The art of fusion: from penams and cephems to penems

This synopsis of published literature summarises the key chemical and bacteriological characteristics of penicillins, i.e. penams, cephalosporins, i.e. cephems, and their hybrid structure, i.e. the penems. Consequently, the antibacterial spectrum of a typical penem, e.g. faropenem, encompasses gram-positive as well as gram-negative species. Dependent from the substituents at position 1 of the five-membered saturated ring fused to the beta-lactam ring oxa-, carba-, or thiopenems can be differentiated. A major determinant of their antibacterial activity and CNS-excitatory potential, however, is the C-2 side chain. The excitatory potential correlates with the basicity of the C-2 side chain as does their antibacterial activity against gram-negative species and non-fermenters like P. aeruginosa. Lipophilicity is a determinant for good in vitro activity against gram-positive bacteria. Several investigational penems exhibit interesting antibacterial spectra, encompassing methicillin resistant staphylococci, enterococci and even P. aeruginosa due to their improved binding affinity to both wild-type and modified low-affinity penicillin binding proteins. The development of these agents may offer therapeutic alternatives for the management of infections.