The C-3′ quaternary ammonium cephems belong to group IV of the microbiological classification of cephalosporins. This group is divided into two subgroups according to the position of the quaternary ammonium moiety (C-3 or C-7). These compounds are structurally related to the third-generation cephalosporins (or group III of the microbiological classification), but in addition are featured with two or more of the following properties: broad-spectrum activity including Pseudomonas aeruginosa; activity against Enterobacteriaceae producing type 1 β-lactamase; the presence of a quaternary moiety. The zwitterionic properties of the C-3′ quaternary cephalosporins allow rapid penetration through the outer membrane of Gram-negative bacteria, stability to and low affinity for type 1 β-lactamases in the periplasmic space and high affinity for the penicillin binding proteins (PBPs). Among the currently available analogues cefpirome and cefozopran exhibit a well-balanced antibacterial spectrum against Gram-negative bacilli and Gram-positive cocci. Cefepime is less active against Staphylococcus aureus.