Zaynich (cefepime/zidebactam) / Wockhardt - LARVOL DELTA

Wockhardt Ltd. announced that the United States Food and Drug Administration (US FDA) has formally accepted the New Drug Application (NDA) for its novel, first-in-class antibiotic Zaynich. (Indian Pharma Post)

FDA filing • Infectious Disease

First report of treatment-emergent resistance to cefepime-zidebactam in Pseudomonas aeruginosa. (PubMed, Clin Infect Dis) - "During treatment cefepime-zidebactam MICs increased from 8/8 to 32/32mg/L. Whole-genome sequence analysis showed new mutations in the MexAB-OprM efflux operon that were associated with cross-resistance to ceftazidime-avibactam and imipenem-relebactam."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Therapeutic challenges in treating ESBL- and/or AmpC-producing non-carbapenemase-producing Enterobacterales: an in vitro evaluation of novel β-lactam/β-lactamase inhibitor combinations and cefiderocol. (PubMed, J Antimicrob Chemother) - "CR non-CPE exhibit heterogeneous resistance profiles, especially in ESBL/AmpC co-producers and CTX-M-33-producing isolates. While cefepime-zidebactam, imipenem-relebactam, and cefiderocol were the most active agents, susceptibility testing remains essential to guide therapy in this emerging and neglected bacterial group."

Journal • Preclinical

The company has submitted a New Drug Application (NDA) to the US Food and Drug Administration (USFDA) for its novel antibacterial agent Zidebactam-Cefepime injection... (The Economic Times) - "The NDA submission follows the successful completion of a pivotal Phase III global clinical trial, conducted across 64 sites in India, the USA, Bulgaria, Estonia, Lithuania, Poland, Slovakia, Mexico, and China, it added."

FDA filing • Infectious Disease

How I manage patients with New Delhi metallo-beta-lactamase and OXA-48-producing Enterobacterales infections: a practical approach. (PubMed, Curr Opin Infect Dis) - "Optimal management of NDM- and OXA-48-producing Enterobacterales requires individualized approach guided by pathogen type, resistance profile, and patient characteristics. Improved diagnostics and surveillance are essential to guide early treatment, while novel agents may enhance therapeutic options in the near future."

Journal • Infectious Disease

Novel beta-lactamase inhibitors with cefepime: where do they fit in clinical practice? (PubMed, Expert Opin Pharmacother) - "We performed a literature review of articles written in English using MEDLINE, PUBMED, and EMBASE, using the search terms 'Cefepime-enmetazobactam,' 'cefepime-taniborbactam,' and 'Cefepime-zidebactam' between January of 2015 and May 2025. On balance, the in vitro activity of cefepime-zidebactam fills critical gaps for the most challenging Gram-negative pathogens, including those that harbor metallo-β-lactamases with or without mutations in penicillin-binding proteins. For each of these agents, clinical data and real-world evidence generation are needed to better define their therapeutic niche, potential for resistance selection, and potential benefits compared to currently available antibiotics."

Journal • Review • Infectious Disease

A Single-center, Open-label, Study Evaluating Safety and Pharmacokinetics of Single Doses of Zidebactam-Cefepime and Metronidazole Alone or in Combination. (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Wockhardt | Recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Feb 2025 | Trial primary completion date: Jul 2025 ➔ Feb 2025

Trial completion • Trial completion date • Trial primary completion date

Efficacy of β-lactam Enhancer Based Zidebactam-Cefepime Combination (WCK 5222) versus Meropenem in Adults with Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) in a Global, Randomized, Double-blind, Phase 3 Trial (IDWeek 2025) - No abstract available

Clinical • P3 data • Infectious Disease

Evaluation of cefepime/zidebactam (FPZ) dynamics in vitro using clinical Pseudomonas aeruginosa strains obtained from a patient treated with FPZ (IDWeek 2025) - No abstract available

Preclinical • Infectious Disease

Antibiotics and non-traditional antimicrobial agents for carbapenem-resistant Acinetobacter baumannii in Phase 1, 2, and 3 clinical trials. (PubMed, Expert Opin Investig Drugs) - "Specifically, 9 antibiotics are in Phase 1 (R-327, xeruborbactam/QPX-7728, upleganan/SPR-206, MRX-8, QPX-9003, zifanocycline/KBP-7072, apramycin/EBL-1003, zosurabalpin/RG-6006, and ANT-3310), two in Phase 2 (BV-100, OMN-6), and two in Phase 3 (zidebactam/WCK-5222, funobactam/XNW-4107) clinical trials...In particular, two monoclonal antibodies (TRL-1068, CMTX-101), a phage therapy (Phagebank), an immune-modulating agent (recombinant human plasma gelsolin/Rhu-pGSN), a microbiome-modulating agent (SER-155), and an engineered cationic antibiotic peptide (PLG-0206). Several agents with promising characteristics against CRAB infections are in clinical development (Phases 1, 2, and 3). The urgent need for therapeutic options against CRAB infections necessitates optimizing efforts and time for introducing successfully studied agents into clinical practice."

Journal • Review • Infectious Disease • GSN

Evaluation of imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam and cefepime-zidebactam activities on a wide collection of French clinical Enterobacterales isolates. (PubMed, Diagn Microbiol Infect Dis) - "This work confirmed the interest of C/Z and A/A combinations against carbapenem-resistant Enterobacterales isolates compared with M/V and I/R. Additionally, the findings indicate that the E-test method can be used for the determination of M/V and I/R MIC for E. coli and K. pneumoniae strains."

Journal • Infectious Disease • Pneumonia

Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation. (PubMed, JAC Antimicrob Resist) - "Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution...The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging...Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms."

Journal • Infectious Disease • Pneumonia • Transplantation

Emerging Resistance to Novel β-Lactam β-Lactamase Inhibitor Combinations in Klebsiella pneumoniae bearing KPC Variants. (PubMed, J Glob Antimicrob Resist) - "Emerging CZA-resistant KPC variants often exhibit collateral FDC resistance, with FPZ seen less frequently. Mutations in blaKPC, cirA, and other genes contribute to resistance. Understanding these emerging resistant patterns linked with new KPC variants is crucial to inform therapeutic decisions, as emerging resistance may limit last-line treatment options in clinical settings."

Journal • Infectious Disease • Pneumonia

Successful use of cefepime/zidebactam in deep-seated infections due to extensively drug-resistant Pseudomonas aeruginosa - a case series. (PubMed, J Glob Antimicrob Resist) - "The in-vitro susceptibility of our XDR PsA isolates to FEP/ZID translated to a successful clinical outcome in our series of deep-seated infections. FEP/ZID is a potential safe and effective treatment option for such serious Gram-negative infections."

Journal • Infectious Disease

A Single-center, Open-label, Study Evaluating Safety and Pharmacokinetics of Single Doses of Zidebactam-Cefepime and Metronidazole Alone or in Combination. (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Wockhardt | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial primary completion date

Emergence of Resistance and Hyper-Susceptibility in Enterobacterales and Pseudomonas aeruginosa to Diazabicyclooctane (DBO) β-Lactamase Inhibitors (ASM Microbe 2025) - "A high-throughput inkjet printer-based susceptibility testing method is used to establish baseline susceptibility of drug-resistant Enterobacterales and P.aeruginosa strains to DBOs, both alone and in combination with five β-lactams (aztreonam, meropenem, cefepime, ceftazidime, mecillinam)...Carbapenemase-producing strains had higher mutation frequencies than non-producers in response to the cefepime/zidebactam combination, with P.aeruginosa strains exhibiting the highest rates...Mutations linked to carbapenemase loss will be investigated using whole-genome sequencing. These findings have important implications for the role of new BL/DBO combinations in clinical development."

Infectious Disease

From genomics to treatment: overcoming pan-drug-resistant Klebsiella pneumoniae in clinical settings. (PubMed, Front Pharmacol) - "We report pan-drug resistant Klebsiella pneumoniae isolates from five patients in a single hospital, including resistance to cefiderocol and cefepime-zidebactam in one isolate...Genomic and phenotypic characterization guided successful compassionate treatment using aztreonam, ceftazidime-avibactam, and amoxicillin-clavulanate at maximum doses. Dissection of the roles of the substitutions present in blaSHV-231 revealed that this variant was responsible for the reduced susceptibility to aztreonam-avibactam, at the expense of a higher susceptibility to clavulanate. Targeted therapy can be successful upon dissection of unexpected mechanisms of resistance that enhance the contribution of endemic β-lactamase."

Journal • Infectious Disease • Pneumonia

In vitro activity of cefepime-zidebactam, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and other comparators against imipenem-non-susceptible Pseudomonas aeruginosa in Taiwan, 2022. (PubMed, Int J Antimicrob Agents) - "The COVID-19 pandemic intensified resistance trends in INS-P. aeruginosa in Taiwan, with increasing prevalence and diversity of carbapenemase-encoding genes. Continuous monitoring and expanded research are essential to combat evolving resistance patterns."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease

Emerging Resistance to Novel -βLactam β-Lactamase Inhibitor Combinations in Klebsiella pneumoniae bearing KPC Variants. (PubMed, bioRxiv) - "This study demonstrates that emerging KPC variants showing resistance to CZA also exhibit resistance to FDC, with collateral resistance to FPZ observed to a lesser extent. Identifying mutations in blaKPC, cirA, and other genes is important to understand resistance mechanisms for effective therapies."

Journal • Infectious Disease • Pneumonia

In vitro susceptibility of NDM-producing clinical isolates of Escherichia coli and Klebsiella pneumoniae to cefepime/zidebactam from a tertiary-care cancer hospital (ESCMID Global 2025) - No abstract available

Preclinical • Infectious Disease • Oncology • Pneumonia

Phase 1, randomised, double-blind, placebo-controlled, single-dose study to evaluate the pharmacokinetics of cefepime/zidebactam (WCK 5222) in healthy adult Chinese subjects (ESCMID Global 2025) - No abstract available

Clinical • P1 data • PK/PD data

Potent in vitro activity of novel beta-lactam/ beta-lactam enhancer cefepime/zidebactam against K. pneumoniae and P. aeruginosa, enriched with carbapenem resistance collected from four tertiary-care hospitals in India (ESCMID Global 2025) - No abstract available

Preclinical • Infectious Disease • Pneumonia

Cefepime/zidebactam: a novel beta-lactam-enhancer mechanism based triple action BCH-DBO antibiotic (ESCMID Global 2025) - No abstract available

In vitro activity of cefepime/zidebactam (FPZ) against extended-spectrum beta-lactamase (ESBL) producers and carbapenem-resistant Enterobacterales (CRE) isolates (ESCMID Global 2025) - No abstract available

Preclinical

Investigational antibiotic cefepime/zidebactam as a therapeutic option for the treatment of an unyielding empyema in a paediatric patient caused by extensively drug-resistant Pseudomonas aeruginosa: a case report. (PubMed, Eur J Clin Microbiol Infect Dis) - "This case highlights both severity of the antimicrobial resistance and hope offered by an under-trial novel antibiotic."

Journal • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases • Tuberculosis