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 Stenotrophomonas maltophilia. However, data on ATM in combination with Other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the in vitro activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and S. maltophilia using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and S. maltophilia (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 S. maltophilia (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 S. maltophilia, ATM-IMI-REL might be a reasonable alternative.

Enterobacteriaceae; Stenotrophomonas; antibiotic resistance; antimicrobial combinations; gram-negative bacteria; β-lactamases.