New β-lactam antibiotics and β-lactamase inhibitors.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Bush
Karen
K
Indiana University, Biology Department, Bloomington, IN 47405, USA. karbush@indiana.edu
Macielag
Mark J
MJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams