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

J Intern Med. 2022 Jan;291(1):51-63. doi: 10.1111/joim.13378. Epub 2021 Oct 9.

Abstract

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 establish lefamulin's activity against a number of Gram-positive, Gram-negative and atypical organisms relevant in the treatment of CABP, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila 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 have 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.

Keywords: bacterial; community-acquired infections; lefamulin; pleuromutilin; pneumonia.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents* / therapeutic use
  • Community-Acquired Infections* / drug therapy
  • Diterpenes / therapeutic use*
  • Humans
  • Pleuromutilins
  • Pneumonia, Bacterial* / drug therapy
  • Polycyclic Compounds / therapeutic use*
  • Thioglycolates / therapeutic use*
  • United States

Substances

  • Anti-Bacterial Agents
  • Diterpenes
  • Polycyclic Compounds
  • Thioglycolates
  • lefamulin