Comparison of testing methods assessing the in vitro efficacy of the combination of aztreonam with avibactam on multidrug-resistant Gram-negative bacilli

Ann Clin Microbiol Antimicrob. 2024 May 25;23(1):47. doi: 10.1186/s12941-024-00708-0.

Abstract

Background: Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches.

Methods: 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher).

Results: According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%).

Conclusions: The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.

Keywords: Antibiotic combination; Antibiotic susceptibility testing; Carbapenemase; Metallo-β-lactamase; Aztreonam-avibactam.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Azabicyclo Compounds* / pharmacology
  • Aztreonam* / pharmacology
  • Bacterial Proteins
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial*
  • Enterobacteriaceae / drug effects
  • Gram-Negative Bacteria* / drug effects
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests* / methods
  • Pseudomonas aeruginosa / drug effects
  • beta-Lactamases / metabolism

Substances

  • Aztreonam
  • Azabicyclo Compounds
  • Anti-Bacterial Agents
  • avibactam
  • Drug Combinations
  • beta-Lactamases
  • Bacterial Proteins
  • carbapenemase