What is the role of lefamulin (Xenleta) in the treatment of community-acquired pneumonia (CAP)?

Updated: Jul 22, 2021
  • Author: Folusakin O Ayoade, MD; Chief Editor: Thomas E Herchline, MD  more...
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Lefamulin (Xenleta) is a first-in-class pleuromutilin antibacterial. It inhibits bacterial protein synthesis through interactions (hydrogen bonds, hydrophobic interactions, and Van der Waals forces) with the A- and P-sites of the peptidyl transferase center (PTC) in domain V of the 23s rRNA of the 50S subunit. It is indicated for the treatment of bacterial CAP due to S pneumoniae, S aureus (methicillin-susceptible isolates), H influenzae, Legionella pneumophila, M pneumoniae, or C pneumoniae in adults. It is administered twice daily as either an intravenous infusion or an oral tablet. Approval was based on LEAP 1 and 2 trials.

In LEAP 1, patients (n=551) were randomized to either lefamulin 150 mg IV q12h or moxifloxacin 400 mg IV q24h. After 6 doses, patients could be switched to oral study drug if prespecified improvement criteria were met. If MRSA was suspected, linezolid or placebo was added to moxifloxacin or lefamulin, respectively. Lefamulin was noninferior to moxifloxacin in terms of early clinical response. Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin.9

The LEAP 2 study (n=738) found oral lefamulin 600 mg q12h for 5 days was noninferior to moxifloxacin 400 mg/day for 7 days in the treatment of bacterial CAP.10

Dosing for lefamulin is as follows:

Lefamulin 150 mg IV q12hr x 5-7 days OR 600 mg PO q12 hr x 5 days

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