The pleuromutilin antibiotics: a new class for human use.

TLDR

Pleuromutilins, first discovered in 1950, entered veterinary use in 1979 and 1999, and were approved for topical human use in 2007, but recent lead optimization has produced orally and intravenously deliverable derivatives with broad activity against common skin and respiratory pathogens. The review aims to present the key properties of pleuromutilin derivatives and evaluate their potential for systemic therapy in humans. These derivatives are primarily engineered by modifying the C(14) side chain to enhance systemic therapeutic potential. BC-3205 and BC-7013, two novel pleuromutilins from Nabriva Therapeutics, have entered clinical trials.

Abstract

Pleuromutilins were discovered as natural-product antibiotics in 1950. Tiamulin was the first pleuromutilin compound to be approved for veterinary use in 1979, followed by valnemulin in 1999. It was not until 2007 that retapamulin became the first pleuromutilin approved for use in humans. However, retapamulin is limited to topical application. Recent advances in lead optimization have led to the synthesis of pleuromutilins that combine potent antibacterial activity with favorable pharmaceutical properties, making these compounds suitable for oral and intravenous delivery. Most pleuromutilins have an antibacterial spectrum that spans the common pathogens involved in both skin and respiratory tract infections. Two new pleuromutilins, BC-3205 and BC-7013 (both Nabriva Therapeutics AG), have entered clinical trials. In this review, the key properties of pleuromutilin derivatives, designed primarily through modifications at the C(14) side chain, are presented, and the potential of these compounds in systemic therapy in humans is discussed.