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

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

Assessment of the activity and mechanisms of resistance to cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, taniborbactam, zidebactam, nacubactam, xeruborbactam, and ANT3310 in emerging double-carbapenemase-producing Enterobacterales. (PubMed, Antimicrob Agents Chemother) - "Minimum inhibitory concentration (MIC) values for ceftazidime, ceftazidime/avibactam, aztreonam, aztreonam/avibactam, aztreonam/nacubactam, cefiderocol, cefepime, cefepime/taniborbactam, cefepime/zidebactam, cefepime/nacubactam, imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, meropenem/xeruborbactam, and meropenem/ANT3310 were determined by reference broth microdilution. Meropenem/ANT3310 (MIC50/MIC90 = 0.5/≥64 mg/L; 47/57 susceptible) and cefepime/taniborbactam (MIC50/MIC90 = 0.5/16 mg/L; 44/57 susceptible) also retained high levels of activity, although they were affected by NDM-type enzymes in combination with porin deficiency. Our findings highlight that cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, nacubactam, taniborbactam, zidebactam, xeruborbactam, and ANT3310 show promising activity against double-carbapenemase-producing Enterobacterales."

Journal

Novel agents in development for the treatment of resistant Gram-negative infections. (PubMed, Expert Rev Anti Infect Ther) - "While many of these novel agents demonstrate in vitro activity against carbapenem-resistant GNB, their efficacy has mainly been evaluated in phase-3 randomized controlled trials (RCT) for infections caused by carbapenem-susceptible GNB. Although evidence from real-world observational studies is generally less robust than that from RCT, it could be crucial for updating clinical guidelines on treating carbapenem-resistant GNB with these new agents in the absence of dedicated RCT."

Gram negative • Journal • Review • Infectious Disease

Impact of chromosomally encoded resistance mechanisms and transferable β-lactamases on the activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa. (PubMed, J Antimicrob Chemother) - "Cefiderocol and new β-lactam/β-lactamase inhibitor combinations show promising and complementary in vitro activity against mutational and transferable P. aeruginosa β-lactam resistance. However, the combined effects of efflux pumps, OprD deficiency and efficient β-lactamases could still result in the loss of all therapeutic options. Resistance surveillance, judicious use of new agents and continued drug development efforts are encouraged."

Journal

Difficult to treat Pseudomonas: successful salvage therapy with cefepime-zidebactam. (PubMed, Trans R Soc Trop Med Hyg) - "A 15-y-old boy presented with 56% thermal burns, followed by skin and soft tissue infection, secondary bacteraemia, complicated parapneumonic effusion and endophthalmitis due to CRPa, which was not susceptible to any of the routinely available antibiotics. He was treated with cefepime-zidebactam for 45 d, with which he recovered."

Journal • Infectious Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Thermal Injury

Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations. (PubMed, Int J Mol Sci) - "Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response."

Journal • Review • Infectious Disease

Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (clinicaltrials.gov) - P3 | N=528 | Recruiting | Sponsor: Wockhardt | Trial completion date: May 2024 ➔ Dec 2024 | Trial primary completion date: Apr 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Infectious Disease • Nephrology

Spread of carbapenemase-producing Morganella spp from 2013 to 2021: a comparative genomic study. (PubMed, Lancet Microbe) - "This global characterisation of, to our knowledge, the widest collection of extensively drug-resistant Morganella spp highlights the need to clarify the taxonomy and decipher intrinsic resistance mechanisms, and paves the way for further genomic comparisons."

Journal • Infectious Disease

Population pharmacokinetic analyses of cefepime and zidebactam based on combined plasma-epithelial lining fluid data from healthy volunteers (ECCMID 2024) - No abstract available

Clinical • PK/PD data