25. Update on Prevalence Of mcr-like Genes Among enterobacterales in a Global Surveillance Program: Decline in Occurrence of mcr-1.1 and Emergence of mcr-9.1 and mcr-10.1

BACKGROUND: Increase in occurrence of infections caused by multidrug resistant organisms has prompted the usage of polymyxins and consequentially, resistance (R) to these antimicrobial peptides has risen. We have previously reported prevalence of mcr alleles from colistin (COL) non-susceptible (non-S) Enterobacterales (ENT) isolates from the SENTRY Antimicrobial Surveillance Program and in this study, we expand that knowledge by screening ENT isolates for this R mechanism collected during 2017 and 2018. METHODS: A total of 4,659 ENT isolates from 33 countries were S tested for COL and comparator antimicrobial agents by reference broth microdilution and sequenced using MiSeq as part of SENTRY Program. Most isolates were sequenced due to R to cephalosporins, carbapenems and/or aminoglycosides, but were not selected due to COL R. Sequences were de novo assembled and blasted against a local database for the mcr alleles: mcr-1.1 through mcr-10.1 and subtypes. RESULTS: COL R rate was 8.1% (MIC(50/90), 0.12/0.5 mg/L) and mcr-like alleles were detected in 128 (2.8%) isolates. mcr-1.1 was present in 12 isolates (9.4%), 8 other mcr-variants were detected in 1 or 2 isolates each while majority of the isolates carried the newly described mcr-9.1 (92; 71.9%, 16 countries) or mcr-10.1 (16; 12.5%, Table). mcr-9.1 (73/92) and mcr-10.1 (15/16) were predominantly detected in Enterobacter cloacae. Isolates carrying mcr-9.1 showed COL MIC distributions similar to wild-type population (MIC(50/90), 0.12/0.25 mg/L), while mcr-10.1 MIC distribution was higher (MIC(50/90), 8/ > 8 mg/L). CONCLUSION: A decline in the prevalence of mcr-1.1 was observed in this study period when compared to our prior studies. In contrast, mcr-9.1 and mcr-10.1 were observed in many isolates collected during 2017–18. Other mcr-variants were detected sporadically among ENT. Evaluating genetic context of these alleles to understand its dissemination and screening of COL non-S isolates for mcr is warranted. Table 1 [Image: see text] DISCLOSURES: Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)