β-Lactamase inhibitors: a review of the patent literature (2010 - 2013).

INTRODUCTION: New β-lactamases with ever-broadening substrate specificity are rapidly disseminating globally, thereby threatening the efficacy of our best β-lactam antibiotics. A potential solution to this problem is the development of wide-spectrum β-lactamase inhibitors, to be coadministered with existing and new β-lactams. AREAS COVERED: This review covers the patent literature in the β-lactamase inhibitor area roughly from 2010 to 2013, with prior background being provided in the cases of key inhibitors and antibiotic/inhibitor combinations. An effort has been made to identify the strong and weak points of each inhibitor and combination. EXPERT OPINION: Research in this field has become increasingly diverse, with several non-β-lactam inhibitor classes now assuming importance. The emphasis has been on finding inhibitors of AmpC, the extended-spectrum β-lactamases and class A and D carbapenemases that can demonstrate synergy with antibiotics against resistant Gram-negative pathogens. Progress has been made. Metallo-β-lactamases (MBL)-mediated resistance, however, represents an unmet challenge. The author believes that it will be extremely difficult to generate a selective, commercially viable MBL inhibitor with sufficient activity against NDM-1 and that alternate design strategies will need to be employed.