Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial.
Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial.
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DOI：
10.1007/s40121-018-0214-1
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发表时间：
2018-12
影响因子：
5.4
通讯作者：
Kaye KS
中科院分区：
文献类型：
--
作者：
Wunderink RG;Giamarellos-Bourboulis EJ;Rahav G;Mathers AJ;Bassetti M;Vazquez J;Cornely OA;Solomkin J;Bhowmick T;Bishara J;Daikos GL;Felton T;Furst MJL;Kwak EJ;Menichetti F;Oren I;Alexander EL;Griffith D;Lomovskaya O;Loutit J;Zhang S;Dudley MN;Kaye KS
碳青霉烯类耐药肠杆菌科（CRE）感染的治疗选择有限，CRE感染仍与高临床失败率和死亡率相关，特别是在弱势患者人群中。2014年至2017年进行了一项III期、多国、开放标签、随机对照试验（TANGO II），以评价美罗培南-伐硼巴坦单药治疗与现有最佳治疗（BAT）相比治疗CRE的疗效/安全性。共77例确诊/疑似CRE感染（菌血症、医院获得性/呼吸机相关细菌性肺炎、复杂性腹腔内感染、复杂性尿路感染/急性肾盂肾炎）的患者接受随机化，47例确诊CRE感染的患者构成主要分析人群（微生物学CRE改良意向治疗，mCRE-MITT）。合格患者以2：1的比例随机分配至美罗培南-戊硼巴坦组（2 g/2 g，3 h，q8 h，持续7-14天）或BAT组（多粘菌素类、碳青霉烯类、氨基糖苷类、替加环素单药/联合治疗;或头孢他啶-阿维巴坦单药治疗）。疗效终点包括临床治愈、第28天全因死亡率、微生物治愈和总体成功（临床治愈+微生物根除）。安全性终点包括不良事件（AE）和实验室检查结果。在mCRE-MITT人群中，治疗结束时的治愈率分别为65.6%（21/32）和33.3%（5/15）[差异的95%置信区间（CI），3.3%-61.3%; P = 0.03）]，治疗结束时的治愈率分别为59.4%（19/32）和26.7%（4/15）（差异的95%CI，4.6%至60.8%; P = 0.02）在治愈测试时;美罗培南-瓦硼巴坦与BAT的第28天全因死亡率分别为15.6%（5/32）和33.3%（5/15）（差异的95%CI，-44.7%至9.3%）。美罗培南-伐硼巴坦组治疗相关AE和肾脏相关AE分别为24.0%（12/50）和4.0%（2/50），BAT组分别为44.0%（11/25）和24.0%（6/25）。对复合临床失败或肾毒性的探索性风险-获益分析支持美罗培南-戊硼巴坦与BAT（31.3% [10/32] vs 80.0% [12/15];差异的95% CI，− 74.6%至− 22.9%; P < 0.001）。与BAT相比，美罗培南-戊硼巴坦单药治疗CRE感染与临床治愈率增加、死亡率降低和肾毒性降低相关。NCT 02168946。药品公司。本文的在线版本（10.1007/s40121-018-0214-1）包含补充材料，可供授权用户使用。
Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem–vaborbactam monotherapy versus best available therapy (BAT) for CRE. A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem–vaborbactam (2 g/2 g over 3 h, q8h for 7–14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings. Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, − 44.7% to 9.3%) for meropenem–vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem–vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk–benefit analyses of composite clinical failure or nephrotoxicity favored meropenem–vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, − 74.6% to − 22.9%; P < 0.001). Monotherapy with meropenem–vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT. NCT02168946. The Medicines Company. The online version of this article (10.1007/s40121-018-0214-1) contains supplementary material, which is available to authorized users.
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影响因子：
19
作者：
Monaco, M.;Giani, T.;Rossolini, G. M.
通讯作者：
Rossolini, G. M.
影响因子：
4.9
作者：
Daikos, George L.;Tsaousi, Sophia;Skoutelis, Athanasios
通讯作者：
Skoutelis, Athanasios
影响因子：
4.9
作者：
Shields, Ryan K.;Chen, Liang;Clancy, Cornelius J.
通讯作者：
Clancy, Cornelius J.
DOI：
10.1016/s1473-3099(13)70190-7
发表时间：
2013-09
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Munoz-Price LS;Poirel L;Bonomo RA;Schwaber MJ;Daikos GL;Cormican M;Cornaglia G;Garau J;Gniadkowski M;Hayden MK;Kumarasamy K;Livermore DM;Maya JJ;Nordmann P;Patel JB;Paterson DL;Pitout J;Villegas MV;Wang H;Woodford N;Quinn JP
通讯作者：
Quinn JP
影响因子：
4.2
作者：
Alexander EL;Loutit J;Tumbarello M;Wunderink R;Felton T;Daikos G;Fusaro K;White D;Zhang S;Dudley MN
通讯作者：
Dudley MN