Trends of -Lactamase Occurrence Among Escherichia coli and Klebsiella pneumoniae in United States Hospitals During a 5-Year Period and Activity of Antimicrobial Agents Against Isolates Stratified by -Lactamase Type

Background. The temporal and longitudinal trends of beta-lactamases and their associated susceptibility patterns were analyzed for Escherichia coli and Klebsiella pneumoniae isolates consecutively collected in 56 United States hospitals during 2016-2020.Methods. Isolates (n = 19 453) were susceptibility tested by reference broth microdilution methods. Isolates that displayed minimum inhibitory concentration (MIC) values >= 2 mg/L for at least 2 of the following compounds-ceftazidime, ceftriaxone, aztreonam, or cefepime-or resistance to the carbapenems were submitted to whole genome sequencing for identification of beta-lactamases. Longitudinal and temporal trends were determined by slope coefficient. New CTX-M and OXA-1 variants were characterized.Results. Extended-spectrum beta-lactamases (ESBLs) were detected among 88.0% of the isolates that displayed elevated cephalosporin/aztreonam MICs without carbapenem resistance. bla(CTX-M-15) was detected among 55.5% of the ESBL producers. ESBL rates were stable over time, but significant increases were noted among bloodstream infection and K pneumoniae isolates, mainly driven by an increase in bla(CTX-M.) Carbapenem resistance and carbapenemase genes were noted among 166 and 145 isolates, respectively, including 137 bla(KPC), 6 bla(SME), 3 bla(OXA-48)-like, and 3 bla(NDM). Ceftazidime-avibactam and carbapenems were very active (> 99% susceptibility) against ESBL producers without carbapenem resistance. Ceftazidime-avibactam inhibited 97.0% of the carbapenem-resistant isolates. This agent and meropenem-vaborbactam inhibited 96.4% and 85.0% of the 2020 isolates, respectively.Conclusions. Overall, ESBL-producing isolates were stable, but an increase was noted for K pneumoniae isolates driven by CTX-M production. Carbapenem-resistant Enterobacterales rates decreased in the study period. The prevalence of metallo-beta-lactamases and OXA-48-like remains low. Continuous surveillance of beta-lactamase-producing isolates is prudent.