New cephalosporins in development pipelines

Abstract

One of the most commercially successful classes of human antibacterials is the cephalosporins, intially introduced in the 1960s, commanding a major market share worldwide. The cephalosporins have evolved slowly, keeping intact the 7R-amino-cephalosporanic acid nucleus, while changing substituents mostly at the C-7 and C-3 positions to develop both oral and parenteral cephalosporins with a wide range of antibacterial activities. With success and wide usage, however, comes resistance, and the current generation of cephalosporins, evolving from the third and fourth generation, are barely keeping one step ahead of β-lactamase and cephalosporinase enzymes that hydrolyse the cephalosporins. More than two dozen oral and parenteral cephalosporins are in development, many seeking a niche position to gain a foothold in a mature therapy area. Key advantages such as β-lactamase and cephalosporinase resistance, coverage of S. pneumoniae, P. aeruginosa or enterococci, reduced side effects, or pharmaco-economic advantage, may distinguish the successful new cephalosporins from the ‘me-too’; cephalosporins.