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髋、膝关节置换术后假体周围感染的诊治进展

2017-03-29 建省福清市医院骨科 陈志福 实用骨科杂志2017年3月第23卷

假体周围感染是髋、膝关节置换术的灾难性并发症,也是导致关节置换术后翻修的主要原因,其诊断及治疗十分困难,常需多次手术及长疗程的抗感染治疗,并发症高、住院时间长、治疗费用昂贵。尽管已采取多项措施预防感染的发生,髋、膝关节置换术后假体周围感染的发病率仍达1%~3%,并且随着接受关节置换的患者人数逐年增长,发生假体周围感染的人数也将不断增加,给患者及医疗保健系统带来沉重的负担。同时,由于假体周围感染的病

假体周围感染是髋、膝关节置换术的灾难性并发症,也是导致关节置换术后翻修的主要原因,其诊断及治疗十分困难,常需多次手术及长疗程的抗感染治疗,并发症高、住院时间长、治疗费用昂贵。尽管已采取多项措施预防感染的发生,髋、膝关节置换术后假体周围感染的发病率仍达1%~3%,并且随着接受关节置换的患者人数逐年增长,发生假体周围感染的人数也将不断增加,给患者及医疗保健系统带来沉重的负担。同时,由于假体周围感染的病原菌分布呈现复杂化、耐药菌甚至多重耐药菌的感染比例不断增加,给临床医师在感染的预防及治疗上带来严峻挑战。因此,本文对假体周围感染的发病机制、危险因素、诊断标准、病原菌分布与耐药性变化、治疗策略等的研究进展做一综述,以期能协助临床医师更好地预防和治疗假体周围感染,进而改善患者的预后。

发病机制及危险因素

髋、膝关节置换术后假体周围感染的发生是病原菌、假体和人体三者间相互作用的结果,病原菌多通过以下三种途径引起感染:a)术中污染。因无菌操作不规范引起污染,病原菌黏附于假体或直接进入手术部位,进而种植引起感染;b)菌血症。各种原因导致术后病原菌经初始感染灶(如:皮肤、消化道、泌尿道、呼吸道等)入血引起菌血症,经血液循环播种到手术部位;c)伤口并发症。因伤口愈合不佳或伤口感染使浅层病原菌侵入,蔓延至受累关节。根据假体周围感染症状持续时间常将其分为:急性感染(小于3个月)、迟发性感染(3~12个月)、慢性感染(大于12个月)。急性与迟发性感染多因术中污染或术后伤口并发症引起病原菌侵入,而慢性感染则多因远处初始感染灶的病原菌入血引起菌血症,经血液循环播散至受累关节。

营养不良、病理性肥胖、糖尿病、贫血、围术期输血、凝血功能障碍、类风湿性疾病、免疫系统抑制、手术部位既往感染史或多次手术史等均为假体周围感染的危险因素,具有危险因素的患者,术后感染的发生率将由无危险因素患者的0.5%提高至1.6%,甚至更高。此外,有研究发现人群的皮肤及鼻腔有较高的葡萄球菌定植率,其中皮肤耐甲氧西林金黄色葡萄球菌(MRSA)及耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的定植率分别达5%和25%,而鼻腔甲氧西林敏感金黄色葡萄球菌(MSSA)及MRSA的定植率分别达26%和6%。术前MRSA的定植是术后假体周围感染的危险因素,将使术后感染的风险增加9倍。NicholSon等研究发现,假体周围感染患者的关节液或组织标本培养分离出的葡萄球菌与鼻腔中分离出的葡萄球菌的匹配率高达85%,进一步证实二者间的相关性。

假体周围感染的诊断标准

假体周围感染的诊断需要结合详细的病史与体格检查、血清学、微生物学、病理学及影像学等检查结果。其中,受累关节的关节液或组织标本的微生物培养结果对假体周围感染的诊断至关重要。假体周围感染的处理原则与无菌性松动完全不同,诊断延误或漏诊将增加治疗失败的风险。多项研究提出了假体周围感染的诊断标准,但目前应用最为广泛的是肌肉骨骼感染协会(MSIS)制定的标准:a)符合以下2个主要标准的任意1个:(a)存在与受累关节相通的窦道;(b)2个或2个以上的关节液或组织标本微生物培养阳性。b)符合以下5个次要标准的任意3个:(a)血沉大于30mm/h、C反应蛋白大于10mg/L;(b)关节液白细胞计数大于3 000/μL;(c)关节液多核中性粒细胞比例大于80%;(d)病理切片5个或5个以上的高倍镜视野下发现超过5个白细胞;(e)一个关节液或组织标本微生物培养阳性。在临床实际工作中,某些患者尽管并未符合以上诊断标准,但仍有可能假体周围感染,此时,就需要临床医生通过详细评估所有的术前及术中资料做出判断。

病原菌分布及耐药性

病原菌分布 假体周围感染的病原菌谱复杂,可由单一病原菌或多种病原菌混合感染引起。病原菌的种类影响宿主对感染的反应、软组织和宿主骨损伤与破坏的程度及治疗的成功率。文献报道,假体周围感染以革兰氏阳性菌为主,占64.6%~74.3%,其中以人体皮肤的定植菌,凝固酶阴性葡萄球菌及金黄色葡萄球菌所占比例最高,分别为16.7%~47%和12%~44%,其次为链球菌及肠球菌,分别为9%~10%、3%~7%。近年来革兰氏阴性菌导致的假体周围感染有所增加,达8%~48.1%,其中以大肠埃希菌所占比例最高,达3%~16.3%,其次为铜绿假单胞菌、变形杆菌、沙门氏菌、克雷伯杆菌等。不同研究报道的多种病原菌导致的混合感染比例有所差异,在10%~20%。而厌氧菌及真菌引起的感染相对罕见,Tande等报道厌氧菌感染的发生率约为3%,Bjerke-kroll等分析785例假体周围感染病例的病原菌分布后发现仅1例(0.6%)是由假丝酵母菌引起。但是,因为厌氧菌及真菌感染常引起严重的并发症,治疗效果差、治疗费用昂贵,故也应引起我们的重视。

越来越多的研究发现,不同地区、不同医疗机构导致假体周围感染的病原菌分布有所差异。Aggarwal等统计美国及欧洲两家医疗机构共1 670例髋、膝关节置换术后假体周围感染的病原菌后发现:在美国由金黄色葡萄球菌导致的感染占31%,而在欧洲仅为13%;凝固酶阴性葡萄球菌导致的感染在美国为20.2%,而在欧洲则高达39.3%;厌氧菌导致的感染美国与欧洲分别为9%和0.9%。此外,在美国引起感染的葡萄球菌对甲氧西林的耐药率要高于欧洲,分别为48.1%和12.8%。此外,由于感染防控政策的改变及不恰当的使用抗菌药物造成的选择性压力等原因,同一医疗机构不同时期假体周围感染的病原菌分布也会发生改变。有学者统计分析该医疗机构14年来引起假体周围感染的病原菌后发现,由MRSA、链球菌及变形杆菌导致的感染比例在不断增加。

病原菌耐药性 由于社区及医疗保健机构不恰当的抗菌药物使用策略,假体周围感染中耐药菌所占比例逐年增长。葡萄球菌引起的感染历来受到重视,不仅因为其具有较高的致病性,还因为其对多种抗菌药物具有较高的耐药性。近年来由耐甲氧西林葡萄球菌导致的假体周围感染比例不断升高,MRCNS及MRSA的感染率分别高达32%~61%和20%~53%。有研究发现当葡萄球菌对甲氧西林耐药将诱导对其他多种抗菌药物的耐药。Anguita等报道耐甲氧西林葡萄球菌对庆大霉素及妥布霉素的耐药率分别达27.27%~40%和35%~56%。此外,近年来的一系列研究也发现,革兰氏阴性菌对头孢菌素类抗菌药物的耐药率也有升高的趋势。Marchaim等发现革兰氏阴性菌对第1代头孢菌素(头孢唑啉)和第2代头孢菌素(头孢呋辛)的耐药率分别高达62%及72%,并且对第3代及第4代头孢菌素的耐药率亦不断增加。

病原菌分布的差异、毒力的增强、耐药率的增加使假体周围感染的治疗更具挑战性。了解病原菌分布与耐药性不仅有助于选择恰当的手术方式及抗感染方案,还有助于避免因使用广谱抗菌药物可能导致的相关并发症(如:肾损害、抗菌药物相关性腹泻、药物过敏、机会性感染等)及耐药菌的产生。

培养阴性原因分析

明确病原菌对假体周围感染的诊断与治疗至关重要。然而在实际工作中,7%~25%的病例尽管存在其他有力证据支持为假体周围感染,但却无法检出病原菌,进而给诊断带来不确定性,并给恰当抗菌药物的选择带来挑战。

多种因素导致假体周围感染患者出现培养阴性,其中最常见的原因包括:a)在获取关节液或组织标本前使用抗菌药物;b)病原菌包含于生物膜内,黏附于假体表面及周围组织,关节液中浮游的病原菌数量极少,传统的培养手段无法检出包含于生物膜内的病原菌;c)不能选择恰当的培养基及培养时间不当。某些非典型致病菌,如:真菌、结核分枝杆菌不能在普通的需氧或厌氧培养基生长,而铜绿假单胞菌及凝固酶阴性葡萄球菌则需要1~2周的培养时间。d)于非感染区获取标本、标本的运送延误或暴露于极端的环境等也将影响病原菌检出。因此,为提高培养阳性率,对可疑的病例在明确诊断前不应使用抗菌药物,对于已使用抗菌药物的患者关节液或组织标本的获取应在停止使用抗菌药物14d后进行。同时,应正确保存标本并及时转运,当怀疑为非典型病原菌感染时(如:真菌或分枝杆菌),应根据菌种选择恰当的培养基,并可适当延长培养时间至2~3周。

假体周围感染的预防

围术期预防性使用抗菌药物是降低关节置换术后感染风险的有效手段,使感染的绝对风险降低8%,相对风险降低81%。美国骨科医师协会(AAOS)建议:髋、膝关节置换术的预防性抗菌药物首选第1代或第2代头孢菌素(如:头孢唑啉或头孢呋辛);当有使用头孢菌素类抗菌药物的禁忌证时可选择克林霉素或万古霉素;对存在MRSA定植或有发生MRSA感染风险的患者可选择万古霉素。理论上,第1代及第2代头孢菌素类抗菌药物的抗菌谱能有效覆盖约40%的革兰氏阴性菌及绝大多数的革兰氏阳性菌。但随着革兰氏阴性菌导致的假体周围感染比例的增加及病原菌对头孢菌素类抗菌药物耐药率的升高,有学者认为有必要根据本地区的病原菌谱及耐药谱来调整预防性抗菌药物的使用方案,并扩大抗菌谱。

BoSco等纳入5389例全髋关节置换术病例,根据预防性抗菌药物的不同分为:联合组(头孢唑啉联合庆大霉素或氨曲南)与头孢唑啉组,发现联合组伤口感染率(0.55%)较头孢唑啉组(1.19%)明显降低,并且由革兰氏阴性菌引起的感染联合组(0.00%)也较头孢唑啉组(0.032%)明显降低。StefanSdottir等报道,将万古霉素作为预防性抗菌药物可显着降低术后由MRSA导致的感染,感染率自0.23%降至0.07%。使用广谱抗菌药物或联合使用多种抗菌药物理论上能更有效地覆盖葡萄球菌属及其他革兰氏阴性菌,但常规使用是否会诱导耐药菌的产生、增加药物不良反应发生率,还有待进一步论证,目前并不推荐常规使用。

此外,流行病学监测数据显示,人群中有较高的葡萄球菌定植率,并且相关研究也已证实,术前MRSA的定植是术后假体周围感染的危险因素。有研究发现,MRSA的筛查与去定植能有效降低假体周围感染发生率。因此,有学者建议对所有拟行关节置换术的患者进行术前鼻部MRSA定植的筛查,对存在MRSA定植的患者,进行去定植治疗,即:术前5d于鼻部涂搽2次莫匹沙星软膏,术前一天晚上及术晨各进行一次洗必泰擦浴,围术期的预防性抗菌药物选择万古霉素,术后继续使用5d莫匹沙星软膏,以降低术后感染风险。

假体周围感染的治疗

假体周围感染的治疗方式包括:长期抑菌疗法、扩创保留假体、一期翻修、二期翻修、关节融合术及截肢术。治疗方式的选择应综合考虑感染持续时间、软组织条件、病原菌种类与耐药性、并存疾病、患者对功能的要求及经济承受能力等因素。对存在手术禁忌证并且对关节功能要求不高的患者,可选择长期抑菌疗法。而对于严重感染威胁生命的患者,若无其他有效控制手段,可能需行关节融合术或截肢术。扩创保留假体、一期翻修及二期翻修相对于前3种治疗方式更常用于假体周围感染的治疗。文献报道,扩创保留假体的治疗成功率为20%~68%,一期翻修的治疗成功率为50%~87%,而二期翻修的治疗成功率相对较高,达56%~100%。目前关于治疗方式的选择还无统一标准,相关研究认为:扩创保留假体仅适用于极小部分感染症状,持续时间小于3个星期或假体植入时间小于30d,并且假体固定良好的患者,此时生物膜尚未形成,通过充分扩创及后续的抗感染治疗有治愈的可能;一期翻修适用于软组织条件良好、术前已明确病原菌,并且病原菌对抗菌药物具有良好敏感性的病例;而对于软组织条件不佳、微生物培养阴性、高毒力致病菌及耐药菌所致的感染,选择二期翻修的治疗成功率更高。

美国感染性疾病协会(IDSA)建议:对选择扩创保留假体或一期翻修的患者,术后应静脉使用敏感抗菌药物2~6周,序贯3个月的口服抗菌药物治疗。对于选择二期翻修的患者,在第一期手术后亦需静脉使用敏感抗菌药物4~6周,序贯3个月的口服抗菌药物治疗。抗菌药物的选择及使用疗程应个体化,综合考虑病原菌的种类、耐药性、药物生物利用度及不良反应等因素。有研究显示,联合利福平的抗感染治疗方案能有效清除葡萄球菌导致的感染、防止感染复发,但为预防利福平耐药性的产生,利福平常需联合其他抗菌药物包括:喹诺酮类(环丙沙星、左氧氟沙星)、复发新诺明及利奈唑胺等。

假体周围感染不仅给患者及医疗保健系统带来沉重的负担,也给关节外科医师带来严峻的挑战。尽管临床医师及相关研究人员在假体周围感染的预防、诊断及治疗方面已取得一些进展,但随着患者人群分布特征的改变、并存疾病患病率的增加、高毒力病原菌及耐药菌感染比例的增长,假体周围感染的治疗依然困难重重。为应对这些挑战,首先应加强病原菌分布及耐药性的监测,以指导治疗方案的制定,提高治疗成功率,并规范抗菌药物的使用,减少耐药菌的产生及不良反应发生率;其次,由于目前假体周围感染培养阴性率仍较高,且对于是否需调整预防性抗感染方案及进行MRSA的筛查与去定植仍存争议,还需进一步研究以提高病原菌检出率,并论证扩大预防性抗菌药物的抗菌谱及MRSA去定植的有效性及合理性;最后,对于假体周围感染的手术方式、抗菌药物的选择及疗程尚未形成统一标准,还需更高质量的研究明确各种手术方式的适应证及抗菌药物的疗程,以指导治疗方案的制定。

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    2017-08-05 yxch48
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    2017-04-25 1e10eabem79(暂无匿称)

    目前本人遇到一例翻修术后感染的病例,是保假体扩创,效果不错。

    0

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  8. [GetPortalCommentsPageByObjectIdResponse(id=1742394, encodeId=cc2b1e42394de, content=<a href='/topic/show?id=39cae96626f' target=_blank style='color:#2F92EE;'>#置换#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79662, encryptionId=39cae96626f, topicName=置换)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3a7c35056336, createdName=yxch48, createdTime=Sat Aug 05 12:55:00 CST 2017, time=2017-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1740454, encodeId=210d1e404549d, content=<a href='/topic/show?id=e0ba916e323' target=_blank style='color:#2F92EE;'>#诊治进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91673, encryptionId=e0ba916e323, topicName=诊治进展)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0c3934772489, createdName=12498cbcm11(暂无昵称), createdTime=Fri Aug 11 10:55:00 CST 2017, time=2017-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=190399, encodeId=d7ac190399b5, content=目前本人遇到一例翻修术后感染的病例,是保假体扩创,效果不错。, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5gJeAA33pg8XSpMyoXQLg4TTWfCC26g4ibkFFUdQVBtofBwAITTWib8S4f1bKDLaYsKVz2KtVfhLQJoia5mISjlibk/0, createdBy=28331949612, createdName=1e10eabem79(暂无匿称), createdTime=Tue Apr 25 07:55:59 CST 2017, time=2017-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754169, encodeId=258b1e5416927, content=<a href='/topic/show?id=7d3330135ac' target=_blank style='color:#2F92EE;'>#关节置换术#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30135, encryptionId=7d3330135ac, topicName=关节置换术)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=050736663344, createdName=apoenzyme, createdTime=Sun Dec 03 13:55:00 CST 2017, time=2017-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1390091, encodeId=60bd139009127, content=<a href='/topic/show?id=c4d0858e23b' target=_blank style='color:#2F92EE;'>#膝关节置换术#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85872, encryptionId=c4d0858e23b, topicName=膝关节置换术)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0802500050, createdName=肉我只吃一口, createdTime=Fri Mar 31 06:55:00 CST 2017, time=2017-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1468320, encodeId=b2d91468320d9, content=<a href='/topic/show?id=2d3d2e5176a' target=_blank style='color:#2F92EE;'>#假体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27517, encryptionId=2d3d2e5176a, topicName=假体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b576903125, createdName=lanyan20020088, createdTime=Fri Mar 31 06:55:00 CST 2017, time=2017-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1576549, encodeId=37e215e654947, content=<a href='/topic/show?id=48fee966468' target=_blank style='color:#2F92EE;'>#置换术#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79664, encryptionId=48fee966468, topicName=置换术)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Fri Mar 31 06:55:00 CST 2017, time=2017-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=183691, encodeId=cd061836918a, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=74221626377, createdName=tofsw, createdTime=Thu Mar 30 08:00:27 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=183545, encodeId=66af18354590, content=学习了新知识!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epr1MZHfgreGEFrpiapjCGIQGZhkpjicialc8h7VoU0AjNiaSgpaZjNuIqq1KVbmI19JwrN2sdwTdWVSw/132, createdBy=f6692009961, createdName=sy3923582, createdTime=Wed Mar 29 16:31:54 CST 2017, time=2017-03-29, status=1, ipAttribution=)]
    2017-03-30 tofsw

    学习了谢谢分享

    0

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    2017-03-29 sy3923582

    学习了新知识!

    0

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