In vitro activity of ceftazidime-avibactam in combination with aztreonam against carbapenem resistant Enterobacterales isolated from intensive care units

Abstract

Background : Carbapenem-resistant (CR) Enterobacterales are established causes of serious healthcare-associated infections. Development of new β-lactam/β-lactamase inhibitors was a breakthrough, but effective antibiotic treatment for metallo-β-lactamase (MBL) producers remained an unmet need. Ceftazidime-avibactam (CZA) combination with aztreonam (ATM) is an emerging option to combat these bugs. Aim: The aim of the study was to evaluate the in vitro activity of ceftazidime-avibactam alone and in combination with aztreonam on CR Enterobacterales isolates from intensive care unit (ICU) patients Methods: A total of 258 Enterobacterales were recovered from patients admitted to ICUs and screened for carbapenem resistance. CR isolates were subjected to antimicrobial susceptibility testing and molecular detection of the five major carbapenemase genes (blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP) using polymerase chain reaction (PCR). In vitro activity of ceftazidime-avibactam and aztreonam combination was evaluated using broth disk elution method. Results: One hundred and twenty (46.5%) of the 258 Enterobacterales isolates were carbapenem resistant. All were also multi-drug resistant (MDR) exhibiting resistance to most antibiotics. MBL producers were the predominant (76.7%). Susceptibility to ceftazidime-avibactam and aztreonam combination was higher in MBL producing group (59/ 92, 64.1%), all were CZA resistant, while the addition of ATM didn’t demonstrate an advantage over CZA alone in MBL non producers. Conclusion: A high rate of CZA resistance was observed among CR Enterobacterales in our ICUs. The molecular mechanisms behind this resistance need to be studied. CZA-ATM combination can be considered for treating MBL producers but only after susceptibility testingز