Four-year longitudinal multicenter susceptibility trends of aztreonam–avibactam and ceftazidime–avibactam and dose optimization in critically ill patient populations against carbapenem-resistant Enterobacterales bloodstream infections

The prevalence of carbapenem-resistant Enterobacterales (CRE) has complicated the treatment of Enterobacterales infections. Aztreonam–avibactam (AZA) exhibits potent activity against CRE, including metallo-β-lactamase-producing strains. This study characterized AZA susceptibility profiles among clinical CRE in China and optimize AZA dosing strategies for critically ill patients. A nationwide surveillance identified CRE isolates among 34,879 Enterobacterales isolates from 18 provinces in China. The minimum inhibitory concentrations (MICs) of aztreonam, ceftazidime, AZA, ceftazidime–avibactam (CZA), eravacycline, tigecycline, and polymyxin B were determined. Monte Carlo simulations (MCS) integrated MIC distributions with pharmacokinetic/pharmacodynamic parameters to evaluate probability of target attainment (PTA) and cumulative fraction of response (CFR) for AZA regimens. CRE accounted for 2,016 isolates (5.78%), which were predominantly carbapenem-resistant Klebsiella pneumoniae (73.71%). AZA showed high overall activity against CRE, with isolates showing a susceptibility rate of 93.70%. Its effectiveness was highest against carbapenem-resistant Enterobacter cloacae (97.09%) and K. pneumoniae (94.93%), substantially outperforming CZA, which yielded a susceptibility rate of 76.54%. PTA/CFR analyses identified optimal AZA regimens by renal function: augmented/normal renal function, 2.0/0.67 g q6h and 1.5/0.5 g q6h; mild to moderate impairment, 1.5/0.5 g q6h and 1.35/0.45 g q6h; severe impairment, 1.0/0.33 g, 0.75/0.25 g and 0.675/0.225 g q6h/q8h; and kidney failure receiving or not receiving RRT, 1.0/0.33 g, 0.75/0.25 g and 0.675/0.225 g q8h/q12h. Each achieved optimal CFR against the three common CRE bacteria ( E. cloacae, Escherichia coli , and K. pneumoniae ). AZA demonstrated potent in vitro activity against CRE isolates collected nationwide in China, outperforming CZA. MCS provides a clinically relevant strategy for optimizing AZA dosing in critically ill patients and improving target attainment.