Resistance of bacteria to antibiotics often involves inactivating enzymes. One approach developed to overcome this mechanism of resistance consists of combining an efficient but possibly unstable antibiotic with a powerful inhibitor of the inactivating enzyme. Attempts have been made with different antibiotics but significant success has only been obtained with the beta-lactams, clavulanic acid and sulbactam being the only compounds currently being used clinically. Sulbactam, a time-dependent irreversible inhibitor of plasmid-mediated penicillinases and of chromosomally mediated penicillinases and cephalosporinases, potentiates the antibacterial activity of beta-lactams but only exhibits a moderate antibacterial activity, which is related to its affinity for the lethal targets of the beta-lactams--the penicillin-binding proteins. In bacterial strains that produce either low amounts of beta-lactamase, or none at all, a synergistic effect can be observed when sulbactam is associated with a beta-lactam antibiotic that has a complementary affinity for the target sites.