头孢他啶/阿维巴坦治疗革兰阴性菌感染疗效和安全性的Meta分析

Efficacy and safety of ceftazidime-avibactam in treatment of Gram-negative bacterial infection: a Meta-analysis

摘要:

目的 评价头孢他啶/阿维巴坦（CAZ/AVI）治疗革兰阴性菌感染的疗效与安全性。 方法 检索国内外数据库关于CAZ/AVI疗效与安全性的随机对照试验（RCT），以临床治愈率为主要结局，微生物清除率与不良反应发生率为次要结局，应用Review Manage 5.3进行Meta分析。 结果 7项RCT（3 792例患者）纳入Meta分析，在患者结束治疗时（RR=0.99，95%CI=0.96~1.01）、检测治愈时（RR=0.99，95%CI=0.96~1.02）、最后随访时（RR=1.00，95%CI=0.96~1.03），CAZ/AVI组与对照组临床治愈率比较，差异均无统计学意义（均P>0.05）；微生物学改良意向治疗（mMITT）患者在检测治愈时，CAZ/AVI组与对照组临床治愈率比较，差异无统计学意义（RR=0.95，95%CI=0.89~1.00，P=0.06），结束治疗时对照组优于CAZ/AVI组（RR=0.95，95%CI=0.92~0.98，P=0.005）。mMITT患者在结束治疗时（RR=1.00，95%CI=0.97~1.03）、检测治愈时（RR=1.07，95%CI=0.92~1.25），CAZ/AVI组与对照组微生物清除率比较，差异均无统计学意义（均P>0.05，），最后随访时CAZ/AVI组优于对照组（RR=1.12，95%CI=1.01~1.23，P=0.03）。CAZ/AVI组不良反应以及因不良反应导致停药发生率与对照组基本相似，但严重不良反应发生率CAZ/AVI组高于对照组（RR=1.26，95%CI=1.01~1.57，P=0.04）。 结论 CAZ/AVI的疗效与其他抗菌药物相似，可以作为严重感染的替代药物，但考虑其严重不良反应发生率高于其他药物，仍需要更多高质量大规模的研究论证CAZ/AVI的安全性。

Abstract:

Objective To evaluate the efficacy and safety of ceftazidime-avibactam (CAZ/AVI) in the treatment of Gram-negative bacterial infection. Methods Randomized controlled trial(RCT) on efficacy and safety of CAZ-AVI were retrieved from domestic and foreign databases, clinical cure rate was assessed as the main outcome, microbial clearance rate and incidence of adverse reaction were as secondary outcome, Meta-analysis was performed with Review Manage 5.3. Results Seven RCTs (3 792 patients) were included in Meta-analysis, clinical cure rate of patients at the end of treatment (EOT, RR=0.99, 95% CI=0.96-1.01), at the time of test of cure (TOC, RR=0.99, 95% CI=0.96-1.02), at the time of last follow-up visit (LFU, RR=1.00, 95% CI=0.96-1.03) were not significantly different between CAZ/AVI group and control group (all P>0.05); clinical cure rate at time of TOC of microbiologically modified intention-to-treat (mMITT) of patients was no significantly different between CAZ/AVI group and control group (RR=0.95, 95%CI= 0.89-1.00, P=0.06), control group was better than CAZ/AVI group at EOT (RR=0.95, 95%CI= 0.92-0.98, P=0.005). There was no significant difference in the microbial clearance between CAZ/AVI group and control group at EOT of mMITT of patients (RR=1.00, 95%CI=0.97-1.03) and at time of TOC (RR=1.07, 95%CI=0.92-1.25) (both P>0.05), CAZ/AVI group was better than control group at time of LFU (RR=1.12, 95%CI=1.01-1.23, P=0.03), incidence of adverse reaction and drug withdrawal due to adverse reaction in CAZ/AVI group was basically similar to that in control group, but incidence of serious adverse reaction in CAZ/AVI group was higher than that in control group (RR=1.26, 95%CI=1.01-1.57, P=0.04). Conclusion The efficacy of CAZ/AVI is similar to other antimicrobial agents, which can be used as a alternative medicine for severe infection, considering that incidence of serious adverse reaction is higher than that of other drugs, more high-quality and large-scale studies are needed to demonstrate the safety of CAZ/AVI.