According to the World Health Organization, infectious diseases remain the second most common cause of death. Historically, antibiotics have been derived from nature and then chemically manipulated to produce next-generation classes of molecules. These agents are systemically administered to animals or humans and can be accompanied by toxicity, development of antibiotic resistance, and changes to the microflora of the gut. The cost of anti-infective development is prohibitively expensive, and the average time from discovery to completion of the preclinical research phase (in vitro and animal testing) is approximately 6 years. Moreover, even if the anti-infective reaches Phase I clinical trial stage the likelihood of FDA approval is only 19%.
Recent technological and computational advances are accelerating the pace of antimicrobial research. However, we need to characterize host-pathogen interactions to ensure that antimicrobial products tested in vitro will perform as well in vivo and under clinical conditions; this would minimize the chances of failure following the preclinical phase, as well as between phases I and II. Preclinical models that incorporate the host response to pathogens are necessary to create alternative antimicrobial strategies (e.g., suppression of pathogenic potential rather than direct killing of pathogens). Ideally, these models would also accelerate the research and development process.
This presentation will describe new antimicrobials and anti-infective development strategies, such as ex vivo tissue from humans and animals, organoids, and coculture systems. These models more closely reflect host conditions than traditional in vitro experiments, and they can be used to characterize antimicrobial agents that prevent infectious diseases either by suppressing pathogenesis, directly killing microorganisms, or inhibiting host targets.