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.