1521. Heterogeneity of Recent Phase 3 cUTI Clinical Trials with New Antibiotics
Session: Poster Abstract Session: Urinary Tract Infection
Friday, October 5, 2018
Room: S Poster Hall
  • 1521_IDWPOSTER2018_Ph3cUTI_V5_BASS.pdf (229.8 kB)
  • Background: For new antibiotics to treat Gram-negative infections, one regulatory pathway includes complicated urinary tract infections (cUTI) clinical trials. Although individual clinical trials comply with regulatory guidelines, they may differ substantially in design and execution. Six recent cUTI trials that supported or are likely to support FDA regulatory review were compared to determine variables that impacted patient selection and outcome parameters.

    Methods: cUTI trials for 6 new antibiotics developed to treat multi-drug resistant Gram‑negative infections were obtained from publicly disclosed information including FDA documents, publications, or presentations at scientific meetings. Antibiotics included were: ceftolozane-tazobactam (CTL‑TAZ), ceftazidime-avibactam (CTZ-AVI), meropenem‑vaborbactam (MER-VAB), cefiderocol, plazomicin, and fosfomycin. Comparison variables included: mMITT sample size, age, % female patients, % acute pyelonephritis, % E. coli and other pathogens at baseline, switch to PO antibiotic, and the non-inferiority margin. Other variables as well as the microbiologic eradication, clinical response, and the combined outcomes will be included in the poster.

    CTL-TAZ CTZ-AVI MER-VAB Cefiderocol Plazomicin Fosfomycin
    mMITT (n) 800 810 374 371 388 362
    Non-inferiority margin (%) 10 10 15 15 15 15
    Age, years (mean) 48.6 52.4 54.3 62 59.4 Not Reported
    % female 74 69.8 65.5 55 52.8 63.5
    Acute pyelonephritis (%) 82 72 59 27 42 53
    E. coli (%) 78.6 73.8 64.7 62.3 69.6 73.4
    IV-to-PO no yes yes no yes no

    Conclusion: Study design and eligibility criteria significantly influences patient characteristics. The proportion of acute pyelonephritis varied greatly and influenced population demographics (age, gender) and baseline microbiology. Studies with a smaller proportion of acute pyelonephritis resulted in an older patient population, fewer females and less E. coli. Larger sample size did not impact outcomes.

    Almasa Bass, PharmD1, Roger Echols, MD, FIDSA1,2, Simon Portsmouth, MD1 and Ann Howell, MS, PharmD1, (1)Shionogi Inc., Florham Park, NJ, (2)ID3C, Easton, CT


    A. Bass, Shionogi Inc.: Employee , Salary .

    R. Echols, Shionogi Inc.: Consultant , Consulting fee .

    S. Portsmouth, Shionogi Inc: Employee , Salary .

    A. Howell, Shionogi Inc.: Employee , Salary .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.