Trends of β-Lactamase Occurrence AmongEscherichia coliandKlebsiella pneumoniaein United States Hospitals During a 5-Year Period and Activity of Antimicrobial Agents Against Isolates Stratified by β-Lactamase Type

Abstract

The temporal and longitudinal trends of β-lactamases and their associated susceptibility patterns were analyzed for Escherichia coli and Klebsiella pneumoniae isolates consecutively collected in 56 U.S. hospitals during 2016-2020. Isolates (n = 19,453) were susceptibility tested by reference broth microdilution methods. Isolates that displayed MIC values ≥2 mg/L for at least two of the following compounds—ceftazidime, ceftriaxone, aztreonam, or cefepime—or resistance to the carbapenems were submitted to whole genome sequencing for identification of β-lactamases. Longitudinal and temporal trends were determined by slope coefficient. New CTX-M and OXA-1 variants were characterized. 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. Overall, ESBL-producing isolates were stable, but an increase was noted for K. pneumoniae isolates driven by CTX-M production. CRE rates decreased in the study period. The prevalence of metallo-β-lactamases and OXA-48-like remains low. Continuous surveillance of β-lactamase-producing isolates is prudent.