In Vitro Activities of the Essential Antimicrobial Agents Including Aztreonam/avibactam, Eravacycline, Colistin, and Other Comparators Against Carbapenem-Resistant Bacteria with Different Carbapenemase Genes: a Multicenter Study in China, 2021

Objective Carbapenem-resistant bacteria (CRB), including carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Enterobacterales (CRE), pose a considerable threat to public health in China. Eravacycline, aztreonam/avibactam, and colistin are important antimicrobial agents for the treatment of serious infections caused by CRB. The study aims to evaluate the prevalence of CRB strains and the susceptibility of commonly used clinical antimicrobial agents against the strains with different carbapenemase genes . Methods We collected 7,194 gram-negative bacteria (GNB) strains from different regions of China and identified 924 carbapenem-resistant strains. All strains were from infections with confirmed diagnoses. Antimicrobial susceptibility testing, covering 21 antimicrobial agents including aztreonam/avibactam, eravacycline, colistin, and other comparators, was performed using the broth microdilution method. Carbapenemase genes (blaKPC, blaNDM, blaOXA, blaIMP, and blaVIM) were screened by PCR amplification and sequence analysis. All statistical analyses were performed using Statistical Package for the Social Sciences version 23.0 software. Results The isolation rates of CRE, CRAB, and CRPA were 6.31% (332/5265), 62.95% (440/699), and 15.20% (152/1000), respectively. The predominant carbapenemase in carbapenem-resistant Escherichia coli (CRECO) was NDM, while in CRKP it was KPC. All CRAB produced OXA-23 and 85.52 % of CRPA did not produce any of the following carbapenemases: NDM, KPC, VIM, IMP and OXA. Aztreonam/avibactam, colistin, and eravacycline exhibited high antimicrobial activity against different species producing various carbapenemases. Compared to ceftazidime/avibactam, aztreonam/avibactam demonstrated superior antimicrobial activity, particularly pronounced in CRECO and strains producing metallo-beta-lactamases (MBLs). In comparisons between tigecycline and eravacycline, the latter maintained higher antimicrobial activity across different species. Antimicrobial agents exhibited varying levels of activities when against strains with different resistance mechanisms. Conclusions Our results support the fact that using aztreonam/avibactam, eravacycline, and colistin to treat infections caused by CRB offers significant advantages. These fingdings will guide clinical practice and optimize antimicrobial administration.