Community-acquired bacterial pneumonia (CABP) remains a significant cause of morbidity and mortality worldwide. Antimicrobial resistance, including in pathogens that cause CABP, continues to spread at an alarming rate. Because of these factors, the development of new antibiotic classes is urgently needed. Lefamulin, previously known as BC-3781, is a semisynthetic pleuromutilin antibiotic that was approved by the Federal Drug Administration for the treatment of CABP in adults. Available in both oral and intravenous (IV) formulations, lefamulin has potent in vitro activity against both typical and atypical CABP pathogens. The first pleuromutilin to be used systemically in humans, lefamulin has a unique mechanism of action that inhibits protein synthesis by preventing the binding of tRNA for peptide transfer. This review summarizes the available data about lefamulin, including recent evidence from two phase III clinical trials (LEAP 1 and LEAP 2), and discusses its potential role in the treatment of CABP.
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