FDA approves cefepime and zidebactam for complicated UTI

The FDA has approved cefepime and zidebactam (ZAYNICH) for the treatment of adult patients with complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible Gram-negative pathogens, according to Wockhardt.¹

The approval was based in part on the phase 3 ENHANCE-1 trial, in which the intravenous antibiotic achieved a higher composite clinical cure and microbiologic response rate than meropenem at the test-of-cure visit.

The approval adds another intravenous treatment option for hospitalized adults with cUTI or acute pyelonephritis caused by susceptible Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Pseudomonas aeruginosa.¹ Cefepime and zidebactam had previously received Qualified Infectious Disease Product and Fast Track designations from the FDA, as well as Priority Review, for cUTI, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia.

The agent combines cefepime, a fourth-generation cephalosporin antibacterial drug, with zidebactam, a non–β-lactam antibacterial and β-lactamase inhibitor. According to Wockhardt, cefepime primarily targets penicillin-binding protein-3 (PBP3) and PBP1a/b in Enterobacterales and PBP3 in other Gram-negative pathogens, while zidebactam selectively inhibits PBP2. The company stated that the agents work synergistically through multi-PBP binding, including in the presence of β-lactamases, metallo-β-lactamases, hyper-efflux, and outer membrane porin channel downregulation.

What ENHANCE-1 data showed

The FDA approval was based in part on ENHANCE-1, a phase 3, randomized, double-blind, multicenter study comparing cefepime and zidebactam with meropenem in hospitalized adults with cUTI or acute pyelonephritis. The trial enrolled 530 patients across 64 sites in the US, Europe, Latin America, China, and India. Cefepime and zidebactam met the primary end point in ENHANCE-1. At the test-of-cure visit, the composite clinical cure and microbiologic response rate was 89.0% with cefepime and zidebactam vs 68.4% with meropenem, for a treatment difference of 20.6% (95% CI, 12.3 to 29.5).

Wockhardt reported that cefepime and zidebactam was generally well tolerated in the phase 3 study. In the prescribing information summarized in the company announcement, the most common adverse reactions occurring in at least 2% of patients receiving cefepime and zidebactam were diarrhea, hypertension, headache, and hypokalemia. The agent is contraindicated in patients with a known history of serious hypersensitivity to cefepime, zidebactam, or other β-lactam antibacterial drugs.

Warnings and precautions include serious hypersensitivity reactions, including anaphylaxis; neurotoxicity associated with cefepime, including encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus; Clostridioides difficile–associated diarrhea; positive direct Coombs’ tests; prolonged prothrombin time; development of drug-resistant bacteria; and interactions with urine glucose testing. Wockhardt noted that most cefepime-associated neurotoxicity cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment.

“Multidrug-resistant bacterial infections are a substantial burden for patients and the health care system, as patients with these infections typically require longer, more intensive care, and are at increased risk of life-threatening complications,” said Keith Kaye, MD, MPH, professor of medicine and division chief for infectious diseases at Rutgers Robert Wood Johnson Medical School in a news release.¹ “There is an ongoing need for new antibiotics to combat these drug-resistant pathogens, and we are pleased that this approval means patients will soon have an exciting unique option that is urgently needed in the US and worldwide”.

Beyond the US approval, Wockhardt stated that cefepime and zidebactam was approved by the Drugs Controller General of India on May 27, 2026, and that the company has submitted a Marketing Authorization Application to the European Medicines Agency. The company also reported that cefepime and zidebactam has been made available through expanded access programs in multiple countries, including the US, for patients with limited treatment options.

REFERENCES

1. Wockhardt. 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. Published May 30, 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-including-pyelonephritis-302786691.html

2. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. Published 2019. Accessed May 27, 2026. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/2019-ar-threats-report-508.pdf

3. Marantidis J, Sussman RD. Unmet needs in complicated urinary tract infections: challenges, recommendations, and emerging treatment pathways. Infect Drug Resist. 2023;16:1391-1405. doi:10.2147/IDR.S382617