Synergism of eravacycline combined with other antimicrobial agents against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii

Objectives: This study aimed to investigate the synergistic activity of eravacycline combined with other antimicrobial agents against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii collected from China. Methods: Sixty carbapenem-resistant strains, including 20 Escherichia coli, 20 Klebsiella pneumoniae, and 20 Acinetobacter baumannii were investigated for the synergy analysis. Imipenem, ceftazidime, cefoperazone-sulbactam, ciprofloxacin, amikacin, and polymyxin B were selected to investigate their efficacy in combination with eravacycline against 60 carbapenem-resistant strains. Minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution method. The efficacy of eravacycline in combination with these agents was determined by the chequerboard method. Results: Antimicrobial susceptibility testing revealed that polymyxin B was most effective against all carbapenem-resistant strains, with resistance rates between 0% and 15%. Eravacycline showed potent activity against E. coli with an 85% susceptibility rate, and may also have activity against K. pneumoniae and A. baumannii with low MIC90 values. The chequerboard method showed that eravacycline-polymyxin B was the most effective combination against E. coli and K. pneumoniae, with more than 30% synergy. The most active combination against A. baumannii was eravacycline-ceftazidime and eravacycline-imipenem, which showed synergy in more than 50% of isolates. Conclusion: Eravacycline combined with beta-lactams or polymyxin B can lead to synergistic effects against clinically common carbapenem-resistant Gram-negative bacteria. The synergistic effects of eravacyclinebased combinations varied in different species. A combination of eravacycline and polymyxin B may be considered for the treatment of carbapenem-resistant E. coli and K. pneumoniae; eravacycline in combination with ceftazidime or a carbapenem antimicrobial may be considered for the treatment of carbapenem-resistant A. baumannii.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )