What is Lefamulin? The Pleuromutilin Antibiotic
Lefamulin, known by the brand name Xenleta, is a semi-synthetic pleuromutilin antibiotic. This class of drugs, originally derived from the fungus Pleurotus mutilus, has been used in veterinary medicine for many years. Lefamulin's unique mechanism of action sets it apart from other antibiotics and makes it effective against certain drug-resistant bacteria.
The Approved Use: Community-Acquired Bacterial Pneumonia (CABP)
The only approved use for lefamulin is for treating community-acquired bacterial pneumonia (CABP) in adults. Clinical trials have shown lefamulin to be safe and effective for this condition. It can be administered intravenously (IV) or orally. Lefamulin is effective against specific bacteria that cause CABP, including common and less typical pathogens, such as Streptococcus pneumoniae (including multi-drug-resistant strains) and Staphylococcus aureus (methicillin-susceptible only).
Mechanism of Action Against Bacteria
Lefamulin inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the bacterial 50S ribosomal subunit. This targeted action does not affect human ribosomes. Its novel mechanism reduces the likelihood of cross-resistance with other antibiotic types.
Comparison: Lefamulin vs. Standard CABP Treatment
Comparing lefamulin to traditional CABP treatments like moxifloxacin highlights key differences:
| Feature | Lefamulin (Xenleta) | Moxifloxacin (Avelox) |
|---|---|---|
| Mechanism of Action | Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. | Inhibits bacterial DNA gyrase and topoisomerase IV, preventing DNA replication. |
| Drug Class | Pleuromutilin | Fluoroquinolone |
| Route of Administration | Oral tablets or intravenous (IV) infusion. | Oral tablets or intravenous (IV) infusion. |
| Standard Duration | Typically 5 to 7 days, depending on individual patient factors and response to treatment. | Typically 7 days, though duration can vary based on clinical assessment. |
| Potential Side Effects | Diarrhea, nausea, vomiting, headache, injection site reactions (for IV). | Gastrointestinal upset, headache, potential QT prolongation (black box warning). |
| Cost | Significantly higher than standard options like moxifloxacin. | Generally more affordable and widely available. |
| Considerations | Novel mechanism is beneficial for resistant strains. Cost is a major barrier to widespread use. | Established efficacy but broader use has led to increased resistance concerns. |
Important Safety Information and Considerations
Lefamulin has important safety warnings.
Risk of QT Prolongation
Lefamulin can prolong the QT interval, potentially causing an irregular heartbeat. Caution is needed in patients with a history of QT prolongation or those on medications that affect the QT interval.
Pregnancy and Breastfeeding
Lefamulin can harm a fetus and should not be used during pregnancy. Women of reproductive age must have a negative pregnancy test before starting treatment and use effective contraception during treatment and for two days after the last dose. It is not advised for breastfeeding mothers due to potential infant side effects.
Drug-Drug Interactions
Other drugs can affect lefamulin levels in the body because it is metabolized by the liver enzyme CYP3A4. A patient's full medication list should be reviewed to avoid interactions.
The Role of Lefamulin in Therapy
Lefamulin provides a targeted and effective option for confirmed or suspected CABP, especially when resistance to other antibiotics is a concern. Its unique mechanism and activity against resistant bacteria make it a valuable tool against rising antibiotic resistance. However, its high cost and specific safety profile, including risks related to QT prolongation and pregnancy, often limit its use to particular situations. Lefamulin's primary role is currently in CABP treatment. More detailed prescribing and FDA approval information can be found in the FDA website.
