Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis A Randomized Trial
Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis A Randomized Trial
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DOI：
10.1001/jama.2012.5833
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发表时间：
2012-06-13
影响因子：
120.7
通讯作者：
Welte, Tobias
中科院分区：
文献类型：
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作者：
Brunkhorst, Frank M.;Oppert, Michael;Welte, Tobias
背景 早期适当的抗菌治疗可降低与严重脓毒症相关的死亡率。由至少 2 种不同机制的抗生素组成的经验性联合治疗的作用仍存在争议。 目的 比较莫西沙星和美罗培南与单独美罗培南对脓毒症相关器官功能障碍的影响。 设计、环境和患者 一项随机、开放、平行组试验，纳入了 600 名符合严重脓毒症或脓毒性休克标准的患者 （单一疗法 n=298，联合疗法 n=302）。该试验于2007年10月16日至2010年3月23日在德国44个重症监护病房进行。可评估患者人数为单药治疗组273例，联合治疗组278例。 干预措施 静脉注射美罗培南（每8小时1 g）和莫西沙星（每24小时400 mg）或单独使用美罗培南。建议干预时间为 7 天，随机分组后最多 14 天，或直至从重症监护室出院或死亡（以先发生者为准）。 主要指标 器官衰竭程度（14 天内每日总序贯器官衰竭评估 [SOFA] 评分的平均值；评分范围：0-24 分，分数越高表示器官衰竭越严重）；次要结局：28 天和 90 天全因死亡率。幸存者随访90天。 结果 在551名可评估患者中，美罗培南联合莫西沙星组（8.3分；95% CI，7.8-8.8分）与单用美罗培南组（7.9分；95% CI，7.5-8.4分）之间的平均SOFA评分无统计学差异（P=.36）。 28 天和 90 天死亡率也没有统计学上的显着差异。截至第 28 天，联合治疗组有 66 例死亡（23.9%；95% CI，19.0%-29.4%），而单药治疗组有 59 例死亡（21.9%；95% CI，17.1%-27.4%）（P=.58）。截至第 90 天，联合治疗组有 96 例死亡（35.3%；95% CI，29.6%-41.3%），而单药治疗组有 84 例死亡（32.1%；95% CI，26.5%-38.1%）（P=.43）。 结论 在成年严重脓毒症患者中，美罗培南和莫西沙星联合治疗与美罗培南相比 单独使用并不能减少器官衰竭。
Context Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial.Objective To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction.Design, Setting, and Patients A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n=298 for monotherapy and n=302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group.Interventions Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first.Main Outcome Measure Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days.Results Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P=.36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P=.58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P=.43).Conclusion Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure.