Ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations

The last penicillin to be made available for clinical use in the United States was the combination drug piperacillin-tazobactam. Since approval of this agent by the Food and Drug Administration (FDA) in 1993, research on new penicillins and new indications for older penicillins has been limited. The lack of recent developments in the penicillin class of antimicrobial agents, however, neither diminishes their historical significance in the battle against infectious diseases nor their continued importance as safe and effective therapeutic agents. Penicillin, the prototype beta-lactam antibiotic, was first isolated from Penicillium notatum by Dr. Alexander Fleming in 1929. Because of difficulties in production and purification, the drug was not available for clinical use until 1941 when it was proven effective for the treatment of streptococcal and gonococcal infections. Subsequently, the evolution and spread of penicillin-resistant organisms along with the need to increase the antimicrobial spectrum of activity of penicillin led to the development of other beta-lactam antibiotics. Most of these were formulated by manipulating the basic penicillin molecule to result in agents with desirable new antimicrobial and pharmacologic properties. Alternatively, existing penicillins were combined with additional compounds that afforded specific protection from hydrolysis by beta-lactamases. This article reviews only the most recent additions to the formulary of penicillins, the ureidopenicillins, and combinations of penicillins with beta-lactamase inhibitors.