1959. Ceftriaxone-Sulbactam-EDTA (CSE) vs. Meropenem (MR) in PLEA (a Phase 3, Randomized, Double-blind Trial): Outcomes in Patients Infected with Ceftriaxone Non-Susceptible, Extended Spectrum Beta-Lactamase and Multi-Drug Resistant Pathogens at Baseline
Session: Poster Abstract Session: Clinical Trials
Saturday, October 6, 2018
Room: S Poster Hall
  • 1959_PLEA_CT_MDR.pdf (1.8 MB)
  • Background:

    CSE, a novel combination of Ceftriaxone, Sulbactam and Disodium EDTA (Class 1 Antibiotic Resistance Breaker), is being developed for the treatment of patients with serious gram-negative infections and has completed a Phase-3 clinical trial (NCT03477422) for treatment of complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). It restores and enhances the in vitro activity of Ceftriaxone against various beta-lactamases (BLs), including enzyme families that belong to Ambler class A (TEM, SHV, CTX-M), class B (NDM, VIM, IMP), class C (some variants of AmpC), and class D {OXA extended spectrum BLs (ESBLs)}. This analysis was performed to assess the clinical and microbiological outcomes in patients infected with Ceftriaxone non-susceptible (C-NS), MDR and ESBL-producing gram-negative pathogens at baseline.


    Patients were randomized 1:1 to receive either CSE (1g Ceftriaxone/500mg Sulbactam/37mg EDTA) every 12h or Meropenem (MR) 1g every 8h as 30 minutes IV infusion for 5-14 days. Oral step-down therapy was not allowed. Biological specimens were analyzed, and resistant pathogens identified. MDR was defined as resistance to at least 3 categories of antimicrobials. Identification of pathogens and antibiotic susceptibility testing were performed and interpreted according to Clinical and Laboratory Standards Institute methodologies. Combined Disc Diffusion Test was used to detect ESBL-production in pathogens.


    Of 230 randomized patients, 143 (62.2%) were included in m-MITT [72/74 (97.3) in CSE and 68/69 (98.6%) in MR groups had C-NS pathogens; 63/74 (85.1%) in CSE and 56/69 (81.2%) in MR groups had ESBL-producing pathogens; 55/74 (74.3%) in CSE and 45/69 (65.2%) in MR group had MDR pathogens]. Mean duration of IV therapy was 7 days. The clinical cure and microbiological eradication rates for CSE and MR at the test of cure (TOC) visit in C-NS, ESBL and MDR pathogens is shown in Figures 1, 2 and 3 respectively.


    At TOC, clinical cure and microbiological eradication rates were higher for CSE as compared to MR across all three analyses sets. Overall, CSE was effective in the treatment of patients with cUTI and AP caused by resistant gram-negative pathogens.




    Mohd Amin Mir, MS, MSc, PGDPM1, Saransh Chaudhary, BSc (Hons)1, Kim Jacob Mammen, MCh (Urology)2, Rajeev Sood, MCh (Urology)3, P.N. Dogra, MCh (Urology)4, Sudhir Chadha, MCh (Urology)5, Ravimohan Mavuduru, MCh (Urology)6, Rahul Janak Sinha, MCh (Urology)7, Manu Chaudhary, PhD8, Gazalla Shiekh, PhD1 and Other Principle Investigators, (1)Venus Medicine Research Centre, Panchkula (Harayana), India, (2)Christian Medical College & Hospital, Ludhiana, Punjab, India, (3)PGIMER Dr. RML Hospital, Baba Kharak Singh Marg, New Delhi, India, (4)All India Institute of Medical Science, New Delhi, India, (5)Sir Ganga Ram Hospital, New Delhi, India, (6)Postgraduate Institute of Medical Education and Research, Chandigarh, India, (7)King George’s Medical University, Lucknow, Uttar Pradesh, India, (8)Venus Remedies Ltd, Panchkula (Harayana), India


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

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

    K. J. Mammen, None

    R. Sood, None

    P. N. Dogra, None

    S. Chadha, None

    R. Mavuduru, None

    R. J. Sinha, None

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

    G. Shiekh, VENUS MEDICINE RESEARCH CENTRE: Employee , Salary .

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