抗生素耐药时代复杂腹腔内感染的最佳治疗：甲硝唑联合治疗疗效与安全性的系统评价和荟萃分析

Optimal Treatment for Complicated Intra-abdominal Infections in the Era of Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Therapy With Metronidazole.

作者信息

Mikamo Hiroshige, Yuasa Akira, Wada Keiko, Crawford Bruce, Sugimoto Naomi

机构信息

Department of Clinical Infectious Diseases , Aichi Medical University Graduate School of Medicine , Nagakute.

Medical Affairs Department , Pfizer Japan Inc.

出版信息

Open Forum Infect Dis. 2016 Jul 7;3(3):ofw143. doi: 10.1093/ofid/ofw143. eCollection 2016 Sep.

Carbapenem-resistant has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. A combination of metronidazole with an antimicrobial agent active against aerobes is an alternative effective treatment for patients with complicated intra-abdominal infections (cIAIs). This study aimed to compare efficacy and safety of metronidazole combination therapies and carbapenem and to provide clinical evidence regarding the optimal treatment of cIAI. A systematic review and a meta-analysis of randomized clinical trials in the treatment of cIAI were conducted. The systematic review with PubMed, Embase, and the Cochrane Database of Systematic Reviews followed the Cochrane Handbook's recommended methodology, and the meta-analysis used a Mantel-Haenszel random-effects model with RevMan, version 5.3. Primary endpoints were clinical success and bacteriological eradication, and secondary endpoints were all-cause mortality and drug-related adverse events. Eight studies comparing metronidazole combination therapies and carbapenem were included in the meta-analysis. No difference was found between combined therapy with metronidazole and carbapenem regarding clinical success (odds ratio [OR] = 1.31; 95% confidence interval [CI], .75-2.31), bacteriological eradication (OR = 1.27; 95% CI, .84-1.91), all-cause mortality (OR = 0.61; 95% CI, .37-1.00), or drug-related adverse events (OR = 0.58; 95% CI, .18-1.88). Sensitivity analyses found similar results. Combined therapy with metronidazole is as effective and safe as carbapenem in treatment of cIAI. Therefore, combined therapy with metronidazole offers an effective alternative to carbapenem with low risk of drug resistance.

在过去十年中，耐碳青霉烯类情况急剧增加，导致感染难以治疗且死亡率高。为防止进一步的抗菌药物耐药性，有必要选择性地使用碳青霉烯类。甲硝唑与一种对需氧菌有活性的抗菌剂联合使用，是治疗复杂性腹腔内感染（cIAIs）患者的一种替代有效疗法。本研究旨在比较甲硝唑联合疗法与碳青霉烯类的疗效和安全性，并提供关于cIAI最佳治疗的临床证据对治疗cIAI的随机临床试验进行了系统评价和荟萃分析。通过PubMed、Embase和Cochrane系统评价数据库进行的系统评价遵循了Cochrane手册推荐的方法，荟萃分析使用RevMan 5.3版本的Mantel-Haenszel随机效应模型。主要终点是临床成功和细菌清除，次要终点是全因死亡率和药物相关不良事件。荟萃分析纳入了八项比较甲硝唑联合疗法与碳青霉烯类的研究。在临床成功方面（优势比[OR]=1.31；95%置信区间[CI]，0.75 - 2.31）、细菌清除方面（OR = 1.27；95% CI，0.84 - 1.91）、全因死亡率方面（OR = 0.61；95% CI，0.37 - 1.00）或药物相关不良事件方面（OR = 0.58；95% CI，0.18 - 1.88），甲硝唑联合疗法与碳青霉烯类之间未发现差异。敏感性分析得出了类似结果。甲硝唑联合疗法在治疗cIAI方面与碳青霉烯类一样有效和安全。因此，甲硝唑联合疗法为碳青霉烯类提供了一种有效的替代方案，且耐药风险低。