Rapid Aztreonam/Avibactam NP test for detection of aztreonam/avibactam susceptibility/resistance in Enterobacterales

J Clin Microbiol. 2023 Oct 24;61(10):e0058823. doi: 10.1128/jcm.00588-23. Epub 2023 Oct 4.

Abstract

Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination, is a treatment option for infections due to carbapenem-resistant Enterobacterales (CRE), including metallo-ß-lactamase producers, regardless of additional production of broad-spectrum serine-ß-lactamases. However, AZA-resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster and more accurate clinical decision-making. We therefore developed a rapid culture-based test for the identification of AZA resistance among multidrug-resistant Enterobacterales. The Rapid Aztreonam/Avibactam NP test is based on resazurin reduction when bacterial growth occurs in the presence of AZA at 8/4 µg/mL (protocol 1) or 12/4 µg/mL (protocol 2). Given the absence of guidelines on AZA susceptibility testing, two tentative breakpoints were indeed used to categorize AZA-susceptible isolates: ≤4 µg/mL in protocol 1 and ≤ 8 µg/mL in protocol 2. Bacterial growth was visually detectable by a blue-to-purple or blue-to-pink color change of the medium. A total of 78 enterobacterial isolates (among which 34 AZA-resistant and 13 AZA-resistant according to protocols 1 and 2, respectively) were used to evaluate the test performance using protocol 1 or protocol 2. The sensitivity and specificity of the test were found to be 100% and 97.7%, respectively, following protocol 1 and 100% and 100%, respectively, following protocol 2, in comparison with broth microdilution. All results were obtained within 4.5 hours corresponding to a time saving of ca. 14 hours compared with currently available methods for AZA susceptibility testing. The Rapid Aztreonam/Avibactam NP test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine.

Keywords: Aztreonam-avibactam; Enterobacterales; diagnostics; monobactam; rapid; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Azabicyclo Compounds / pharmacology
  • Aztreonam* / pharmacology
  • Ceftazidime / pharmacology
  • Drug Combinations
  • Humans
  • Microbial Sensitivity Tests
  • beta-Lactamase Inhibitors / therapeutic use
  • beta-Lactamases

Substances

  • Aztreonam
  • Anti-Bacterial Agents
  • avibactam
  • beta-Lactamases
  • Azabicyclo Compounds
  • beta-Lactamase Inhibitors
  • Drug Combinations
  • Ceftazidime