Combating Carbapenem-Resistant Enterobacterales: Comparative In Vitro Efficacy of Aztreonam–Avibactam and Ceftazidime–Avibactam and Distribution of Carbapenemase Genes
Makaleler > Tam Makale · 2026
Yazarlar: Melike Yaşar Duman, Mervenur Kanat, Elif Seren Tanrıverdi, Fatma Feriha ÇİLLİ, Şöhret Aydemir
Antibiotics, Uluslararası, Wos, 2026, cilt 15, ss 724-724
DOI: 10.3390/antibiotics15080724
Özet
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.