Evaluation of Ceftazidime-Avibactam Susceptibility in Carbapenem-Resistant Gram-Negative Bacteria

Objective: Resistance to carbapenem antibiotics, commonly preferred to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, is gradually increasing. Ceftazidime-avibactam (CZA) is a novel beta-lactam/beta-lactamase inhibitor combination, proposed as an alternative treatment option for severe infections caused by carbapenem-resistant Gram-negative bacteria. This study aimed to determine the susceptibility of carbapenem-resistant Klebsiella pneumoniae (CR-KP), carbapenem-resistant Escherichia coli (CR-EC), and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) isolates to CZA using the Kirby-Bauer disk diffusion method (DDM) and the BD Phoenix automated system, and to compare the results. Material and Method: A total of 320 strains (209 CR-KP, 53 CR-EC, and 58 CR-PA) resistant to at least one carbapenem (ertapenem, imipenem, and meropenem), collected between August 2021 and August 2023, were included in the study. CZA susceptibility testing was performed using the DDM and the CPO detect panel of the BD Phoenix automated system (Becton Dickinson, USA). Results were interpreted in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. Results: While CZA susceptibility rates determined by the automated system were 74.1% for CR-KP, 64.5% for CR-EC, and 90.9% for CR-PA, the DDM method yielded susceptibility rates of 87.8% for CR-KP, 94.4% for CR-EC, and 81.3% for CR-PA. Categorical agreement was observed in 86.9% of 115 isolates tested by both methods. Although not statistically significant, a declining trend in CZA susceptibility was observed over the years with both methods. Conclusion: CZA susceptibility rates among carbapenem-resistant Gram-negative isolates in our hospital were consistent with current global data. Determining accurate CZA susceptibility results is important for guiding effective treatment strategies against infections caused by carbapenem-resistant bacteria. The observed discrepancies in susceptibility results between the DDM and the automated system, particularly across different species, underscore the need for further species-specific studies to identify the most reliable testing methodology for CZA susceptibility.