Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial
Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial
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DOI：
10.1016/s1473-3099(18)30099-9
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发表时间：
2018-04-01
影响因子：
56.3
通讯作者：
Leibovici, Leonard
中科院分区：
文献类型：
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作者：
Paul, Mical;Daikos, George L.;Leibovici, Leonard
Background Colistin-carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria.我们的目的是测试联合疗法是否改善了由抗碳青霉烯剂或产生革兰氏阴性细菌引起的感染的成年人的临床结果。方法是在以色列，格雷克和意大利的六家医院中进行的随机控制优势。我们包括患有菌血症的成年人，呼吸机相关的肺炎，医院获得的肺炎或由碳青霉烯敏感的革兰氏阴性细菌引起的。将患者随机分配（1：1），通过计算机生成的置换块，通过中心分层，将患者分配给静脉内菌丝（900万单位加载剂量，然后每天两次4500万单位）或Meropenem（2-G延长） infusion three times per day). The trial was open-label, with blinded outcome assessment.治疗成功被定义为生存期，血液动力学稳定性，改善或稳定的顺序器官衰竭评估评估评估评估评估评估评估评估评估评估评估，动脉氧对肺炎患者的动脉氧与过期氧的部分压力的稳定或改善比率，以及细菌血症患者的微生物治疗。主要结果是临床失败，定义为在随机分析后14天内未通过意对于治疗分析符合所有成功标准。该试验在ClinicalTrials.gov上注册，Number NCT01732250，并在2013年10月1日至2016年12月31日之间进行计费。我们将406名患者随机分配给了两个治疗组。大多数患者患有肺炎或菌血症（355/406，87％），大多数感染是由鲍曼尼（Baumannii）杆菌引起的（312/406，77％）。在随机分析后14天（风险差异-5.7％，95％CI -13.9至2.4）时，观察到菌群单一疗法（156/198，79％）和联合疗法（152/208，73％）之间无显着差异；风险比[RR] 0.93，95％CI 0.83-1.03）。鲍曼尼I感染患者的结果相似（RR 0.97，95％CI 0.87-1.09）。联合疗法增加了腹泻的发生率（56 [27％] vs 32 [16％]患者，并降低了轻度肾衰竭的发病率（124 vs 25 [20％]的125例患者中，有或肾脏损伤）。解释组合疗法并不优于单一疗法。在严重的Baumannii感染中，将Meropenem添加到大肠菌素中并不能改善临床衰竭。该试验未能专门解决其他细菌。
Background Colistin-carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination therapy improves clinical outcomes for adults with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria.Methods A randomised controlled superiority trial was done in six hospitals in Israel, Greece, and Italy. We included adults with bacteraemia, ventilator-associated pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non-susceptible Gram-negative bacteria. Patients were randomly assigned (1:1) centrally, by computer-generated permuted blocks stratified by centre, to intravenous colistin (9-million unit loading dose, followed by 45 million units twice per day) or colistin with meropenem (2-g prolonged infusion three times per day). The trial was open-label, with blinded outcome assessment. Treatment success was defined as survival, haemodynamic stability, improved or stable Sequential Organ Failure Assessment score, stable or improved ratio of partial pressure of arterial oxygen to fraction of expired oxygen for patients with pneumonia, and microbiological cure for patients with bacteraemia. The primary outcome was clinical failure, defined as not meeting all success criteria by intention-to-treat analysis, at 14 days after randomisation. This trial is registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual.Findings Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406 patients to the two treatment groups. Most patients had pneumonia or bacteraemia (355/406, 87%), and most infections were caused by Acinetobacter baumannii (312/406, 77%). No significant difference between colistin monotherapy (156/198, 79%) and combination therapy (152/208, 73%) was observed for clinical failure at 14 days after randomisation (risk difference -5.7%, 95% CI -13.9 to 2.4; risk ratio [RR] 0.93, 95% CI 0.83-1.03). Results were similar among patients with A baumannii infections (RR 0.97, 95% CI 0.87-1.09). Combination therapy increased the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at risk of or with kidney injury).Interpretation Combination therapy was not superior to monotherapy. The addition of meropenem to colistin did not improve clinical failure in severe A baumannii infections. The trial was unpowered to specifically address other bacteria.