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

Abstract

BackgroundCeftriaxone–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.MethodsAdult patients were randomized 1:1 to receive either CSE (1 g ceftriaxone/500 mg Sulbactam/37 mg EDTA) every 12 h or MR 1g every 8 hours 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 nonsusceptible to MR were not included in the mMITT population.ResultsOf 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 1 μg/mL in MR (associated with >20% failures). Overall, both clinical cure and microbiological eradication rates were higher in CSE as compared with MR (95.9% Vs. 89.9% and 94.6% vs. 88.4% respectively) (Table 1).CSEMRMIC(μg/mL)Clinical Cure n/N (%)Microbiological Eradication n/N (%)MIC(μg/mL)Clinical Cure n/N (%)Microbiological Eradicationn/N (%)<0.2516/16 (100)16/16 (100)<0.2520/22 (90.9)21/22 (95.4)0.254/4 (100)4/4 (100)0.2512/12 (100)11/12 (91.7)0.53/3 (100)2/3 (66.7)0.514/14 (100)13/14 (92.7)19/10 (90)9/10 (90)116/21 (76.2)16/21 (76.2)223/23 (100)23/23 (100)416/17 (94.1)16/17 (94.1)80/1 (0)0/1 (0)Overall71/74 (95.9)70/74 (94.6)Overall62/69 (89.9)61/69 (88.4)ConclusionCSE 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.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. A. Pyasi, Venus Medicine Research Centre: Employee, Salary.