1974. Ceftriaxone-Sulbactam-EDTA vs. Meropenem in PLEA (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 Trials
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • 1974_PLEA_CT_MIC.pdf (3.3 MB)
  • Background: Ceftriaxone-Sulbactam-Disodium EDTA (CSE) is being developed for gram-negative infections caused by multidrug-resistant (MDR) bacteria. PLEA was a Phase-3, double-blind, multicenter, randomized study of CSE vs. Meropenem (MR) for treatment of adults with complicated urinary tract infections (cUTI) or Acute Pyelonephritis (AP). Non-inferiority of CSE over MR at the EMA/FDA primary endpoints has been reported. The effect of baseline MIC on clinical and microbiological outcome at the test of cure (TOC) visit was investigated.

    Methods: Adult patients were randomized 1:1 to receive either CSE (1g Ceftriaxone/500mg Sulbactam/37mg EDTA) every 12h or MR 1g every 8h as 30 minutes IV infusion for 5-14 days. Oral step-down therapy was not allowed. Prior to dosing, urine specimens were collected, and MICs were conducted using CLSI methods for both study drugs. Patients that were non-susceptible to MR were not included in the mMITT population.

    Results: Of 230 subjects randomized, 143 (62.2%) were included in the mMITT population. Baseline Enterobacteriaceae was found in 131 (91.6%) patients, 67/74 (90.5%) in CSE and 64/69 (92.8%) in MR arm. Mean duration of IV therapy was 7 days. Favorable clinical and microbiological outcomes were observed in ≥90% patients for all MICs across the two study groups, with the exception of MIC 1μg/mL in MR (associated with >20% failures). Overall, both clinical cure and microbiological eradication rates were higher in CSE as compared to MR (95.9% Vs 89.9% and 94.6% vs 88.4% respectively) (Table 1).

    CSE

    MR

    MIC

    (μg/mL)

    Clinical Cure

    n/N (%)

    Microbiological Eradication

    n/N (%)

    MIC

    (μg/mL)

    Clinical Cure n/N (%)

    Microbiological Eradication

    n/N (%)

    <0.25

    16/16 (100)

    16/16 (100)

    <0.25

    20/22 (90.9)

    21/22 (95.4)

    0.25

    4/4 (100)

    4/4 (100)

    0.25

    12/12 (100)

    11/12 (91.7)

    0.5

    3/3 (100)

    2/3 (66.7)

    0.5

    14/14 (100)

    13/14 (92.7)

    1

    9/10 (90)

    9/10 (90)

    1

    16/21 (76.2)

    16/21 (76.2)

    2

    23/23 (100)

    23/23 (100)

    4

    16/17 (94.1)

    16/17 (94.1)

    8

    0/1 (0)

    0/1 (0)

    Overall

    71/74 (95.9)

    70/74 (94.6)

    Overall

    62/69 (89.9)

    61/69 (88.4)

    Conclusion: CSE showed a high in vitro-in vivo correlation of >97% for MICs up to 4 μg/mL and is a potential new treatment option in patients with cUTI or AP.

    Pankaj Mandale, MBBS, MPH1, Mohd Amin Mir, MS, MSc, PGDPM1, Saransh Chaudhary, BSc (Hons)1, Manu Chaudhary, PhD2, Rajeev Sood, MCh (Urology)3, N. S Patil, MD (Microbiology)4, Salil Narang, MD (Pathology)5, Anurag Pyasi, PhD1, Mohammad Shameem, MD, FRCP6 and Other Principal Investigators , (1)Venus Medicine Research Centre, Panchkula (Harayana), India, (2)Venus Remedies Ltd, Panchkula (Harayana), India, (3)PGIMER Dr. RML Hospital, Baba Kharak Singh Marg, New Delhi, India, (4)Capitol Hospital, Jalandhar, India, (5)Unipath Diagnostic, New Delhi, India, (6)J.N.M.C. Aligarh Muslim University, Aligarh, India

    Disclosures:

    P. Mandale, Venus Medicine Research Centre: Employee , Salary .

    M. A. Mir, VENUS MEDICINE RESEARCH CENTRE: Employee , Salary .

    S. Chaudhary, Venus Medicine Research Centre: Employee and Shareholder , Salary .

    M. Chaudhary, VENUS MEDICINE RESEARCH CENTRE: Board Member and Shareholder , Salary .

    R. Sood, None

    N. S. Patil, None

    S. Narang, None

    A. Pyasi, Venus Medicine Research Centre: Employee , Salary .

    M. Shameem, None

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