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Background Lefamulin (LEF), a novel pleuromutilin protein synthesis inhibitor in development for use as an empiric IV and oral monotherapy for CABP, recently demonstrated safety and efficacy in two phase 3 trials in adults with CABP (PORT II–V). LEF IV or IV/oral (5–7 days; 10 days for methicillin-resistant Staphylococcus aureus [MRSA]) and LEF oral (5 days) were noninferior to MOX IV or IV/oral (7 days; 10 days for MRSA) and MOX oral (7 days) in patients with CABP caused by the most prevalent typical and atypical bacterial pathogens. This study investigated the in vitro activity of LEF and comparators against bacterial respiratory pathogens collected in the United States in 2017 and 2018. Methods As part of the SENTRY Surveillance Programme, isolates (n = 2299, 1/patient) were collected from 39 medical centers in the United States from patients with community-acquired respiratory tract infections (1812/2299 [78.8%]) and pneumonia in hospitalized patients (487/2299 [21.2%]). LEF and comparators were tested by broth microdilution and CLSI (2019) breakpoints were applied. Results LEF demonstrated potent antibacterial activity against all pathogens tested and was unaffected by resistance to other antibiotic classes (table). Streptococcus pneumoniae isolates were largely susceptible ( &gt;80%) to most comparators; however, 45.6% and 20.4% were resistant (R) to macrolides and tetracycline, respectively. LEF exhibited a MIC50/90 of 0.12/0.25 mg/L for S. pneumoniae, including all R subsets. Among S. aureus isolates, and particularly MRSA, resistance to macrolides was high (48.5% and 81.2% R, respectively). LEF showed a MIC50/90 of 0.06/0.12 mg/L for S. aureus, including all R subsets. Haemophilus influenzae isolates were susceptible to all comparators except for ampicillin (31.4% R) and trimethoprim-sulfamethoxazole (35.3% R). LEF displayed a MIC50/90 of 0.5/2 mg/L for H. influenzae isolates. Moraxella catarrhalis isolates, which were largely β-lactamase positive (98%), were susceptible to all comparators. Conclusion LEF displayed potent in vitro activity against contemporary CABP pathogens collected in the United States. LEF activity was unaffected by resistance to other antibiotic classes, including fluoroquinolones, macrolides, β-lactams, and tetracyclines. Disclosures All authors: No reported disclosures.

open forum infectious diseases

703. In Vitro Activity of Lefamulin Against Bacterial Pathogens Causing Community-Acquired Bacterial Pneumonia (CABP): SENTRY Surveillance 2017–2018 Results From the United States (US)