A multicenter performance evaluation of aztreonam-avibactam gradient diffusion susceptibility testing for...

Area of Science:

• Clinical Microbiology
• Antimicrobial Susceptibility Testing
• Infectious Diseases

Background:

• Aztreonam-avibactam (AZA) is a critical antibiotic for treating multidrug-resistant Gram-negative infections.
• Accurate antimicrobial susceptibility testing (AST) is essential for guiding AZA therapy.
• Previous AST methods for AZA were complex; the ETEST AZA gradient diffusion strip offers a streamlined approach.

Purpose of the Study:

• To evaluate the performance of the ETEST AZA gradient diffusion method against reference broth microdilution.
• To assess ETEST AZA accuracy using both U.S. Food and Drug Administration (FDA) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints.
• To determine the suitability of ETEST AZA for routine clinical microbiology laboratories.

Main Methods:

• Compared ETEST AZA gradient diffusion with broth microdilution for 650 Enterobacterales isolates (77 challenge, 573 clinical).
• Analyzed results using FDA and EUCAST interpretive criteria.
• Evaluated essential agreement (EA), categorical agreement (CA), very major errors (VME), major errors (ME), and minor errors (mE).

Main Results:

• Using FDA breakpoints: Combined isolates showed 95.7% EA, 98.0% CA, 0% VME, 0.2% ME, and 1.8% mE.
• Using EUCAST breakpoints: Combined isolates showed 94.3% EA, 98.9% CA, 0.2% ME, and 20.7% VME (attributed to breakpoint limitations).
• Reproducibility testing demonstrated 100% agreement within ±1 doubling dilution.

Conclusions:

• ETEST AZA provides accurate and reproducible susceptibility results for Enterobacterales.
• The method meets regulatory performance requirements when interpreted with FDA or EUCAST criteria.
• ETEST AZA is a practical and effective alternative for clinical laboratories performing AZA susceptibility testing.