抗生素治疗
治疗的金标准是氨基糖苷类药物(链霉素或庆大霉素)。美国疾病预防控制中心 (Centers for Disease Control and Prevention, CDC) 根据经验和疗效,推荐将链霉素作为首选药物,庆大霉素是一种可接受的替代药物。[16]Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for health care providers, fifth edition. 2018 [internet publication].https://www.cdc.gov/ticks/tickbornediseases/index.html世界卫生组织 (World Health Organization, WHO) 推荐将庆大霉素作为首选药物(因为该药的可用性更广),将链霉素作为替代药物(在可用的情况下)。[17]World Health Organization (WHO). WHO Guidelines on tularaemia. 2007 [internet publication].http://www.who.int/csr/resources/publications/WHO_CDS_EPR_2007_7.pdf?ua=1 药物的选择最终取决于当地的指导方针和这些药物的可及性。
氟喹诺酮类药物(例如环丙沙星)似乎对病情较轻的土拉菌病病例有效,但关于此类药物的使用经验有限。[16]Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for health care providers, fifth edition. 2018 [internet publication].https://www.cdc.gov/ticks/tickbornediseases/index.html[19]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;59:e10-e52.http://cid.oxfordjournals.org/content/59/2/e10.fullhttp://www.ncbi.nlm.nih.gov/pubmed/24973422?tool=bestpractice.com
对于经判断病情严重到需要住院的任何患者,应经胃肠外给予氨基糖苷类药物治疗。仅建议在病情较轻者的门诊治疗中使用氟喹诺酮类药物口服治疗。[5]Johansson A, Berglund L, Gothefors L, et al. Ciprofloxacin for treatment of tularemia in children. Pediatr Infect Dis J. 2000;19:449-453.http://www.ncbi.nlm.nih.gov/pubmed/10819342?tool=bestpractice.com[12]Penn RL. Francisella tularensis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 8th ed. New York, NY: Churchill Livingstone; 2015.
四环素类药物和氯霉素仅为抑菌药物,终止治疗后可能复发。与氟喹诺酮或氨基糖苷相比,多西环素是次选药物。由于氯霉素的不良反应发生情况,不再推荐使用该药。检测过的大多数土拉弗朗西斯菌临床分离菌株对第三代头孢菌素和亚胺培南/西司他丁耐药,并且已观察到对红霉素等大环内酯类药物耐药。[12]Penn RL. Francisella tularensis. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 8th ed. New York, NY: Churchill Livingstone; 2015.
对于氨基糖苷类药物,建议采用至少 10 天疗程。环丙沙星给药应持续 10-14 天。四环素具有抑菌作用,需要 14-21 天的较长疗程。在更严重的感染时,治疗期可能更长,具体取决于临床反应。[16]Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for health care providers, fifth edition. 2018 [internet publication].https://www.cdc.gov/ticks/tickbornediseases/index.html[17]World Health Organization (WHO). WHO Guidelines on tularaemia. 2007 [internet publication].http://www.who.int/csr/resources/publications/WHO_CDS_EPR_2007_7.pdf?ua=1 可能复发,此时应当额外治疗 7 至 14 天。
尽管用于提供指南的经验很少,但应当联合使用环丙沙星和一种氨基糖苷类药物治疗土拉菌病脑膜炎。
妊娠患者与非妊娠患者的治疗并无不同,因为在妊娠期,使用这些药物的获益大于风险。儿童与成人采用一样的治疗。