对于非霍乱弧菌引发的脓毒症或严重全身性感染患者的治疗方法包括第三代头孢菌素(如静脉使用头孢他啶或头孢曲松)加用多西环素或米诺环素。脓毒症具有高死亡率,因此在等待血液培养确定结果期间,经验性抗生素治疗中必须包括针对弧菌感染的治疗。[37]Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304-377.http://link.springer.com/article/10.1007%2Fs00134-017-4683-6http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com如患者伴有坏死性皮肤/软组织感染,还需在早期对失活组织进行彻底清创。对于坏死性筋膜炎患者,入院后 12 小时内的手术干预能够大幅降低死亡风险。[40]Chao WN, Tsai CF, Chang HR, et al. Impact of timing of surgery on outcome of Vibrio vulnificus-related necrotizing fasciitis. Am J Surg. 2013;206:32-39.http://www.ncbi.nlm.nih.gov/pubmed/23414632?tool=bestpractice.com仅出现局部皮肤/软组织伤口感染的患者可在门诊接受口服抗生素治疗。胃肠炎综合征使用补液进行治疗。如果腹泻持续超过 5 天,则需要口服抗生素。
脓毒症被定义为宿主对感染的反应失调导致危及生命的器官功能障碍。脓毒性休克被定义为脓毒症的一个亚组,伴有循环、细胞或代谢功能障碍,死亡风险较高。[37]Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304-377.http://link.springer.com/article/10.1007%2Fs00134-017-4683-6http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
脓毒症或严重全身性感染
创伤弧菌会迅速导致免疫功能受损或患有基础性肝病的患者出现致命性的脓毒性休克。这种病原体最常与严重疾病和/或死亡相关。[16]Hsueh PR, Lin CY, Tang HJ, et al. Vibrio vulnificus in Taiwan. Emerg Infect Dis. 2004;10:1363-1368.http://wwwnc.cdc.gov/eid/article/10/8/04-0047_articlehttp://www.ncbi.nlm.nih.gov/pubmed/15496235?tool=bestpractice.com[17]Neill MA, Carpenter CCJ. Chapter 212, Other pathogenic vibrios. In: Mandell GL, Douglas RG, Bennett JE, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 6th ed. Philadelphia, PA: Elsevier, Churchill Livingstone; 2005:2544-2548.对于酗酒或肝硬化患者,副溶血性弧菌可能导致脓毒症,该病的死亡率高达 29%。[41]Daniels NA, MacKinnon L, Bishop R, et al. Vibrio parahaemolyticus infection in the United States, 1973-1998. J Infect Dis. 2000;181:1661-1666.http://www.ncbi.nlm.nih.gov/pubmed/10823766?tool=bestpractice.com
脓毒症患者应在重症监护病房内进行治疗。较高的患者存活率取决于早期有针对目标的复苏和广谱抗生素疗法的早期干预,包括使用第三代头孢菌素和四环素。[37]Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304-377.http://link.springer.com/article/10.1007%2Fs00134-017-4683-6http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com[39]Liu JW, Lee IK, Tang HJ, et al. Prognostic factors and antibiotics in Vibrio vulnificus septicemia. Arch Intern Med. 2006;166:2117-2123. [Erratum in: Arch Intern Med. 2007;167:194.]http://archinte.jamanetwork.com/article.aspx?articleid=411127http://www.ncbi.nlm.nih.gov/pubmed/17060542?tool=bestpractice.com一项回顾性研究表明,在立即接受手术干预的患者中,使用头孢他啶加用米诺环素,或者单用喹诺酮类药物后存活率高于单用头孢他啶的患者。[42]Chen SC, Lee YT, Tsai SJ, et al. Antibiotic therapy for necrotizing fasciitis caused by Vibrio vulnificus: retrospective analysis of an 8 year period. J Antimicrob Chemother. 2012;67:488-493.http://jac.oxfordjournals.org/content/67/2/488.longhttp://www.ncbi.nlm.nih.gov/pubmed/22117030?tool=bestpractice.com在体外,头孢噻肟和米诺环素可协同对抗创伤弧菌。[43]Chuang YC, Liu JW, Ko WC, et al. In vitro synergism between cefotaxime and minocycline against Vibrio vulnificus. Antimicrob Agents Chemother. 1997;41:2214-2217.http://www.ncbi.nlm.nih.gov/pubmed/9333050?tool=bestpractice.com对小鼠脓毒症模型进行的体外和体内研究表明,相比于头孢噻肟加用米诺环素的疗法,使用喹诺酮类药物(例如莫西沙星、环丙沙星)单药治疗可以提升存活率。[44]Tang HJ, Chang MC, Ko WC, et al. In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus. Antimicrob Agents Chemother. 2002;46:3580-3584.http://aac.asm.org/content/46/11/3580.fullhttp://www.ncbi.nlm.nih.gov/pubmed/12384368?tool=bestpractice.com单用头孢噻肟、单用米诺环素、单用环丙沙星、头孢噻肟加用米诺环素、头孢噻肟加用环丙沙星的体外时间 - 杀菌研究显示,头孢噻肟加用环丙沙星有杀灭创伤弧菌的优势。这些结果在小鼠存活模型中得以重现,其部分原因是环丙沙星可以抑制创伤弧菌产生细胞毒素 rtxA1。[26]Jang HC, Choi SM, Kim HK, et al. In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis. PLoS One. 2014;9:e101118.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101118http://www.ncbi.nlm.nih.gov/pubmed/24978586?tool=bestpractice.com标准抗菌疗法参考建议为:第三代头孢菌素(例如头孢他啶、头孢曲松)加用多西环素或米诺环素作为主要治疗方案。[45]Gilbert DN, Moellering RC, Eliopoulos GM, et al, eds. The Sanford guide to antimicrobial therapy 2014. 44th ed. Sperryville, VA: Antimicrobial Therapy, Inc.; 2014.喹诺酮是合适的替代方案。应根据患者个体情况确定治疗持续时间,但最少应在 10 至 14 天。出现脓毒性休克以及针对弧菌活性的抗生素治疗延迟,将导致死亡率显著升高。[39]Liu JW, Lee IK, Tang HJ, et al. Prognostic factors and antibiotics in Vibrio vulnificus septicemia. Arch Intern Med. 2006;166:2117-2123. [Erratum in: Arch Intern Med. 2007;167:194.]http://archinte.jamanetwork.com/article.aspx?articleid=411127http://www.ncbi.nlm.nih.gov/pubmed/17060542?tool=bestpractice.com适当时,应利用微生物学和临床数据对抗生素疗法进行重新评估,以缩小抗菌谱范围。[37]Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304-377.http://link.springer.com/article/10.1007%2Fs00134-017-4683-6http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
对于并发坏死性皮肤/软组织感染患者,手术治疗对于改善存活率和缩短 ICU 救治及住院时间至关重要。可通过在早期对失活组织进行彻底清创得以实现。[40]Chao WN, Tsai CF, Chang HR, et al. Impact of timing of surgery on outcome of Vibrio vulnificus-related necrotizing fasciitis. Am J Surg. 2013;206:32-39.http://www.ncbi.nlm.nih.gov/pubmed/23414632?tool=bestpractice.com[46]Halow KD, Harner RC, Fontenelle LJ. Primary skin infections secondary to Vibrio vulnificus: the role of operative intervention. J Am Coll Surg. 1996;183:329-334.http://www.ncbi.nlm.nih.gov/pubmed/8843261?tool=bestpractice.com[47]Kuo YL, Shieh SJ, Chiu HY, et al. Necrotizing fasciitis caused by Vibrio vulnificus: epidemiology, clinical findings, treatment and prevention. Eur J Clin Microbiol Infect Dis. 2007;26:785-792.http://www.ncbi.nlm.nih.gov/pubmed/17674061?tool=bestpractice.com[48]Huang KC, Hsieh PH, Huang KC, et al. Vibrio necrotizing soft-tissue infection of the upper extremity: factors predictive of amputation and death. J Infect. 2008;57:290-297.http://www.ncbi.nlm.nih.gov/pubmed/18755513?tool=bestpractice.com[49]Chen S, Chan K, Chao W, et al. Clinical outcomes and prognostic factors for patients with Vibrio vulnificus infections requiring intensive care: a 10 year retrospective study. Crit Care Med. 2010;38:1984-1990.http://www.ncbi.nlm.nih.gov/pubmed/20657269?tool=bestpractice.com一项研究表明,在局部麻醉条件下对感染部位进行包括切开、引流和冲洗等步骤的初步延缓性手术,24 小时后采取积极的手术治疗,要比一开始就在全身麻醉条件下采取积极手术治疗的死亡率更低,分别为 26% 和 60%。可能的原因是延缓性手术组在全身麻醉前处于生理稳定状态。[50]Hong GL, Dai XQ, Lu CJ, et al. Temporizing surgical management improves outcome in patients with Vibrio necrotizing fasciitis complicated with septic shock on admission. Burns. 2014;40:446-454.http://www.ncbi.nlm.nih.gov/pubmed/24138809?tool=bestpractice.com