PMID- 30270406
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220521
IS  - 2193-8229 (Print)
IS  - 2193-6382 (Electronic)
IS  - 2193-6382 (Linking)
VI  - 7
IP  - 4
DP  - 2018 Dec
TI  - Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in 
      Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II 
      Randomized Clinical Trial.
PG  - 439-455
LID - 10.1007/s40121-018-0214-1 [doi]
AB  - 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.
FAU - Wunderink, Richard G
AU  - Wunderink RG
AD  - Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School 
      of Medicine, Northwestern University, Chicago, IL, USA. 
      r-wunderink@northwestern.edu.
FAU - Giamarellos-Bourboulis, Evangelos J
AU  - Giamarellos-Bourboulis EJ
AD  - 4th Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, Athens, Greece.
FAU - Rahav, Galia
AU  - Rahav G
AD  - Infectious Disease Unit and Laboratories, Sheba Medical Center and Sackler 
      Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Mathers, Amy J
AU  - Mathers AJ
AD  - Infectious Diseases and International Health, Department of Medicine, University 
      of Virginia School of Medicine, Charlottesville, VA, USA.
FAU - Bassetti, Matteo
AU  - Bassetti M
AD  - Infectious Diseases Clinic, Department of Medicine, University of Udine and 
      Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.
FAU - Vazquez, Jose
AU  - Vazquez J
AD  - Division of Infectious Diseases, Medical College of Georgia/Augusta University, 
      Augusta, GA, USA.
FAU - Cornely, Oliver A
AU  - Cornely OA
AD  - Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated 
      Diseases (CECAD), Zentrum fur klinische Studien (ZKS Koln), and Department I of 
      Internal Medicine, University Hospital of Cologne, Cologne, Germany.
FAU - Solomkin, Joseph
AU  - Solomkin J
AD  - Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, 
      OH, USA.
FAU - Bhowmick, Tanaya
AU  - Bhowmick T
AD  - Division of Allergy, Immunology, and Infectious Diseases, Department of Medicine, 
      Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
FAU - Bishara, Jihad
AU  - Bishara J
AD  - Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital and Sackler 
      Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Daikos, George L
AU  - Daikos GL
AD  - First Department of Medicine, National and Kapodistrian University of Athens, 
      Laiko Hospital, Athens, Greece.
FAU - Felton, Tim
AU  - Felton T
AD  - University Hospital of South Manchester and Division of Infection, Immunity and 
      Respiratory Medicine, University of Manchester, Manchester, UK.
FAU - Furst, Maria Jose Lopez
AU  - Furst MJL
AD  - Unidad de Infectologia, Sanatorio Municipal Dr. Julio Mendez, Buenos Aires, 
      Argentina.
FAU - Kwak, Eun Jeong
AU  - Kwak EJ
AD  - Division of Infectious Diseases, Department of Medicine, University of Pittsburgh 
      Medical Center, Pittsburgh, PA, USA.
FAU - Menichetti, Francesco
AU  - Menichetti F
AD  - Dipartimento di gastroenterologia e malattie infettive, Azienda 
      Ospedaliero-Universitaria Pisana, Pisa, Italy.
FAU - Oren, Ilana
AU  - Oren I
AD  - Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel.
FAU - Alexander, Elizabeth L
AU  - Alexander EL
AD  - The Medicines Company, Parsippany, NJ, USA.
FAU - Griffith, David
AU  - Griffith D
AD  - The Medicines Company, San Diego, CA, USA.
FAU - Lomovskaya, Olga
AU  - Lomovskaya O
AD  - The Medicines Company, San Diego, CA, USA.
FAU - Loutit, Jeffery
AU  - Loutit J
AD  - The Medicines Company, San Diego, CA, USA.
FAU - Zhang, Shu
AU  - Zhang S
AD  - The Medicines Company, Parsippany, NJ, USA.
FAU - Dudley, Michael N
AU  - Dudley MN
AD  - The Medicines Company, San Diego, CA, USA.
FAU - Kaye, Keith S
AU  - Kaye KS
AD  - Professor of Internal Medicine, Director of Clinical Research, Division of 
      Infectious Diseases, University of Michigan Medical School, 5510A MSRB I, SPC 
      5680, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109-5680, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02168946
GR  - U19 AI135964/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20181001
PL  - New Zealand
TA  - Infect Dis Ther
JT  - Infectious diseases and therapy
JID - 101634499
PMC - PMC6249182
OTO - NOTNLM
OT  - Best available therapy
OT  - Carbapenem-resistant Enterobacteriaceae
OT  - Meropenem-vaborbactam
OT  - Randomized clinical trial
OT  - TANGO II
EDAT- 2018/10/03 06:00
MHDA- 2018/10/03 06:01
PMCR- 2018/10/01
CRDT- 2018/10/02 06:00
PHST- 2018/08/13 00:00 [received]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2018/10/03 06:01 [medline]
PHST- 2018/10/02 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - 10.1007/s40121-018-0214-1 [pii]
AID - 214 [pii]
AID - 10.1007/s40121-018-0214-1 [doi]
PST - ppublish
SO  - Infect Dis Ther. 2018 Dec;7(4):439-455. doi: 10.1007/s40121-018-0214-1. Epub 2018 
      Oct 1.