pleuromutilinbased

Pleuromutilin-based refers to a class of antibiotics derived from pleuromutilin, a natural product isolated from the fungus *Pleurotus mutilus*. These antibiotics function by inhibiting bacterial protein synthesis. Specifically, they bind to the 50S ribosomal subunit, interfering with the peptidyl transferase center and preventing the formation of peptide bonds. This mechanism of action is distinct from many other antibiotic classes, which can be advantageous in overcoming existing resistance mechanisms.

The pleuromutilin scaffold is a tetracyclic diterpene structure. Modifications to this core structure have led to the development of various semi-synthetic derivatives with improved pharmacokinetic properties and broader antibacterial spectra. Key examples include tiamulin, valnemulin, and retapamulin. Tiamulin and valnemulin are primarily used in veterinary medicine to treat respiratory and enteric infections in livestock and poultry, while retapamulin is used topically in humans for the treatment of bacterial skin infections.

Resistance to pleuromutilin-based antibiotics can arise through mutations in the ribosomal RNA genes or ribosomal proteins that are part of the antibiotic binding site, or through efflux pump mechanisms. Despite the emergence of resistance, pleuromutilin derivatives remain valuable therapeutic agents, particularly in veterinary settings, due to their efficacy against certain Gram-positive and Gram-negative bacteria, including some resistant strains. Research continues to explore new pleuromutilin derivatives for potential human and animal applications.