RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections
RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections
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DOI：
10.1093/cid/ciz530
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发表时间：
2020-05-01
影响因子：
11.8
通讯作者：
Paschke, Amanda
中科院分区：
文献类型：
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作者：
Motsch, Johann;de Oliveira, Claudia Murta;Paschke, Amanda
背景：β-内酰胺酶抑制剂瑞巴坦可以恢复亚胺培南对亚胺培南不敏感的革兰氏阴性病原菌的活性。我们评价了亚胺培南/瑞巴坦治疗亚胺培南非敏感感染的疗效。对亚胺培南不敏感(但对粘菌素和亚胺培南/释放巴坦敏感)致医院获得性/呼吸机相关性肺炎、并发腹部感染或并发尿路感染的住院患者随机分为2：1至5-21天的亚胺培南/释放巴坦或粘菌素+亚胺培南。主要终点：在改良微生物治疗意向(MMITT)人群中的良好总体反应(由每种感染类型的相关终点定义)(合格的基线病原体和>；=1剂量研究治疗)。次要终点：临床反应、全因死亡率和治疗后出现的肾毒性。安全性分析包括1剂量研究治疗的患者。结果：31名患者接受亚胺培南/释放巴坦治疗，16名患者接受粘菌素+亚胺培南治疗。在MITT患者中(n=21例亚胺培南/瑞巴坦，n=10例粘菌素+亚胺培南)，29%的患者有急性生理学和慢性健康评估II评分15，23%的患者肌酐清除=65岁。合格的基线病原菌：铜绿假单胞菌(77%)、克雷伯氏菌。(16%)，其他肠杆菌科(6%)。总有效率分别为71%和70%(90%可信区间分别为-27.5和21.4)，28天有效率分别为71%和40%(90%可信区间分别为1.3和51.5)，28天死亡率分别为10%和30%(90%可信区间分别为-46.4和6.7)。严重不良事件发生率分别为10%和31%，药物相关不良反应发生率分别为16%和31%(无药物相关死亡)，治疗后肾毒性发生率分别为10%和56%(P=.002)。结论：亚胺培南/释放巴坦是治疗碳青霉烯类非敏感感染的有效且耐受性良好的治疗方案。
Background: The beta-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections.Methods: Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenem-nonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5-21 days imipenem/relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and >= 1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with >= 1 dose study treatment.Results: Thirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance = 65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, -27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, -46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drug-related deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively.Conclusions: Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections.