Medical Microbiology and Pharmacology/Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
Crit Care Med. 2010 Aug;38(8):1651-64. doi: 10.1097/CCM.0b013e3181e96b91.
To assess whether a potential benefit with combination antibiotic therapy is restricted to the most critically ill subset of patients, particularly those with septic shock.
OVID MEDLINE (1950-October 2009), EMBASE (1980-October 2009), the Cochrane Central Register of Controlled Trials (to third quarter 2009), the ClinicalTrial.gov database, and the SCOPUS database.
Randomized or observational studies of antimicrobial therapy of serious bacterial infections potentially associated with sepsis or septic shock. Fifty studies met entry criteria.
Study design, mortality/clinical response, and other variables were extracted independently by two reviewers. When possible, study datasets were split into mutually exclusive groups with and without shock or critical illness.
Although a pooled odds ratio indicated no overall mortality/clinical response benefit with combination therapy (odds ratio, 0.856; 95% confidence interval, 0.71-1.03; p = .0943; I = 45.1%), stratification of datasets by monotherapy mortality risk demonstrated substantial benefit in the most severely ill subset (monotherapy risk of death >25%; odds ratio of death, 0.51; 95% confidence interval, 0.41-0.64; I = 8.6%). Of those datasets that could be stratified by the presence of shock/critical illness, the more severely ill group consistently demonstrated increased efficacy of a combination therapy strategy (odds ratio, 0.49; 95% confidence interval, 0.35-0.70; p < .0001; I = 0%). An increased risk of death was found in low-risk patients (risk of death <or=15% in the monotherapy arm) exposed to combination therapy (odds ratio, 1.53; 95% confidence interval, 1.16-2.03; p = .003; I = 8.2%). Meta-regression indicated that efficacy of combination therapy was dependent only on the risk of death in the monotherapy group.
Combination antibiotic therapy improves survival and clinical response of high-risk, life-threatening infections, particularly those associated with septic shock but may be detrimental to low-risk patients.
评估联合抗生素治疗的潜在益处是否仅限于病情最严重的患者亚组,特别是那些患有感染性休克的患者。
OVID MEDLINE(1950 年-2009 年 10 月)、EMBASE(1980 年-2009 年 10 月)、Cochrane 中央对照试验注册中心(至 2009 年第三季度)、ClinicalTrials.gov 数据库和 SCOPUS 数据库。
与脓毒症或感染性休克相关的严重细菌感染的抗生素治疗的随机或观察性研究。有 50 项研究符合入选标准。
两位评审员独立提取研究设计、死亡率/临床反应和其他变量。在可能的情况下,将研究数据集分为有和没有休克或危重病的相互排斥的组。
尽管汇总的优势比表明联合治疗并没有总体死亡率/临床反应获益(比值比,0.856;95%置信区间,0.71-1.03;p =.0943;I = 45.1%),但是根据单药治疗死亡率风险对数据集进行分层显示,在病情最严重的亚组中获益显著(单药治疗死亡率风险>25%;死亡比值比,0.51;95%置信区间,0.41-0.64;I = 8.6%)。在可以根据休克/危重病存在情况分层的数据集组中,病情更严重的组始终显示出联合治疗策略的更高疗效(比值比,0.49;95%置信区间,0.35-0.70;p <.0001;I = 0%)。在接受联合治疗的低危患者(单药治疗组的死亡率风险<或=15%)中发现死亡风险增加(比值比,1.53;95%置信区间,1.16-2.03;p =.003;I = 8.2%)。Meta 回归表明,联合治疗的疗效仅取决于单药治疗组的死亡率风险。
联合抗生素治疗可提高高危、危及生命的感染的生存率和临床反应,特别是那些与感染性休克相关的感染,但可能对低危患者有害。