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

Introduction: Global detection of bacteria harboring metallo-β-lactamase (MBL) genes at an alarming speed coupled with no simultaneous increase in the antibiotics for treatment has made such infections a public health emergency.Newer antibiotics ceftazidime /avibactam plus aztreonam, cefiderocol are some of the alternative antibiotics available for clinical use.Though aztreonam remains stable against MBL producing Enterobacterales, there is often co-production of other enzymes such as extended spectrum β -lactamases, AmpC β-lactamases, serine βlactamases that can lead to aztreonam resistance.The combination of ceftazidime/avibactam and aztreonam is an attractive alternative, as the avibactam can inactivate the other β -lactamases to render the aztreonam active.Methods: The synergistic activity of ceftazidime /avibactam and aztreonam among aztreonam resistant strains was studied by Strip stacking method previously described.The results were expressed as numbers and percentages.Results: Out of the 50 isolates 43 (86%) were resistant to Aztreonam, while 5(10%) were found to be Intermediate and 2 (4%) were sensitive to Aztreonam.Ceftazidime /avibactam in combination with aztreonam showed synergistic effect in all 43 (100%) isolates that were resistant to aztreonam, the MIC of the ranging from <0.016 to 4 µg/ml.Discussion-Synergistic action between aztreonam and ceftazidime/avibactam restores the activity of aztreonam against MBL, as the avibactam, a novel β-lactam inhibitor has 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.