加倍剂量替加环素治疗呼吸机相关性肺炎的有效性和安全性研究

Efficacy and safety of high dose tigecycline in treatment of patients with ventilator-associated pneumonia

目的：观察加倍剂量替加环素治疗呼吸机相关性肺炎（VAP）的有效性和安全性。方法连续收集2012年2月至2015年12月浙江省人民医院急诊重症监护病房（EICU）收治的使用替加环素治疗的71例 VAP 患者的临床资料，并进行回顾性分析，其中31例接受标准剂量替加环素治疗（50 mg，1次/12 h），40例接受加倍剂量替加环素治疗（100 mg，1次/12 h），采用 t（秩和）检验或χ^2检验对两组患者抗菌药物使用情况、临床疗效、微生物检出和清除及安全性等指标进行比较。同时将71例 VAP 患者分为临床治愈（34例）和临床失败（37例），采用多因素 Logistic 回归分析影响临床疗效的相关因素。结果替加环素标准剂量组和加倍剂量组在单独使用替加环素和联合使用其他抗菌药物方面差异均无统计学意义（P 〉0．05），加倍剂量组的临床治愈率（24/40，60％）高于标准剂量组（10/31，32．3％）（χ^2＝5．386，P 〈0．05）。检出71株细菌，其中以鲍曼不动杆菌（42株）和肺炎克雷伯菌（17株）检出最多，加倍剂量组的细菌清除率（20/40，50．0％）高于标准剂量组（8/31，25．8％）（χ^2＝4．280，P 〈0．05）。Logistic 回归分析发现，使用加倍剂量替加环素（OR ＝0．322，95％CI：0．105-0．989）是 VAP 患者临床治愈的独立预测因素，而不正确的初始抗菌药物治疗（OR ＝8．207，95％ CI：1．802-37．367）则是临床治疗失败的预测因素。两组血尿素氮、血肌酐、丙氨酸转氨酶、总胆红素、血红蛋白及血小板等指标在治疗前后差异均无统计学意义（P 〉0．05）。结论加倍剂量替加环素治疗能提高 VAP 患者的临床治愈率，而不正确的初始抗菌药物治疗会导致治疗失败。两种剂量替加环素均具有良好的安全性。

Objective To assess the efficacy and safety of high dose tigecycline （TGC） in treatment of patients with ventilator-associated pneumonia （VAP）.Methods The clinical data collected from 71 patients with VAP in emergency intensive care unit of Zhejiang Provincial People’s Hospital from February 201 2 to December 201 5 were analyzed retrospectively.Thirty one patients were treated with TGC 50 mg q1 2h （standard dose group）,and 40 patients were treated with TGC 1 00 mg q1 2h （high dose group）.t（rank-sum）-test or chi-square test were used to analyze the data including antibiotics use,clinical cure rate,microbiological eradication rate and drug safety.Multivariate logistic regression analysis was performed to determine the factors associated with clinical treatment.Results There were no significant differences in TGC alone and in combination with other antibiotics between two groups （P 〉0.05 ）. Among71 patients,34 were defined as clinical cure and 37 as treatment failure.The clinical cure rate in the high dose group （24 /40,60.0%）was higher than that in the standard dose group （10 /31 ,32.3%）（χ^2 =5.386,P 〈0.05 ）.Seventy one strains of bacteria were identified,of which carbapenem-resistant＆amp;nbsp;Acinetobacterbaumannii （42 isolates ） and Klebsiellapneumoniae （1 7 isolates ） were the main isolated pathogens.Bacterial clearance rate in the high dose group （20 /40,50.0%）was also higher than that in the standard dose group （8 /31 ,25.8%）（χ^2 =4.280,P 〈0.05）.Logistic regression analysis demonstrated that the use of high dose tigecycline was independent predictor of clinical cure （OR =0.322,95% CI：0.1 05-0.989）,while initial inadequate antimicrobial treatment was predictor of treatment failure （OR =8.207,95% CI：1 .802-37.367 ）.There were no statistical differences in blood urea nitrogen,serum creatinine,alanine aminotransferase,total bilirubin,hemoglobin and blood platelet count before and after treatment between two groups （P 〉0.05）.Conclusions High dose TGC can improve the clinical cure rate in treatment of patients with VAP,initial inadequate antimicrobial use would result in the treatment failure. Both high dose and standard dose TGC are safe in administration.