Version 3: Analysis of a simple disk diffusion method to evaluate Ceftazidime-avibactam/Aztreonam combination synergism against NDM clinical isolates.

The rise of multidrug resistant Enterobacterales and Pseudomonas aeruginosa has diminished the reliability of conventional antibiotics for treating MDR infections. The combination of Ceftazidime-avibactam with Aztreonam  has demonstrated  in-vitro synergism against multidrug resistant organisms, notably metallo-beta-lactamase producing strains. Treatment with Ceftazidime-avibactam/Aztreonam combination may provide a clinical benefits for patients with multidrug resistant bacterial infection. The present study aimed to detect genes encoding carbapenem resistance in clinical strains and to determine the efficacy of ceftazidime-avibactam/Aztreonam against carbapenemase co-producers. A  cross-sectional  research was done on 62 carbapenem resistant clinical isolates collected from November 2022 to February 2024. Ceftazidime-avibactam/Aztreonam synergy against 55 carbapenemase producers (NDM, IMP, VIM & OXA-48) was determined using disk diffusion method. Data analysis was done by Chi-square test. Ceftazidime-avibactam/Aztreonam synergy was identified  against 25 (64.1%) out of 39 isolates exhibiting the NDM gene, 7 (77.8%) out of 9 isolates that were  co-producers of NDM and OXA-48 genes, 2 (50%) out of 4 isolates co- producing  NDM and VIM carbapenemase gene and a single isolate (33.3%) out of 3 isolates with NDM, VIM and OXA-48 genes. A wide zone of   3-23 mm diameter was observed for Enterobacterales and 6-7mm for P. aeruginosa with Ceftazidime-avibactam/Aztreonam in relative to Ceftazidime-avibactam and Aztreonam disk when tested alone. More than  30% isolates showed a statistically significant difference in  zone diameter for Ceftazidime-avibactam/Aztreonam combination (p value:<0.05), when compared to the zone size for Ceftazidime-avibactam and Aztreonam disk when tested alone. The present study showed  the in-vitro effectiveness of the Ceftazidime-avibactam/Aztreonam combination against 63.6% carbapenem resistant isolates studied. Disc diffusion method requires less technical expertise, and the test result aid in  identifying   true clinical synergy by observing the widening of the zone diameter that exceeds the Aztreonam susceptibility breakpoint.