Cefiderocol与imipenem-cilastatin治疗复杂引起的尿路感染的革兰氏阴性尿路病原体:第二阶段,随机,双盲non-inferiority试验。
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朴茨茅斯,van Veenhuyzen D, Echols R,町田M,费雷拉JCA, Ariyasu M, Tenke P,经营着道明
Cefiderocol与imipenem-cilastatin治疗复杂引起的尿路感染的革兰氏阴性尿路病原体:第二阶段,随机,双盲non-inferiority试验。
柳叶刀感染说。2018年12月,18 (12):1319 - 1328。doi: 10.1016 / s1473 - 3099 (18) 30554 - 1。Epub 2018 10月25。
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30509675 (在PubMed]
- 文摘
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背景:特拉革兰氏阴性菌占全球抗生素耐药性最高优先级处理。Cefiderocol (s - 649266),一个新的含铁细胞头孢菌素,对肠杆菌科和不发酵细菌广泛的活动,如绿脓假单胞菌和鲍曼不动杆菌,包括特紧张。我们评估的有效性和安全性cefiderocol和imipenem-cilastatin复杂尿路感染患者的治疗耐多药革兰氏阴性感染的风险。方法:我们做了第二阶段、多中心、双盲、与这些相应平行的组织non-inferiority审判在15个国家的67家医院。成人(> / = 18年)住院复杂的尿路感染的临床诊断有或没有与急性肾盂肾炎或简单的肾盂肾炎被随机分配(2:1)通过一个交互式web或语音应答系统接收1 h静脉输液cefiderocol (2 g)或imipenem-cilastatin (1 g)每天三次,每8 h为7 - 14天。患者被排除在外,如果他们有一个基线尿液文化与两个以上的尿路病原体,真菌性尿路感染或病原体耐碳青霉烯。的复合主要终点是临床和微生物的测试结果治疗(即停止治疗后7天),这是用于建立non-inferiority cefiderocol与imipenem-cilastatin的利润率(15%和20%)。主要功效是修改后的意向处理分析人口,其中包括所有随机分配接受至少一个剂量的研究药物和有资格革兰氏阴性尿路病原体(> / = 1 x 10(5)菌落(CFU) /毫升)。安全评估在所有随机分配个人收到至少一个研究药物的剂量,根据他们收到的治疗。这项研究是在ClinicalTrials.gov注册,NCT02321800数量。 FINDINGS: Between Feb 5, 2015, and Aug 16, 2016, 452 patients were randomly assigned to cefiderocol (n=303) or imipenem-cilastatin (n=149), of whom 448 patients (n=300 in the cefiderocol group; n=148 in the imipenem-cilastatin group) received treatment. 371 patients (n=252 patients in the cefiderocol group; n=119 patients in the imipenem-cilastatin group) had qualifying Gram-negative uropathogen (>/=1 x 10(5) CFU/mL) and were included in the primary efficacy analysis. At test of cure, the primary efficacy endpoint was achieved by 183 (73%) of 252 patients in the cefiderocol group and 65 (55%) of 119 patients in the imipenem-cilastatin group, with an adjusted treatment difference of 18.58% (95% CI 8.23-28.92; p=0.0004), establishing the non-inferiority of cefiderocol. Cefiderocol was well tolerated. Adverse events occurred in 122 (41%) of 300 patients in the cefiderocol group and 76 (51%) of 148 patients in the imipenem-cilastatin group, with gastrointestinal disorders (ie, diarrhoea, constipation, nausea, vomiting, and abdominal pain) the most common adverse events for both treatment groups (35 [12%] patients in the cefiderocol group and 27 [18%] patients in the imipenem-cilastatin group). INTERPRETATION: Intravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing. FUNDING: Shionogi & Co Ltd, Shionogi Inc.
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