Comparative Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Enterobacteriaceae Isolates Producing Extended-Spectrum β-Lactamases from United States Hospitals.

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Comparative Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Enterobacteriaceae Isolates Producing Extended-Spectrum β-Lactamases from United States Hospitals.

Antimicrob Agents Chemother. 2019 May 13;:

Authors: Castanheira M, Doyle TB, Mendes RE, Sader HS

Abstract
The activity of ceftazidime-avibactam, ceftolozane-tazobactam, and comparators was evaluated for 733 isolates displaying resistance to broad-spectrum cephalosporins and carrying extended-spectrum β-lactamase (ESBL) genes detected by whole genome sequencing analysis. Isolates were collected during 2017 in US hospitals. ESBL-producers were 486 E. coli, 190 K. pneumoniae, 42 E. cloacae and 3 other species. The most common group of ESBL-encoding genes were bla CTX-M-15-like (n = 491) and bla CTX-M-15 alone (n = 168) or plus bla OXA-1 (n = 260), followed by isolates carrying bla CTX-M-14-like (n = 162) that included bla CTX-M-27 and bla CTX-M-14 (104 and 51 isolates) and bla SHV-12 and bla SHV-7 (48 and 22 isolates). ESBL producers carried other β-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, 97.5/95.1% of isolates carrying bla CTX-M-14-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 when compared to genetically related ceftolozane-tazobactam susceptible 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.

PMID: 31085510 [PubMed - as supplied by publisher]