A Study on Ceftazidime/Avibactam and Aztreonam Synergy Among Aztreonam-resistant Metallo-β-lactamase Producing Enterobacterales in a Tertiary Care Hospital

Abstract

Introduction: Global detection of bacteria harboring metallo-β-lactamase (MBL) genes has increased at an alarming rate. However, there is no concurrent increase in available antibiotics for treatment, which has turned these infections into a public health emergency. Newer antibiotics, such as ceftazidime/avibactam in combination with aztreonam and cefiderocol, constitute alternative options available for clinical use. While aztreonam remains stable against MBL-producing Enterobacterales, there is often concurrent production of other enzymes, such as extended-spectrum β-lactamases, AmpC β-lactamases, and serine carbapenemases, which can result in aztreonam resistance. The combination of ceftazidime/avibactam and aztreonam is an appealing alternative, as avibactam can deactivate other β-lactamases, thereby activating aztreonam. Materials and Methods: The synergistic activity between ceftazidime/avibactam and aztreonam in aztreonam-resistant strains was investigated using the strip stacking method previously described. The findings are presented as numbers and percentages. Results: Out of the 50 isolates, 43 (86%) demonstrated resistance to aztreonam, five (10%) were classified as intermediate, and two (4%) were sensitive to aztreonam. Aztreonam and ceftazidime/avibactam demonstrated a synergistic effect in all 43 (100%) isolates resistant to aztreonam. Synergistic action between aztreonam and ceftazidime/avibactam restores the activity of aztreonam against MBL. Avibactam, a novel β-lactam inhibitor, extends potent activity against class A β-lactamases and AmpC determinants. Conclusion: This study demonstrated 100% synergistic activity between aztreonam and ceftazidime/avibactam among MBL-producing Enterobacterales.

Keywords

• carbapenemase
• e-strip
• mbl
• strip stacking