a minimum 1-year follow-up. 10 were treated within 5 days of the onset of symptoms, and of this group only one went on to have a re- infection. In contrast, of the remaining 18 patients that were treated more than 5 days after the onset of symptoms, 7 had re- infections. We emphasise the importance of a swift and accurate diagnosis, ensuring prompt treatment to maximise the likelihood that the prosthesis will be salvaged.
急性感染
保留假体等植入物的清创术
如患者伴有短期症状的早期或晚期感染、假体等植入物稳定、没有明显的免疫抑制及软组织和皮肤情况较好，可以进行患处冲洗、清创并更换假体的活动部分（股骨头和髋臼），保留受感染的假体植入物部分。进行快速干预的目的在于，通过施行清创术防止致病菌生物膜的形成，对治疗能否成功至关重要。治疗中的困难包括：确定感染发生的时间并在能够保留假体植入物的允许时间内开始治疗。Davis等建议早期感染和晚期急性血源性感染的治疗窗分别为2周和72小时，而Zimmerli等建议两种感染的时间窗均为3周。有时尽管进行了迅速的冲洗和清创治疗，急性THA感染仍有可能演变成为复发性感染。文献所报道的成功率在10%至50%之间。如保留假体未能成功，应建议患者接受进一步的治疗，包括分期翻修术或挽救手术。
单次清创、翻修术
在笔者的医院，对于在清创术后的出现急性假体周围感染（未用骨水泥），通常使用ALC进行单次翻修术，因为这是去除细菌及其生物膜的最好机会。在过去7年中，28例急性髋部假体感染的患者中，有21例在最少1年的随访中未再出现感染(75%)，10例在症状出现后的5天内接受了治疗，并且其中仅有一例出现了感染复发。另外的18例患者在症状出现的5天后接受了治疗，其中7例感染复发。因此，我们强调迅速、准确地诊断的重要性，以便尽可能确保假体能够得到保留。




Chronic infection
Reimplantation into a sterile bed is the goal of treatment and can either be performed at the same stage as debridement as part of a single-stage procedure, using cemented components with ALC or, alternatively, as part of a two or multi-stage procedure where debridement and reimplantation are separated by a period of antibiotic delivery, both locally and systemically.[43] and [44]
Single-stage revision
The advantages of simultaneous debridement and exchange of the prosthesis include the avoidance of additional surgical procedures for patients who have major medical problems, for whom the risks of additional procedures are cumulative. Success rates for eradication of infection with single-stage revisions ranged between 76-82% in most studies when ALC has been utilised in comparison to only 58% without ALC.[35], [45] and [46] When ALC is used for prosthesis fixation in single and two or multi-stage revisions, the dosage recommended is usually 1 or 2 g per 40 g of bone cement to avoid mechanical weakening.47 However, Jackson et al.48 in a review of the literature reported that the indications for direct exchange are limited by several factors including
• Failures associated with polymicrobial infection, gram-negative organisms (especially Pseudomonas sp) and certain gram-positive organisms such as methicillin-resistant Staphylococcus epidermidis and Group D Streptococcus
• Patients with significant bone stock deficiency cannot be managed with this technique because single-stage revision requires that the implant be inserted with ALC
• Lack of data on the use of bone graft in association with single-stage revision
• Difficulties with removal of a solidly fixed cemented prosthesis without destroying the remaining proximal femoral bone stock should the procedure fail to eradicate the infection.
Nevertheless, single-stage revision remains a viable option which is associated with less morbidity and is cheaper than delayed exchange when used in carefully selected patients.
Two-stage revision
Two-stage reimplantation is the gold standard for the treatment of infected total hip replacements. The successful eradication of a THA infection is over 90%.[49] and [50] Furthermore, it permits uncemented reconstruction and the use of allografts, which is particularly important given the frequency of femoral and acetabular defects associated with THA infections. [51], [52] and [53] Alexeff et al.54 used massive structural allografts in the second stage of a two-stage procedure in 11 patients. They reported no additional sepsis at a mean follow-up of 4 years. The principles of two-stage revision include removal of the implant along with all cement and necrotic tissue which contain the infecting organisms, administration of systemic antibiotics postoperatively for 6 to 12 weeks followed by implantation of a new prosthesis. A patient is deemed free of infection and able to proceed to second-stage arthroplasty when repeat joint aspirates after 4 weeks of discontinuing antibiotics are negative, and the ESR and CRP return to normal values.
Two-stage revision arthroplasty using ALC but without a prolonged course of antibiotic therapy has also been reported by Stockley et al.63 in a series of 114 patients for chronic THA infections. Infection was successfully eradicated in 100 patients (87.7%) at a mean follow-up of two years.
Multi-stage revision
A three-stage reimplantation procedure is suitable for treatment of extensive bone defects in which the use of a large amount of morcellised allograft can be anticipated. The bone bed created is allowed to incorporate for about 6 months and, in most cases, a cementless implant is then inserted.64 Multi-stage revision is also indicated when clinical presentation, blood parameters and cultures are suggestive of persistent infection requiring further debridement and possible repeat of PROSTALAC to eradicate infection after the first stage of revision.
Long term suppressive antibiotics
Chronic suppressive therapy for periprosthetic infections is indicated when an operation is refused by the patient or is has an unacceptable risk in medically unfit patients. Infection is controlled rather than eradicated. The infecting organism must be identified and sensitive to the chosen antibiotic which should be effective orally and tolerable by the patient. Failures of treatment are due to the patient developing side effects or recurrent candidiasis and the emergence of resistant strains.
慢性感染
治疗的目标是建立无菌的植物床，以保证植入物被重新植入体内。通常治疗方法有两种：一是单次翻修手术，在清创的同时，使用ALC进行假体修复；二是多次手术，在清创术和重新植入手术之间，进行一段时间的局部或系统的抗生素治疗。
单次翻修手术
同时进行翻修和假体置换的优点在于使病情较重的患者免于接受多次手术，因为这些患者的手术风险较高。多数研究证实，使用ALC的单次翻修术，成功率在76-82%之间，未使用ALC时，成功率仅为58%。在单次或多次翻修术中使用ALC进行假体固定，其抗生素的推荐剂量为、1 或2 g/40 g 骨水泥，以避免其固定强度的降低。Jackson等发表的综述提示，直接进行假体更换的指征收到以下一些因素的影响：
• 与多种细菌感染相关的手术失败，包括格兰阴性菌(特别是假单胞菌)和某些格兰阴性菌，如耐甲氧西林的表皮葡萄球菌和D族葡萄球菌
• 患者骨存量明显不足，不能使用单次翻修手术治疗，因为该疗法要求在植入物中加入
• 与单次翻修手术相关的骨移植物使用的数据仍然较少
• 在移除使用骨水泥坚强固定假体的同时，必须保证不影响远端股骨的骨存量，是非常困难的，因此，手术往往难以彻底地清除感染。
尽管如此，单次翻修术仍是较好的选择，因为其相比延迟手术，患者的死亡率较低，手术费用更少。
分期翻修手术
分期进行翻修手术是治疗全髋关节置换术后感染的金标准，其成功率超过90%。而且，术者能够在不使用骨水泥的情况下，进行假体重建，同时术者可以使用异体骨移植，这对于THA感染后股骨和松质骨缺损是非常重要的。Alexeff等在分期翻修术的第二阶段中，使用了大块同种异体骨移植。在对接受手术的11例患者进行的平均时间为4年的随访中，未见患者出现其他感染。分期翻修术的原则包括：在移除移植物的同时，去除全部的骨水泥和坏死组织（因为坏死组织能够保存致病菌）；术后系统性应用抗生素6到12周，再重新植入新的假体。此后，患者在感染彻底消除后，才能进一步接受第二阶段的关节成形术。感染去除的标准为：在停用抗生素后4周，反复关节穿刺结果为阴性，同时ESR和CRP恢复正常水平。
Stockley等还报道了在分期翻修术中使用ALC，但未长期使用抗生素的治疗效果。在114例慢性THA感染患者中，平均时间为2年的随访提示，共有100例(87.7%)患者的感染彻底得到消除。
多阶段的翻修手术
三阶段翻修术适用于骨缺损程度重的患者，因为在治疗中能够使用粉碎的议题骨移植物。股床建立后，有6个月的时间允许术者进行骨移植。对于大多数患者，在6个月内，都接受了无骨水泥的植入物手术。多阶段翻修手术的适应证还包括：临床表现、血检指标和培养提示感染持续存在，需要进一步清创或需要在第一阶段翻修术后，重复使用含抗生素骨水泥假体（PROSTALAC）以根除感染。
长期使用抗生素
对假体周围感染的长期抑菌治疗指征为：患者拒绝接受手术或患者的身体情况难以耐受手。此时，控制感染比根除感染更为重要。在治疗过程中，应该明确致病菌，选择敏感的口服抗生素，提高患者的依从性。治疗的失败往往是由于患者出现不良反应，或复发性念珠菌病，或出现出现耐药菌的感染。















Salvage procedures
Girdlestone arthroplasty
In life threatening or intractable hip infection or when limb viability is at risk, hip excision arthroplasty should be considered.50 Other indications include the elderly patient incapable of mobilising independently, those who are mentally impaired and may be unable to cooperate with the postoperative rehabilitation process, uncooperative patients such as intravenous drug abusers and immuno-compromised patients.8 Girdlestone arthroplasty is primarily aimed at pain relief and infection control. However, such patients must be warned to expect at least 2–3 cm of limb shortening and reliance upon a walking aid postoperatively.66 The greater the bone loss, the more unsatisfactory an excision arthroplasty becomes.
Arthrodesis
This is an alternative treatment in THA infection described by Kostuik and Alexander67 in a series of 14 patients where the indications were a young age, male gender and strenuous functional demands. Although all hips eventually fused and patients were able to mobilise independently, patients had an average of 4.6 cm limb-length discrepancy.
Amputation
Amputation is rarely necessary and is generally reserved for patients with life threatening infections, multiple unsuccessful revisions and vascular injuries.
挽救手术
Girdlestone关节成形术
但感染危机生命、难以进行控制，或患肢的活力受到影响时，应考虑进行髋关节切除加成形术。其他的指征还包括难以独立进行活动的老年患者，智能障碍以至不能配合术后康复性训练的患者，以及不能配合治疗的静脉药物成瘾或免疫缺陷患者。Girdlestone关节成形术主要旨在缓解患者的疼痛，并控制感染。但是，患者应在术前被告知，在术后患肢可能会缩短2–3 cm，并且在术后需要依赖于行走的辅助设备。切除骨量越多，治疗的效果越难以另患者满意。
关节固定术
该手术可以作为THA感染的选择之一，由Kostuik和Alexander首先提出。在其报道的14例患者中，手术指征是年轻、男性和患者较高的功能要求。尽管所有的髋部最终会融合，患者能够独立进行活动，患者的肢体仍不可避免地平均缩短4.6。
截肢
通常不考虑进行截肢术，只有在患者出现危及生命的感染，或经历多次不成功的翻修手术及伴有血管损伤的时，才考虑进行截肢手术。






ALC spacers
Using ALC as spacers during the intervening treatment period to deliver antibiotics locally has been popular due to the even higher rates of eradicating infection achieving up to 95% in several studies.[55] and [56] It increases local antibiotic levels up to 200 times higher than those for systemic administration and prevents debris from accumulating in the potential joint space and soft-tissue contractures.57 When used in temporary spacers, antibiotic dosages up to 20 g per 40 g of bone cement can be achieved without reported systemic side effects.58 For fungal infections, 100 to 150 mg of amphotericin B is typically added to the 40 g of bone cement in addition to other antibiotics chosen.
There are various types of spacers. Although ALC beads were used previously, they are rarely used today in the treatment of the infected THA due to the associated scarring and as a result, the difficulty in identifying and removing them at the 2nd stage procedure.59
Static/nonarticulating spacers
Static or simple block spacers aim to maintain the dead space and are mostly used in the acetabulum. They facilitate surgical dissection at reimplantation and allow delivery of the antibiotics of choice according to sensitivities. Typically 20 g of bone cement mixed with at least 2 or 3 g of powdered antibiotic provides an adequate volume for the acetabular defect. The disadvantage of a static spacer is that it does not allow physiological motion of the joint but this has been associated with less generation of debris in comparison with mobile spacers.
Medullary dowels
A tapered cement dowel fashioned from the nozzle of a cement gun provides an excellent size and shape for a spacer to be inserted into the medullary canal of the femur during treatment of an infected THA. A small bulb is left at the end of the dowel to prevent distal migration and help facilitate removal. Disadvantages include the potential for proximal femoral migration and they cannot be used in patients with severe femoral bone loss.[60] and [61]
Mobile/articulating spacers
The aim of this technique is to allow the patient to move the joint through a range of motion between prosthesis removal and insertion of the new prosthesis. The Prosthesis of Antibiotic Loaded Acrylic Cement (PROSTALAC) first developed by Duncan and Beauchamp62 was composed of a metal femoral endoskeleton component covered with ALC. The cement of the femoral head articulated with the bone of the acetabular bed, which unfortunately could lead to bone erosion and discomfort. Therefore an acetabular cement component was introduced; preventing loss of acetabular bone, but the cement-on-cement articulation limited motion and caused discomfort. The PROSTALAC system now consists of a constrained cemented acetabular component with an articulating polyethylene liner and a femoral component with a modular head made intra-operatively using a series of moulds with ALC surrounding a stainless steel endoskeleton. Whilst providing high doses of local antibiotic delivery, this system also allows earlier mobilisation out of bed and accelerated rehabilitation and permits discharge from the hospital between stages of treatment avoiding the complications associated with prolonged hospital stay and immobilisation.8 Recently a preformed PROSTALAC equivalent with fixed low-dose antibiotic content has become available. Prefabricated moulds of different sizes are also now available, allowing the surgeon to select antibiotic dose and content.
The disadvantages of preformed mobile spacers include limitation in implant sizes and antibiotic dose, often allowing delivery of only a single antibiotic. Mobile spacers formed in the operating room have the advantage of adjustable antibiotic dosing; a combination of antibiotics and the addition of an antifungal option as necessary. Disadvantages of mobile spacers formed in the operating room include additional time to construct the implant in the operating room, a limited number of sizes, additional cost, and complications may similarly occur (Figure 1, Figure 2 and Figure 3).
ALC填充物
在介入治疗期间使用ALC作为填充物以局部给予抗生素的方法目前已经广泛得到开展，某些研究显示，使用该方法完全清除感染的成功率可近95%。较其他系统给药的方法，该方法能够使局部抗生素浓度提高近200倍，并且能使坏死组织在潜在的关节间隙和软组织挛缩处聚集。该方法能够在未出现明显系统性不良反应的情况下，使抗生素的剂量接近20g/40g骨水泥。对于真菌感染，通常在40g骨水泥中追加100-150mg 的两性霉素B。
填充物的种类很多，以往常用的ALC珠链，由于其相关的瘢痕生成后容易导致在二次手术中难以移除，近来已经很少使用。
静止型/非关节型填充物
静止型或单纯堵塞型填充物能够闭合死腔，通常用于髋臼中。使用该方法使术者在重新进行植入物放置时，解剖较为简单，并能够根据敏感性选择合适的抗生素进行给药。通常，将20g骨水泥和2-3 g的抗生素粉末混合，能够为髋臼缺损提供足够的抗生素剂量。该方法的缺陷为是使关节难以进行生理性活动，但相比活动型填充物，静止型填充物能够减少或避免坏死组织的产生。
髓内定位销
在THA感染的治疗中，使用骨水泥喷枪将骨水泥定位销置入股骨髓腔内，能够使其大小和形状都适合髓腔的形态，在定位销的远端留置一个小球，以预防远端移位，并且使术者在今后更容易移除植入物。缺陷包括：潜在的近端股骨移位的可能性以及该方法不适用于严重股骨骨质丧失的患者。
活动型/关节型填充物
该方法使患者能够在接受假体移除和假体重新置入的间歇，进行一定范围内的关节活动。PROSTALAC假体首先由Duncan和Beauchamp开展使用，其主要部分为一个金属股骨内骨骼组件（使用ALC包裹）。股骨头处的骨水泥能够使股骨头与髋臼骨床向衔接，可能导致骨质磨损，造成患者的不适。因此，近来开始使用一种髋臼骨水泥，可以预防髋臼的骨质损失，但可能会限制关节的运动并造成患者的不适。PROSTALAC系统由带有聚乙烯内衬的限制型髋关节含骨水泥式髋臼窝组件和一个组配式股骨头组件构成，在术中可以使用各种模具将ALC包裹在不锈钢内骨骼。当需要局部给与较高剂量的抗生素时，这一系统仍可以使患者早期下床活动、加速康复性训练及尽早出院，避免了长期住院和制动相关的并发症的发生。最近一种预成型的PROSTALAC(带有固定低剂量抗生素)已经投入临床使用，并且各种大小的预组合型号也可供选择，这使术者能够自由选择抗生素的剂量和假体的组件类型。
预组合活动型填充物的缺陷在于其限制了植入物的大小和抗生素的剂量，并且通常术者只能使用一种抗生素。在手术室中进行组装活动型填充物，能够提供术者所需要的抗生素剂量，而且可以在需要抗真菌治疗时，在使用抗生素的基础上，加用抗真菌药物，但其缺陷为手术时间延长，手术费用增加，可选择的大小数量少，同时可能导致某些并发症。(图 1, 图 2 和图3)。









Complications of spacers
Implant and periprosthetic fractures
Surgeon made spacers in the operating room may be at higher risk for a fracture, especially with a mobile spacer, as a result of cement heterogeneity and mixing inconsistencies. The use of higher antibiotic doses also leads to increased risk of fracture. A noncongruent femoral component fit on host femoral bone may lead to subsidence and fracture of the implant. Therefore, the surgeon should avoid impacting the mobile cement spacer during cementing which may predispose both the prosthesis and the bone stock deficient proximal femur to fracture.60
Antibiotic toxicity
This rare complication may be more common with surgeon constructed spacer implants when high doses of antibiotics are added to the cement.57 As renal failure may potentiate antibiotic toxicity include renal failure, renal function and antibiotic levels monitoring is crucial in this group of patients and should this complication occur, removal of the implant must be considered.
Instability
This occurs more frequently with knee spacers. However, in the hip, the use of a snap-fit polyethylene liner has reduced the incidence.
填充物的并发症
植入物和假体周围骨折
由术者在术中制作的填充物可能会增加骨折的风险，特别是活动型填充物，因为活动型填充物中骨水泥往往不均匀且混合程度不一致。随着抗生素使用剂量的增大，骨折的风险也随之增加。当股骨组件和患者的股骨不相吻合时，可能会导致假体沉降或植入物的骨折。因此，术者应避免在使用骨水泥时，对活动型骨水泥填充物造成不良影响，以免出现股存量的损失，导致近端股骨或假体的骨折。
抗生素毒性
这一并发症较为少见，通常当术者在制作活动型填充物时，使用了较高剂量的抗生素后发生。肾功能衰竭可能加重抗生素的毒性。因此，对于肾衰竭患者，肾功能和抗生素水平的检测尤为重要，当出现抗生素毒性时，应考虑移除植入物。
植入物不稳定
这一并发症通常发生于使用膝关节填充物时。在髋部，使用快速安装聚乙烯内衬，能够减少该并发症的发生。






Challenges and future plans for management
The management of THA infection can be challenging and advances in diagnosis, treatment and prevention may improve the outcome of patients with an infected prosthesis.
Investigations
Bottner68 investigated the role of Interleukin-6, procalcitonin and tumour necrosis factor (TNF-alpha) and compared them with CRP and ESR in a prospective study of 78 patients undergoing revision total hip or knee replacement. Results showed that CRP >3.2 mg/dl and interleukin-6 >12 pg/ml had the highest sensitivity (0.95). However, Interleukin-6 was less specific than CRP (0.87 versus 0.96) and combining CRP and interleukin-6 identified all patients with deep infection of the implant. An advantage of interleukin-6 over both CRP and ESR is that levels return to normal within 48 to 72 hours after operation; this may have an essential role in the future for detecting early infection post THA.69 Procalcitonin (> 0.3 ng/ml) and TNF-alpha (> 40 ng/ml) were very specific (0.98 versus 0.94) but had a low sensitivity (0.33 versus 0.43). Molecular diagnostic techniques including polymerase chain reaction (PCR) have enabled the detection of infection in culture negative cases. However, Panousis 70 in a prospective study of 91 patients undergoing revision total hip or knee arthroplasties for infection concluded that PCR cannot be recommended for the routine detection of prosthetic infection due to the low positive predictive value (34%). Molecular biology continues to develop in the meantime, and may well have an essential role in the future in identifying infection with the advantage of reducing the amount of time needed to obtain results in comparison with conventional culture methods.
Antibiotics
The growing incidence of resistant microorganisms has led to the introduction of new antibiotics with good antimicrobial and pharmacokinetic properties, such as linezolid, the first approved oxazolidinone. This has been reported in several studies to be an effective agent against methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococci, resistant coagulase-negative staphylococci and macrolide-resistant streptococci.[71] and [72] It is well absorbed and oral administration gives serum levels comparable with those following intravenous injection of the same dose which has markedly reduced hospital stay costs when long term antibiotic therapy is indicated. Linezolid has also demonstrated acceptable elution kinetics from ALC when tested in vitro in combination with gentamicin; however, further experimental research and animal studies should clarify any possible side effect of linezolid-loaded cement before definitive use in the clinical practice.73
ALC substitutes
Antimicrobial therapy and eradication of infection improved with the introduction of ALC. However, using polymethylmethacrylate (PMMA) as the standard material for delivering depot antibiotics has raised concerns as it is surface friendly to biofilm-forming bacteria. Therefore, many biodegradable materials have been evaluated as alternatives including protein-based materials (collagen, fibrin, thrombin, clotted blood), bone-graft, bone-graft substitutes and extenders (hydroxyapatite, beta-tricalcium phosphate, calcium sulphate, bioglass), and synthetic polymers. Unfortunately, considering the limited clinical data that is currently available, the use of these materials still is experimental and clinical application should be cautious, limiting the total antibiotic load.
展望
随着在THA感染处置的诊断、治疗和预防等方面的进展，将进一步提高对假体感染患者治疗的效果。
实验室检查
在对78例接受全髋翻修术或全膝关节置换术的患者进行的前瞻性研究中，Bottner初步研究了白介素6, 降钙素原和肿瘤坏死因子(TNF-a)的作用，并将它们与CRP和ESR进行了对比。结果显示，CRP >3.2 mg/dl和白介素6 >12 pg/ml具有最高的敏感性(0.95)，但是白介素6的特异性较CRP略低 (0.87对0.96)，结合CRP和白介素6的结果，能够诊断出所有的植入物深部感染的患者。白介素6较CRP和ESR为优之处在于，白介素6能够在术后48到72小时之内恢复正常；这对于将来早期发现THA术后感染非常有价值。降钙素原(> 0.3 ng/ml)和 TNF-a(> 40 ng/ml)对于感染的诊断特异性较高(0.98和0.94)，但是敏感性较低 (0.33和0.43).。分子诊断技术如多聚酶链式反应 (PCR)，已经能够诊断出培养阴性的感染患者。但在Panousis进行的一项91例接受全髋翻修术或全膝关节置换术患者的前瞻性研究中，结论显示，由于PCR阳性预测值较低(34%),故不能作为假体感染的常规诊断手段。随着分子生物学的发展，其优势日益明显，如大大缩短检查所需时间等，使未来该技术在诊断感染中的作用大大提高。
抗生素
耐药菌发生率的增高已经促使抗生素得到了进一步的发展，其抗菌能力和药物动力学特性均有所进步，如首个噁唑烷酮类药物利奈唑胺的出现。多个研究证实利奈唑胺对MRSA、耐万古霉素的场球菌、凝固酶阴性葡萄球菌和耐大环内酯类抗生素的葡萄球菌均由作用。并且其具有其他静脉用药物相当的血药浓度，吸收也较好，能够大大缩短患者住院时间及长期使用抗生素的巨额花费。利奈唑胺在体外实验中与庆大霉素联合使用，能够较好的从ALC中洗脱。但在正式应用于临床前，仍需进行进一步实验和动物研究已明确利奈唑胺装载的骨水泥，是否存在不良反应。
ALC替代物
抗感染疗法和根治感染的需要促使了ALC的问世。但是，使用聚甲基丙烯酸甲酯作为释放抗生素的标准材料，目前已经出现了很多问题，如其容易促进细菌生物膜的形成。因此，很多能够生物降解的材料被认为是聚甲基丙烯酸甲酯较好的替代材料，包括蛋白基质材料（胶原、纤维蛋白、凝血酶, 血凝块)、骨移植物、骨移植替代物和增量剂(羟基磷灰石、, b-磷酸三钙,硫酸钙, 生物玻璃),和合成高分子。但是限于目前临床资料较少，使用这些材料仍然只能用于试验研究，如用于临床，可能会限制抗生素的使用量。







Conclusion
Revision THA remains a very expensive procedure to the patient and healthcare systems and no matter how much progress in diagnostic and treatment methods are achieved, the cost and morbidity of infected THA suggest that preventative measurements as discussed earlier are the single most important factor in managing this problem.
结论
对于患者和医疗系统来说，THA翻修术费用仍然较高，不论其诊断和治疗方法取得多大程度的进展，感染性THA的治疗费用和死亡率始终提醒我们，预防才是最重要的措施。