In vitro activity of ceftazidime-avibactam/aztreonam combination against MBL-producing Pseudomonas aeruginosa strains

The emergence of multidrug-resistant P. aeruginosa isolates poses a challenge to healthcare systems worldwide. Rising numbers in deaths, duration of hospitalization as well as failing treatments prove the hazards posed by these pathogens. This and the lack of promising therapeutic options highlight the urgency of antibiotic drug development. As interim solution or alternative to the development of new antibiotic drugs, investigation of novel combinations of existing antibiotic drugs can be an economic and swift approach. Therefore, this study addresses the evaluation of in vitro activity of the antibiotic combination of ceftazidime-avibactam/aztreonam against MBL-producing P. aeruginosa strains. We tested 153 isolates from six university hospitals via microdilution against their susceptibility to meropenem, aztreonam, ceftazime-avibactam and the minimal inhibitory concentration of the combination of ceftazidime-avibactam/aztreonam. 64 isolates produced carbapenemases of which 61 were VIM-, 2 NDM- and 1 OXA-producer. We were able to show that the synergetic effects of this regimen with an avibactam concentration of 4 mg/l and an aztreonam concentration of 16 mg/l could successfully lower the number of MBL-producing isolates that showed a high minimal inhibitory concentration compared to a carbapenemase-negative control group in vitro. The antibiotic combination consisting of ceftazidime-avibactam/aztreonam represents a possible approach to the treatment of patients infected with multidrug-resistant P. aeruginosa isolates.