1862. Clinical Outcomes of Serious Infections due to Carbapenem-Resistant Enterobacteriaceae (CRE) in TANGO II, a Phase 3, Randomized, Multi-National, Open-Label Trial of Meropenem-Vaborbactam (M-V) Versus Best Available Therapy (BAT)
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • 1862_TANGO2AllInfectionTypes_IDWeek 2017_092917 RESIZED 90x45.pdf (337.0 kB)
  • Background: Meropenem-vaborbactam (M-V) is a new beta-lactam-beta-lactamase inhibitor combination that restores the potency of meropenem in Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE). TANGO II is a randomized, open-label trial in patients with complicated urinary tract infection (cUTI), acute pyelonephritis (AP), hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), bacteremia, or complicated intra-abdominal infection (cIAI), due to known or suspected CRE. Clinical outcomes across indications in patients with documented CRE at baseline are presented.

    Methods: Subjects were randomized 2:1 to monotherapy with M-V (2g/2g every 8h as a 3h infusion) or Best Available Therapy (BAT) for 7-14 days. BAT included the following alone or in combination: carbapenems, aminoglycosides, polymyxin B, colistin, tigecycline or ceftazidime-avibactam (monotherapy only). Clinical cure was defined as a complete resolution of signs or symptoms such that no further antimicrobial therapy was required.

    Results: 72 patients were enrolled; 50 (69.4%) had a gram-negative baseline organism (m-MITT), and 43 (59.7%) had a baseline CRE (mCRE-MITT). Within mCRE-MITT, 20 patients had bacteremia, 15 had cUTI/AP, 5 had HABP/VABP, and 3 had cIAI. The most common baseline CRE pathogens were K. pneumoniae (86%) and Escherichia coli (7%). There was no consensus BAT regimen; however, combination therapy was used in 66.7% of cases. Treatment duration was similar across arms (mean 8.5 days for M-V and 8.1 days for BAT). Cure rates at end of treatment (EOT) and test of cure (TOC; 7 days after EOT) in mCRE-MITT and m-MITT populations are shown:

    mCRE-MITT

    Time Point

    M-V (n=28)

    N, %

    BAT (n=15)

    N, %

    % Difference

    (M-V – BAT)

    95% CI

    EOT

    18 (64.3%)

    6 (40.0%)

    24.3%

    (-6.2% to 54.8%)

    TOC

    16 (57.1%)

    4 (26.7%)

    30.5%

    (1.6% to 59.4%)

    m-MITT

    Time Point

    M-V (n=31)

    N, %

    BAT (n=19)

    N, %

    % Difference

    (M-V – BAT)

    95% CI

    EOT

    21 (67.7%)

    8 (42.1%)

    25.6%

    (-2% to 53.3%)

    TOC

    18 (58.0%)

    6 (31.6%)

    26.5%

    (-0.7% to 53.7%)

     

    Conclusion: M-V was associated with a higher rate of clinical cure at EOT and TOC than BAT across all indications in both m-MITT and mCRE-MITT populations. M-V is a promising new option for the treatment of CRE infections.

    Keith S. Kaye, MD, MPH1, Jose Vazquez, MD, FACP, FIDSA2, Amy Mathers, MD3, George Daikos, MD4, Elizabeth Alexander, MD, MSc5, Jeffrey S. Loutit, MBChB6, Shu Zhang, PhD5, Michael N. Dudley, Pharm.D., FIDSA6 and Oliver Cornely, MD, FACP, FIDSA, FAAM7, (1)University of Michigan Medical School, Ann Arbor, MI, (2)Henry Ford Hospital, Detroit, MI, (3)University of Virginia Health System, Charlottesville, VA, (4)University of Athens, Athens, Greece, (5)The Medicines Company, Parsippany, NJ, (6)The Medicines Company, San Diego, CA, (7)University Hospital of Cologne, Cologne, Germany

    Disclosures:

    K. S. Kaye, Xellia: Consultant , Consulting fee
    Merck: Consultant and Grant Investigator , Consulting fee and Research support
    The Medicines Company: Consultant and Grant Investigator , Consulting fee and Research support

    J. Vazquez, None

    A. Mathers, None

    G. Daikos, Achaogen: Consultant , Consulting fee
    Rempex: Consultant , Consulting fee
    Pfizer: Consultant , Research Contractor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium

    E. Alexander, The Medicines Company: Shareholder , Salary

    J. S. Loutit, The Medicine's Company: Employee and Shareholder , Salary

    S. Zhang, The Medicines Company: Shareholder , Salary

    M. N. Dudley, The Medicine's Company: Employee and Shareholder , Salary

    O. Cornely, Archaogen: Consultant , Consulting fee
    Anacor: Consultant , Consulting fee
    Amplyx: Consultant , Consulting fee
    Actelion: Consultant and Investigator , Consulting fee and Research grant
    Astellas: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Basilea: Consultant , Investigator and Speaker's Bureau , Research grant
    Cidara: Consultant and Investigator , Consulting fee and Research support
    Da Volterra: Consultant , Consulting fee
    F2G: Consultant and Investigator , Consulting fee and Research grant
    Gilead: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Janssen: Consultant , Consulting fee
    Matinas: Consultant , Consulting fee
    Menarini: Consultant , Consulting fee
    Merck/MSD: Consultant and Investigator , Consulting fee and Research support
    Paratek: Consultant , Consulting fee
    Scynexis: Consultant and Investigator , Consulting fee and Research grant
    Seres: Consultant and Investigator , Consulting fee
    Summit: Consultant , Consulting fee
    Tetraphase: Consultant , Consulting fee
    Vical: Consultant , Consulting fee
    Aranis: Investigator , Research grant
    AstraZeneca: Investigator , Research grant
    Bayer: Research Contractor , Research grant
    Duke University: Research Contractor , Research support
    GSK: Investigator , Research grant
    MedPace: Investigator , Research support
    Melinta: Investigator , Research support
    Miltenyi: Investigator , Research support
    Pfizer: Investigator , Research support
    Rempex: Investigator , Research support
    Roche: Investigator , Research support
    Sanofi Pasteur: Investigator , Research support
    German Federal Ministry of Research and Education and the European Commission: Investigator , Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.