Antibiotic drug development: Moving forward into the clinic

Abstract

The cornerstone of all antibacterial drug discovery and development organizations is the microbiology and microbiological profiling from early hit analyses in drug discovery to post-launch in the marketplace. In the early stages of drug discovery, many inhibitors of bacterial targets can be identified, but if that activity does not translate into bacterial killing and pharmacological properties, the molecule will not advance to phase III clinical studies. An understanding of microbiology is essential in lead optimization where the activity against the targeted pathogens is to be optimized along with additional pharmacological traits such as in vitro and in vivo safety and efficacy. In early drug development, an agent needs to clearly demonstrate safety and efficacy in preclinical models and, thereby, explore the spectrum of potential clinical use and predict safety and efficacy in humans. In phase II and phase III clinical trials, microbiology is essential for the demonstration of pathogen eradication and correlation with clinical outcome for the establishment of clinical breakpoints for the differentiation of susceptible and resistant bacterial populations. Finally, microbiology remains an essential component of life cycle management mandatory regulatory agency periodic safety updates, antimicrobial surveillance programs for monitoring emergence of resistance, and support for supplementary indications.