坏死性筋膜炎是一种外科急症,需要对感染的皮下组织进行快速清创,结合广泛性针对可能发病原因的抗生素治疗。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845[19]Cheung JP, Fung B, Tang WM, et al. A review of necrotising fasciitis in the extremities. Hong Kong Med J. 2009 Feb;15(1):44-52.http://www.hkmj.org/system/files/hkm0902p44.pdf[20]Angoules AG, Kontakis G, Drakoulakis E, et al. Necrotising fasciitis of upper and lower limb: a systematic review. Injury. 2007 Dec;38 Suppl 5:S19-26.[22]Sartelli M, Malangoni MA, May AK, et al. World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections. World J Emerg Surg. 2014 Nov 18;9(1):57.https://wjes.biomedcentral.com/articles/10.1186/1749-7922-9-57 交叉学科团队协作(外科医生、感染性疾病顾问医生、微生物学家)为最佳治疗提供了基础。
初期治疗
由于感染的皮下组织失活,因此迅速进行手术移除感染组织对治疗成功与否至关重要。一旦怀疑该诊断,就应该立即进行外科会诊。等待手术时,应监测患者的全身毒性(全身炎症反应综合征的征状)以及坏死性筋膜炎区域扩展的体征及症状。应立即开始经验性抗生素治疗。通过静脉输液提供强化血流动力学支持是治疗的一个重要方面。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845[22]Sartelli M, Malangoni MA, May AK, et al. World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections. World J Emerg Surg. 2014 Nov 18;9(1):57.https://wjes.biomedcentral.com/articles/10.1186/1749-7922-9-57 一旦患者手术开始,手术切口应延伸到可见坏死区域之外,并切除整个坏死区域。应获取包括组织和体液的手术样本,以进行微生物培养。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845[22]Sartelli M, Malangoni MA, May AK, et al. World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections. World J Emerg Surg. 2014 Nov 18;9(1):57.https://wjes.biomedcentral.com/articles/10.1186/1749-7922-9-57 大多数病例需要进行进一步的外科评估和清创,可能需要多次手术以确保坏死组织清除干净。
对发生链球菌休克综合征患者的治疗策略是相似的(即支持性治疗措施、手术清创术和抗生素治疗)。对由 A 族链球菌所致的 II 型坏死性筋膜炎的治疗,除了青霉素之外,应始终包括克林霉素,因为克林霉素可抑制 A 族链球菌毒素的生成。
也可考虑加用静脉注射免疫球蛋白 (IVIG),但关于有效性的数据存在矛盾。一些观察性研究表明了适度的益处,但是一项小型双盲安慰剂对照试验(由于患者招募缓慢而提前终止),以及一项 IVIG 对清创坏死性筋膜炎患者(存在由 A 族链球菌或金黄色葡萄球菌引起的休克)的影响的大型回顾性分析发现,辅助 IVIG 与改善生存率无关。[29]Carapetis JR, Jacoby P, Carville K, et al. Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group A streptococcal infections. Clin Infect Dis. 2014 Aug 1;59(3):358-65.[30]Kaul R, McGeer A, Norrby-Teglund A, et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis. 1999 Apr;28(4):800-7.[31]Linnér A, Darenberg J, Sjölin J, et al. Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome: a comparative observational study. Clin Infect Dis. 2014 Sep 15;59(6):851-7.[32]Darenberg J, Ihendyane N, Sjölin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003 Aug 1;37(3):333-40.[33]Kadri SS, Swihart BJ, Bonne SL, et al. Impact of intravenous immunoglobulin on survival in necrotizing fasciitis with vasopressor-dependent shock: a propensity score-matched analysis from 130 US hospitals. Clin Infect Dis. 2017 Apr 1;64(7):877-85. 美国感染病学会 (Infectious Diseases Society of America, IDSA) 指南不包含对发生链球菌中毒性休克综合征的坏死性筋膜炎患者使用静脉注射免疫球蛋白 (IVIG) 的建议,并指出需要额外的疗效研究。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845 世界急诊外科学会 (World Society of Emergency Surgery) 指南提倡考虑对有器官功能障碍证据的坏死性筋膜炎患者使用 IVIG(弱推荐),同时指出关于使用 IVIG 治疗坏死性软组织感染仍存在争议。[22]Sartelli M, Malangoni MA, May AK, et al. World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections. World J Emerg Surg. 2014 Nov 18;9(1):57.https://wjes.biomedcentral.com/articles/10.1186/1749-7922-9-57
抗生素的选择
在微生物病因及其敏感性确认之前,应给予广谱抗生素,该抗生素应覆盖 I 型感染的最常见病因(混合性感染的拟杆菌属或消化链球菌属等厌氧菌,肠杆菌科 [大肠埃希氏菌、肠杆菌属、克雷伯氏菌属、变形杆菌属]、耐甲氧西林金黄色葡萄球菌或非 A 族链球菌等兼性厌氧菌),以及 II 型感染的 A 族链球菌。推荐的经验性方案(微生物未知情况下)包括:万古霉素、利奈唑胺、泰地唑胺或达托霉素联合以下之一:哌拉西林/他唑巴坦;碳青霉烯类(例如美罗培南、亚胺培南/西司他丁、厄他培南);头孢曲松+甲硝唑;或氟喹诺酮类(例如环丙沙星)+甲硝唑。克林霉素或甲硝唑联合氨基糖苷类(例如庆大霉素)或氟喹诺酮类可能用于对青霉素过敏的患者。
除非已排除 A 族链球菌的存在,否则应按照经验将抑制毒素产生的抗微生物药物包含在治疗中。存在最强有力的证据支持使用克林霉素;利奈唑胺也可能是一种有效的替代药物。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845[34]Bonne SL, Kadri SS. Evaluation and management of necrotizing soft tissue infections. Infect Dis Clin North Am. 2017 Sep;31(3):497-511.
虽然真菌病原体(特别是毛霉菌目)是坏死性筋膜炎的罕见病因,但不推荐根据经验将抗真菌药物包含在治疗中。
推荐用于 I 型混合感染的抗生素包括万古霉素、利奈唑胺、泰地唑胺或达托霉素与以下治疗之一联用:哌拉西林/他唑巴坦;碳青霉烯类(例如美罗培南、亚胺培南/西司他丁、厄他培南);头孢曲松+甲硝唑;或氟喹诺酮类(例如环丙沙星)+甲硝唑。克林霉素或甲硝唑联合氨基糖苷类(例如庆大霉素)或氟喹诺酮类也可能用于对青霉素过敏的患者。美国感染病学会 (IDSA) 支持其中一些方案。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845
当可获得更多信息并已确定病原菌时,应修正抗生素治疗方案,进行针对性的确诊治疗。 由于目前没有确定性的临床试验,IDSA 推荐持续抗生素治疗,直至不需要进行进一步的外科清创,患者临床症状好转,持续 48-72 小时没有发热症状。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845
II 型感染最常由 A 族链球菌引起;建议使用克林霉素加青霉素。对于有青霉素过敏的患者,可以使用万古霉素单药疗法。当金黄色葡萄球菌是疑似病原体时,在培养确认药敏之前,应使用有抗 MRSA 活性的抗生素。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845[22]Sartelli M, Malangoni MA, May AK, et al. World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections. World J Emerg Surg. 2014 Nov 18;9(1):57.https://wjes.biomedcentral.com/articles/10.1186/1749-7922-9-57 多西环素用于治疗由创伤弧菌和嗜水气单胞菌引起的 II 型坏死性筋膜炎。真菌病原体是引起坏死性筋膜炎的罕见原因;脂质两性霉素 B 是 II 型毛霉感染患者的初始治疗方案。
后续治疗
对于难治性患者,应考虑再次清创和/或更改抗生素治疗方案(基于皮下组织或血液培养结果)。[5]Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52.https://academic.oup.com/cid/article/59/2/e10/2895845 如果对坏死性筋膜炎的广泛性外科清创术导致功能和外观缺陷,则可能需要重建手术。
[Figure caption and citation for the preceding image starts]: 外科清创术后分层皮片移植来源于:Hasham S, Matteucci P, Stanley PRW, et al. Necrotising fasciitis. BMJ. 2005 Apr 9;330(7495):830-3 [Citation ends].