碳青霉烯类抗菌药物延长或持续输注治疗严重感染的疗效及安全性的系统评价

目的：系统评价碳青霉烯类抗菌药物延长或持续输注方式（2~4 h输注或持续24 h输注）对比传统间断输注方式（0.5~1 h输注）治疗严重感染的疗效和安全性，以期为临床治疗提供循证参考。方法：计算机检索Cochrane图书馆、EMBase、PubMed、维普中文科技期刊数据库、中国期刊全文数据库、万方数据库，检索碳青霉烯类抗菌药物延长或持续输注方式（观察组）对比间断输注方式（对照组）治疗严重感染的随机对照研究（RCTs），由2位研究者独立筛选文献、提取资料，并评价纳入研究的偏倚风险后，采用RevMan 5.3软件进行Meta分析。结果：共纳入20个RCTs，合计1 695例患者。Meta分析结果显示：（1）观察组患者临床有效率RR=1.27，95% CI（1.18，1.36），P<0.000 01]和细菌清除率RR=1.28，95% CI（1.18，1.39），P<0.000 01]显著高于对照组，且持续输注的细菌清除效果优于延长输注；（2）观察组的耐药菌产生率显著降低RR=0.30，95% CI（0.14，0.65），P=0.002]；（3）亚组分析显示持续输注组MD=-6.08，95% CI（-6.68，-5.48），P<0.000 01]和延长输注组MD=-3.06，95% CI（-3.56，-2.56），P<0.000 01]均能使ICU住院时间显著缩短；（4）观察组碳青霉烯类抗菌药物用药疗程也显著缩短MD=-0.76，95% CI（-1.29，-0.22），P=0.005]；（5）观察组不良反应发生率RR=0.98，95% CI（0.70，1.36），P=0.89]与对照组比较，差异无统计学意义；（6）对于呼吸系统感染，与对照组相比，观察组具有较好的临床疗效，且不良反应发生率未增加。结论：与间断输注方式相比，延长或持续输注碳青霉烯类抗菌药物可提高治疗严重感染的疗效，两者安全性相当。上述结论尚需开展更多高质量研究予以验证。

Efficacy and safety of extended or continuous intravenous infusion of carbapenemes against severe infection:a systematic review

OBJECTIVE To systematically review the efficacy and safety of extended or continuous intravenous infusion (EI/CI) versus short-term intravenous infusion (STI) of carbapenemes in adult patients with severe infection.METHODS Databases were electronically searched, including the Cochrane Library, PubMed, EMbase, VIP, CNKI and Wanfang Data, to collect random controlled trials (RCTs) about EI/CI versus STI of carbapenemes against severe infection. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software.RESULTS A total of 20 RCTs involving 1 695 patients were included. The results of Meta-analysis showed that, compared with the STI group, the EI/CI could significantly improve the clinical effective rateRR=1.27, 95%CI (1.18, 1.36), P<0.000 01] and bacterial eradication rateRR=1.28, 95%CI (1.18, 1.39), P<0.000 01], and the CI was superior to the EI in bacterial eradication; compared with STI, emergence of drug resistant strains was significantly reducedRR=0.30, 95%CI (0.14, 0.65), P=0.002]; subgroup analysis revealed that both CIMD=-6.08, 95%CI (-6.68, -5.48), P<0.000 01] and EIMD=-3.06, 95%CI (-3.56, -2.56), P<0.000 01] can significantly shorten ICU stay time; the carbapenemes' treatment course of EI/CI was significantly shorter than STIMD=-0.76, 95%CI (-1.29, -0.22), P=0.005]; there were no significant differences in incidence of adverse reactionsRR=0.98, 95%CI (0.70, 1.36), P=0.89]; for respiratory infection, compared with CI/EI, the STI had better clinical curative effect, and did not increase the incidence of adverse reactions.CONCLUSION Compared with STI of carbapenemes,EI/CI can improve efficacy in the treatment of severe infections with similar safety. The conclusion still need to be further verified by more high quality studies.