Lefamulin (150 mg IV q12h or 600 mg PO q12h) is the first systemic pleuromutilin antibiotic FDA-approved as an alternative agent for treatment of CAP in patients without structural lung disease. Lefamulin exerts its antibacterial effect through interactions with the 50S subunit of the bacterial ribosome, resulting in inhibition of bacterial protein synthesis and cell death. The agent is active against S. aureus (including MRSA), S. pneumoniae, Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Lefamulin is not active against Enterobacterales, Pseudomonas, and most anaerobes. Dose adjustment is indicated in severe hepatic impairment. Lefamulin is extensively metabolized via CYP3A4, resulting in the potential for drug interactions with agents that significantly inhibit or induce this enzyme.

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