1689. In Vitro Activity of Lefamulin Against Bacterial Pathogens Collected From Pneumonia Patients in United States and Latin America Medical Centers in 2020-2021
Authors: Paukner Susanne , Ryan Arends S J , Mendes Rodrigo E , Gelone Steven P , Sader Helio S 
Published: December 2022

Abstract

Background
Lefamulin is a novel pleuromutilin protein synthesis inhibitor approved in the US, Canada, and Europe for the oral and intravenous treatment of community-acquired bacterial pneumonia (CABP) in adults due to typical and atypical pathogens. This study evaluated the in vitro activity of lefamulin and comparators against bacterial isolates from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia in the US and Latin America.

Methods
1,907 unique isolates were collected within the SENTRY surveillance program from 29 medical centers in the US and 8 medical centers in Latin America (Argentina, Brazil, Chile, Colombia, Mexico, Panama). Isolates were susceptibility tested by CLSI reference broth microdilution methods. CLSI breakpoints (M100, 2022) were applied.

Results
Lefamulin inhibited 100% of S. pneumoniae isolates at or below its susceptible (S) breakpoint of ≤ 0.5 mg/L, regardless of resistance to other antibiotics used to treat CABP (MIC90 values of 0.12 or 0.25 mg/L, Table). The penicillin-resistant (R; 12.7%), azithromycin-R (43.7%), and tetracycline-R S. pneumoniae (20.4%) displayed reduced susceptibility to the other CABP drugs tested, except moxifloxacin ( &gt; 98.2% S) and lefamulin (100% S). Lefamulin was highly potent against S. aureus, including MRSA, azithromycin-R, and moxifloxacin-R isolates, with 100% of isolates inhibited at or below the lefamulin S breakpoint of ≤ 0.25 mg/L. Susceptibility to azithromycin and moxifloxacin was particularly low for MRSA (13.9% and 25.0%, respectively). The fastidious Gram-negative H. influenzae and M. catarrhalis, of which 24.0% and 98.8%, respectively, were ß-lactamase positive, were S to lefamulin ( &gt; 93%) and the other tested CABP drugs ( &gt; 89%). Table.
Susceptibility of pneumonia pathogens from US and Latin America to lefamulin and other CABP drugs

Conclusion
Lefamulin displayed potent in vitro activity against contemporary CABP pathogens from the US and Latin America. Its activity was unaffected by resistance to other antibiotic classes, including fluoroquinolones, macrolides, β-lactams, and tetracyclines. Lefamulin represents a valuable empiric treatment option for ambulatory and hospitalized patients with CABP, particularly when the causative pathogen is not identified or in settings with high prevalence of resistance.

Disclosures
Susanne Paukner, PhD, Nabriva Therapeutics: Inventor|Nabriva Therapeutics: Employee|Nabriva Therapeutics: Stocks/Bonds SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Steven P. Gelone, PharmD, Nabriva Therapeutics: Board Member|Nabriva Therapeutics: Inventor|Nabriva Therapeutics: Employee|Nabriva Therapeutics: Stocks/Bonds|Nabriva Therapeutics: Stocks/Bonds Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support.