Evaluation of Cefepime-Taniborbactam Activity

MIC values were determined using the CLSI broth microdilution reference method with concurrent quality control (30 , 31 ). Taniborbactam was provided by Venatorx Pharmaceuticals, Inc. (Malvern, PA, USA) and tested at a fixed concentration of 4 μg/mL with cefepime (31 ). Other agents were purchased from commercial sources. Broth microdilution panels were prepared at IHMA using cation-adjusted Mueller Hinton broth (CAMHB; Becton, Dickinson) and stored at −70°C until the day of testing.
MICs were interpreted using 2021 CLSI breakpoints (31 ) with two exceptions. Meropenem-vaborbactam MICs for P. aeruginosa were interpreted using EUCAST breakpoints (≤8 μg/mL, susceptible; >8 μg/mL, resistant) (32 ). Cefepime-taniborbactam MICs against both Enterobacterales and P. aeruginosa were interpreted using provisional breakpoints of ≤16 μg/mL (susceptible) and >16 μg/mL (resistant) that were based upon published in vivo efficacy data from neutropenic murine infection models (thigh, complicated urinary tract) (33 (link), 34 (link)) and data from a safety and pharmacokinetics studies in human volunteers (35 (link), 36 (link)). These provisional breakpoints are also supported by probability of taniborbactam target attainment analyses based on simulation of human plasma exposures (J. Dowell, unpublished data).