FDA approves cefepime and zidebactam intravenous antibiotic to treat adults with cUTI

Wockhardt has announced that the FDA has approved cefepime and zidebactam (ZAYNICH; Wockhardt), a novel intravenous antibiotic designed to treat adults with complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible Gram-negative pathogens. The approval offers a new therapeutic option for patients facing aggressive, drug-resistant infections. Prior to this approval, the drug received Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA.

In the United States, cUTIs are responsible for over 600,000 hospitalizations annually. A growing proportion of these infections are driven by antimicrobial-resistant bacteria, which represent a leading cause of bacteremia and carry significant morbidity and mortality risks. These multidrug-resistant infections place a heavy burden on the healthcare system, as affected patients typically require more intensive, prolonged care and experience higher rates of life-threatening complications.

"The threat of drug-resistant infections is an escalating crisis, leaving clinicians with fewer tools to treat patients facing these aggressive pathogens. The FDA approval of ZAYNICH is a monumental step forward in validating a new option for these underserved populations," said Dr. Dennis Deruelle, Chief Medical Officer at Wockhardt.

Cefepime and zidebactam multi-target synergy

Cefepime and zidebactam is an injectable antibiotic combination consisting of cefepime, a cephalosporin antibacterial drug, and zidebactam, a non-beta-lactam antibacterial and beta-lactamase inhibitor. Unlike most conventional beta-lactam and beta-lactamase inhibitor combinations, cefepime and zidebactam simultaneously targets multiple penicillin-binding proteins (PBPs)—specifically PBP 1a/b, 2, and 3—in the majority of clinically relevant Gram-negative pathogens expressing diverse resistance mechanisms.

In this dual-action formulation, cefepime primarily targets PBP3 and PBP1a/b in Enterobacterales, as well as PBP3 in other Gram-negative pathogens, whereas zidebactam selectively inhibits PBP2. This multi-target synergy triggers effective bacterial cell death even in the presence of beta-lactamases, including metallo-beta-lactamases (MBLs) which zidebactam does not directly inhibit. The mechanism also overcomes non-enzymatic cefepime resistance strategies, such as hyper-efflux and the downregulation of outer membrane porin channels.

Cefepime and zidebactam vs meropenem in phase 3 trial

The regulatory approval was based in part on data from ENHANCE-1, a phase 3, randomized, double-blind, multicenter trial evaluating the efficacy, safety, and tolerability of cefepime and zidebactam compared to meropenem. The study enrolled 530 hospitalized adults with cUTI or acute pyelonephritis across 64 sites spanning the United States, Europe, Latin America, China, and India.

Cefepime and zidebactam achieved its primary end point, demonstrating a composite clinical cure and microbiological response rate of 89%, compared to 68.4% for meropenem, representing a treatment difference of 20.6% (95% CI; 12.3, 29.5). The novel antibiotic combination was reported to be generally well-tolerated throughout the phase 3 trial.

The drug is indicated for adult patients with cUTIs caused by specific susceptible microorganisms:

• Escherichia coli
• Klebsiella pneumoniae
• Proteus mirabilis
• Enterobacter cloacae complex
• Pseudomonas aeruginosa.

To mitigate the development of drug-resistant bacteria and preserve the long-term effectiveness of the drug, clinicians are advised to use cefepime and zidebactam only for infections proven or strongly suspected to be caused by susceptible bacteria. The medication is contraindicated in individuals with a known history of serious hypersensitivity to its components or other beta-lactam antibacterial drugs.

Cefepime and zidebactam was approved by the Drugs Controller General of India (DCGI) on May 27, 2026, and Wockhardt has submitted a Marketing Authorization Application to the European Medicines Agency.

Reference:

Wockhardt Receives U.S. FDA Approval for ZAYNICH™ (cefepime and zidebactam), a Novel Intravenous Antibiotic for the Treatment of Adult Patients with Complicated Urinary Tract Infection Including Pyelonephritis. News release. Published June 1, 2026. Accessed June 1, 2026. https://www.prnewswire.com/news-releases/wockhardt-receives-us-fda-approval-for-zaynich-cefepime-and-zidebactam-a-novel-intravenous-antibiotic-for-the-treatment-of-adult-patients-with-complicated-urinary-tract-infection-including-pyelonephritis