# Resistance to Lefamulin: An Evaluation of Data from In Vitro Antimicrobial Susceptibility Studies

## TL;DR

Lefamulin shows strong in vitro effectiveness against common pneumonia-causing bacteria, with low resistance rates, making it a promising treatment option.

## Contribution

This study provides a comprehensive evaluation of lefamulin's antimicrobial activity and resistance patterns against key pathogens.

## Key findings

- Resistance rates for S. pneumoniae, H. influenzae, and S. aureus were below 5%.
- MIC90 values were low for most pathogens, except for some Enterococcus spp. isolates.
- Lefamulin remains effective against resistant strains like MRSA and β-lactamase-producing H. influenzae.

## Abstract

Lefamulin, a new, first-in-class pleuromutilin antibiotic, was recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of patients with community-acquired bacterial pneumonia (CABP). In this context, this review aimed to evaluate its activity against the most common pathogens causing this infection. A thorough search was performed in five databases (Embase, Scopus, Web of Science, PubMed, PubMed Central) from their inception to 14th of October 2025. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints were applied. Out of a total of 224 articles identified, 11 were deemed eligible for inclusion. Resistance among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus isolates was 0–2.6%, 0–2.4%, and 0–4.3%, respectively. Even among isolates with specific mechanisms of resistance, such as β-lactamase-producing H. influenzae and methicillin-resistant S. aureus, resistance was below 2.4% and 3.4%, respectively. Among isolates for which no breakpoints were available (Moraxella catarrhalis, atypical pathogens, Enterococcus spp., Streptococcus spp., Haemophilus spp., and Staphylococcus spp.), MIC90 values were low. An exception were isolates belonging to Enterococcus spp., which displayed MIC90 values ranging from 0.25 to >16 mg/L in the two studies with relevant data. Lefamulin demonstrated broad in vitro activity against key pathogens causing CABP, making it a considerable addition to the therapeutic options for such infections, especially in cases where first-line agents cannot be used for reasons such as allergy or previous failure.