The NitroSpeed Taniborbactam NP test as a rapid test for detection of β-lactamase-mediated susceptibility to taniborbactam.

Abstract

Taniborbactam (TAN) is an investigational β-lactamase inhibitor in clinical development combined with cefepime for the treatment of bacterial infections caused by broad-spectrum β-lactamase-expressing bacteria. Its spectrum of inhibition encompasses all classes of β-lactamases, including clinically important metallo-β-lactamases (MBLs) NDM-1 and VIM-2. However, TAN lacks a significant inhibition of imipenemase-type β-lactamases. Rare TAN-resistant New Delhi metallo-β-lactamase (NDM) or Verona integron-encoded metallo-β-lactamase (VIM) variants (namely NDM-9, NDM-30, and VIM-83) have been identified. The NitroSpeed Taniborbactam NP test was developed to rapidly assess the β-lactamase inhibitory activity of TAN against various β-lactamases, particularly serving as an efficient tool for identifying compounds with potential activity against different types of MBLs. The test is based on the hydrolysis of (i) nitrocefin (to determine the presence or absence of β-lactamase), (ii) ertapenem (to confirm the presence or the absence of carbapenemase), and (iii) TAN (to assess whether the carbapenemase is inhibited by TAN). The test was validated using a collection of 134 genetically characterized clinical isolates (103 Enterobacterales and 31 Pseudomonas aeruginosa). The NitroSpeed Taniborbactam NP test is simple, easy to perform, and provides results within ≤15 min. When evaluated against a broad set of β-lactamases, the test demonstrated 100% sensitivity, specificity, and accuracy.