Spectrum of Beta-Lactamase Inhibition by the Cyclic Boronate QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases: Enhancement of Activity of Multiple Antibiotics against Isogenic Strains Expressing Single Beta-Lactamases
Olga Lomovskaya, Ruslan Tsivkovski, Kirk Nelson, Debora Rubio-Aparicio, Dongxu Sun, Maxim Totrov, Michael N. Dudley
Abstract
QPX7728 is an ultrabroad-spectrum boronic acid beta-lactamase inhibitor, with potent inhibition of key serine and metallo-beta-lactamases being observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MICs of multiple antibiotics administered intravenously only (ceftazidime, piperacillin, cefepime, ceftolozane, and meropenem) and orally bioavailable antibiotics (ceftibuten, cefpodoxime, tebipenem) alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against panels of laboratory strains of Pseudomonas aeruginosa and Klebsiella pneumoniae expressing over 55 diverse serine and metallo-beta-lactamases.