Review of Cefepime and Zidebactam: A Novel Antibiotic Approved to Treat Complicated Urinary Tract Infections

On May 30, 2026, the US Food and Drug Administration (FDA) approved cefepime/zidebactam (Zaynich) for the treatment of complicated urinary tract infections (cUTIs) and pyelonephritis in adults caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Pseudomonas aeruginosa.^1,2

This antibiotic previously received qualified infectious disease product and fast track designations from the FDA.¹ It combines the fourth-generation cephalosporin, cefepime, with zidebactam, a β-lactamase inhibitor and non–β-lactam.² Cefepime targets penicillin-binding protein 3 (PBP3) in gram-negative organisms, and zidebactam selectively inhibits PBP2.²

They work simultaneously by targeting multiple penicillin-binding proteins. This synergy occurs even with difficult-to-treat β-lactamases, including metallo-β-lactamases, which are not inhibited by zidebactam, and other nonenzymatic cefepime resistance mechanisms, such as hyper-efflux and downregulation of outer membrane porin channels.² This unique collaboration presents bactericidal killing against susceptible multidrug-resistant gram-negative bacteria and provides a treatment option where there are often limitations for resistant organisms.^1,2

FDA approval was based partly on the results from the ENHANCE-1 trial.^1,2 In this multinational, double-blind noninferiority trial, 530 adults with documented cUTI, including pyelonephritis, were randomly assigned 2:1 to receive cefepime 2 g/zidebactam 1 g or meropenem 1 g every 8 hours for 7 to 10 days.² Efficacy at the primary end point included achieving a composite clinical cure and microbiological response at the test-of-cure visits (10 days after treatment completion).² Clinical cure was defined as complete resolution (or return to premorbid state) of the baseline signs and symptoms of cUTI or pyelonephritis that were present at screening (and no new or worsening urinary symptoms).² Microbiological response was defined as a decrease in the baseline qualifying pathogen(s) to less than 10³ CFUs/mL in urine.² Cefepime and zidebactam demonstrated efficacy at the primary end point, achieving a composite clinical cure and microbiological response rate of 89% compared with 68.4% with meropenem, with a treatment difference of 20.6% (95% CI, 12.3%-29.5%).^1,2

The recommended dosage is 2 g cefepime/1 g zidebactam intravenously every 8 hours in patients with normal renal function for 7 to 10 days.² According to the prescribing information, the dose should be adjusted in adults with renal impairment, defined as an estimated glomerular filtration rate of less than 60 mL/min.² It is contraindicated in patients with known hypersensitivity to cefepime or zidebactam or other β-lactam antibiotics. Patients should be questioned regarding previous hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other β-lactams. Other warnings and precautions include the risk of neurotoxicity while taking cefepime with Clostridioides difficile infection. Most documented cases of neurotoxicity have occurred in patients with renal impairment taking cefepime doses that were not renally adjusted.² Patients should also be monitored for prolonged prothrombin time, development of drug-resistant bacteria, positive direct Coombs test results, and false-positive reactions for glucose in the urine.² The most commonly encountered adverse reactions included diarrhea, headache, hypertension, and hypokalemia. Pertinent drug interactions occur with aminoglycosides and diuretics. Serious neurologic reactions have occurred in older patients with compromised renal function when given incorrect doses; therefore, dose and frequency should be adjusted based on renal function.² 

The FDA approval of cefepime and zidebactam provides an intravenous treatment option for difficult-to-treat, multidrug-resistant gram-negative bacterial infections. The Centers for Disease Control and Prevention identify antimicrobial resistance as an urgent public health threat, with at least 1.27 million deaths worldwide.³ In the United States, cUTIs account for more than 625,000 hospitalizations yearly.⁴ The rise of antimicrobial-resistant infections contributes to the increase in hospitalizations and health care costs each year.⁴ This novel antibiotic delivers another therapeutic option for providers when encountering difficult-to-treat, multidrug-resistant cUTIs and supports the urgent public health threat of antimicrobial resistance.

References

1. 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. Wockhardt. May 30, 2026. Accessed June 17, 2026. https://www.wockhardt.com/wp-content/uploads/2026/05/wockhardt-zaynich-fda-approval-press-release.pdf

2. Zaynich. Prescribing information. Wockhardt Suisse USA LLC; 2026.

3. About antimicrobial resistance. Centers for Disease Control and Prevention. January 31, 2025. Accessed June 18, 2026. https://www.cdc.gov/antimicrobial-resistance/about/index.html

4. 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