Lefamulin – upgrading our arsenal against community-acquired pneumonia

Lefamulin (formerly BC-3781) is a novel semi-synthetic pleuromutilin antibiotic that has been granted marketing authorization in the US for the treatment of patients with Community-acquired bacterial pneumonia (CABP).  It shows potent in vitro activity against atypical and typical pathogens that cause CABP. Lefamulin interferes with the peptidyl transferase center and inhibits the prokaryotic ribosomal protein synthesis. This is achieved through its binding at the A- and P-site of the 50S ribosomal submit, resulting in the interruption of peptide bond formation. This is a novel mechanism for inhibiting bacterial peptide chain elongation. By virtue of its favorable clinical response and reasonable safety data in two non-inferiority phase III clinical trials (Lefamulin Evaluation against Pneumonia - LEAP1 & LEAP2 trials), the drug has been granted regulatory approval. The drug is highly bound to plasma protein and the mean half-life is 8 hours. The drug is metabolized by cytochrome P450 (CYP450) enzyme. This narrative review discusses the efficacy, safety, pharmacokinetics, and current status of lefamulin in the management of CABP.