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Background LSVT-1701, formerly SAL200, is a novel, recombinantly-produced, bacteriophage-encoded lysin that specifically targets staphylococci via cell wall enzymatic hydrolysis. We reported the in vitro activity of LSVT-1701 against clinical isolates of S. aureus and coagulase-negative staphylococci (CoNS) collected worldwide. Methods LSVT-1701 and comparators were tested against 415 S. aureus (n=315) and CoNS (n=100) clinical isolates expressing various resistance phenotypes. The isolates were collected in 2002-2019 from medical centers located in the United States (50 medical centers; 174 isolates; 41.9% overall), Europe (37 medical centers; 140 isolates; 33.7% overall), Asia-Pacific region (15 medical centers; 55 isolates; 13.3% overall), and Latin America (12 medical centers; 46 isolates; 11.1% overall). These isolates originated mostly from the year 2019 (n=323).The isolates were susceptibility tested by the CLSI broth microdilution method. MIC interpretations were based on CLSI and EUCAST criteria where available. Results LSVT-1701 was highly active against S. aureus and CoNS isolates with MIC90 values of 2 mg/L for all S. aureus, methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and CoNS (Table). The highest LSVT-1701 MIC values were 4 and 8 mg/L among S. aureus and CoNS, respectively. LSVT-1701 retained potent activity against S. aureus isolates showing resistance or decreased susceptibility to oxacillin, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, or lefamulin; MIC50 values ranged from 0.5 to 1 mg/L and MIC90 values ranged from 1 to 4 mg/L among S. aureus resistant subsets. Summary of LSVT-1701 activity against S. aureus, CoNS and resistant subsets Conclusion LSVT-1701 demonstrated potent in vitro activity against contemporary clinical isolates of S. aureus and CoNS collected from medical centers worldwide and against resistant S. aureus isolates with uncommon resistance phenotypes. The results of this study support further clinical development of LSVT-1701 to treat staphylococcal infections. Disclosures David Huang, MD, PhD, Lysovant (Consultant) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Paul R Rhomberg, Cidara Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee)