1866. Meropenem-Vaborbactam vs. Piperacillin-Tazobactam in TANGO I (a Phase 3 Randomized, Double-blind Trial): Outcomes by Baseline MIC in Adults with Complicated Urinary Tract Infections or Acute Pyelonephritis
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • 1866_TANGO I_cUTI outcomes by MIC_IDWeek 2017_10217 RESIZED 90x45.pdf (510.0 kB)
  • Background: Meropenem-vaborbactam (M-V) is being developed for gram-negative infections, including complicated urinary tract infections (cUTIs) and multidrug-resistant bacterial infections. TANGO I was a Phase 3, multicenter, double-blind, randomized study of M-V vs. piperacillin-tazobactam (P-T) for treatment of adults with cUTI/acute pyelonephritis (AP). Superiority of M-V over P-T at the FDA primary endpoint has been reported. The effect of baseline MICs of Enterobacteriaceae to both study drugs and by susceptibility vs. non-susceptibility to P-T on clinical/microbiological outcome at end of intravenous treatment (EOIVT) was investigated.

    Methods: MICs were conducted on baseline urinary isolates using CLSI methods. Susceptibility to P-T was defined as MIC ≤16 µg/mL (FDA/CLSI).

    Results: Of 550 subjects randomized, 374 (68.0%) were included in m-MITT (165/192 [85.9%] in M-V and 154/182 [84.6%] in P-T groups had baseline Enterobactericeae). Mean duration of IV therapy was 8 days. Clinical outcomes were >90% across all MICs (Table 1).

    Table 1. Outcomes by Baseline MIC for Enterobacteriaceae at EOIVT (m-MITT)

    M-V

    P-T*

    MIC

    (µg/mL)

    Clinical Cure

    n/N’ (%)

    Microbial Eradication

    n/N’ (%)

    MIC

    (µg/mL)

    Clinical Cure

    n/N’ (%)

    Microbial Eradication

    n/N’ (%)

    ≤0.06

    146/149 (98.0)

    146/149 (98.0)

    ≤0.05

    10/10 (100)

    10/10 (100)

    0.12

    12/12 (100)

    11/12 (91.7)

    1

    14/15 (93.3)

    14/15 (93.3)

    0.25

    2/2 (100)

    2/2 (100)

    2

    57/60 (95.0)

    56/60 (93.3)

    0.5

    1/1 (100)

    1/1 (100)

    4

    21/22 (95.5)

    20/22 (90.9)

    32

    1/1 (100)

    1/1 (100)

    8

    6/6 (100)

    6/6 (100)

    16

    10/11 (90.9)

    10/11 (90.9)

    32

    10/11 (90.9)

    8/11 (72.7)

    64

    2/2 (100)

    2/2 (100)

    >64

    17/17 (100)

    16/17 (94.1)

    Totals

    162/165 (98.2)

    161/165 (97.6)

    147/154 (95.5)

    142/154 (92.2)

    * FDA/CLSI non-susceptibility breakpoint of Enterobacteriaceae to P-T is >16 µg/mL

    Although 19.5% of baseline Enterobacteriaceae isolates were non-susceptible to P-T, clinical and microbiologic outcomes were similar for subjects with susceptible and non-susceptible isolates (p > 0.1).

    Conclusion: At EOIVT, clinical cure and microbial eradication rates were >90% for both groups with no trend in responses according to baseline study drug MIC. M-V is highly active against Enterobacteriaceae in vitro and in patients, and is a potential new treatment option for cUTI/AP.

    Thomas J. Walsh, MD1, Tanaya Bhowmick, MD2, Rabih Darouiche, MD3, Valerii Zaitsev, MD, PhD4, Evangelos Giamarellos-Bourboulis, MD, PhD5, Andrew F. Shorr, MD, MPH6, Elena Fedosiuk, MD7, Thomas M. File Jr., MD, MSc, MACP, FIDSA, FCCP8, Jeffrey S. Loutit, MBChB9, Olga Lomovskaya, Ph.D.9, Michael N. Dudley, Pharm.D., FIDSA9 and David Perlin, Ph.D.10, (1)Weill Cornell Medical Center of Cornell University, New York, NY, (2)Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, (3)Baylor College of Medicine, Houston, TX, (4)Bucovinian State Medical University, Chernivtsi, Ukraine, (5)ATTIKON University Hospital, Athens, Greece, (6)Washington Hospital Center, Washington, DC, (7)Brest Regional Hospital, Brest, Belarus, (8)Summa Health System, Akron, OH, (9)The Medicines Company, San Diego, CA, (10)Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ

    Disclosures:

    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

    T. Bhowmick, None

    R. Darouiche, None

    V. Zaitsev, None

    E. Giamarellos-Bourboulis, None

    A. F. Shorr, Astellas Pharma Global Development, Inc: Consultant and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    Cidara: Consultant , Consulting fee
    Merck: Consultant , Scientific Advisor and Speaker's Bureau , Research support and Speaker honorarium

    E. Fedosiuk, None

    T. M. File Jr., Allergan: Consultant , Consulting fee
    Cempra: Consultant , Consulting fee
    The Medicines Company: Consultant , Consulting fee
    Merck: Consultant , Consulting fee
    MotifBio: Consultant , Consulting fee
    Pfizer: Consultant , Consulting fee
    Paratek: Consultant , Consulting fee
    Nabriva: Investigator , Research grant

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

    O. Lomovskaya, The Medicine's Company: Employee and Shareholder , Salary

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

    D. Perlin, None

    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.