Changes in the Frequencies of β-Lactamase Genes among Enterobacteriaceae Isolates in U.S. Hospitals, 2012 to 2014: Activity of Ceftazidime-Avibactam Tested against β-Lactamase-Producing Isolates

Among 15,588 Enterobacteriaceae isolates collected in 63 U.S. hospitals from 2012 to 2014, 2,129 (13.7%) displayed an extended-spectrum β-lactamase (ESBL) phenotype. These rates were similar over time (13.2 to 13.9%); however, differences among Escherichia coli (12.7 and 15.1% in 2012 and 2014; P = 0.007) and Klebsiella pneumoniae (18.9 and 15.5% in 2012 and 2014; P = 0.006) were noted when comparing 2014 and 2012. Carbapenem-resistant Enterobacteriaceae (CRE) (2.3 and 1.8%) and carbapenem-resistant K. pneumoniae (6.8 and 5.1%; P = 0.003) rates were lower in 2014 than in 2012. Isolates carrying blaCTX-M-15-like genes were stable (42.1 to 42.4%), but a decrease among E. coli isolates (59.1 and 49.7%; P = 0.008) and an increase among K. pneumoniae isolates (32.7 and 41.2%; P = 0.022) in 2014 were observed. Isolates carrying blaKPC (304) decreased over the years (16.5 and 10.9%; P = 0.008), mainly due to the decrease in K. pneumoniae isolates harboring blaKPC (n = 285; 35.6 and 28.4%; P = 0.041) in hospitals in the Mid-Atlantic and South Atlantic regions, where these isolates were highly prevalent during 2012 and 2013. Isolates carrying blaCMY-2-like and blaCTX-M-14-like genes increased (8.2 and 11.9% and 9.1 and 12.9%, respectively; P = 0.04 for both), and those producing blaSHV ESBL decreased (24.9 and 12.7%; P < 0.001) over the studied years, due to a decreased occurrence of the enzymes among K. pneumoniae isolates. Other enzymes were detected in smaller numbers of isolates, including four K. pneumoniae isolates carrying blaNDM-1 metallo-β-lactamase (two in 2012 and two in 2014). Ceftazidime-avibactam, a recently approved β-lactamase inhibitor combination, was very active against the ESBL phenotype isolates (MIC50/90, 0.12 and 1 μg/ml; 99.7% susceptible) and CRE strains (MIC50/90, 0.5 and 2 μg/ml; 98.5% susceptible) that displayed elevated MIC values for many comparator agents. In conclusion, significant changes were noted in the frequencies of isolates harboring various β-lactamases among U.S. hospitals between 2012 and 2014 that will require continued monitoring.