beta-lactamase insensitive or inhibitory beta-lactams: two approaches to the challenge of ampicillin-resistant E. coli.

The rising incidence of Gram-negative bacteria resistant to ampicillin in hospitals has brought about a need to develop novel beta-lactam antibiotics. This challenge is being met in two ways. First, attempts have been made to develop compounds insensitive to beta-lactamase hydrolysis. This has proved difficult in the penicillin series, but cefuroxime and cefoxitin are cephalosporin derivatives with the necessary properties. The second approach has been to discover novel beta-lactam nuclei capable of inhibiting beta-lactamases. So far this had led to the production of the clavulins and the olivacins, the latter class of molecules being closely related chemically to thienamycin.