Universität zu Köln

Wunderink, Richard G., Giamarellos-Bourboulis, Evangelos J., Rahav, Galia, Mathers, Amy J., Bassetti, Matteo ORCID: 0000-0002-0145-9740, Vazquez, Jose, Cornely, Oliver A., Solomkin, Joseph, Bhowmick, Tanaya ORCID: 0000-0001-5734-8911, Bishara, Jihad, Daikos, George L., Felton, Tim, Lopez Furst, Maria Jose, Kwak, Eun Jeong, Menichetti, Francesco, Oren, Ilana, Alexander, Elizabeth L., Griffith, David, Lomovskaya, Olga, Loutit, Jeffery, Zhang, Shu, Dudley, Michael N. and Kaye, Keith S. (2018). Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial. Infect. Dis. Ther., 7 (4). S. 439 - 456. LONDON: SPRINGER LONDON LTD. ISSN 2193-6382

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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 (2g/2g over 3h, q8h for 7-14days) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wunderink, Richard G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Giamarellos-Bourboulis, Evangelos J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahav, Galia UNSPECIFIED UNSPECIFIED UNSPECIFIED Mathers, Amy J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bassetti, Matteo UNSPECIFIED orcid.org/0000-0002-0145-9740 UNSPECIFIED Vazquez, Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Solomkin, Joseph UNSPECIFIED UNSPECIFIED UNSPECIFIED Bhowmick, Tanaya UNSPECIFIED orcid.org/0000-0001-5734-8911 UNSPECIFIED Bishara, Jihad UNSPECIFIED UNSPECIFIED UNSPECIFIED Daikos, George L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Felton, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Lopez Furst, Maria Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Kwak, Eun Jeong UNSPECIFIED UNSPECIFIED UNSPECIFIED Menichetti, Francesco UNSPECIFIED UNSPECIFIED UNSPECIFIED Oren, Ilana UNSPECIFIED UNSPECIFIED UNSPECIFIED Alexander, Elizabeth L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Griffith, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Lomovskaya, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Loutit, Jeffery UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Shu UNSPECIFIED UNSPECIFIED UNSPECIFIED Dudley, Michael N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaye, Keith S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-163871
DOI:	10.1007/s40121-018-0214-1
Journal or Publication Title:	Infect. Dis. Ther.
Volume:	7
Number:	4
Page Range:	S. 439 - 456
Date:	2018
Publisher:	SPRINGER LONDON LTD
Place of Publication:	LONDON
ISSN:	2193-6382
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-LACTAMASE; MORTALITY; PREDICTORS Multiple languages Infectious Diseases Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16387