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Background Omadacycline (OMC) is a new aminomethylcycline antibacterial drug belonging to the tetracycline class, for intravenous or oral administration. It is well tolerated and has proven effective in the treatment of a variety of bacterial infections. OMC is active against bacterial strains expressing the most common clinically relevant tetracycline resistance mechanisms, namely efflux and ribosomal protection. Methods 7,000 clinical isolates were collected during 2019 in the SENTRY Surveillance Program from 31 medical centers in the United States (US). Isolates were obtained from bloodstream infection (23.8%), skin and skin structure infection (21.6%), pneumonia in hospitalized patients (22.7%), urinary tract infection (14.5%), intraabdominal infection (6.2%), community acquired respiratory tract infection (10.3%) and other infection types (0.9%). Identifications were confirmed by MALDI-TOF. One isolate/patient/infection episode was tested. Broth microdilution susceptibility testing was conducted according to CLSI M07 (2018) and M100 (2020) guidelines. Results were interpreted using US FDA and CLSI breakpoint criteria. Results OMC demonstrated potent in vitro activity against Staphylococcus aureus isolates representing multiple infection types (MIC90, 0.12-0.25 mg/L; 94.7%-99.0% susceptible [S]) including MRSA (MIC90, 0.25 mg/L; 96.5% S) (Table). All S. lugdunensis (MIC90, 0.06 mg/L), Enterococcus faecalis (MIC90, 0.12-0.25 mg/L), and Haemophilus influenzae (MIC90, 1 mg/L) isolates were S to OMC. OMC was active against Streptococcus pyogenes isolates from SSSI (MIC90, 0.12 mg/L; 93.3%-98.5%S) including macrolide-resistant (R) strains. Similarly, S. pneumoniae isolates from RTI were S to OMC (MIC90, 0.06-0.12 mg/L; 98.8%-100%S) regardless of resistance to tetracycline or penicillin. Overall, 90.2%-93.6% of Enterobacter cloacae (MIC90, 4 mg/L) and 89.7%-94.7% of Klebsiella pneumoniae (MIC90, 4-8 mg/L) isolates from multiple infection types were S to OMC. Conclusion OMC demonstrated potent in vitro activity against Gram-positive and -negative bacterial pathogens from multiple infection types including SSSI and RTI and isolates displaying resistance to tetracycline, macrolides, and penicillin. Table 1 Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (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)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (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 &amp; Co, Inc. (Research Grant or Support)Merck &amp; Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

1253. In Vitro Activity of Omadacycline against 7000 Bacterial Pathogens from the United States Stratified by Infection Type (2019)