多黏菌素单药方案与联合方案治疗碳青霉烯耐药革兰阴性菌感染的有效性及安全性的系统评价

Safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection:a systematic review and meta-analysis

目的系统评价多黏菌素单药方案与联合方案治疗碳青霉烯耐药革兰阴性菌感染的有效性及安全性。方法检索中国知网、万方数据库、PubMed、Embase和Cochrane library,纳入多黏菌素单药对比联合方案治疗碳青霉烯耐药革兰阴性菌感染的随机对照研究,采用Cochrane系统评价手册5.2进行质量评价,以全因病死率为主要结局指标,感染相关病死率、临床有效率、细菌清除率和肾毒性、肝毒性不良反应发生率为次要结局指标。采用RevMan 5.3软件进行meta分析。结果最终纳入7篇文献,共859例患者。单药治疗组和联合治疗组患者的全因病死率[风险比(relative risk,RR)=1.07,95%CI:0.93~1.24,P>0.05]、感染相关病死率(RR=1.35,95%CI:0.98~1.87,P>0.05)、细菌清除率(RR=0.85,95%CI:0.71~1.02,P=0.08)、肝毒性不良反应发生率(RR=0.68,95%CI:0.41~1.13,P=0.14)、肾毒性不良反应发生率(RR=1.01,95%CI:0.85~1.22,P>0.05)之间比较差异均无统计学意义,联合治疗组的临床有效率高于单药治疗组(RR=0.81,95%CI:0.66~0.98,P=0.03)。亚组分析显示,多黏菌素单药和联合治疗碳青霉烯耐药鲍曼不动杆菌感染患者的全因病死率之间差异无统计学意义(RR=1.00,95%CI:0.86~1.12,P>0.05),多黏菌素给药剂量的高低、是否给予负荷剂量对全因病死率无影响。结论以多黏菌素为基础的联合用药治疗碳青霉烯耐药革兰阴性菌尤其是鲍曼不动杆菌感染的临床有效率高于单药治疗,但患者病死率较单药治疗未见降低,未来仍需要大规模随机对照研究去验证。

Objective To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection.Methods CNKI,Wanfang database,PubMed,Embase and Cochrane library were systematically searched.Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled.The Cochrane Reviewers′Handbook 5.2 was employed to evaluate the quality of the enrolled studies.The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality,clinical response,bacterial clearance,nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software.Results Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate(relative risk[RR]=1.07,95%CI:0.93-1.24,P>0.05),infection-related mortality rate(RR=1.35,95%CI:0.98-1.87,P>0.05),bacterial clearance rate(RR=0.85,95%CI:0.71-1.02,P=0.08),hepatotoxicity development rate(RR=0.68,95%CI:0.41-1.13,P=0.14),and nephrotoxicity development rate(RR=1.01,95%CI:0.85-1.22,P>0.05)between colistin monotherapy and combination therapy.The clinical response rate was higher in combination therapy than that in colistin monotherapy(RR=0.81,95%CI:0.66-0.98,P=0.03).In the subgroup analysis,no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection(RR=1.00,95%CI:0.86-1.12,P>0.05).The dosage of colistin with or without loading dose was not associated with the treatment response.Conclusions Although colistin-based combination therapy has a better clinical response against carbapenem-resistant bacteria infection,especially for Acinetobacter baumannii infection,the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future.