In-vitro Evaluation of Synergy Testing of Ceftazidime-Avibactam-Aztreonam among Carbapenem-Resistant Gram-Negative Organisms

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The prevalence of severe infections due to Carbapenemase –resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) has increased worldwide. The treatment has become challenging and limited among the metallo-β-lactamases (MBLs) producing organisms due to the rise in polymyxin resistance. Due to the paucity of novel drugs, the ceftazidime-avibactam-aztreonam serves as a wonder drug combination for these infections. In 2024, Clinical and Laboratory Standards Institute (CLSI) approved broth disk elution method for synergy testing. This study was performed to evaluate the ceftazidime-avibactam-aztreonam synergy testing against the MBL-producing clinical isolates. We used a total of 34 archived multidrug-resistant organisms (MDROs) from the Microbiology department over a six-month period, from July to December 2023. All these isolates were subjected to modified carbapenem inactivation method (m CIM) and EDTA carbapenem inactivation method (e CIM) for phenotypic detection of carbapenemases. The ceftazidime-avibactam-aztreonam synergy testing was performed by two methods: Disk diffusion method and disk elution method among MBL-producing isolates. The study revealed that among the 34 MDR clinical isolates, 21 (62%) were MBL producers, followed by 5 (15%) Serine beta lactamase producers, 3 (9%) Indeterminate and 5(15%) were negative. MBL producers were subjected to two methods of synergy testing. Among 21 MBL-producing isolates, synergy was observed in 13 (38.2%) and no synergy was seen in eight (24%) isolates by both methods. There were no discrepant results. Detection of synergism for ceftazidime-avibactam-aztreonam combination can be determined by the disk diffusion method in a low-resource setting and thereby aid in clinical decision-making.

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