一旦经合理判断诊断为落基山斑疹热 (RMSF),则应对患者施以多西环素治疗,而不是等待确诊检查结果。在病程前 5 天内进行抗立克次氏体治疗,治疗效果最好。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com尽管重复四环素疗程可能导致幼儿恒牙染色,但是无证据显示多西环素可导致此种牙齿染色。[14]Lochary ME, Lockhart PB, Williams WT. Doxycycline and staining of permanent teeth. Pediatr Infect Dis J. 1998;17:429-431.http://www.ncbi.nlm.nih.gov/pubmed/9613662?tool=bestpractice.com[15]Volovitz B, Shkap R, Amir J, et al. Absence of tooth staining with doxycycline treatment in young children. Clin Pediatr (Phila). 2007;46:121-126.http://www.ncbi.nlm.nih.gov/pubmed/17325084?tool=bestpractice.com[16]Todd SR, Dahlgren FS, Traeger MS, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr. 2015;166:1246-1251.http://www.jpeds.com/article/S0022-3476(15)00135-3/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25794784?tool=bestpractice.com由于多西环素因的疗效、每日给药两次、价格低廉且安全性好,因此成为治疗各年龄段 RMSF 患者的首选药物。
替代疗法
氯霉素是治疗 RMSF 的替代药物,并且曾被认为是治疗 8 岁以下 RMSF 患儿的首选药物。然而,由于多种原因,在怀疑 RMSF 的成人和儿童中,多西环素比氯霉素更可取。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
与使用多西环素治疗相比,使用氯霉素治疗可导致 RMSF 患者病死率增加。病死率:有中等质量证据表明,仅使用氯霉素进行治疗的患者比仅使用四环素进行治疗的患者病死率显著增加。[17]Holman RC, Paddock CD, Curns AT, et al. Analysis of risk factors for fatal Rocky Mountain spotted fever: evidence for superiority of tetracyclines for therapy. J Infect Dis. 2001;184:1437-1444.http://jid.oxfordjournals.org/content/184/11/1437.longhttp://www.ncbi.nlm.nih.gov/pubmed/11709786?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。
多西环素可有效治疗人单核细胞埃里希体病,粒细胞无形体病和其他临床上类似于 RMSF 的斑疹热型立克次体病,但氯霉素可能不能。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
氯霉素会产生许多不良反应,在美国,氯霉素口服制剂已不再使用,但是氯霉素口服制剂目前仍广泛用于欧洲和其他几个国家/地区。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
对疑似 RMSF 孕妇进行治疗时,应请感染科会诊医生会诊。
由于四环素类药物对胎儿和母体都有潜在毒性,因此禁用于妊娠女性。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
尚未在妊娠女性的对照研究中对多西环素的安全性进行评估;但是,一篇综述认为不太可能有致畸性的风险,然而数据尚不足以得出无风险的结论。[18]US Food and Drug Administration. Doxycycline (vibramycin, monodox, doryx, doxy, atridox, periodox, vibra-tabs) use by pregnant and lactating women. January 2015. http://www.fda.gov/ (last accessed 17 November 2016).http://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm131011.htm多西环素已成功用于治疗妊娠女性的立克次体病,且无不良反应;但是,评估毒性的随访有限。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
传统观念认为氯霉素是治疗妊娠女性 RMSF 的首选药物。但是,由于妊娠女性中多西环素安全性数据不断增多、多西环素在 RMSF 中的疗效高、氯霉素在某些地区难以获得,以及氯霉素对胎儿的潜在毒性,可能需要对此建议进行修订。
其他可能的细菌感染
对于可能符合其他细菌引发的严重感染症状的患者,应先开始推定治疗,即先根据经验给予患者抗生素治疗,直至血液培养或临床病程可排除其他诊断。具有抗脑膜炎奈瑟球菌活性的抗生素(如第三代注射用头孢药物)也适用于其他类似 RMSF 的细菌感染(如无脾宿主中的肺炎球菌血症)。若无法排除由金黄色葡萄球菌引发的脓毒症或中毒性休克综合征,宜根据经验使用万古霉素进行治疗。
如果 RMSF 患者在发病后一周内接受治疗,通常症状可得到明显改善,如在开始使用多西环素治疗 72 小时内可退热;若无症状改善则说明需要考虑其他诊断。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com[6]Buckingham SC, Marshall GS, Schutze GE, et al. Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children. J Pediatr. 2007;150:180-184.http://www.ncbi.nlm.nih.gov/pubmed/17236897?tool=bestpractice.com
危重病
需要住院进行治疗的 RMSF 患者应接受积极的支持性治疗干预。需要密切监测体液平衡和血清电解质。某些患者可能需要输注浓缩红细胞或血小板。危重病患者可能需要针对癫痫发作、颅内高压、休克、成人呼吸窘迫综合征 (ARDS)、肾衰或其他并发症进行辅助治疗。[1]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016;65:1-44.http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com[11]Lantos PM, McKinney R. Rickettsial and ehrlichial diseases. In: Cherry JD, Harrison GJ, Kaplan SL, et al, eds. Feigin and Cherry’s textbook of pediatric infectious diseases. 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:2647‐2666.