Multicenter evaluation of activity of aztreonam in combination with avibactam, relebactam, and vaborbactam against metallo-β-lactamase-producing carbapenem-resistant gram-negative bacilli

Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-β-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and <i>Stenotrophomonas maltophilia</i>. However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the <i>in vitro</i> activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and <i>S. maltophilia</i> using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and <i>S. maltophilia</i> (ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and <i>S. maltophilia</i> (ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and <i>S. maltophilia</i>, ATM-IMI-REL might be a reasonable alternative.