Clinical use of lefamulin: A first-in-class semisynthetic pleuromutilin antibiotic.

Lefamulin is a novel antibiotic agent within the pleuromutilin derivative class approved for the treatment of community-acquired bacterial pneumonia (CABP) by the United States Food and Drug Administration and the European Commission in 2019 and 2020, respectively. The objective of this article is to provide a summary of clinically relevant data underlying lefamulin and to provide recommendations for its place in therapy. In vitro data establishes lefamulin's activity against a number of Gram-positive, Gram-negative, and atypical organisms relevant in the treatment of CABP, including S. pneumoniae, H. influenzae, M. catarrhalis, L. pneumophila, M. pneumoniae, and C. pneumoniae. Two phase-3 studies, the Lefamulin Evaluation Against Pneumonia trials, established non-inferiority of lefamulin against moxifloxacin in the treatment of CABP, including the sequential transition from intravenous to oral therapy and across a broad set of patient demographics and severities. Pooled and post-hoc analyses have confirmed these effects for a variety of subgroups and secondary endpoints. Real-world study data post-approval has largely not yet emerged for lefamulin, and there is a need for further investigation into safety/efficacy for off-label indications such as acute bacterial skin and skin structure infections and sexually transmitted infections. Further data regarding tolerability, particularly with long term use, as well as the emergence of resistance over time, are still undefined.