Pleuromutilin and its Derivatives: Promising Novel Anti-Infective Agents

Due to the emergence and spread of the drug resistance to numerous antibiotics, global research attempts focus on new classes of antibiotics with different mechanisms of action from currently used drugs. Pleuromutilin was first identified as a natural antibiotic in 1951 from the New York Botanical Garden and Columbia University. The substance was isolated from Pleurotus mutilus and Pleurotus passeckerianus. Nevertheless, pleuromutilin was first launched in 1979 (tiamulin) for use in veterinarians. However, antibiotics with new targets or employing a different action mechanism are always attractive because they conquered recognized resistance by the bacteria and were not resisted against approved antibiotic classes. Pleuromutilin has a unique antibacterial activity that binds to the peptidyl transferase at the central area of the bacteria's 50S ribosome to inhibit protein synthesis. Pleuromutilin antibiotics have antimicrobial activity against Gram-positive pathogens. Besides, they cover some fastidious Gram-negative bacteria. As Gram-positive bacteria increased resistance against currently approved antibiotics, the pleuromutilin antibiotic was investigated to develop a systemically antibacterial drug to be used in humans. In 2006, lefamulin was developed and started to encounter studying for systemic infection in humans. Lefamulin is a semisynthetic pleuromutilin antibiotic, and the US FDA approved it for community-acquired bacterial pneumonia (CABP) treatment in August 2019. This review will focus on this antibiotic's critical issues, the relevant bacterial spectrum activity, preclinical and clinical information, and potentially therapeutic properties of pleuromutilin antibiotic.