1833. Per Pathogen Outcomes from the ZEUS study, a Multi-center, Randomized, Double-Blind Phase 2/3 Study of ZTI-01 (fosfomycin for injection) versus Piperacillin-Tazobactam (P-T) in the Treatment of Patients with Complicated Urinary Tract Infections (cUTI) including Acute Pyelonephritis (AP)
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • Zavante_Poster1833_revCCKS.pdf (94.7 kB)
  • Background: ZTI-01 (fosfomycin for injection) is a novel injectable epoxide antibiotic with a unique mechanism of action by inhibiting MurA at an early step in cell wall synthesis. ZTI‑01 as a broad spectrum of activity, including multidrug-resistant pathogens, and is being developed for the treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis (AP) in the US.

    Methods: ZEUS was a multicenter, randomized, double-blind Phase 2/3 trial designed to evaluate the safety and efficacy of ZTI-01 in treatment of hospitalized adults with cUTI or AP versus piperacillin/tazobactam (P-T). The primary endpoint of overall success was defined as clinical cure plus microbiologic eradication in the microbiologic modified intent-to-treat (m‑MITT) population at test-of-cure (TOC) visit (Day 19). Patients were randomized to receive 6 g ZTI-01 as 1-hour IV infusion q8h or 4.5 g IV P-T as 1-hour IV infusion q8h for 7 days (up to 14 days if concurrent bacteremia). Clinical cure was defined as complete resolution or significant improvement of signs/symptoms of cUTI or AP present at baseline and no new symptoms, and microbiologic eradication as baseline bacterial pathogen(s) reduced to <104CFU/mL on urine culture and negative on repeat blood culture.

    Results: Of the patients enrolled (N=465), 77.8% had >1 baseline pathogen (m-MITT); the most common baseline pathogens were E. coli (266) and K. pneumoniae(52). Clinical cure and microbial eradication are presented by pathogen with a frequency of >10 patients with pathogen at baseline (Table 1).

    Table 1. Clinical Cure/Microbial Eradication by Pathogen (TOC, m-MITT)

    Baseline Pathogen

    Clinical Cure

    n/N1 (%)

    Micro Eradication

    n/N1 (%)

    ZTI-01 (N=184)

    P-T (N=178)

     ZTI-01 (N=184)

    P-T (N=178)

    E. coli

    120/133 (90.2)

    120/133 (90.2)

    91/133 (68.4)

    79/133 (59.4)

    K. pneumoniae

    25/27 (92.6)

    25/25 (100)

    18/27 (66.7)

    12/25 (48.0)

    P. mirabilis

    8/9 (88.9)

    3/5 (60.0)

    7/9 (77.8)

    1/5 (20.0)

    E. cloacae spp

    8/9 (88.9)

    3/3 (100)

    5/9 (55.6)

    3/3 (100)

    P. aeruginosa

    8/8 (100)

    9/9 (100)

    2/8 (25.0)

    3/9 (33.3)

    E. faecalis

    2/3 (66.7)

    6/7 (85.7)

    1/3 (33.3)

    4/7 (57.1)

    Conclusion: Clinical outcome rates by pathogen at the TOC visit were high and similar for both ZTI-01 and P-T. ZTI-01 is effective in the treatment of cUTI and AP due to Gram-negative uropathogens.

    David Skarinsky, BS1, Paul B Eckburg, MD1, Anita Das, PhD2, Kristina Manvelian, MS1 and Evelyn J. Ellis-Grosse, PhD1, (1)Zavante Therapeutics, Inc., San Diego, CA, (2)Das Statistical Consulting, Guerneville, CA

    Disclosures:

    D. Skarinsky, Zavante Therapeutics, Inc.: Employee and Shareholder , Salary

    P. B. Eckburg, Zavante Therapeutics, Inc.: Consultant and Shareholder , Consulting fee

    A. Das, Zavante Therapeutics, Inc.: Consultant , Consulting fee

    K. Manvelian, Zavante Therapeutics, Inc.: Employee and Shareholder , Salary

    E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee and Shareholder , Salary

    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.