Assessment of broth disk elution method for aztreonam in combination with ceftazidime/avibactam against Enterobacterales isolates

Abstract

ABSTRACT The combination of aztreonam with ceftazidime/avibactam is considered a potential therapeutic approach for the treatment of infections caused by metallo-β-lactamase (MBL)-producing isolates. In this study, in vitro antibacterial activity of aztreonam with avibactam against 204 carbapenemase-producing Enterobacterales was determined by broth disk elution (BDE) method of two detection volumes (5- and 2-mL broth), with broth microdilution (BMD) method as a reference. For the BDE-5mL test, the categorical agreement (CA) of ATM+CZA-lo tube (aztreonam/ceftazidime/avibactam: 6/6/4 mg/L) was 99.5%, with 0.5% major error (ME) and 0% very major error (VME); the CA of 2ATM+CZA-lo tube (12/6/4 mg/L) was 100%, with no ME and VME. For the BDE-2mL test, the CA of ATM+2CZA-hi tube (15/10/4 mg/L) was 98.5%, with 0% ME and 37.5% VME; the CA of 2ATM+2CZA-hi tube (30/10/4 mg/L) was 97.1%, with 0% ME and 75% VME. The BDE-5 mL test is an economical and practical method for clinical microbiology laboratories to determine the antibacterial susceptibility of aztreonam with avibactam against Enterobacterales, especially the 2ATM+CZA-lo tube with a final concentration of 12/6/4 mg/L of aztreonam/ceftazidime/avibactam.IMPORTANCEInfections caused by metallo-β-lactamase (MBL)-producing Enterobacterales are increasingly reported worldwide, and it is a significant challenge for clinical infection treatment. MBLs are adept at hydrolyzing almost all traditional β-lactam antibiotics except aztreonam, and the enzyme activity cannot be inhibited by traditional or novel β-lactamase inhibitors. The good thing is that the combination of aztreonam with ceftazidime/avibactam has been proven to be one of the potential therapeutic approaches for treating infections related with MBL-producing isolates. Broth microdilution (BMD) method is recommended as a reference method for its accuracy, but it is too complex to perform in most routine laboratories. Finding a more convenient, practical, and accurate susceptibility testing method for aztreonam/avibactam in clinical microbiology laboratories is very necessary. Here, we evaluated the performance of broth disk elution (BDE) method for aztreonam in combination with ceftazidime/avibactam against Enterobacterales isolates, with BMD as a reference.

Keywords

• Enterobacterales
• aztreonam
• ceftazidime/avibactam
• antimicrobial susceptibility testing
• broth disk elution method