Determination of MIC Quality Control Ranges for Ceftibuten-Avibactam (Fixed 4 μg/mL), a Novel β-Lactam/β-Lactamase Inhibitor Combination

J Clin Microbiol. 2023 Jul 20;61(7):e0165722. doi: 10.1128/jcm.01657-22. Epub 2023 Jul 3.

Abstract

Ceftibuten/ARX-1796 (avibactam prodrug) is a novel oral antibacterial combination in early clinical development for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis. ARX-1796 is the novel avibactam prodrug being combined with ceftibuten for oral dosing that is converted to active avibactam in vivo. A Clinical and Laboratory Standards Institute (CLSI) M23 (2018) tier 2 broth microdilution quality control (QC) study was conducted with ceftibuten-avibactam to establish MIC QC ranges. Ceftibuten-avibactam broth microdilution QC ranges were approved for Escherichia coli ATCC 25922 (0.016/4 to 0.12/4 μg/mL), E. coli NCTC 13353 (0.03/4 to 0.12/4 μg/mL), Klebsiella pneumoniae ATCC 700603 (0.06/4 to 0.25/4 μg/mL), K. pneumoniae ATCC BAA-1705 (0.03/4 to 0.25/4 μg/mL), and K. pneumoniae ATCC BAA-2814 (0.12/4 to 0.5/4 μg/mL) by the CLSI Subcommittee on Antimicrobial Susceptibility Testing in January 2022. Approved ceftibuten-avibactam QC ranges will support future clinical development, device manufacturers, and routine patient care.

Keywords: M23; avibactam; ceftibuten; quality control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Ceftibuten
  • Escherichia coli
  • Humans
  • Klebsiella pneumoniae
  • Lactams
  • Microbial Sensitivity Tests
  • Prodrugs*
  • Quality Control
  • beta-Lactamase Inhibitors* / pharmacology
  • beta-Lactamase Inhibitors* / therapeutic use
  • beta-Lactamases

Substances

  • Ceftibuten
  • beta-Lactamase Inhibitors
  • avibactam
  • Lactams
  • Prodrugs
  • Anti-Bacterial Agents
  • beta-Lactamases