1592. In Vitro Activity of Ceftolozane/Tazobactam (C/T) Against Enterobacteriaceae and Pseudomonas aeruginosa Circulating in Chile

Abstract

BackgroundThe widespread dissemination of carbapenem-resistant (CR) P. aeruginosa and Enterobacteriaceae has created a major global public health crisis. C/T is a recently approved therapeutic which consists of the combination of a novel cephalosporin (ceftolozane) and tazobactam (a β-lactamase inhibitor). C/T has shown good activity against a wide range of multidrug-resistant (MDR) Gram negatives, being particularly interesting as an alternative for MDR P. aeruginosa. We aimed to determine the activity of C/T against clinical strains of Enterobacteriaceae and P. aeruginosa recovered in 4 large clinical centers from Chile.MethodsWe analyzed 434 isolates of Enterobacteriaceae (347 E. coli, 66 K. pneumoniae, 21 Enterobacter cloacae complex) and 57 P. aeruginosa collected during 2017 from 4 tertiary care institutions in Santiago, Chile. Identification was performed as per each local clinical microbiology lab. Susceptibility testing was performed by broth microdilution using customized Sensititre plates (Trek). Carba-NP was performed to screen for carbapenemase production. Susceptibilities were analyzed as per 2019 CLSI breakpoints.ResultsThe MIC50/90 for C/T against Enterobacteriaceae and P. aeruginosa were 1/4 μg/mL and 2/16 μg/mL, respectively. In Enterobacteriaceae, susceptibility to C/T reached 92% in E. coli (Figure 1A), 91% in E. cloacae complex (Figure 1B) and 70% in K. pneumoniae (Figure 1C). Remarkably, C/T remained active against 58% (33/57) of CR Enterobacteriaceae (Figure 2A). Among Carba-NP-negative CR isolates (46%, 26/57), susceptibility to C/T was 54% (Figure 3 A–C). In P. aeruginosa, the overall susceptibility to C/T was 81% (Figure 1D), maintaining activity against 69% (25/36) of CR strains (Figure 2B). Importantly, susceptibility to C/T in CR P. aeruginosa isolates with a negative Carba-NP (67%, 24/36) was 83% (20/24) (Figure 3D).ConclusionIn this multicenter study, we observed that C/T was highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa. Of note, C/T remained active against a large proportion of CR clinical strains. Moreover, the activity of C/T was particularly high against CR P. aeruginosa isolates with a negative Carba-NP. Disclosures All authors: No reported disclosures.