Evolution of ß‐Lactamase Inhibitors

Abstract

After the introduction of penicillin G into therapeutics, bacteria became increasingly resistant to this penicillin and subsequent ß‐lactam antibiotics. The major cause of this resistance is ß‐lactamase, an enzyme produced by the bacterium, that destroys the antibiotic before it reaches its target within the bacterial cell. One of the ways to combat this resistance has been the use of ß‐lactamase inhibitors, which protect the antibiotic by inactivating the destructive enzyme before the antibiotic reaches the infection site. At present, at least two ß‐lactamase inhibitors are in clinical use, clavulanic acid and sulbactam, that are effective against most ß‐lactamases, although relatively inactive against class I ß‐lactamases, the cephalosporinases. Newly developed ß‐lactamase inhibitors, however, especially BRL‐42715, show some promise against these enzymes.