A model-based PK/PD antimicrobial chemotherapy drug development platform to simultaneously combat infectious diseases and drug resistance

Abstract

The impact of antibiotics on health care likely exceeds that of any other class of drugs by greatly reducing the likelihood of debilitating disease and/or death prevalent in the preantibiotic era. However, the coincidence of (1) medicinal chemists' continuing struggle to produce druggable antibiotics with novel targets that overcome emergence of drug resistance altogether, (2) the general decline of active development of new antimicrobial agents, (3) the prevalence (and growth because of increased use) of antimicrobial resistance to legacy molecules, and (4) the ever-present threat of bioterrorism, mean that antibiotic drug development must necessarily focus on resistance counter-measures throughout the discovery and development process. Thus, in essence, antiinfective discovery and development programs are (or should be) intrinsically charged with the combined responsibility of minimization of resistance selection and targeting drug resistant infections from the outset. © American Association of Pharmaceutical Scientists 2011.