Dual Mechanism of Action
A novel β-lactam enhancer combination
ZAYNICH™ is the first U.S.-approved antibacterial combination of:
- Zidebactam, which selectively targets PBP2 and provides β-lactamase inhibition
- Cefepime, a 4th generation cephalosporin which targets PBP1 and PBP3
In vitro activity does not necessarily correlate with clinical efficacy results.
The ZAYNICH™ difference
A multi-targeted approach that helps to overcome both enzymatic and non-enzymatic resistance mechanisms
- Synergistically targets multiple penicillin-binding proteins (PBP1a/b, 2 and 3)
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How ZAYNICH™ helps overcome resistance
Helping overcome porin downregulation
Down regulation of porin channels by Gram-negative bacteria is a common resistance mechanism that challenges β-lactam antibiotic effectiveness.
By using a synergistic and multi-targeted approach, ZAYNICH™ addresses multiple PBPs and may overcome this typical resistance strategy.
Helping overcome β-lactamase hyperproduction
Another common bacterial resistance strategy is β-lactamase hyperproduction, which is used to break open the β-lactam structure of antibiotics. Zidebactam inhibits certain class A and class C serine β-lactamases, including KPC, CTX-M and CMY. The complementary mechanisms and PBP2 enhancer activity helps ZAYNICH™ retain activity in the presence of these resistant pathogens. Zidebactam is a non-β-lactam and is less susceptible to degradation by clinically challenging β-lactamases including MBLs.
Helping address alterations in penicillin-binding proteins (PBPs)
PBPs are bacterial enzymes that build and maintain the cell wall. Traditional β-lactam antibiotics work by binding to these proteins and disrupting cell-wall construction, eventually causing bacterial death. Bacteria have acquired mutations and developed non-enzymatic resistance mechanisms that cause structural changes in a PBP. These alterations reduce the drug’s ability to bind to the PBP and allow cell-wall construction to continue despite antibiotic exposure.
ZAYNICH™ attacks cell-wall synthesis through two complementary targets: cefepime primarily targets PBP3, and zidebactam binds with high affinity to PBP2. Inhibiting both PBPs simultaneously produces complementary morphological effects; ultimately, making it harder for a bacterium to survive through an alteration affecting only one pathway.
In vitro activity does not necessarily correlate with clinical efficacy results.
References: 1. ZAYNICH (cefepime and zidebactam) US Prescribing Information. Wockhardt Bio AG; 2026. 2. Moya B, Barcelo IM, Bhagwat S, et al. WCK 5107 (zidebactam) and WCK 5153 are novel inhibitors of PBP2 showing potent "β-lactam enhancer" activity against Pseudomonas aeruginosa, including multidrug-resistant metallo-β-lactamase-producing high-risk clones. Antimicrob Agents Chemother. 2017;61(6):e02529-16. doi:10.1128/AAC.02529-16 3. Papp-Wallace KM, Nguyen NQ, Jacobs MR, et al. Strategic approaches to overcome resistance against gram-negative pathogens using β-lactamase inhibitors and β-lactam enhancers: activity of three novel diazabicyclooctanes WCK 5153, zidebactam (WCK 5107), and WCK 4234. J Med Chem. 2018;61(9):4067-4086. doi:10.1021/acs.jmedchem.8b00091 4. Rajavel M, Kumar V, Nguyen H, et al. Structural characterization of diazabicyclooctane β-lactam "enhancers" in complex with penicillin-binding proteins PBP2 and PBP3 of Pseudomonas aeruginosa. mBio. 2021;12(1):e03058-20. doi:10.1128/mBio.03058-20 5. Bhavsar S, Joshi S, Pawar S, et al. Structure activity relationship (SAR) driven design and discovery of WCK 5107 (zidebactam): novel β-lactam enhancer, potent against multidrug-resistant gram-negative pathogens. Med Chem Res. 2023;32(10):2245-2255. 6.Pan X, Zhao X, Song Y, et al. Molecular characterization of WCK 5222 (cefepime/zidebactam)-resistant mutants developed from a carbapenem-resistant Pseudomonas aeruginosa clinical isolate. Microbiol Spectr. 2022;10(1):e0267821. doi:10.1128/spectrum.02678-21 7. Pucci MJ, Boice-Sowek J, Kessler RE, Dougherty TJ. Comparison of cefepime, cefpirome, and cefaclidine binding affinities for penicillin-biding proteins in Escherichia coli K-12 and Pseudomonas aeruginosa SC8329. Antimicrob Agents Chemother. 1991;35(11):2312-2317. doi:10.1128/AAC.35.11.2312 8. Reygaert WC. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol. 2018;4(3):482-501. doi:10.3934/microbiol.2018.3.482 9. Moya B, Bhagwat S, Cabot G, Bou G, Patel M, Oliver A. Effective inhibition of PBPs by cefepime and zidebactam in the presence of VIM-1 drives potent bacterial activity against MBL-expressing Pseudomonas aeruginosa. J Antimicrob Chemother. 2020;75(6):1474-1478. doi:10.1093/jac/dkaa036