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Background The MRSA Chilean-Cordobes (ChC) clone belongs to the clonal complex 5 (CC5) and typically carries SCCmec I. The ChC clone predominated widely throughout several countries of Latin America (LA), but during the mid-2000s a CA-MRSA CC8 LA variant (USA300-LV) quickly replaced the ChC in Colombia and Ecuador. Most notably, this replacement was not observed in Peru or Chile. Here, we aimed to understand the phylogenomic relatedness of the CC5 ChC clone obtained from different countries of LA. Methods We sequenced and analyzed the genomes of 115 MRSA isolates obtained between 2011–2014 from bloodstream infections in 6 LA countries (Argentina, Brazil, Colombia, Chile, Peru, and Venezuela). All isolates were confirmed as ChC clone by pulsed-field gel electrophoresis (PFGE). We used core genome-based phylogenomic reconstructions and molecular clock analysis to infer the relationships and time of divergence between clades. Results Whole-genome-based multilocus sequence typing determined that 110/115 isolates belonged to ST5 and carried SCCmec I. The phylogenomic reconstruction showed ChC isolates clustered into 4 major clades distinctly segregated by country of origin (Figure 1). Interestingly, isolates recovered from Chile divided into 2 different clades that segregate according to the city of origin (Santiago [SCL] or Concepción [CON]), suggesting these clades evolved independently. Molecular clock analyses suggested all clades share a common ancestor with the divergence of the Chilean clades occurring earlier (Figure 2). Of note, analysis of heavy metal genes suggested the divergence between Chilean isolates was characterized by the loss of a mercury resistance gene cluster, which is present in an 88% of CON isolates, but only in 28% of SCL (Figure 2). Conclusion MRSA isolates belonging to the ChC clone from 6 LA countries clustered in 4 clades according to the geographical region of isolation. This segregation suggests divergent adaptations that may respond to different selective pressures. Heavy metal resistance could play a role in the ability of the MRSA ChC to disseminate in specific geographical locations. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The 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. Methods We 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. Results The 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). Conclusion In 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. [ABSTRACT FROM AUTHOR]