Melike Yaşar Duman, Mervenur Kanat, Elif Seren Tanrıverdi, Feriha Çilli, Şöhret Aydemir
Background: Carbapenem-resistant Enterobacterales (CRE) are a major therapeutic challenge, particularly in settings where metallo-β-lactamases are prevalent. Aztreonam-avibactam (AZA) may provide activity against metallo-β-lactamase-producing isolates, whereas ceftazidime-avibactam (CZA) has limited activity against the isolates that harbor these enzymes. This study aimed to evaluate the in vitro activity of aztreonam-avibactam and ceftazidime-avibactam against invasive carbapenem-resistant Enterobacterales isolates and to characterize the distribution of carbapenemase genes in a tertiary-care center in Türkiye. Methods: A total of 100 non-duplicate CRE isolates recovered from blood cultures and sterile body fluids between January 2024 and January 2026 were included. Species identification and routine antimicrobial susceptibility testing were performed using MALDI-TOF MS and an automated system. CZA and AZA MICs were determined by gradient diffusion testing, whereas CZA-aztreonam synergy was assessed separately using a disk/gradient diffusion-based method. Carbapenemase genes were detected by real-time PCR. Whole-genome sequencing was performed for the two AZA-resistant Escherichia coli isolates. Results: The isolate collection was dominated by Klebsiella pneumoniae (87.0%), and most isolates were recovered from blood cultures (80.0%). CZA susceptibility was observed in 31.0% of isolates, with MIC50/90 values of 256/256 mg/L. In contrast, AZA showed high in vitro activity, with 98.0% of isolates categorized as susceptible and MIC50/90 values of 0.25/0.50 mg/L. CZA-aztreonam synergy was detected in 98.0% of isolates. Qualitative CZA-aztreonam synergy testing did not fully concord with direct AZA MIC-based susceptibility categorization: one AZA-resistant isolate showed a positive synergy result, whereas one synergy-negative isolate remained AZA-susceptible. Carbapenemase genes were detected in 99.0% of isolates; blaNDM was the most frequent gene (81.0%), followed by blaOXA-48 (72.0%), blaKPC (14.0%), and blaVIM (4.0%). The most common carbapenemase profile was blaNDM + blaOXA-48 (62.0%). blaNDM carriage was strongly associated with CZA resistance, and CZA MICs were significantly higher among blaNDM-positive isolates. The two AZA-resistant E. coli isolates belonged to ST500 and ST410, and both carried a YRIK insertion in PBP3; one of them additionally showed ompF disruption associated with a 4 bp insertion. Conclusions: AZA demonstrated potent in vitro activity against invasive CRE isolates in this setting, whereas CZA activity was substantially limited, likely reflecting the high prevalence of blaNDM and frequent carbapenemase co-carriage. These findings support the potential value of AZA in regions with emerging metallo-β-lactamase predominance and highlight the importance of local molecular surveillance to guide antimicrobial strategies.