Drug Update · Infectious Disease

FDA Approves ZAYNICH for cUTI: 89.0% Test-of-Cure in Trial 1

September 11, 2026

Approval date

2026-05-29

Approved indication

cUTI including pyelonephritis in adults

Recommended adult dose (eGFR ≥ 60 mL/min)

3 grams (2 g cefepime + 1 g zidebactam) IV every 8 hours over 1 hour for 7 to 10 days

Primary efficacy (mMITT, TOC)

Composite response 89.0% ZAYNICH vs 68.4% meropenem

Trial

Trial 1 (NCT04979806), randomized 2:1, multinational, double‑blind, noninferiority

Clinical Perspective

This approval affects clinicians who treat adult patients with complicated urinary tract infections, including pyelonephritis, and adult patients meeting the labeled indications. The FDA action is supported by Trial 1 demonstrating a composite test‑of‑cure rate of 89.0% with ZAYNICH versus 68.4% with meropenem in the mMITT population, with documented clinical cure and microbiological response improvements ^[4]^[2]. Key practical questions include how ZAYNICH will be used in local empiric and targeted therapy algorithms and how real‑world susceptibility patterns will influence its role in therapy?

Dr. Simran Kohli, MBBS, MD (General Medicine), DM (Infectious Diseases) · Infectious Diseases

The FDA approved ZAYNICH (cefepime and zidebactam) for the treatment of adult patients with complicated urinary tract infections (cUTI), including pyelonephritis, on 05/29/2026. The approval was supported by a multinational, double-blind, noninferiority trial (Trial 1, NCT04979806) in which ZAYNICH achieved a composite test-of-cure (clinical cure and microbiological response) of 89.0% versus 68.4% with meropenem in the mMITT population at the Test of Cure visit ^[4]^[3]^[2].

Clinical Context

ZAYNICH is a fixed‑combination intravenous product that pairs cefepime, a cephalosporin antibacterial, with zidebactam, a beta‑lactamase inhibitor and non‑beta‑lactam antibacterial, and is marketed by Wockhardt Bio AG ^[2]^[3]. Zidebactam has been described as having dual activity that includes binding to Gram‑negative penicillin‑binding protein 2 (PBP2) and β‑lactamase inhibition in preclinical and pharmacokinetic evaluations ^[1]. The FDA prescribing information lists the indicated susceptible microorganisms for cUTI, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Pseudomonas aeruginosa ^[2]. The approved adult dosing is 3 grams (2 grams cefepime and 1 gram zidebactam) IV every 8 hours infused over 1 hour for 7 to 10 days for patients with eGFR ≥ 60 mL/min, with renal dose adjustments specified in the label ^[2].

Key Findings

Trial 1 (mMITT population) showed ZAYNICH achieved a composite response (clinical cure and microbiological response) of 89.0% versus 68.4% with meropenem at the Test of Cure visit (n=281 ZAYNICH, n=136 meropenem) ^[4].
Clinical cure rates at Test of Cure were 96.8% with ZAYNICH and 94.9% with meropenem; microbiological response rates were 91.1% with ZAYNICH and 70.6% with meropenem in the mMITT population ^[4].
In patients with baseline bacteremia, composite response at Test of Cure was 16/18 (89%) for ZAYNICH and 4/9 (44%) for meropenem in the mMITT population; pathogen‑level composite response rates for common Gram‑negative pathogens are reported in the trial data ^[4].

Safety & Tolerability

Serious hypersensitivity reactions, including anaphylaxis, have been reported with ZAYNICH ^[2].
Neurotoxicity, including encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus, has been reported with cefepime, a component of ZAYNICH; many cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment ^[2].
Clostridioides difficile infection has been reported with antibacterial agents including ZAYNICH ^[2].
Positive direct Coombs’ tests with or without hemolysis have been reported during treatment with cefepime, a component of ZAYNICH ^[2].
The most common adverse reactions occurring in ≥2% of patients treated with ZAYNICH were diarrhea, headache, hypertension, and hypokalemia ^[2].

Study Design

Trial 1 (NCT04979806) was a multinational, double‑blind, randomized, noninferiority trial that enrolled 530 adults with cUTI including pyelonephritis and randomized patients 2:1 to ZAYNICH (2 g cefepime + 1 g zidebactam IV every 8 hours infused over 1 hour) versus meropenem (1 g IV every 8 hours infused over 1 hour) for 7 to 10 days; the primary efficacy analysis used the microbiological modified intent‑to‑treat (mMITT) population ^[4]. The mMITT population included 281 patients in the ZAYNICH group and 136 patients in the meropenem group; no IV‑to‑oral switch was permitted ^[4].

FAQ

Q1 What is ZAYNICH approved for?

ZAYNICH (cefepime and zidebactam) is approved for the treatment of adult patients with complicated urinary tract infections (cUTI), including pyelonephritis, caused by designated susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Pseudomonas aeruginosa. The approval is for adults and is supported by Trial 1 results described in the prescribing information.

Q2 How does ZAYNICH work?

ZAYNICH combines cefepime, a cephalosporin antibacterial, with zidebactam, described in the literature as a beta‑lactamase inhibitor and non‑beta‑lactam antibacterial agent. Zidebactam has been reported to have dual activity, including binding to Gram‑negative penicillin‑binding protein 2 (PBP2) and inhibiting beta‑lactamases, which together with cefepime provide antibacterial activity against specified Gram‑negative pathogens.

Q3 What is the recommended dose of ZAYNICH?

The recommended adult dosage of ZAYNICH for patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min is 3 grams (2 grams cefepime and 1 gram zidebactam) every 8 hours by intravenous infusion over 1 hour for 7 to 10 days. Dosage adjustment is recommended for adult patients with renal impairment with specific eGFR‑based dosing provided in the label. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects?

The most common adverse reactions reported in clinical trials occurring in ≥2% of patients treated with ZAYNICH were diarrhea, headache, hypertension, and hypokalemia. The prescribing information also includes warnings for serious hypersensitivity reactions, neurotoxicity associated with cefepime, Clostridioides difficile infection, and positive direct Coombs’ tests. Clinicians should review the full label for detailed safety information.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves ZAYNICH for cUTI: 89.0% Test-of-Cure in Trial 1

Direct Clinical Takeaway & Evidence Summary

FDA Approves ZAYNICH for cUTI: 89.0% Test-of-Cure in Trial 1

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Cite & Reference This Monograph

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