Nacubactam

Nacubactam (OP0595 free acid) is a potent non-β-lactam-β-lactamase inhibitor with activity against class A and C β-lactamases. Nacubactam acts as a penicillin binding protein (PBP) 2-active antibacterial, and gives β-lactamase-independent potentiation of β-lactams targeting other PBPs. Nacubactam potentiates the antimicrobial activities of Piperacillin (HY-B1923), Cefepime (HY-B0692), and Meropenem (HY-13678) against CTX-M-15-positive Escherichia coli and KPC-positive Klebsiella pneumoniae^{[1][2][3][4][5][6]}. IC50 & Target:non-β-lactam-β-lactamase^[1] In Vitro:Nacubactam (4 μg/mL) can reduce the minimum inhibitory concentrations (MICs) of Piperacillin (HY-B1923), Cefepime (HY-B0692), and Meropenem (HY-13678) against CTX-M-15-positive Escherichia coli and KPC-positive Klebsiella pneumoniae, enhancing the antibacterial activity^[1].
Nacubactam shows MICs ranging from 1 to >256 μg/mL against 11 Gram-negative isolates^[2].
Nacubactam (8 μg/mL) can reduce the MIC₅₀ of Meropenem by 8-fold, making all isolates susceptible or intermediately susceptible to Meropenem^[4].
Nacubactam can inhibit Carbapenem-resistant Klebsiella pneumoniae producing KPC and restore the antibacterial activity of Meropenem^[5].
In Vivo:Nacubactam (2.5 mg/kg; s.c.; administered once at 1, 3, and 5 h after infection), when combined with Cefepime, can significantly reduce the bacterial load of CTX-M-15-positive Escherichia coli and KPC-positive Klebsiella pneumoniae in a neutropenic murine thigh infection model^[1].
Nacubactam (10-80 mg/kg; s.c.; administered every 8 h), when combined with Meropenem, shows the greatest in-vivo efficacy against 9 out of 10 Gram-negative isolates in a neutropenic murine complicated urinary tract infection model, reducing the bacterial load by 3 log from the 48-h control^[2].