Designing development programs for non-traditional antibacterial agents

Abstract

In the face of rising rates of antibacterial resistance, many responses are being pursued in parallel, including 'non-traditional' antibacterial agents (agents that are not small-molecule drugs and/or do not act by directly targeting bacterial components necessary for bacterial growth). In this Perspective, we argue that the distinction between traditional and non-traditional agents has only limited relevance for regulatory purposes. Rather, most agents in both categories can and should be developed using standard measures of clinical efficacy demonstrated with non-inferiority or superiority trial designs according to existing regulatory frameworks. There may, however, be products with non-traditional goals focused on population-level benefits that would benefit from extension of current paradigms. Discussion of such potential paradigms should be undertaken by the development community.

Fig. 1

STAR: The four novel product categories. Both traditional and non-traditional antibiotic products can be placed into one four fundamental categories: Standalone (effective as monotherapy), Transform (extends the range of activity of an existing product), Augment (enhances the effect of an otherwise effective product), and Restore (rejuvenates the activity of an antibiotic that otherwise lost utility)