Open AccessSpectrum 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
Author(s) -
Olga Lomovskaya,
Ruslan Tsivkovski,
Kirk Nelson,
Debora Rubio-Aparicio,
Dongxu Sun,
Maxim Totrov,
Michael N. Dudley
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00212-20
Subject(s) - microbiology and biotechnology , piperacillin , klebsiella pneumoniae , cefepime , beta lactamase inhibitors , antibiotics , meropenem , beta lactamase , serine , pseudomonas aeruginosa , ceftazidime , imipenem , chemistry , beta (programming language) , biology , bacteria , biochemistry , enzyme , escherichia coli , antibiotic resistance , gene , programming language , computer science , genetics
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.