@article{3106783,
    title = "Effect and Safety of Meropenem–Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial",
    author = "Wunderink, R.G. and Giamarellos-Bourboulis, E.J. and Rahav, G. and Mathers, A.J. and Bassetti, M. and Vazquez, J. and Cornely, O.A. and Solomkin, J. and Bhowmick, T. and Bishara, J. and Daikos, G.L. and Felton, T. and Furst, M.J.L. and Kwak, E.J. and Menichetti, F. and Oren, I. and Alexander, E.L. and Griffith, D. and Lomovskaya, O. and Loutit, J. and Zhang, S. and Dudley, M.N. and Kaye, K.S.",
    journal = "Infectious Diseases and Therapy",
    year = "2018",
    volume = "7",
    number = "4",
    pages = "439-455",
    publisher = "Springer Healthcare",
    issn = "2193-8229, 2193-6382",
    doi = "10.1007/s40121-018-0214-1",
    keywords = "aminoglycoside;  avibactam plus ceftazidime;  carbapenem;  creatinine;  meropenem plus vaborbactam;  polymyxin;  tigecycline, acute kidney failure;  adult;  anemia;  antimicrobial therapy;  Article;  bacteremia;  bacterium isolation;  carbapenem-resistant Enterobacteriaceae;  controlled study;  diarrhea;  disk diffusion;  drug efficacy;  drug safety;  drug withdrawal;  Enterobacteriaceae infection;  female;  human;  hypokalemia;  hypotension;  Klebsiella pneumoniae;  major clinical study;  male;  MIC50;  monotherapy;  mortality;  multicenter study;  nephrotoxicity;  phase 3 clinical trial;  priority journal;  prospective study;  randomized controlled trial;  risk benefit analysis;  septic shock;  treatment failure",
    abstract = "Introduction: 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. Methods: 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. Results: 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). Conclusions: Monotherapy with meropenem–vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT. Clinical Trials Registration: NCT02168946. Funding: The Medicines Company. © 2018, The Author(s)."
}