Aztreonam in combination with imipenem-relebactam against clinical and isogenic strains of serine and metallo-beta-lactamase-producing enterobacterales

Objective: The objective of this study was to evaluate the in vitro activity of aztreonam plus imipenem-relebactam against clinical and isogenic strains of Escherichia coli and Klebsiella pneumoniae co-harboring NDM and >1 serine beta-lactamase. Methods: Thirteen isolates were included: 4 clinical E. coli, 4 clinical K. pneumoniae, and 5 isogenic E. coli. Drugs were tested in time-kill analyses alone, in dual beta-lactam combinations, and in triple drug combinations against all strains. Results: All isolates were resistant to imipenem and imipenem-relebactam, and 85% were aztreonam-resistant. Neither imipenem nor imipenem-relebactam was bactericidal alone while aztreonam was bactericidal against 54% of isolates. The combination of aztreonam+imipenem was bactericidal and synergistic against 7/13 and 10/13 isolates. The addition of relebactam to this combination resulted in synergy against all 11 aztreonam-resistant clinical isolates. Conclusion: Aztreonam plus imipenem-relebactam may be a viable treatment option for aztreonam-non-susceptible NDM and serine beta-lactamase-producing E. coli and K. pneumoniae. (c) 2022 Elsevier Inc. All rights reserved.