消化内镜预防性使用抗生素指南

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编者按 本文是消化内镜在常见临床情况下应用的系列讨论之一, 由美国消化内镜学会提供. 在撰写这一指南的过程中, 除MEDLINE检索到的文章外, 还参考一些专家推荐的文章. 内镜的合理应用指南是基于目前的一些重要的综述和专家共识. 还需要大量的临床对照研究加以确定和必要的修订. 临床上遇到情况和指南有所差异时应适当调整.

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Correspondence to: N/A

Received: August 17, 2004
Revised: September 10, 2004
Accepted: September 24, 2004
Published online: November 15, 2004

Abstract

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1 消化内镜检查和感染并发症的风险

预防性应用抗生素的目的是减少发生严重的感染并发症. 然而可能永远都不会有这方面的随机、双盲、安慰剂对照的临床研究. 能从文献中得到的是已报道的与日常内窥镜操作有关的感染并发症的数量和菌血症的发生率. 本文更新了ASGE1995年公布的该方面的指南[1].

尽管每年有大量的内窥镜检查, 但操作后并发细菌性心内膜炎的报道非常少[2-16]. 15例并发心内膜炎的患者中有4例与引起菌血症的高风险操作有关, 如食管扩张[4,8]、食管硬化剂注射治疗[11,14], 剩余11例发生在胃镜[2-3,9,13,15-16]、乙状结肠镜[5-7,12]和结肠镜[10]检查. 其他与食管硬化疗法和扩张治疗有关的罕见感染并发症包括细菌性腹膜炎、中枢神经系统感染和肾周脓肿[17].

高风险操作是指菌血症发生率高的操作[1]. 尽管菌血症有可能发生而且被认为是感染性心内膜炎潜在的危险因素, 临床上严重感染罕见. 食管狭窄扩张治疗和曲张静脉硬化治疗的菌血症发生率最高[18]. 原先估计食管扩张和硬化治疗的菌血症发生率分别是45%和31%, 是分别综合了四项研究的59例[19-22]和61例[23-26]病例的结果. 血培养分离出的病原菌主要是口腔共生菌, 如草绿色链球菌. 然而一项针对探条扩张术的研究表明菌血症似乎源于扩张器上的病原菌而非口腔共生菌[19]. 因为各种研究的方法不同, 菌血症真实的发生率可能被高估了.

最近有3项前瞻性研究可能更准确评估了食管探条扩张术后菌血症的发生率, 即12-22%[27-29]. 在第1项研究中, 103例无心瓣膜病的患者在食管狭窄扩张前后做了血培养, 对照组为50例接受内镜检查但未扩张的患者, 菌血症的发生率分别是21%和2%. 24例血培养阳性的标本中19例分离出草绿色链球菌, 其中又有2例(10%)菌血症持续近30 min[27]. 没有感染并发症的发生. 第2项研究包括86例患者共完成了100次扩张, 22%术后血培养阳性, 其中恶性狭窄菌血症的发生率高于良性狭窄, 多次扩张高于单次扩张. 血培养得到的病原菌并非来源于扩张器. 亦无感染并发症的发生[28]. 第3项研究目的是调查口服抗生素洗液的疗效. 59例良恶性食管狭窄扩张后菌血症总的发生率是12%. 分离到的细菌都是口腔共生菌. 无感染并发症发生[29].

食管曲张静脉套扎术(EVL)因为疗效好、并发症少通常可替代食管硬化治疗[30]. 6项关于EVL的研究报道该操作菌血症的发生率为1-25%, 平均8.8%[31-36]. 对通常被认为是低风险的内窥镜操作也作了菌血症发生率的评估. 胃镜(取或未取活检)菌血症发生率为0-8%, 平均4.4%[37-45], 通常持续时间短(不到30 min), 不会发生任何感染并发症. 两项研究报道可曲式乙状结肠镜菌血症发生率很低, 分别为0和1%[46-47]. 结肠镜相关的菌血症发生率是0-25%, 平均为4.4%[17].

迄今无研究证实预防性应用抗生素能有效减少内窥镜操作过程中感染并发症的发生[29,48]. 另外, 接受内窥镜操作的患者预防性应用抗生素也并不总能成功地防止发生感染性心内膜炎[49]. 一项病例对照研究还提示预防性应用抗生素可能并不影响操作后心内膜炎的发生率[50]. 其他研究则表明现有预防方案的依从性差[51-53].

预防性应用抗生素以防止心内膜炎的发生应用于有感染高风险的患者(表1). 不主张在消化内镜操作过程中无选择地应用抗生素, 因为其增加了不必要的费用和潜在的不良反应.

表1 内镜操作预防性使用抗生素.

患者状况	操作	预防性应用抗生素
高风险:	狭窄扩张
瓣膜修补	曲张静脉硬化治疗	主张
心内膜炎病史	对阻塞的胆管行ERCP
肺体分流	其他内镜操作包括食管胃
人造血管移植(<1年)复杂的紫绀型先天性心脏病	十二指肠镜和结肠镜(无论是否活检/息肉切除)、曲张静脉套扎	可选择
中度风险:	狭窄扩张
多数其他的先天性异常	曲张静脉硬化治疗	可选择
获得性瓣膜功能不全(如风湿性心脏病)	对阻塞的胆管行ERCP
肥厚性心肌病	其他内镜操作包括食管胃
二尖瓣脱垂伴反流或叶瓣增厚	十二指肠镜和结肠镜(无论是否活检/息肉切除)、曲张静脉套扎	不主张
低风险:
其他心脏情况(冠状动脉搭桥术, 已修复的间隔缺损或导管未闭、不伴反流的二尖瓣脱垂、单纯原发孔房间隔缺损、生理性/功能性/无病理意义的心脏杂音、无瓣膜功能不全的风湿热, 安装了起搏器、除颤器)	所有内镜操作	不主张
胆管阻塞	ERCP	主张
胰腺囊性病灶	ERCP、EUS-FNA	主张
急性消化道出血的肝硬化	所有内镜操作	主张
腹水、免疫功能受损患者	食管狭窄扩张曲张静脉硬化治疗	无建议
	其他内镜操作包括食管胃十二指肠镜和结肠镜(无论是否活检/息肉切除)、 曲张静脉套扎	不主张
所有患者	内镜下经皮置胃管	推荐(胃肠外给予头孢菌素或其他等效抗生素)
人造关节	所有内镜操作	不主张
心内膜炎预防方案(1 h前口服, 30 min前静推或肌注)阿莫西林口服或氨苄青霉素静推: 成人 2.0 g, 儿童50 mg/kg, 青霉素过敏: 氯林可霉素(成人600 mg, 儿童20mg/kg ), 或先锋霉素Ⅳ 或头孢羟氨苄(成人2.0 g, 儿童50 mg/kg), 或阿奇霉素或克拉霉素(成人500 mg, 儿童15 mg/kg)或先锋霉素V(成人1.0 g, 儿童25 mg/kg静推/肌注), 或万古霉素(成人1.0 g, 儿童10-20 mg/kg静推).

2 消化内镜预防性应用抗生素的共识

2.1 预防感染性心内膜炎

2.1.1 发生感染性心内膜炎高风险的心脏病变[54]: (1)心脏瓣膜修补, 包括生物瓣膜和同种移植瓣膜; (2)既往有细菌性心内膜炎病史; (3)手术重建肺体分流; (4)复杂的紫绀型先天性心脏疾病(如单心室、大动脉错位、Fallot四联征).

2.1.2 与普通人群相比, 不会增加感染性心内膜炎风险的心脏病变[54]: (1)冠状动脉搭桥术; (2)安装有心脏起搏器或植入式除颤器; (3)二尖瓣脱垂或既往有风湿热病史但无瓣膜功能不全或反流; (4)单纯原发孔房间隔缺损; (5)房间隔缺损、室间隔缺损、动脉导管未闭; (6)生理性、功能性或无病理意义的心脏杂音; (7)有川崎病病史但不伴有瓣膜功能不全.

2.1.3 与普通人群相比, 增加感染性心内膜炎的风险但程度低于高风险的心脏病变[54-56]: (1)其他多数先天性心脏畸形(除上述列举之外); (2)获得性瓣膜功能不全(如风湿性心脏病); (3)肥厚性心肌病; (4)二尖瓣脱垂伴瓣膜反流和/或叶瓣增厚.

2.1.4 建议: (1)对于多数内窥镜操作, 如上消化道内镜、乙状结肠镜、结肠镜, 无论是否做黏膜活检、息肉切除和/或非曲张静脉止血: 与普通人群相比有中度风险以及无风险的患者不主张预防性应用抗生素, 例如对于二尖瓣脱垂患者无论是否伴有反流在接受上述操作时无须预防性应用抗生素; 有不充分的依据推荐对于高风险患者应常规预防性应用抗生素. 内镜医生应根据具体病例分析决定; (2)增加一过性菌血症机会的内窥镜操作包括食管狭窄的扩张、曲张静脉硬化治疗以及对明确有或可能有阻塞的胆管行逆行胆管造影: 高风险患者主张预防性应用抗生素; 无风险的心脏病患者不主张应用, 然而所有明确有或怀疑有胆管阻塞的患者接受ERCP操作前, 主张预防性应用抗生素; 有不充分的依据推荐中等风险的心脏病患者常规预防性应用抗生素. 内镜医师应根据具体情况分析决定.

2.1.5 方案[54]: (1)标准常规预防方案: 操作前1 h口服阿莫西林2.0 g(成人)或50 mg/kg(儿童). 不能口服者的替代方案为操作前30 min内氨苄青霉素2.0 g静推/肌注(成人)或50 mg/kg静推/肌注(儿童); (2)青霉素过敏者: 操作前1 h口服氯林可霉素600 mg(成人)或20 mg/Kg(儿童). 替代方案: 操作前1 h口服先锋霉素IV或头孢羟氨苄2.0 g(成人)或50 mg/kg(儿童); 阿奇霉素或克拉霉素操作前1 h口服500 mg(成人)或15 mg/kg(儿童); (3)青霉素过敏但无法口服的患者: 操作前30 min内氯林可霉素600 mg静推(成人)或20 mg/kg静推(儿童). 替代方案: 操作前30 min内先锋霉素V 1.0 g静推/肌注(成人)或25 mg/kg静推/肌注(儿童). 万古霉素1.0 g静推(成人)或10-20 mg/kg(儿童).

2.2 人造血管移植术后患者

人造血管的移植材料感染有着可怕的发病率和死亡率, 但移植物感染的风险随时间的推移会下降. 肾下动脉聚脂纤维移植术后的狗接种金黄色葡萄球菌, 术后1 mo内的狗全部获得感染, 术后1年狗感染数目明显减少. 单次初始剂量的抗生素显著降低了感染率. 当全部的假内膜被覆盖后就不会发生感染, 因此有理由推测假内膜覆盖在1年内完成. 建议: 人造血管移植术后1年内的患者接受食管狭窄扩张、曲张静脉硬化治疗或在明确有或怀疑有胆管阻塞情况下行逆行胆管造影时, 应预防性使用抗生素. 对于其他内镜操作, 常规应用抗生素的依据尚不充分. 内镜医生应根据具体情况分析决定.

2.3 安装了人造关节或整形假体的患者

内镜操作后医源性人造关节感染极其罕见. 与内镜操作(Nd: YAG激光治疗已失去手术机会的食管癌)相关的感染并发症(化脓性膝关节炎)仅见1例报道[57]. 在感染性疾病培训基金的项目主管间进行一次调查, 询问他们关于带有整形假体的患者接受消化内镜操作时是否需要预防性应用抗生素的意见. 然而针对假体安装6 mo内患者接受结肠息肉电切术时是否应使用抗生素意见都有分歧[58]. 建议: 有尚不充分的依据主张带有人造关节或整形假体患者接受消化道内镜操作时应预防性使用抗生素.

2.4 伴胆管阻塞、胰腺假性囊肿或需行细针抽吸术(FNA)的胰腺囊性病灶患者

胆管炎和败血症是已知的逆行胰胆管造影(ERCP)的并发症, 发生率接近3.0%. 胆管阻塞和不恰当的引流会增加临床严重感染的风险[59-69]. 这类患者身上有许多病原菌都能导致感染. 胆汁培养液的抗生素测试证实多数病原菌对氟喹诺酮类药物敏感[70]. 一项近期的荟粹分析表明这类患者预防性应用抗生素有减少菌血症发生的趋势[71]. 然而败血症的发生率无显著差异. 最近另一具有决定性意义的分析表明预防性使用抗生素能降低胆管炎的发生率并减少患者费用[72]. 与上述发现一致, 尽管似乎对胆管引流不畅(如胆石症、恶性肿瘤等)的患者预防性应用抗生素是有意义的[72-81], 许多临床随机对照试验的结果相互矛盾.

2.4.1 假性囊肿: 逆行胰管造影、可能还有超声内镜引导的FNA都会造成假性囊肿的感染[62,66,68]. 明确的治疗措施是减压和引流. 尚没有随机对照研究比较预防性应用抗生素和安慰剂的疗效. 然而考虑到感染的风险, 预防性应用抗生素显然是慎重的.

2.4.2 EUS引导的实性或囊性病灶的FNA: 一项评价EUS引导下的占位性病灶FNA疗效的研究中没发现发生临床有意义的菌血症[82]. 随机对照研究尚未明确EUS引导下胰腺囊肿FNA中预防性应用抗生素的意义. 一项分组分析表明胰腺囊肿FNA发生感染并发症的风险是14%[83]. 建议: 所有明确有或怀疑有胆管阻塞的患者、胰腺假性囊肿的患者在行ERCP检查前应预防性应用抗生素, 并同时对阻塞的胆管或囊肿行恰当的引流. 内镜下胰腺假性囊肿的透壁引流同样可能会导致腔内感染. 另外, EUS引导下的胰腺囊性病灶的FNA也有这种可能性. 尽管尚未被随机对照研究所证实, 仍主张在引流假性囊肿或类似的胰腺病灶前预防性使用抗生素. 推荐使用抗菌谱覆盖胆道细菌菌落如肠革兰氏阴性菌, 肠球菌和假单孢杆菌的抗生素. 实性占位性病灶行FNA不需要预防性应用抗生素.

2.5 内镜下经皮放置胃管

多项前瞻性随机对照研究表明在经皮胃切开置管前30 min预防性使用抗生素能显著减少胃周伤口的感染[84-88]. 然而也有一些随机研究得到相反的结果[89-90]. 最近对7项研究(其中3项未采用盲法)的荟粹分析证实接受抗生素预防的患者其胃周伤口感染率显著低于未使用者(分别是6.4%、24%)[91].

建议: 所有接受内镜下经皮置胃管术的患者均应预防性使用抗生素以预防软组织感染. 应在操作前30 min胃肠外给予先锋霉素V或抗菌谱相同的其他抗生素. 如患者已使用了等效抗生素, 那么不需要另外预防性应用抗生素.

2.6 肝硬化、腹水及免疫功能受损患者

除个案报道和回顾性研究之外, 几乎没有资料可用来明确肝硬化、腹水和免疫功能受损患者常规内镜操作前是否需预防性应用抗生素.

2.6.1 注射硬化剂: 硬化治疗菌血症的发生率接近50%[23,25,32,47,92-96]. 临床试验中接近5%患者有明显发热和/或细菌性腹膜炎[92-94,96-99]. 已报道的其他并发症还包括中枢神经系统的感染和肺部浸润. 一项研究报道胃曲张静脉的硬化治疗菌血症发生率接近32%, 其中大约1/3患者有发热, 50%的患者接受了抗生素治疗[100]. 一些随机对照研究支持硬化治疗前使用抗生素[48,101-103], 然而研究者未采用安慰剂对照的盲法研究. 有一随机试验表明预防性应用头孢氨噻患者硬化治疗后腹膜炎的发生率减低[48].

2.6.2 内镜下曲张静脉套扎治疗: 据报道套扎后菌血症的发生率近25%, 腹膜炎的发生率不到5%[31,33,35-36]. 尚无这方面随机双盲安慰剂对照的有关预防性应用抗生素的临床研究.

2.6.3 消化道出血: 肝硬化因消化道出血而收治入院者感染(尤其是细菌性腹膜炎)的风险大大增加[31,48,94]. 目前消化道出血被认为是肝硬化患者发生感染的独立的危险因子[97]. 抗生素的使用能减少感染并发症并降低死亡率[48,101-103].

2.6.4 狭窄扩张: 在免疫功能正常患者中的情况前面已经讨论过了, 免疫功能受损患者食管扩张导致临床有意义菌血症的比率有待明确.

建议: 肝硬化及其他免疫功能受损患者易因一过性菌血症而发生感染, 接受侵入性操作时风险更高[104-113]. 内镜医师应根据具体病例分析决定在进行高风险操作如食管硬化治疗和狭窄扩张时是否使用抗生素. 但所有消化道出血的肝硬化患者均应预防性使用抗生素[31,48,94,100-102].

对于其他内镜操作包括预防性曲张静脉套扎术, 不主张常规使用抗生素. 然而亦应根据具体情况来分析决定. 肝硬化腹水患者有发生感染的较高的潜在风险. 移植患者大量使用非甾体药物也增加了感染易感性, 抗生素的选择应根据特定的情况分析决定.

总之, 高风险心脏疾病患者接受一过性菌血症发生率高的内窥镜操作时主张预防性应用抗生素以防止发生感染性心内膜炎(专家意见). 人造血管移植术后1年内的患者在接受高风险内镜操作时应预防性使用抗生素(专家意见). 安装了人造关节或整形假体的患者接受任何内镜操作时预防应用抗生素的意义还不明确或未达成共识(专家意见). 所有明确或怀疑有胆管阻塞患者以及胰腺假性囊肿患者在接受ERCP检查前应使用抗生素并辅以恰当的对阻塞胆管(前瞻性对照临床研究)或囊肿的引流(专家意见). EUS引导下胰腺囊性病灶细针抽吸术前主张预防性应用抗生素, 对胰腺实性病灶则不需要(专家意见). 所有接受内镜下经皮置胃管术的患者应预防性使用抗生素以限制软组织感染的风险(前瞻性对照临床研究). 所有消化道出血的肝硬化患者应预防性使用抗生素以降低感染并发症及死亡率(前瞻性对照临床研究).

备注

编辑:N/A

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