Aztreonam-Avibactam Susceptibility Testing 

Aztreonam-Avibactam is a combination antimicrobial agent consisting of aztreonam, a monobactam antibiotic, and avibactam, a non-β-lactam β-lactamase inhibitor. This combination is particularly effective against metallo-β-lactamase (MBL)-producing Gram-negative bacteria, which hydrolyze most β-lactam antibiotics, including carbapenems, but lack hydrolytic activity against monobactams.

Testing Methods and Standards

The susceptibility of aztreonam-avibactam is assessed using various standardized methodologies, including:

• Broth Microdilution (BMD) Method:
  • Considered the gold standard for aztreonam-avibactam testing.
  • Typically performed using cation-adjusted Mueller-Hinton broth (CAMHB) with a fixed concentration of avibactam (4 mg/L) and serial dilutions of aztreonam.
• Disk Diffusion Method:
  • Uses a 30-μg aztreonam disk supplemented with 4 μg/mL avibactam.
  • Zones of inhibition are measured and correlated with MIC values.
• Gradient Strip (Etest) Method:
  • Utilizes a strip with a concentration gradient of aztreonam in the presence of avibactam.
  • MIC values are determined by the point where bacterial growth intersects the strip.

Application and Clinical Relevance

• Treatment of MBL-Producing Enterobacterales and Pseudomonas aeruginosa:
  • Aztreonam-avibactam is highly effective against MBL-expressing strains (e.g., NDM, VIM, IMP-type carbapenemases), which are resistant to most β-lactams.
• Surveillance of Emerging Resistance Patterns:
  • Regular susceptibility testing helps in monitoring resistance evolution, particularly avibactam resistance due to porin mutations or efflux pump overexpression.
• Guiding Antimicrobial Stewardship Programs:
  • Enables targeted therapy selection for multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative infections.

Aztreonam-avibactam represents a critical advancement in the treatment of MBL-mediated resistance among Gram-negative pathogens. Accurate and standardized susceptibility testing methodologies are essential for guiding its use, monitoring resistance trends, and improving patient outcomes.