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大剂量替加环素治疗多重耐药病原体所致呼吸机相关性肺炎的不良事件。

Adverse events of high-dose tigecycline in the treatment of ventilator-associated pneumonia due to multidrug-resistant pathogens.

作者信息

Chen Zihan, Shi Xiaoyan

机构信息

Department of NeuroScience Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Medicine (Baltimore). 2018 Sep;97(38):e12467. doi: 10.1097/MD.0000000000012467.

Abstract

The off-label uses of tigecycline (TGC) to treat ventilator-associated pneumonia (VAP) have aroused worldwide concerns. The efficacy about TGC has been recently reported. However, the adverse events (AEs) remain controversial. Our study aims to analyze the safety of the high-dose (HD) regimens in the treatment of VAP due to multidrug-resistant (MDR) pathogens.The clinical data of 134 patients who were diagnosed with VAP from January 2013 to December 2015 in the NeuroScience Care Unit (NCU) were analyzed retrospectively. The incidence and the occurrence time of AEs, 28-day mortality, and the factors of clinical effectiveness were explored.A total of 54 patients received the standard dose group (SD), 69 in the HD, and 11 in the nonstandard HD group (NHD). Acinetobacter baumannii were the main pathogenic bacteria. There was no statistic difference in the incidence of AEs and the 28-day mortality among the 3 groups (P > .05). Total bilirubin (TBIL) increased significantly after SD of TGC treatment (P = .004). Liver dysfunction occurred the latest (10.83 ± 7.08), not in the duration of HD group (9.63 ± 3.92), whereas in the SD group (13.00 ± 7.57) and NHD group (12.64 ± 3.70). Patients with septic shock, MODS, and higher APACHE II score were of high risk in mortality. The HD group was associated with higher clinical effective rate and bacteria clearance rate.HD TGC was relatively safe and tolerable in ICU patients. The risk of side effects was related to the TGC duration, although not increased as the dosage rose. Full course of the HD regimen was associated with better outcomes for the treatment of VAP patients, especially for the MDR gram-negative bacilli infection. Inappropriate antimicrobial treatment might lead to clinical treatment failure.

摘要

替加环素(TGC)用于治疗呼吸机相关性肺炎(VAP)的超说明书用药已引起全球关注。近期已有关于TGC疗效的报道。然而,其不良事件(AE)仍存在争议。我们的研究旨在分析高剂量(HD)方案治疗多重耐药(MDR)病原体所致VAP的安全性。回顾性分析了2013年1月至2015年12月在神经科学监护病房(NCU)诊断为VAP的134例患者的临床资料。探讨了AE的发生率和发生时间、28天死亡率以及临床疗效的影响因素。共有54例患者接受标准剂量组(SD)治疗,69例接受HD治疗,11例接受非标准HD组(NHD)治疗。鲍曼不动杆菌是主要病原菌。三组间AE发生率和28天死亡率无统计学差异(P>0.05)。TGC治疗SD后总胆红素(TBIL)显著升高(P = 0.004)。肝功能障碍出现最晚(10.83±7.08),不在HD组治疗期间(9.63±3.92),而在SD组(13.00±7.57)和NHD组(12.64±3.70)。发生感染性休克、多器官功能障碍综合征(MODS)且急性生理与慢性健康状况评分系统II(APACHE II)评分较高的患者死亡风险高。HD组临床有效率和细菌清除率较高。HD TGC在ICU患者中相对安全且耐受性良好。副作用风险与TGC治疗疗程有关,尽管未随剂量增加而升高。HD方案全程治疗对VAP患者,尤其是MDR革兰阴性杆菌感染患者的治疗效果更好。抗菌治疗不当可能导致临床治疗失败。

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