Zidebactam is a penicillin-binding protein 2 (PBP2) inhibitor and β-lactam antibiotic enhancer.1 It inhibits P. aeruginosa PBP2 (IC50 = 0.26 ?g/ml) and is selective for PBP2 over PBP1a, -1b, -3, -4, and -5/6 (IC50s = >4 ?g/ml for all). Zidebactam enhances the bactericidal activity of cefepime against multidrug-resistant strains of P. aeruginosa, as well as against E. coli, Klebsiella, Enterobacter, S. marcescens, and A. baumannii.2 In vivo, zidebactam enhances cefepime-induced reductions in bacterial loads in mouse models of K. pneumoniae-induced peritonitis and thigh infection.3 Formulations containing zidebactam in combination with cefepime have been used in the treatment of various bacterial infections.
1.Moya, B., Barcelo, I.M., 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 clonesAntimicrob. Agents Chemother.61(6)e02529-02516(2017) 2.Sader, H.S., Rhomberg, P.R., Flamm, R.K., et al.WCK 5222 (cefepime/zidebactam) antimicrobial activity tested against Gram-negative organisms producing clinically relevant β-lactamasesJ. Antimicrob. Chemother.72(6)1696-1703(2017) 3.Moya, B., Barcelo, I.M., Cabot, G., et al.In vitro and in vivo activities of β-lactams in combination with the novel β-lactam enhancers zidebactam and WCK 5153 against multidrug-resistant metallo-β-lactamase-producing Klebsiella pneumoniaeAntimicrob. Agents Chemother.63(5)e00128-00119(2019)