New β-lactam antibiotics and β-lactamase inhibitors.

IMPORTANCE OF THE FIELD: β-Lactam antibiotics are among the most frequently prescribed antibiotics used to treat bacterial infections. However, their utility is being threatened by the worldwide proliferation of β-lactamases with broad hydrolytic capabilities, especially in multidrug-resistant Gram-negative bacteria.

AREAS COVERED IN THIS REVIEW: This review describes new β-lactams and β-lactamase inhibitors described in the patent literature primarily between 2007 and 2010, together with supportive meeting abstracts and relevant descriptive literature.

WHAT THE READER WILL GAIN: Readers will learn which classes of β-lactam antibiotics are being explored as the most promising groups of compounds to counteract resistance in Gram-negative pathogenic bacteria. Somewhat surprisingly, few traditional β-lactam classes such as penicillins or cephalosporins were described in the literature, other than in combinations with other β-lactams or β-lactamase inhibitors that are being developed to inhibit enzymes from all molecular classes.

TAKE HOME MESSAGE: β-Lactam antibiotics are currently being developed as monotherapy by only a few companies. The major emphasis in the past 4 years has been the discovery of novel β-lactamase inhibitors or inhibitor combinations that will allow use of β-lactams against multidrug-resistant bacteria. The use of β-lactams as single agents appears to be a limited option for the future.