Comparative Activities of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Enterobacteriaceae Isolates Producing Extended-Spectrum β-Lactamases from US Hospitals

The activities of ceftazidime-avibactam, ceftolozane-tazobactam, and comparators were evaluated for 733 isolates displaying resistance to broad-spectrum cephalosporins and carrying extended-spectrum beta-lactamase (ESBL) genes detected by whole-genome sequencing analysis. Isolates were collected during 2017 in U.S. hospitals. The ESBL producers were 486 Escherichia coli, 190 Klebsiella pneumoniae, and 42 Enterobacter cloacae isolates and isolates from 3 other species. The most common groups of ESBL-encoding genes were bla(CTX-M-15)-like (n = 491 isolates) and bla(CTX-M-15) alone (n = 168) or plus bla(OXA-1) (n = 260), followed by bla(CTX-M-14 )like (n = 162), which included bla(CTX-M-27) and bla(CTX-M-14) (104 and 51 isolates, respectively), and bla(SHV-12) and blaSHV-7 (48 and 22 isolates, respectively). ESBL producers carried other beta-lactamases, including 1 E. cloacae harboring bla(KPC-3). All ESBL producing isolates were susceptible to ceftazidime-avibactam, and 90.2/83.9% (CLSI/EUCAST breakpoints) were susceptible to ceftolozane-tazobactam. Tigecycline (98.1/95.8% susceptible) and colistin (99.2%) were comparators that displayed the greatest activity against these isolates. Ceftolozane-tazobactam inhibited 91.4/83.9% of isolates carrying bla(CTX-M-15)-like and 97.5/95.1% of isolates carrying bla(CTX-M-15)-like, and its activity was more limited against the 91 isolates carrying bla(SHV )(66.7/61.1% susceptible). Ceftolozane-tazobactam inhibited 95.5% of the E. coli isolates but only 83.0%, 64.3%, and 80.0% of K. pneumoniae, E. cloacae, and other species harboring ESBL-encoding genes (CLSI breakpoints), respectively. Outer membrane protein sequences for ceftolozane-tazobactam-nonsusceptible isolates did not exhibit significant differences compared to those in genetically related ceftolozane-tazobactamsusceptible isolates. Ceftazidime-avibactam was more active than other agents tested, including ceftolozane-tazobactam, and the activity of this combination was stable regardless of species or ESBL gene carried.