Synergistic effect of ceftazidime-avibactam and aztreonam combination against carbapenem resistant Klebsiella spp., E.coli and Pseudomonas spp.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) represents an escalating threat to global public health due to its resistance to last-resort of antibiotics. One potential treatment strategy to combat these resistant microorganisms is the combination therapy like ceftazidime-avibactam (CZA) and aztreonam (ATM). The study evaluated the in vitro activity of the CZA-ATM combination against 156 CR-GNB including Klebsiella spp., Escherichia coli (E. coli), and Pseudomonas spp. using E-strip disk diffusion, broth disk elution (BDE), and disk stacking plus micro-elution (DSE) method at the Department of Microbiology & Immunology, Bangladesh Medical University (BMU), Bangladesh. Among the 156 isolates, Klebsiella spp. was the most prevalent (62.8 %), followed by Pseudomonas spp. (30.1 %) and E. coli (7.1 %). Of these, 52.6 % (82/156) were identified as carbapenemases producers. The mCIM and eCIM methods identified 23 (28.1 %) as serine carbapenemases and 59 (71.9 %) as metallo β-lactamases (MBL) producers. Resistance rates for CZA and ATM were 74.4 % and 94.2 % respectively. The E-strip disk diffusion method showed susceptibility in 65.52 % of isolates, while the BDE and DSE methods demonstrated susceptibility in 54.31 % and 58.62 %, respectively. Resistance to the CZA-ATM combination was notably high in Pseudomonas spp., likely due to non-carbapenemases mechanisms like efflux pump activity or porin mutations. Compared to the E-strip disk diffusion method, BDE method showed an agreement of 78.4 %, while DSE method exhibited an agreement of 89.7 %. The in vitro evaluation of the CZA-ATM combination highlights its potential as a therapeutic option for treating carbapenemase producing organisms.