In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases

Objectives: Infections caused by carbapenemase-producing Gram-negative pathogens have become a significant global public health challenge due to limited treatment options. Pathogens producing metallo-β-lactamase are particularly problematic since they are not inhibited by conventional β-lactamase inhibitors. Herein, we assess the in vitro activity of aztreonam in combination with relebactam against a collection carbapenemase producing organisms, including strains producing both serine‑β-lactamase and IMP-type metallo-β-lactamase that are commonly encountered in Japan. Methods: A total of 119 carbapenemase-producing clinical isolates were used in this study. Minimum inhibitory concentrations (MICs) of aztreonam and imipenem alone and aztreonam/relebactam, aztreonam/avibactam and imipenem/relebactam combinations were determined by the broth microdilution method. Results: Aztreonam MICs were reduced in combination with relebactam for strains producing ESBL or AmpC in addition to IMP-type, NDM-type, GES-type or OXA-48 carbapenemases and for Stenotrophomonas spp. Additionally, aztreonam/relebactam combination MICs were significantly lower than MICs of aztreonam alone among IMP producers, NDM producers and Stenotrophomonas spp. Significant differences between aztreonam/relebactam and aztreonam MICs were also observed for strains of E. coli, K. pneumoniae and Enterobacter spp., many of which produced both metallo-β-lactamase and serine‑β-lactamase. The aztreonam/relebactam combination showed comparable to higher MICs compared with the aztreonam/avibactam combination. Conclusion: The addition of relebactam has a potential to restore the activity of aztreonam against strains that produce metallo-β-lactamase and serine‑β-lactamase. The combination may have a role in the treatment of infections due to these strains in countries without access to ceftazidime-avibactam.