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Comparative evaluation of practical in-vitro methods for testing synergy between ceftazidime-avibactam and aztreonam against metallo-β-lactamase and serine carbapenemase-producing Enterobacterales species
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DOI：10.1016/j.ijmmb.2026.101073.png)
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Abstract
En 中文
Background: The emergence of multidrug-resistant (MDR) strains, including those producing metallo-beta-lactamases (MBL), necessitates the development of effective therapeutic strategies. The combination of ceftazidimeavibactam (CZA) and aztreonam (ATM) has shown promise as a potential treatment option. This study aimed to evaluate practical and accessible antimicrobial susceptibility testing (AST) methods for assessing the synergy of CZA and ATM in carbapenemase-producing Enterobacterales species, particularly in resource-limited settings with high patient volumes. Methods: This cross-sectional study was conducted at a tertiary care hospital in Central India from October 2023 to July 2024. It compared different synergy testing methods to the gold-standard broth microdilution (BMD) method in genotypically confirmed carbapenemase-producing isolates. The study evaluated various synergy methods, such as the E-strip, disk replacement, inverse D-zone, and disk approximation. Results: Of the 60 Enterobacterales isolates, most carried the blaNDM gene (88.33%, 53/60). Using the BMD method, 73.33% (44/60) of the isolates showed synergy between CZA and ATM. The E-strip method was found to have almost perfect agreement (x = 1) with BMD, making it highly reliable. However, it may be impractical for high-volume laboratories due to cost and complexity. On the other hand, the disk replacement and inverse Dzone methods demonstrated high sensitivity and specificity, with perfect (x = 0.874) and substantial (x = 0.803) agreement with BMD, respectively, providing more practical and cost-effective alternatives. However, the disk approximation method showed lower sensitivity and moderate agreement with BMD (x = 0.510), making it less reliable. Conclusion: The combination of CZA and ATM demonstrated significant synergistic results in MBL and serine carbapenemase-producing Enterobacterales species. The disk replacement and inverse D-zone methods are feasible and cost-effective for CZA and ATM synergy testing in routine AST within resource-limited settings, guiding treatment decisions.
Keywords:
Aztreonam
Carbapenemase
Ceftazidime-avibactam
Enterobacterales
Synergy
Journal
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