Cephems. Fifty Years of Continuous Research.

Since 1964, seven waves of parenteral cephems have been reported. All of them were designed to meet medical needs. The first (group I) and the third (group III) waves were very successful and drugs belonging to group III are widely used in the treatment of severe infections. A new series of compounds (group VII), with a new compound underdevelopment was designed for the treatment of Staphylococcus aureus strain resistant to methicillin but also to glyco- and lipoglycopeptides. By modifying the substituent at position 3 and 7 of the cephems rings optimal moieties have been fixed leading to potent anti-Gram-positive drugs. Alterations of substituents are still in progress to obtain optimal anti-Gram-positive (anti-MRSA) compounds. The first oral cephem cephalexin was introduced in clinical practice in 1967. Since this time, many esterified and non-esterified cephems have been synthesized and introduced in clinics. There are two groups of compounds, alpha-amino and non-alpha-amino cephems which are classified in six groups according to their chemical structure. The absorption route was explored and three transporting systems have been described according to the physico-chemical properties of these compounds, in addition prodrugs are passively absorbed.