Chapter 13:Drug Discovery for Lower Respiratory Tract Infections

Lower respiratory tract infections are the leading cause of death due to infectious diseases in both the developing world and developed world. The clinical problem is more complicated than the high profile killers, HIV, tuberculosis and malaria, since the infections are caused by a wide variety of infectious agents, including bacteria and viruses, and covers a variety of clinical conditions. For some of the infectious agents, effective vaccines are available, but in all cases there is a need for new medicines, especially in antibacterial therapy. Over the last fifty years many new classes of antibiotics have been discovered, and antimicrobial therapy created the era of modern medicine. However, this trend has slowed down in recent years. The existing progress is being eroded by emergence of resistance against most of the classes of antibiotics. The challenge is that there is now very little research and development of new antibiotics within the pharmaceutical industry: it has become a neglected disease. The majority of drugs under development are improvements on existing classes of medicines. There are two major reasons for this lack of investment. First, the difficulty of achieving a return on investment, given the costs of drug development and the short period of therapy. Second, in recent years, there have been many uncertainties around the regulatory pathway. On top of all this, the promised fruit of the pathogen sequencing and target-based high-throughput screens has not added much to our armamentarium. However, given the mortality and morbidity, the identification of new antibiotics is still a fertile area for research, and a major commitment is needed to keep us from falling behind in the fight against these infections. Without new classes of drugs to fight infection, the long term consequence will be dramatic: a return to the pre-antibiotic era.