New β-lactam antibiotics and β-lactamase inhibitors

Importance of the field: beta-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 beta-lactamases with broad hydrolytic capabilities, especially in multidrug-resistant Gram-negative bacteria. Areas covered in this review: This review describes new beta-lactams and beta-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 beta-lactam antibiotics are being explored as the most promising groups of compounds to counteract resistance in Gram-negative pathogenic bacteria. Somewhat surprisingly, few traditional beta-lactam classes such as penicillins or cephalosporins were described in the literature, other than in combinations with other beta-lactams or beta-lactamase inhibitors that are being developed to inhibit enzymes from all molecular classes. Take home message: beta-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 beta-lactamase inhibitors or inhibitor combinations that will allow use of beta-lactams against multidrug-resistant bacteria. The use of beta-lactams as single agents appears to be a limited option for the future.