1868. Meropenem-Vaborbactam vs. Best Available Therapy for Carbapenem-Resistant Enterobacteriaceae Infections in TANGO II: Outcomes in Immunocompromised Patients
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • 1868_TANGO2_ClinOutcomesImmunocompIDWeek 2017_092917 RESIZED 90x45.pdf (268.3 kB)
  • Background: Immunocompromised patients are at high risk for mortality due to carbapenem-resistant Enterobacteriaceae (CRE). Meropenem-vaborbactam (M-V) is a novel cyclic boronic acid beta-lactamase inhibitor combination being developed for treatment of serious gram-negative infections, including CRE. This analysis reports outcomes among immunocompromised subjects in TANGO II, a randomized, open-label comparative trial with best available therapy (BAT) in subjects with complicated urinary tract infection (cUTI), acute pyelonephritis (AP), HABP/VABP, bacteremia, and cIAI, due to known or suspected CRE.

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

    Results: Of the 50 subjects who had a baseline pathogen (m-MITT population), 19 (38.0%) were immunocompromised (4 leukemia/lymphoma, 5 medication, 10 transplant). Among the 43 subjects with a baseline CRE pathogen (mCRE-MITT), 18 (41.9%) were immunocompromised. The most common infection types among immunocompromised subjects (mCRE-MITT) were bacteremia (61.1%), cUTI/AP (16.7%), HABP/VABP (11.1%), and cIAI (11.1%). Clinical efficacy and mortality among immunocompromised in the mCRE-MITT population are shown. M-V was associated with fewer drug-related adverse events (30.8% vs. 40.0%), serious adverse events (38.5% vs. 50.0%), and renal-related adverse events (7.7% vs. 40.0%) than BAT.

    Outcomes in mCRE-MITT

    M-V (n=10)

    BAT (n=8)

    ALL (n=18)

    Difference (95% CI)

    Clinical Cure at End of Therapy (EOT)

    6 (60%)

    2 (25%)

    8 (44.4%)

    +35% (-13.5% to 72.8%)

    Clinical Cure at Test of Cure (EOT+7 days)

    7 (70%)

    0 (0%)

    7 (38.9%)

    +70% (26.9% to 93.3%)

    All-Cause Mortality Day 28

    2 (20%)

    3 (37.5%)

    5 (27.8%)

    -17.5% (-59.2% to 29.3%)

    Conclusion: In immunocompromised subjects, receipt of M-V was associated with higher clinical cure rates and a lower mortality rate than BAT (m-MITT, mCRE-MITT populations). M-V is a promising treatment option for CRE in this population.

    David L. Paterson, MB BS PhD FRACP FRCPA1, Eun J. Kwak, MD2, Tanaya Bhowmick, MD3, Elizabeth Alexander, MD, MSc4, Jeffrey S. Loutit, MBChB5, Shu Zhang, PhD4, Michael N. Dudley, Pharm.D., FIDSA5 and Thomas J. Walsh, MD6, (1)Royal Brisbane and Women's Hospital, Herston, Australia, (2)University of Pittsburgh, Pittsburgh, PA, (3)Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, (4)The Medicines Company, Parsippany, NJ, (5)The Medicines Company, San Diego, CA, (6)NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY

    Disclosures:

    D. L. Paterson, Achaogen: Consultant , Consulting fee
    Merck: Consultant and Investigator , Consulting fee and Research grant
    Shionogi: Consultant , Consulting fee
    GlaxoSmithKline: Consultant , Consulting fee

    E. J. Kwak, None

    T. Bhowmick, None

    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

    T. J. Walsh, The Medicines Company: Consultant and Investigator , Consulting fee and Research grant
    Astellas: Consultant and Investigator , Consulting fee and Research grant
    Allergan: Consultant and Investigator , Consulting fee and Research grant
    Merck: Consultant and Investigator , Consulting fee and 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.