Pleuromutilins
Fungus-derived antibiotics that block the peptidyl transferase centre of the 50S ribosome; lefamulin treats community-acquired pneumonia.
What they are
Semisynthetic derivatives of pleuromutilin, a natural product of Pleurotus fungi discovered in the 1950s and first used in veterinary medicine. Two are used in humans: retapamulin, topical for impetigo, and lefamulin, oral and intravenous, the first systemic member of the class.
Mechanism of action
They bind the 50S subunit near the A and P sites of the peptidyl transferase centre; the pocket closes around the drug and transfer RNA cannot settle, so no peptide bond forms. The site partly overlaps those of other 50S inhibitors, but the binding mode is unique and cross-resistance is uncommon.
Target: Peptidyl transferase centre of the 50S ribosomal subunit (23S rRNA, A and P sites)
Drugs in this class
Others in the class
- retapamulin
Test yourself
Think of the answer, then tap the question to see it.
Which step of protein synthesis do pleuromutilins block?
Peptide bond formation at the peptidyl transferase centre of the 50S subunit.
What is the only systemic pleuromutilin for humans, and what is it used for?
Lefamulin, for community-acquired bacterial pneumonia in adults.
Why does lefamulin not work for an E. coli urinary infection?
Pleuromutilins have no useful activity against Enterobacterales.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Lefamulin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.