pleuromutilins

Pleuromutilins are a small class of antibiotics derived from natural products produced by fungi of the Pleurotus genus. The core pleuromutilin scaffold has been developed into several agents used in veterinary medicine and, more recently, for human use. Notable members include tiamulin and valnemulin (primarily veterinary), retapamulin (topical), and lefamulin (systemic human use).

The mechanism of action involves binding to the 50S ribosomal subunit and inhibiting the peptidyl transferase center of protein synthesis. This blocks peptide bond formation and elongation, resulting in inhibition of bacterial protein synthesis. Pleuromutilins typically exhibit bacteriostatic activity and have good activity against many Gram-positive bacteria and certain atypical pathogens, with activity extending to some anaerobes. They generally show limited activity against many Gram-negative bacteria, in part due to permeability barriers.

Clinical use spans both veterinary and human medicine. In animals, tiamulin and valnemulin are used to treat various infections in pigs and other species. Retapamulin is applied topically for superficial skin infections, such as impetigo, caused by susceptible organisms. Lefamulin is approved for systemic use in humans, notably for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections; it is available in oral and intravenous formulations. The pleuromutilin class thus provides an alternative mechanism of action for infections caused by susceptible Gram-positive pathogens and certain atypical organisms.

Resistance can arise through mutations in the ribosomal RNA or ribosomal proteins, reducing drug binding, and cross-resistance can occur within the class. Safety and regulatory status vary by compound and country, with lefamulin representing the primary human-use pleuromutilin and several other agents mainly serving veterinary needs.