Current Trends in β-Lactam Based β-Lactamases Inhibitors

The introduction of antibiotics to treat bacterial infections either by killing or blocking their growth has been accompanied by the development of resistance mechanism that allows the bacteria to survive and proliferate. In particular the successive series of beta-lactams have selected several generations of beta-lactamases including ESBLs, AmpC beta-lactamases, KPC carbapenamases in Enterobacteriaceae, the metallo beta-lactamases VIMs and IMPs, and very recently the threatening NDM-1 that confers resistance to virtually any clinically used antibiotic. The increasing use of carbapenems due to the spread of resistance to other existing antibacterial agents has facilitated the spread of resistance, especially in Acinetobacter spp. due to OXA- and metallo-carbapenemases. The pharmaceutical industry, that abandoned this field at the end of the nineties, is now trying to recover by developing some novel beta-lactam antibiotics and novel beta-lactamase-inhibitors, the latter to be used in combination with new as well as seasoned beta-lactam antibiotics. This article provides a survey of patent and scientific literature for beta-lactamase inhibitors discovered in the period 2006-2010.