单髁置换术后假体周围感染的抗生素使用专家共识（2025版）

一、共识制订流程

本共识聚焦于UKA-PJI抗生素使用问题,系统性地解答了如何规范化使用抗生素和新型分子诊断技术在UKA-PJI的应用价值。本共识在国际实践指南注册与透明化平台完成注册(注册号:PREPARE-2025CN060)。

(一) 共识专家组组建

本共识由国家骨科医学中心保膝联盟、中国老

年保健协会骨关节保护与健康分会共同组建的单髁置换术后感染抗生素使用专家共识工作组发起并制订,由相关领域方法学专家提供方法学和证据评价支持。启动时间为2024年1月,定稿时间为2025年5月。

(二) 临床问题的产生与重要性评价

通过德尔菲法严格筛选临床问题:通过开放式问卷收集来自全国各级医院医生的55个临床问题。首轮投票汇总筛选出36个问题进入专家函询环节,由专家根据临床经验和证据重要性评分(1~9分)。将广泛认可[超过75%的专家认为它“非常重要”(评分≥7分)]或极少反对[认为它“不重要”(评分≤3)的专家比例<15%]的临床问题进行下一轮讨论。16个问题进入第二轮讨论,经工作组解构、精简后最终确定纳入9个核心临床问题。

(三) 循证医学证据检索

针对9个临床问题,按PICOS原则解构后,系统检索了PubMed、Embase、Web of Science、Cochrane Library、中国知网及万方数据库(建库至2025年1月1日,2025年5月2日更新),优先纳入近5年的系统评价、指南及随机对照试验(randomized controlled trial,RCT),证据不足时扩展至其他临床研究。检索策略围绕“单髁置换术”“假体周围感染”及“抗生素使用与管理”3个核心主题展开,分别采用包括“单髁置换”“UKA”“假体周围感染”“PJI”“抗生素”“专家共识”“Antibiotic-Loaded Bone Cement”等一系列中英文主题词与自由词,并将3组检索词进行组合,以全面收集相关证据。文献筛选严格遵循纳入(UKA-PJI抗生素治疗相关综述、系统评价及原著)与排除标准(重复或无关研究)。

(四)推荐意见形成与证据等级判断

双人独立完成质量评价(系统评价采用AMSTAR、RCT采用Cochrane、观察性研究采用NOS量表)及数据提取,最终结合证据质量、患者偏好和经济学因素,通过2轮德尔菲法形成9条推荐意见[14]。本共识的制订采用指南研究与评价工具(appraisal of guidelines research and evaluation, AGREE II)及世界卫生组织指南制备订手册的临床实践指南构建框架。制订过程严格遵循预先制定的计划书,并参考卫生实践指南报告标准 reporting items for practice guidelines in healthcare, RIGHT)进行报告(表1~2)。

二、共识推荐意见

临床问题1:UKA-PJI,抗生素的最佳使用疗程

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表1 推荐强度分级

|推荐强度|推荐依据| |---|---| |1强推荐|I级证据,获益明确>风险| |2中等推荐|II级证据,获益可能>风险| |3弱推荐|III/IV级证据,获益与风险平衡|

表2 GRADE证据质量分级及定义

|证据质量分级|定义| |---|---| |A(高)|非常有把握观察值接近真实值| |B(中)|对观察值有中等把握:观察值 有可能接近真实值,但也有可能 差别很大| |C(低)|对观察值的把握有限:观察值可能 与真实值有很大差别| |D(极低)|对观察值几乎没有把握:观察值与 真实值可能有极大差别|

为多久？

推荐意见1:UKA-PJI的抗生素最佳使用疗程与其采用的治疗方式有关。针对不同手术方式的抗生素疗程推荐如下:DAIR术后推荐不少于6周的抗生素治疗(证据等级及推荐强度:1C);一期翻修推荐12周的抗生素治疗,其中需至少包含2周的静脉应用抗生素(证据等级及推荐强度:1C);二期翻修间期:推荐至少10周的抗生素治疗,占位器刚置入时,需静脉应用万古霉素联合头孢曲松或氟喹诺酮类≥2周(证据等级及推荐强度:1C),随后口服敏感抗生素≥8周(证据等级及推荐强度:2C);二期翻修假体再植入后,推荐口服敏感抗生素3个月(证据等级及推荐强度:2C)。

推荐意见说明:目前,关于UKA-PJI采取DAIR、一期翻修或二期翻修治疗后的抗生素方案研究仍显不足。相较于二期翻修,DAIR 一样一期翻修具有创伤小、术后膝关节功能评分更优、骨量与软组织损失少,以及成本相对较低等优势。文献报道,PJI患者行DAIR术后应接受至少6周的抗生素治疗。研究虽未明确给药途径,但纳入患者的平均抗生素疗程为7周[15-16]。多项研究对比了不同抗生素疗程后发现,疗程长短并非治疗失败的预测因子,且不少于6周的短期方案在疗效上并不逊于LTAT,展现出非劣效性优势。Bernard等[17]的回顾性观察性研究发现,在60例患者中6周抗生素疗程的疗效与12周相当。Puho等[18]的研究也表明,8周抗生素治疗的效果不劣于标准3~6个月长程方案。此外,Chaussade等[19]

的研究进一步支持 DAIR 术后6周与12周疗程预后无显著差异的结论。

一期翻修术后抗生素治疗的持续时间及其对成功率的影响仍存争议。现行指南推荐术后静脉抗生素4~6周,继以3个月的口服抗生素治疗,但支持该方案疗效的高质量证据有限[5]。值得注意的是,部分医院采用了不同的策略,即在术后仅进行10~14 d靶向静脉抗生素治疗,也报告了优异疗效[20]。目前,针对一期膝关节翻修术后静脉抗生素的最佳疗程尚未达成共识。现有研究报道了差异显著的抗生素方案及其结果。Klatte等[21]采用短期方案(10 d静脉联合5周口服抗生素),报告PJI 治愈率达90%。Razii 等[22]的抗生素疗程为7周,成功率同样在90%以上。相反,Klemt 等[23]的研究中,抗生素疗程延长至12周以上,但185例PJI患者的总体治愈率仅75%。Tuecking 等[24]的回顾性多中心分析进一步支持了这一现象,其采用的方案为2周静脉抗生素联合10周口服抗生素治疗(共12周),成功率同样较低(73%)。

根据 IDSA 指南,二期翻修间期推荐静脉或口服敏感抗生素治疗4~6周[5]。Bernard 等[17]的前瞻性观察性研究对比了6周与12周抗生素疗程的疗效,结果显示6周疗程效果已较为满意,延长至12周未能显著提高PJI治愈率。多项文献报道,二期翻修间期≤6周的抗生素方案均可取得满意临床结局[25-27]。值得注意的是,即使对于耐甲氧西林金黄色葡萄球菌(Methicillin-resistant Staphylococcus aureus, MRSA)和链球菌所致PJI, >6周的疗程亦未提升治愈率。Mittal 等[26]的回顾性研究表明,此类感染接受6周与12周治疗的成功率差异无统计学意义。

关于再植入前是否需主动停用一段时间抗生素(以暴露潜在感染症状并避免培养假阴性),目前存在争议。Bejon等[28]发现,再植入前是否停药2周,培养阳性率无差异。Ascione等[29]对196例PJI患者直接比较显示;持续抗生素治疗组(n=114)再植入时培养阳性率更低(7.0%比11.0%),且再植入后治愈率显著更高(91%比79%),支持持续用药策略。而Tan等[30]对409例接受不同抗生素间歇期的患者分析表明,间歇期时长(中位30d;39例<1周,80例<2周,174例<4周)与治疗失败率无显著关联,提示抗生素间歇期持续时间不影响复发风险。假体再植入后,新植入假体可能发生再感染,此为治疗失败的主要原因[31]。复发感染可由原致病菌或新

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发致病菌引起[32]。研究表明,再植入术后延长抗生素治疗可降低再感染风险。口服抗生素延长至3个月可能减少复发[33]。然而,亦有研究主张若再植入时培养阴性,术后抗生素使用应限制在10 d内[34]。Zywiel等[35]将膝关节二期翻修患者分为两组:围手术期静脉抗生素组(24~72 h)与术后口服抗生素组(28~43 d)。12个月随访显示,静脉组再感染率为16%,显著高于口服组的4%。一多中心RCT证实,接受3个月口服抗生素者因感染复发导致的手术失败率低于未用药组[33]。近年研究对长疗程必要性提出质疑。Fang等[36]的回顾性分析显示,术后短疗程(≤1个月)与长疗程(>1个月)的感染控制率无显著差异;后续的RCT将60例患者随机分为12周长疗程组与2周短疗程组;随访>12个月后,短疗程组在感染控制率上展现出非劣效性。值得注意的是,该方案的适用前提是病原学明确。

临床问题2: UKA-PJI,由静脉转为口服抗生素的最佳时机是什么?

推荐意见2:DAIR及一期翻修推荐静脉应用敏感抗生素2周后转口服(证据等级及推荐强度:1B);二期翻修占位器置入后,静脉5~7d转口服(证据等级及推荐强度:1C);二期翻修假体再植入后,无需静脉过渡,直接口服敏感抗生素3个月(证据等级及推荐强度:2C);培养阴性的PJI(culture-negative PJI, CN-PJI)需静脉联用广谱抗生素(如万古霉素联合头孢曲松)4周后转口服(证据等级及推荐强度:2C);静脉转为口服需满足体温正常≥48h、切口稳定且C-反应蛋白、红细胞沉降率较峰值下降>50%(证据等级及推荐强度:1A)。

推荐意见说明:确定静脉转口服抗生素的时机需综合评估患者临床反应(如症状改善程度)及实验室指标(如炎症标志物水平)。对于CN-PJI,初始需静脉联用广谱抗生素以覆盖潜在病原体(包括金黄色葡萄球菌、凝固酶阴性葡萄球菌及肠杆菌等)。万古霉素因对革兰氏阳性菌的广谱活性被广泛使用;达托霉素适用于CN-PJI患者中肾功能不全或万古霉素耐药病例。值得注意的是,环丙沙星联合利福平方案被证明对部分CN-PJI更有效[37]。一项前瞻性研究证实,此类患者术后平均静脉用药4d后转为口服治疗,治愈率可超90%[19]。

UKA-PJI行 DAIR后常规给予抗生素已成共识。虽最佳给药途径证据有限,但建议DAIR术后初始阶段应采用静脉抗生素治疗。多数研究采纳的方案

为静脉用药7~14 d, 继以3~6个月含抗生物膜活性抗生素的口服治疗(如利福平联合环丙沙星)[38-39]。当前主流方案为静脉用药2周后,转为口服抗生素4~6周[40]。

一期翻修的抗生素使用相关文献显示,静脉输注转为口服抗生素的时机存在差异。短期静脉抗生素治疗(平均2周)后转为长期口服抗生素(平均至少6周)是常见方案[22, 41-42]。Singer等[43]的回顾性研究证实,静脉注射2周后,口服4周的成功率可达95%,证明该方案疗效确切。另一项采用口服5周疗程的研究也报告了超过90%的治疗成功率[21]。值得注意的是,过度延长单纯静脉抗生素输注时间可能不利于PJI治疗。Siddiqi等[44]的多中心回顾性研究发现,仅采用长时程静脉抗生素治疗(未转为口服)的治愈率仅为78.9%。

在二期翻修的间期,证据支持更短的静脉抗生素疗程。研究表明,静脉输注5~7d后转为口服抗生素并未显著增加感染风险[45],且可避免长时间静脉给药相关的并发症(如导管相关感染、血栓性疾病)[46]。多项研究证实,早期由静脉转为口服抗生素并未降低最终疗效[47-49]。Hsieh 等[50]比较研究显示,患者接受4~6周标准静脉的治疗组与仅接受1周短期静脉治疗组,在平均43个月的随访中,感染控制率分别为89%和91%。McKenna 等[51]的研究中,术后仅给予5d静脉抗生素后即完全停药,在平均35周的随访中,30例患者均未出现感染复发。尽管缺乏高质量文献直接对比不同转换时机对结局的影响,但现有证据一致表明,静脉给药5~7d后转为口服敏感抗生素方案未显著降低疗效[17]。Oussedik等[52]的研究也支持此观点,其采用静脉5d后口服6周的抗生素使用方案,实现了95%的感染清除率。

临床问题3:DAIR术中冲洗液中添加抗生素,是否提高UKA-PJI的感染控制率?

推荐意见3:DAIR术中冲洗液中添加抗生素并未显著增加感染清除率,因此不建议冲洗液中添加抗生素(证据等级及推荐强度:2A)。

推荐意见说明:研究表明,含万古霉素、庆大霉素或链霉素的冲洗液在降低手术部位感染方面效力更强[53]。万古霉素冲洗液(1000 mg/L)能显著降低初次关节置换术后急性感染率,提示其潜在预防PJI的价值[54]。尽管冲洗是治疗急性或慢性PJI外科手术的基础步骤[55-56],但目前对于最佳冲洗液成分、持续时间或组合方案尚无共识[57]。临床研究缺乏比较

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不同冲洗液效果的强有力证据,且各种添加剂的疗效存在不确定性,因此确定最佳方案具有挑战性[56]。

关于冲洗液在DAIR术中的效果,现有研究结果存在显著差异。多项使用含抗生素生理盐水(通常为9L)冲洗的研究报告感染控制率较低:一项纳入104例DAIR患者的研究为44%[58],一项纳入153例DAIR患者的研究为35%[59]。然而,其他研究显示更高成功率。Tsumura等[60]针对DAIR患者在术中根据培养结果使用病原体敏感抗生素冲洗,DAIR术后感染控制成功率达77.8%。Fukagawa等[61]将敏感抗生素直接输注至膝关节,报告感染清除率为100%。值得注意的是,仅使用无菌生理盐水(9L)冲洗也取得了良好效果,Bryan等[62]的回顾性研究中90例DAIR患者,报告感染控制功率为87%;Tornero等[63]的前瞻性研究显示感染控制率为88%。

综上,现有证据提示在DAIR术中使用针对病原体的敏感抗生素冲洗可能与UKA-PJI控制率存在关联,但尚无法确证其具有独立的直接提升作用。感染控制率受多种复杂因素影响,如抗生素选择、病原体特性及冲洗量等。因此,冲洗液中添加抗生素的确切价值仍需通过设计严谨的高质量研究进一步阐明。

临床问题4: UKA-PJI, 局部使用抗生素的价值?

推荐意见4:对于UKA-PJI,优先选择局部喷洒万古霉素粉剂或置管持续输注抗生素的方式维持局部高抗生素浓度,但需关注其对关节软骨可能存在的影响(证据等级及推荐强度:1B)。

推荐意见说明：相较于全身性给药，局部应用抗生素可在感染部位实现更高药物浓度，减少全身暴露，从而降低抗生素相关副作用、保护肠道微生物群并延缓耐药性发展。局部抗生素可单独使用或结合载体以优化释放[64-65]。抗生素骨水泥(antibiotic-loaded bone cement, ALBC)已用于DAIR，报道感染控制率为75%~100%[66-67]。然而，ALBC存在局限性:(1)抗生素释放非恒量，2~3d后浓度急剧下降;(2)不可生物降解性易致细菌黏附及生物膜形成;(3)存在划伤关节软骨的风险;(4)仅适用热稳定抗生素。为克服上述缺陷，可生物降解的硫酸钙微珠被提出，因其可负载抗生素且无需二次手术移除，在DAIR和一期翻修中更受关注。研究报道其在骨髓炎治疗中感染清除率较高[68]。然而，另有研究显示，DAIR术中应用硫酸钙微珠的感染控制率仅为52%，且存在伤口渗液、异位骨化及高钙血症等并发症

风险[69]。

局部喷洒抗生素粉末(如万古霉素)是初次关节置换术预防PJI的常用策略。研究证实其可显著降低深部手术部位革兰氏阳性菌感染率[70],且不增加聚乙烯磨损[65]。MRSA膝关节感染动物模型显示,万古霉素粉末局部联合静脉给药的抗感染成功率达100%[71]。药代动力学研究证实,局部应用万古霉素粉末可在关节内维持高治疗浓度,同时保持低全身血药浓度[72]。临床实践中,Roy等[73]通过局部给药和静脉给药比较了关节液中万古霉素的浓度,研究发现局部给药万古霉素产生的峰值水平比静脉注射方法高。Riesgo等[74]在DAIR术中采用深/浅筋膜放置万古霉素粉末联合聚维酮碘的方法,将感染控制率从63%提升至83.3%。

然而,局部喷洒粉末后引流液中抗生素浓度常在72 h内迅速下降[72],提示维持局部高浓度需定期补充给药。关节内注射抗生素在MRSA PJI动物模型中显示出减少生物膜、骨质流失及软组织炎症的潜力[75]。Mu等[76]通过关节局部直接注射抗生素,DAIR 后感染控制总体成功率为87.67%,且未发现血清肿形成病例。董国华等[77]报道了1例固定平台UKA后MRSA感染病例,DAIR术后采用静脉联合局部高浓度抗生素治疗,感染控制良好,关节功能恢复满意。Whiteside等[78]在一项膝关节PJI病例研究中,术中关于关节内放置Hickman导管并定期给予万古霉素和庆大霉素治疗,最终18例MRSA感染PJI患者,仅1例出现复发感染。

尽管尚无直接针对UKA-PJI治疗后局部使用抗生素的高质量研究证据,但基于DAIR术后局部抗生素输注展现的良好临床结局及相对较低的并发症报告,建议对于UKA-PJI可考虑尝试局部抗生素输注,但仍需警惕局部高浓度药物对关节软骨的潜在影响。

临床问题5: UKA-PJI, DAIR后利福平是否为联合使用抗生素所必须?

推荐意见5: 利福平是葡萄球菌PJI治疗中对抗生物膜的关键药物,但必须严格遵循联合用药原则(首选氟唑酮类,或联用β-内酰胺类、糖肽类)、使用标准剂量(600 mg/d)、警惕药物相互作用及肝毒性,并进行个体化决策和密切监测。违背这些原则(如单用、与禁忌药物联用、剂量不当)可能导致治疗失败或增加肝损伤、细菌耐药等风险(证据等级及推荐强度:1B)。

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推荐意见说明:利福平在PJI治疗领域占据特殊地位,可有效穿透细菌生物膜,且对葡萄球菌属(包括金黄色葡萄球菌和凝固酶阴性葡萄球菌)具有显著抗菌活性,使其成为葡萄球菌PJI治疗极具潜力的药物[79-80]。多项研究验证了利福平在葡萄球菌PJI中改善临床预后的价值[81-82]。一项纳入669例患者的分析显示,使用利福平组的治疗失败率显著低于未使用组(32.2%比54.2%),且利福平是治疗成功的独立预测因素(OR=0.30, 95%CI: 0.20-0.45)[83]。然而,其临床应用仍存争议,主要源于日益增加的耐药性、显著的药物相互作用以及复杂的应用场景。

目前,探讨利福平在PJI治疗中的作用的RCT较少。Zimmerli 等[84]在甲氧西林敏感金黄色葡萄球菌(Methicillin-sensitive Staphylococcus aureu, MSSA) PJI患者中比较了环丙沙星联合利福平与环丙沙星联合安慰剂的治疗效果,结果显示联合利福平组治愈率显著提高(100%比58%)。Pushkin等[85]在利福平联合夫西地酸治疗的PJI患者中进行药代动力学评估时发现,所有受试者体内的夫西地酸浓度均远低于预期,这种浓度降低极可能增加利福平耐药风险并导致治疗失败,因此该研究被迫提前终止。Karlsen等[86]开展的RCT纳入99例接受DAIR治疗的PJI患者,最终仅48例纳入统计分析,两年随访结果显示,是否联合利福平在根除感染成功率上差异无统计学意义。这种利福平理论上的抗菌优势与部分RCT中联合利福平无显著疗效的差距,构成了临床决策的核心困境。此外,在临床治疗过程中,利福平的给药剂量范围跨度较大,为600~900 mg/d[87-89]。进一步研究表明,剂量超过600 mg/d时患者耐受性降低,且未带来额外治疗获益[90-91]。

利福平通常需与氟喹诺酮类、万古霉素或β-内酰胺类药物联用。作为强效细胞色素P450酶(尤其是CYP3A4)诱导剂,它会降低多种联用抗生素的血浆浓度,如多西环素、利奈唑胺、甲氧苄氨嘧啶-磺胺甲噁唑(trimethoprim sulfamethoxazole, TMP-SMX)、克林霉素和夫西地酸[85,92-95],可能降低其治疗效果。同样,利福平会降低唑类抗真菌药(如酮康唑、伊曲康唑、氟康唑)的血浆浓度水平,进而影响抗真菌治疗效果。尽管这些相互作用已被广泛记录,但并未一致地转化为临床治疗失败。小鼠模型显示利奈唑胺联合利福平治疗PJI效果与静脉抗生素联合利福平相当[96]。然而,PJI患者中利福平联合方案的临床证据有限且结果不一。一项观察性研究提示,利福平

与氟喹诺酮类或克林霉素以外的抗生素联用,治疗失败率较高[83]。而另一项回顾性研究则发现,利福平联合利奈唑胺、TMP-SMX或克林霉素的治疗失败率,高于利福平联合氟喹诺酮类或阿莫西林的失败率,甚至高于利奈唑胺或TMP-SMX单药的失败率[63]。利福平在管理PJI(尤其由生物膜形成菌,如葡萄球菌引起的PJI)方面潜力巨大,现有证据支持其纳入联合方案,以提升疗效和改善预后。然而,其临床应用面耐药性产生风险、肝毒性以及复杂的药物相互作用等严峻挑战,因此临床实践中需采取谨慎且个体化的用药策略。

临床问题6: UKA-PJI,骨水泥占位器如何选用ALBC?

推荐意见6: ALBC的选择应基于术前病原学和药敏试验结果。对于培养阳性PJI,常用的革兰氏阳性菌抗生素包括万古霉素、克拉霉素,革兰氏阴性菌常用庆大霉素、氨苄西林或美罗培南。对于CN-PJI,通常采用万古霉素分别与妥布霉素、美罗培南等联合抗生素,以覆盖更广泛的病原体(证据等级及推荐强度:1B)。

推荐意见说明：外科医生常通过植入含ALBC的占位器实现局部高浓度抗生素释放。研究显示，ALBC占位器可在局部产生高达全身给药后血药浓度700倍的抗生素浓度[97]。在UKA中，由于关节腔隙较小，局部应用ALBC更易在腔隙内维持高抗生素浓度，从而显著增强抗感染效能，该策略已被广泛采用[98]。

骨水泥中抗生素的选择对 PJI 治疗至关重要,需满足临床安全性、热稳定性、低过敏性、水溶性、广谱抗菌活性及无菌粉末状态等特性[99]。若在二期翻修术前或通过窦道培养明确致病菌及药敏结果,应据此在骨水泥中添加相应抗生素[100]。骨水泥中最常用的抗生素是妥布霉素、庆大霉素、万古霉素和头孢菌素[101]。

在革兰氏阳性菌(主要为金黄色葡萄球菌、表皮葡萄球菌、MRSA和耐甲氧西林表皮葡萄球菌)引起的PJI中,万古霉素是最常用的骨水泥抗生素[102],克林霉素和氨基糖苷类亦有应用,但革兰氏阳性球菌对氨基糖苷的耐药性呈上升趋势[103]。对于MRSA引起的PJI,通常采用骨水泥中混入万古霉素联合静脉输注万古霉素的方案进行治疗[104]。在膝关节PJI二期翻修中,上述方案感染控制率为60%~74%[26, 105]。革兰氏阴性菌PJI虽较少见,但治疗更为复杂。庆大霉

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素是针对革兰氏阴性菌最常用的骨水泥抗生素[102], 美罗培南骨水泥也被证实对革兰氏阴性菌骨髓炎有效[106]。若致病菌单一且药敏明确,骨水泥中可仅添加一种抗生素。

对于CN-PJI,骨水泥中联合应用广谱抗生素是常规策略。万古霉素常为核心成分,妥布霉素和美罗培南亦为常用添加药物。实践中,为优化抗生素洗脱率和维持有效浓度,骨科医生多采用手动混合ALBC,但因手动混合缺乏统一操作标准,导致全球范围内抗生素种类、剂量及混合技术差异显著[107]。庆大霉素联合万古霉素或妥布霉素联用方案(旨在覆盖革兰氏阳性和阴性菌)最为普遍[108]。该策略已被证实可提升疗效并延缓耐药性发展。

ALBC在PJI(尤其慢性感染)治疗中的价值已获多项研究支持,在规范联合治疗(如配合全身抗生素)前提下,可有效降低感染[107-109]。在慢性PJI治疗中,高抗生素负载量的ALBC已被多数研究共识视为核心治疗方案之一。尽管针对CN-PJI的ALBC应用尚缺乏高质量证据,但基于覆盖UKA后CN-PJI常见潜在致病菌的考量,建议在此类患者治疗中采用含庆大霉素分别联合万古霉素或妥布霉素的ALBC方案。

临床问题7: UKA-PJI 假体再植入时,术中培养阳性,抗生素应如何抉择?

推荐意见7:对于在二期翻修再植入手术时,发现术中培养阳性会增加再感染风险,推荐采取积极的抗生素治疗(疗程6周)(证据等级及推荐强度:2B)。

推荐意见说明:目前尚无明确指标指导二期翻修的再植入时机决策,临床医生主要依据患者临床症状及血清学标志物进行评估[110]。再植入术中培养阳性(positive intraoperative cultures, PIC)仍是临床面临的严峻挑战,其显著增加再感染风险。Akgün等[111]在一项基于前瞻性数据收集的回顾性研究中纳入了163例接受二期翻修的PJI患者,其中27例出现PIC。该亚组中:15例接受术后12周抗生素治疗,4例失败;12例接受常规6周治疗,4例失败。Suardi等[112]观察到,二期翻修再植入术中≥2个样本培养阳性的患者,再植入后因再感染导致的治疗失败率更高。Theil 等[113]进一步指出,无论阳性样本数量多少均增加再感染风险,但单一阳性样本不应视为污染。尽管部分研究认为PIC与治疗结局无显著相关性[114]。但综合现有证据,目前仍推荐对二期翻修

再植入术中≥2处培养阳性的患者实施术后抗生素治疗。Xu 等[115]通过回顾性队列研究及荟萃分析的亚组分析探讨了上述策略(术后6周静脉、口服单药或联合抗生素)对PIC患者的疗效。结果显示,尽管6周抗生素治疗降低了PIC患者再感染率,但该类患者再感染的风险仍较二期翻修再植入术中培养阴性者高出3倍以上。

临床问题8:分子诊断学结果,如宏基因组二代测序(metagenomic next generation sequencing, mNGS),能否作为CN-PJI的抗生素使用依据?

推荐意见8:对于CN-PJI而mNGS结果阳性的患者,应进行系统治疗。首先,必须仔细评估mNGS结果假阳性的风险;之后应根据mNGS检出的病原体种类及药敏结果选择靶向抗生素治疗。尽管CN-PJI的抗生素治疗时间相对较长且并发症发生率较高,但基于mNGS结果的靶向治疗可取得与培养阳性PJI相当的成功率(证据等级及推荐强度:1A)。

推荐意见说明:有标准建议,≥2个关节液或组织标本培养出相同微生物应作为PJI的主要诊断标准[116]。然而,高达50%的PJI病例呈培养阴性状态[117]。其成因复杂,包括近期抗生素暴露、标本数量不足或质量不足、苛养微生物感染、生物膜相关微生物难以分离,以及多重感染诱导微生物进入可存活但不可培养状态[118]。此外,痤疮丙酸杆菌等生长缓慢慢微生物需延长培养时间[119]。

分子诊断学技术在PJI病原体鉴定方面展现出较高的敏感性和特异性,且受既往使用抗生素抗菌治疗的影响较小。另有标准建议,当诊断仍不确定时,考虑进行分子检测[116]。mNGS作为一种非靶向测序技术在PJI诊断中展现出显著优势[120]。一项纳入10项研究(n=955)的荟萃分析显示其诊断敏感性与特异性分别为93%和95%[121],检测耗时显著短于培养[(1.4±0.4)d比(5.1±2.6)d[122]。mNGS通过直接检测样本遗传物质,不依赖微生物生长,对复杂感染、特殊病原体及抗生素暴露患者(尤其用药>3d时)的检出率更显著优于传统培养[123]。多项研究已经证实在CN-PJI诊断中,mNGS价值尤为突出。Tarabichi等[124]报道在CN-PJI中mNGS的病原体检出率达81.8%;而Thoendel等[125]和Ivy等[126]分别报告在CN-PJI样本中mNGS的病原体检出率为43.9%和16.0%。此外,Tan等[127]和He等[128]发现采用超声裂解液处理样本后进行mNGS检测,其病原体检出灵敏度分别为90.7%和94.7%。上述证据表明,

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mNGS可显著提升 CN-PJI 的病原识别能力。

在CN-PJI 的治疗中,靶向抗生素治疗至关重要。抗生素选择不当或无效可导致治疗反应延迟甚至失败,凸显了早期准确病原体诊断的关键意义。近期研究强调了分子诊断技术,特别是mNGS,在指导UKA-PJI 有效抗菌治疗方案制定方面的重要价值[129]。虽然mNGS成本高于传统培养,但其提供快速、全面病原体检测的能力,可通过实现及时、靶向的抗菌治疗降低总体医疗成本[130]。相较于传统培养指导治疗,mNGS可能缩短患者住院时长、减少广谱抗生素使用需求,从而改善患者预后并降低总体治疗成本。Hu等[131]回顾性分析235例PJI患者,对比有无mNGS检测在罕见病原体检出率及治疗效果等方面的差异,发现mNGS显著降低了抗生素相关并发症、住院时间及抗生素使用时长,并提高了治疗成功率,这些益处在CN-PJI病例中尤为显著。Cai等[132]建立了一套mNGS指导培养的系统性PJI病原体诊断流程,涵盖术前至术中检测、多学科判断及疗效评估,临床应用价值高,有望改善患者预后。一项观察性研究显示,79.3%的二期翻修术后失败病例,其感染微生物与移除假体时mNGS鉴定结果一致[133]。

Wang等[134]评估了两组 CN-PJI 患者的临床结局: 一组依据 mNGS 结果接受靶向抗生素治疗,另一组接受经验性广谱抗生素治疗。研究显示,靶向治疗组治疗成功率(100%)显著高于经验治疗组(83.3%)。此外,经验治疗组的费用高出靶向治疗组两倍以上,且抗菌药物相关并发症发生率更高。在其他感染领域,一项涉及超过40000例尿路感染和7000例伤口感染样本的研究同样发现,mNGS常能在再感染病例的早期随访中检出病原体。当抗生素选择精准覆盖mNGS描述的感染特征时,这些患者的复发风险显著低于抗生素覆盖不足的患者[135]。在治疗伴发热的急性坏死性胰腺炎时,基于mNGS结果正确使用抗生素的比例(81.4%)远高于经验性治疗中正确使用抗生素的比例(18.7%)[136]。因此,鉴于mNGS在感染性微生物检出方面的显著优势。依据其结果进行靶向抗生素给药可显著改善临床预后。

临床问题9: LTAT在UKA-PJI 管理中的作用?

推荐意见9: LTAT可作为无法接受根治性手术患者的姑息性选择,或作为DAIR术后的辅助治疗手段,可能降低短期治疗失败风险;但需严格限定疗程、严密监测药物不良反应(证据等级及推荐强度:3C)。

推荐意见说明:对于因全身状态禁忌手术、预期功能改善有限(如多次手术失败者,术后功能仍难改善)或拒绝手术的UKA-PJI患者,LTAT作为非手术干预手段可能具有应用价值。在DAIR患者中,多项回顾性研究表明术后LTAT可降低治疗失败率[62, 137-138]。Zanirato 等[139]对9例慢性UKA-PJI行DAIR的患者分析发现:接受LTAT的4例中3例成功(75%),而未接受LTAT的5例均失败。然而,Byren 等[140]的研究提示,无论抗生素疗程长短,停药后PJI治疗失败风险均显著升高,表明LTAT可能仅延迟,而非根本预防感染复发。因此需审慎考量LTAT的疗程设定——无论何种类型PJI,抗菌药物不良反应均呈时间依赖性累积[141-142]。尽管LTAT在特定情境下可能有效,目前仍缺乏比较有限程与无限期LTAT疗效差异的高质量研究。

三、总结

PJI 是关节置换术后的严重并发症,显著降低患者生活质量并加重医疗系统负担。抗生素治疗虽为PJI 管理的核心手段,其合理应用仍面临多重挑战。本共识针对UKA-PJI抗生素使用的多个关键方面,如不同治疗模式下的最佳疗程、静脉-口服转换时机、局部抗生素价值及特殊情境处理,基于现有证据提出专家建议,旨在规范临床实践、提升治疗有效性并降低并发症风险。然而,当前研究存在显著局限:部分关键问题缺乏高质量临床证据,导致推荐意见等级受限;研究间异质性亦影响结论的普适性。需要指出的是,本共识引用的多数研究证据来源于全膝关节置换术后PJI的管理经验。由于UKA在手术入路、保留结构(如交叉韧带、对侧间室)、假体体积及固定界面等方面与全膝置换术显著不同,直接将针对全膝关节置换术后PJI的治疗方案应用于UKA-PJI可能存在潜在风险。因此,本共识在指导UKA-PJI治疗实践方面存在固有的证据缺口,其结论需谨慎解读,并认识到UKA-PJI可能需要更具针对性的诊断和治疗策略。未来亟需开展大规模、多中心、前瞻性高质量研究,以明确精准化抗生素策略,填补知识空白并减少临床不确定性。同时应深化基础研究,阐释PJI发病机制及细菌耐药机制,为新型抗生素研发与优化应用提供理论支撑。此外,强化多学科协作对优化PJI诊断、治疗及全程管理至关重要,最终改善患者预后并促进关节置换领域的可持续发展。

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参与本共识编写和讨论的成员名单

顾问:黄野(首都医科大学附属北京积水潭医院),张文明(福建医科大学附属第一医院),朱晨(中国科学技术大学附属第一医院)

执笔:罗瑶(中国科学技术大学附属第一医院);方心俞(福建医科大学附属第一医院);张薇薇(中国科学技术大学附属第一医院)

共识专家组成员(按姓氏拼音排序): 曹光磊(首都医科大学附属北京积水潭医院), 陈德生(天津市天津医院), 陈广祥(苏州市立医院), 陈晶(北京大学航天中心医院), 丁弼(西安交通大学附属红会医院), 黄威(中国科学技术大学附属第一医院), 李兵(中国医科大学北京航空总医院), 李慧武(上海交通大学医学院附属第九人民医院), 刘国彬(河北医科大学附属第一医院), 刘宁(哈尔滨医科大学附属第一医院), 刘培来(山东大学齐鲁医院), 柳剑(首都医科大学附属北京积水潭医院), 米玛扎西(陆军第九五三医院), 那日苏(内蒙古国际蒙医院), 彭晓春(上海交通大学医学院附属第六人民医院), 乔锋(西安交通大学附属红会医院), 曲新华(上海交通大学医学院附属仁济医院), 沙宇(河南省直第三人民医院), 尚寿禧(中国科学技术大学附属第一医院), 谭红略(河南省洛阳正骨医院), 田洪涛(华中科技大学同济医学院附属附属协和医院), 培建(浙江省中医院), 王健(南方医科大学南方医院), 王强[皖南医学院附属第一医院(皖南医学院弋矶山医院)], 王广积(郑州市骨科医院), 王加兴(上海交通大学医学院附属第六人民医院), 王金良(郑州市骨科医院), 王渭君(南京大学医学院附属鼓楼医院), 王武炼(福州市第二总医院), 王松(中南大学湘雅三医院), 杨德金(首都医科大学附属北京积水潭医院), 杨久山(山东中医药大学附属医院), 杨伟毅(广东省中医院), 查国春(徐州医科大学附属医院), 张辉(安徽医科大学第一附属医院), 张民(山西医科大学第二医院), 张媛(陆军军医大学第二附属医院), 张启栋(中日友好医院), 张薇薇(中国科学技术大学附属第一医院), 张贤祚(中国科学技术大学附属第一医院), 张向鑫(苏州市立医院)

学术秘书:张陶、孙海博、张睿、庞臻、胡先粒、陈墨(中国科学技术大学附属第一医院)

利益冲突 所有参与撰写该共识的编写委员会专家均声明不存在利益冲突。

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(收稿日期:2025-06-12)

(本文编辑:张朔)

国家骨科医学中心保膝联盟,中国老年保健协会骨关节保护与健康分会,单髁置换术后感染抗生素使用专家共识工作组. 单髁置换术后假体周围感染的抗生素使用专家共识(2025版)[J/CD].中华损伤与修复杂志(电子版),2025,20(6):476-489.DOI:10.3877/cma.j.issn.1673-9450.2025.06.004.

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