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January 14, 2026Open Forum Infectious Diseases0 citationsOpen Access

P-1209. Efficacy of β-lactam Enhancer Based Zidebactam-Cefepime Combination (WCK 5222) versus Meropenem in Adults with Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) in a Global, Randomized, Double-blind, Phase 3 Trial

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IVIvan VELEVBMBoris MladenovDSD. Slaitas

Key Points

  • To compare the efficacy and safety of β-lactam enhancer zidebactam combined with cefepime against meropenem in treating cUTI and AP.
  • Phase 3, randomized, double-blind, active-controlled trial
  • Conducted at 44 global sites, enrolling hospitalized adults with clinical diagnosis of cUTI or AP
  • Patients randomized to receive ZID-FEP (1+2 g) or meropenem (1 g) for 7-10 days
  • Overall success rate at test-of-cure was 89.0% for ZID-FEP and 68.4% for meropenem
  • ZID-FEP was statistically superior to meropenem for the primary endpoint
  • Treatment difference was 20.6% with a 95% CI of 12.3 to 29.5

Abstract

Abstract Background The combination of β-lactam enhancer zidebactam and cefepime (ZID-FEP) is in development for the treatment of diverse infections caused by a wide range of MDR/XDR Gram-negative bacteria including MBL-producers. In a registration-enabling Phase 3 study (ENHANCE), efficacy and safety of ZID-FEP was compared against meropenem in adults with cUTI or AP.Clinical cure, microbiological eradication and overall success rates at test-of-cure visit in mMITT population Methods This Phase 3, randomized, double-blind, active-controlled and non-inferiority trial was conducted at 44 global sites across U.S., EU, India, Mexico, and China, enrolling hospitalized adults (≥18 years old) with a clinical diagnosis of cUTI or AP ± concurrent bacteremia. Eligible patients were randomized 2:1 to receive ZID-FEP 1+ 2 g (1 h infusion) or meropenem 1 g (0.5 h infusion) for 7 to 10 days with dosage adjustments based on renal function. The primary efficacy outcome (FDA 65 years represented 62% of the mMITT population and bacteremia was present in 6.5% of patients. The overall success rate at TOC was 89.0% in the ZID-FEP group versus 68.4% in the meropenem group; treatment difference ZID-FEP versus meropenem, 20.6%; 95% CI, 12.3 to 29.5) (Table 1). ZID-FEP was statistically superior to meropenem for the primary endpoint at the TOC in e-mMITT. Treatment difference for all analyzed sub-groups, which include cUTI versus AP, older adults, renal-insufficiency, obese patients and cefepime-resistant uropathogens were consistent with the overall study results. Conclusion ZID-FEP demonstrated statistical superiority over meropenem in the overall success rates and results were consistent regardless of patient or pathogen characteristics. Disclosures All Authors: No reported disclosures

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Cite This Study

VELEV et al. (2026) studied this question.

synapsesocial.com/papers/6966f30613bf7a6f02c00980https://doi.org/10.1093/ofid/ofaf695.1402
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