Sulbactam/ampicillin was recently marketed for use in several infections caused by beta-lactamase-producing organisms. Sulbactam is the second beta-lactamase inhibitor to become available in the United States. Interest in inhibition of beta-lactamases arose in the late 1960s when a combination consisting of an antibacterial agent and an enzyme inhibitor was found effective in the treatment of certain resistant gram-negative infections. It is now well accepted that the addition of a beta-lactamase inhibitor to a beta-lactam antibiotic may expand its usefulness in a variety of infections.The penicillin derivatives, known as beta-lactam antibiotics, possess a four-membered ring (beta-lactam ring) fused to a second ring (Figure). It is the beta-lactam ring that is essential for the inhibition of bacterial cell wall synthesis and subsequent bactericidal activity of these agents. The development of resistance to beta-lactam antibiotics may occur by a number of mechanisms, although the most important is bacterial production of enzymes (beta-lactamases) that are capable of beta-lactam ring hydrolysis and inactivation.Sulbactam resembles the penicillin derivatives in structure (Figure) and is able to preserve their activity by its ability to inhibit the action of beta-lactamases, particularly those of the Richmond classes II-V (gram-negative) and the group A beta-lactamases (gram-positive). Sulbactam is referred to as a “suicide inhibitor” because while forming an irreversible complex with the enzyme, it is destroyed in the process. By virtue of its ability to render the beta-lactamases inactive, sulbactam has been combined with ampicillin in an effort to restore its activity against a number of pathogens that have developed resistance by this mechanism.