Skip to Main Content

Lefamulin, the only commercially available antibiotic from the pleuromutilin class, is used in community-acquired bacterial pneumonia. Lefamulin is active against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, atypical bacteria (eg, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila), Staphylococcus aureus (including methicillin-resistant strains), Enterococcus faecium (including vancomycin-resistant strains), and Streptococcus pyogenes. It lacks appreciable activity against Enterobacteriaceae and Pseudomonas aeruginosa.


Lefamulin halts bacterial protein synthesis by interacting with the 23s ribosomal RNA of the 50S subunit of ribosomes. Lefamulin is active against S pneumoniae, H influenzae, M catarrhalis, atypical bacteria (eg, M pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila), S aureus (including methicillin-resistant strains), E faecium (including vancomycin-resistant strains), and S pyogenes. It lacks appreciable activity against Enterobacteriaceae and P aeruginosa.


Lefamulin is available as an oral and intravenous formulation dosed twice daily. Oral doses should be separated at least 1 hour before or 2 hours after a meal to maximize absorption. Lefamulin is widely distributed in tissues, including the lungs. Because lefamulin is metabolized in the liver by CYP3A4, patients receiving this medication should be screened for drug-drug interactions. Less than 15% is excreted unchanged in the urine. Thus, no dosage adjustment is needed in kidney disease. Patients with liver disease do require a dose reduction.


Lefamulin is noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia.


Lefamulin prolongs the QT interval and should be avoided in patients with preexisting prolonged QT or ventricular arrhythmias and in patients taking other QT-prolonging agents. The most common adverse effects with the oral formulation are GI (eg, diarrhea, nausea, and vomiting). Administration site reactions, such as pain and phlebitis, have been reported with the intravenous formulation. Lefamulin may also cause elevations in hepatic enzymes.

Alexander  E  et al. Oral lefamulin vs moxifloxacin for early clinical response among adults with community-acquired bacterial pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019;322:1661.
[PubMed: 31560372]  
File  TM  et al. Efficacy and safety of intravenous-to-oral lefamulin, a pleuromutilin antibiotic, for the treatment of community-acquired bacterial pneumonia: the phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis. 2019;69:1856.
[PubMed: 30722059]  

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.