cefepime/zidebactam IV (WCK 5222) / Wockhardt - LARVOL DELTA

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

Acinetobacter baumannii Complex Infections: New Treatment Options in the Antibiotic Pipeline. (PubMed, Microorganisms) - "Furthermore, many older agents, such as polymyxin and colistin, have limited lung penetration and are associated with significant toxicities. In order to place these newer molecules in context and to help clinicians appreciate the emerging potential drug development pipeline, we describe the in vitro activity, mechanisms of action, and clinical trial data not only for the commercially now available alternatives, such as cefiderocol and sulbactam-durlobactam, but also review these topics for molecules undergoing phase II and III clinical trials. Specifically, we discuss and analyze data related to four novel drugs from ABC: BV-100, cefepime-zidebactam, zosurabalpin, and OMN6."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock

β-Lactam/β-Lactamase Inhibitor Combination Antibiotics Under Development. (PubMed, Pathogens) - "The incorporation of ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam has provided new therapeutic options in the treatment of patients with infections due to MDR pathogens. Cefiderocol along with cefepime/enmetazobactam, avibactam/aztreonam, and sulbactam/durlobactam have been recently added to these agents as therapeutic choices, particularly for metallo-β-lactamase producing Gram-negative bacteria...However, only a few have advanced through phase 1, 2, and 3 clinical trials. Among them, in this article, we focus on the most promising combinations of cefepime/zidebactam, cefepime/taniborbactam, and imipenem/cilastatin/funobactam, which are currently under investigation in phase 3 trials."

Journal • Review • Infectious Disease

Antimicrobial resistance among imipenem-non-susceptible Escherichia coli and Klebsiella pneumoniae isolates, with an emphasis on novel β-lactam/β-lactamase inhibitor combinations and tetracycline derivatives: The Taiwan surveillance of antimicrobial resistance program, 2020-2022. (PubMed, J Microbiol Immunol Infect) - "This study highlights significant resistance patterns of INS-EC and INS-KP isolates in Taiwan. The declining susceptibility rates and the rising prevalence of genetic resistance determinants highlight the importance of ongoing surveillance and antimicrobial stewardship."

Journal • Infectious Disease • Pneumonia

Decreased susceptibility to cefepime/zidebactam among carbapenemase-producing Escherichia coli from Stockholm, Sweden with alterations in PBP2. (PubMed, J Antimicrob Chemother) - "Our results indicate that DS to cefepime/zidebactam among clinical isolates of E. coli could arise due to targeted mutations in PBP2."

Journal

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

New P1 trial

Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (clinicaltrials.gov) - P3 | N=530 | Completed | Sponsor: Wockhardt | Recruiting ➔ Completed

Trial completion • Infectious Disease • Nephrology

Advancements in the fight against globally distributed OXA-48 carbapenemase: evaluating the new generation of carbapenemase inhibitors. (PubMed, Antimicrob Agents Chemother) - "To assess the potential of these compounds, this study compared the efficacy against OXA-48 of novel β-lactamase inhibitors, specifically the 1,6-diazabicyclo[3,2,1]octanes (DBOs) avibactam, relebactam, zidebactam, nacubactam, and durlobactam, along with the cyclic and bicyclic boronates vaborbactam, taniborbactam, and xeruborbactam...Combinations, such as cefepime/zidebactam, meropenem/nacubactam, and sulbactam/durlobactam, show promising activity against OXA-48-producing Enterobacterales, while ceftazidime/avibactam, cefepime/taniborbactam, and meropenem/xeruborbactam combinations also appear highly active, largely due to the excellent kinetics of these new inhibitors. Overall, this comprehensive analysis provides important insights into the effectiveness of new BLIs against OXA-48-producing Enterobacterales, highlighting xeruborbactam, durlobactam, and avibactam as leading candidates. Additionally, BLIs like zidebactam, nacubactam, and taniborbactam also showed..."

Journal • Infectious Disease

In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China. (PubMed, Int J Antimicrob Agents) - "Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance."

Journal • Preclinical • Infectious Disease • Pneumonia

Tackling the unyielding: testing two novel approaches against NDM-producing Enterobacterales and Pseudomonas aeruginosa isolates collected in India. (PubMed, Microbiol Spectr) - "NDM being a dominant carbapenemase among Enterobacterales and P. aeruginosa in India, the variable activity of cefiderocol against NDM producers is a concern. Post approval, cefepime/zidebactam could offer a promising treatment option against NDM producers."

Journal • Infectious Disease • Pneumonia

In vitro activity of zidebactam/cefepime (WCK 5222), a β-lactam enhancer/ β-lactam combination against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates. (PubMed, Diagn Microbiol Infect Dis) - "Zidebactam/cefepime combination was highly active against multi-clonal, carbapenem-non-susceptible and colistin-resistant K. pneumoniae isolates producing OXA-48-like (Ambler class D) or/and NDM (Ambler class B) carbapenemases, thus potentially offering a valuable treatment options for infections caused by such pan-drug resistant resistotypes. Though, zidebactam is not an inhibitor of class B and D β-lactamases, potent activity of zidebactam/cefepime combination is attributable to β-lactam enhancer mechanism."

Journal • Preclinical • Infectious Disease • Pneumonia