New approaches to developing antimicrobials for resistant bacteria.

Abstract

Few medical advances in the twentieth century which we have just completed have had as much potential to change the health of the world’s population as the discovery and clinical application of antibacterial agents. These agents were truly “miracle drugs” and they made it possible to treat a whole series of diseases that formerly were universally fatal or produced a heavy toll of morbidity. The list of such infections that threatened the human race in the preantibiotic era included a variety of venereal diseases, such as syphilis and gonorrhea, as well as pneumococcal pneumonia, tuberculosis, typhoid fever, bubonic plague, and a host of other diseases. The initial antimicrobial agents were discovered by scientists in Germany (arsphenamine and the sulfonamides) and the United Kingdom (penicillin). Subsequently a great deal of work on the discovery of new antimicrobial agents was carried out in the United States and Japan. Indeed, the Japanese contribution to the discovery of new antimicrobial agents is truly remarkable. There are more than 117 useful antibiotics and related agents that have been discovered by Japanese scientists and, of these, 41 agents have been licensed for clinical use throughout the world. The luster of this discovery has been tarnished over the ensuing years by the progressive development of resistance in multiple species of bacteria. Because of this, as we enter the twenty-first century there is again a major need for new antibacterial agents. At the same time, the number of new agents being developed for clinical use has been progressively decreasing. There are several key reasons for the recent decline in the number of newly marketed antimicrobial agents. In the first place, most of the easy targets allowing selective toxicity for antimicrobials have been discovered. Moreover, it is increasingly costly to bring a new antimicrobial agent to the market. It is currently estimated that the average cost to develop a new prescription drug from the discovery phase to active marketing of the drug is