[The efficacy and safety of different antimicrobial regimens in carbapenem-resistant Klebsiella pneumoniae bloodstream infections].

Objective: To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018. All subjects were separated into three groups based on antibiotics regimens over 72 hours, including meropenem 2.0 g every 8 hours, tigecycline 200 mg as initial dose and 100 mg every 12 hours, and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline. Results: A total of 86 patients were finally recruited, including 14, 52 and 20 patients in groups of meropenem, tigecycline and polymyxin B salvage, respectively. All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially, while 2 of them became resistant to tigecycline during treatment. The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5%, 32/52) and (12/20), respectively (P<0.01), while as no significant difference was seen in the last two groups (χ(2)=0.014, P>0.05). The incidences of hepatic impairment [3.8%(2/52) vs. 1/20] and renal dysfunction (0 vs. 1/20) between tigecycline group and polymyxin B salvage group were both comparable (P>0.05). Conclusion: The meropenem-based therapy is not recommended for CRKP-related bloodstream infections. Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours. Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.目的： 评价不同抗感染方案在治疗碳青霉烯类抗生素耐药肺炎克雷伯杆菌（CRKP）血流感染中的疗效与安全性。 方法： 2017年1月至2018年1月在浙江大学医学院附属第一医院诊断为CRKP血流感染的患者，根据不同药物治疗方案分为(1)美罗培南组：静脉滴注美罗培南2.0 g，每8小时1次，联合除替加环素和多黏菌素以外的其他药物，治疗时间超过72h者；（2）替加环素组：以替加环素为基础的联合治疗，替加环素剂量最低首剂200 mg，维持剂量100 mg每12小时1次，静脉滴注，根据临床需要联合其他抗菌药物（不包括多黏菌素B），治疗时间72 h以上者；（3）多黏菌素B挽救治疗组：符合替加环素组要求，替加环素治疗72~96 h，期间因临床需要加用多黏菌素B，并治疗72 h以上者，多黏菌素B剂量1.25 mg/kg每12小时1次，静脉滴注。分析3组患者的疗效和不良反应。 结果： 86例患者纳入本研究，其中美罗培南组14例，替加环素组52例，多黏菌素B挽救治疗组20例。86例患者首次血培养的CRKP均对替加环素和多黏菌素B敏感，2例患者替加环素治疗期间出现对替加环素耐药。所有CRKP均对美罗培南耐药。以首次血培养阳性标本留取日起计算28 d病死率，美罗培南组（13/14）高于替加环素组（61.5%）和多黏菌素B挽救治疗组（12/20）（P<0.01），替加环素组与多黏菌素B挽救治疗组间28 d病死率差异无统计学意义（χ(2)=0.014,P>0.05）。肝功能损害替加环素组2例（3.8%），多黏菌素B挽救治疗组1例（1/20），差异无统计学意义（P>0.05）。肾功能损害替加环素组0例，多黏菌素B挽救治疗组1例（1/20），差异无统计学意义（P>0.05）。 结论： 以美罗培南为基础的抗感染治疗方案对CRKP所致血流感染疗效差；使用以替加环素为基础的联合治疗病死率达60%；多黏菌素B未能改善替加环素初始疗效不佳患者的结局，联合多黏菌素B治疗未明显加重肾功能损害。.