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

On May 30 2026, the FDA approved cefepime and zidebactam (Zaynich) for the treatment of complicated urinary tract infections (cUTI) 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 beta-lactamase inhibitor and non-beta-lactam.² Cefepime targets penicillin-binding protein-3(PBP3) in gram-negative organisms, and zidebactam selectively inhibits penicillin-binding protein-2(PBP2).²

They work simultaneously by targeting multiple penicillin binding proteins. This synergy occurs even with difficult to treat beta-lactamases, including metallo-beta-lactamases (MBLs), which are not inhibited by zidebactam, and other non-enzymatic cefepime resistance mechanisms, such as hyper-efflux and down regulation of outer membrane porin channels.² This unique collaboration presents bactericidal killing against susceptible multi-drug 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 randomized 2:1 to receive cefepime 2 grams/zidebactam 1-gram or meropenem 1 gram every 8 hours for 7-10 days.² Efficacy at the primary endpoint 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 <10³ CFU/mL in urine.² Cefepime and zidebactam demonstrated efficacy at the primary endpoint, achieving a composite clinical cure and microbiological response rate of 89% compared to 68.4% with meropenem, with a treatment difference of 20.6% (95% CI; 12.3, 29.5).^1,2

The recommended dosage is 2 grams of cefepime/1-gram zidebactam intravenously every 8 hours in patients with normal renal function for 7-10 days.² According to the prescribing information, the dose should be adjusted in adults with renal impairment, defined as eGFR less than 60 mL/min.² It is contraindicated in patients with known hypersensitivity to cefepime or zidebactam or other beta-lactam antibiotics. Patients should be questioned regarding previous hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactams. Other warnings and precautions include risk of neurotoxicity while taking cefepime and 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’ Tests, 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 geriatric 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, complicated urinary tract infections account for more than 625,000 hospitalizations yearly.⁴ The rise of antimicrobial resistant infections contributes to the increase in hospitalizations and healthcare costs each year.⁴ This novel antibiotic delivers another therapeutic option for providers when encountering difficult to treat multidrug-resistant complicated urinary tract infections and supports the urgent public health threat of antimicrobial resistance.

References

1. Wockhardt Limited. Wockhardt Receives U.S. FDA Approval for ZAYNICH^TM (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 17, 2026. https://www.wockhardt.com/wp-content/uploads/2026/05/wockhardt-zaynich-fda-approval-press-release.pdf

2. ZAYNICH [Prescribing Information]. Newark, DE. Wockhardt Suisse USA LLC. May 2026.

3. Centers for Disease Control and Prevention. Antimicrobial Resistance. Published Jan 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