Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerland.
Sci Rep. 2019 Oct 29;9(1):15290. doi: 10.1038/s41598-019-51711-x.
Infections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies - covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73-0.93, p = 0.002, I = 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.
产碳青霉烯酶、多重耐药（MDR）或广泛耐药（XDR）革兰氏阴性菌引起的感染是一个重大的治疗挑战。联合抗生素治疗是否优于单药治疗尚不清楚。本系统评价和荟萃分析检索了 OVID MEDLINE、EMBASE、PubMed、The Cochrane Library 和 Scopus 数据库，以获取 2016 年 12 月前发表的比较产碳青霉烯酶、MDR 或 XDR 革兰氏阴性菌感染的单药与联合抗生素治疗的随机对照试验（RCT）和观察性研究。死亡率和临床治愈率分别作为主要和次要结局指标。在最初确定的 8847 项研究中，有 53 项研究（涵盖肺炎[ n = 10 项]、血流感染[ n = 15 项]、骨关节炎[ n = 1 项]和混合感染[ n = 27 项]）被纳入。41%（ n = 1848）的患者接受了单药治疗，59%（ n = 2666）接受了联合治疗。在病例系列/队列研究中（ n = 45），联合治疗的死亡率低于单药治疗（RR 0.83，95%CI 0.73-0.93， p = 0.002， I 2 = 24%）。亚组分析显示，在至少两种体外有活性的抗生素联合治疗、血流感染和产碳青霉烯酶肠杆菌科感染中，联合治疗的死亡率较低。在病例对照研究（ n = 6）和 RCT（ n = 2）中未观察到死亡率差异。无论研究类型如何，治愈率均无差异。两项纳入的 RCT 均具有较高和未知的偏倚风险。6 项病例对照研究中有 16.7%（1/6），45 项病例系列/队列研究中有 37.8%（17/45）的研究质量良好，其余研究质量较差。总之，联合应用抗菌药物治疗多重耐药革兰氏阴性菌似乎在死亡率方面优于单药治疗。
