Derivation of a Precise and Consistent Timeline for Antibiotic Development.

Antibiotic resistance is a global health crisis. New classes of antibiotics that can treat drug-resistant infections are urgently needed. To communicate this message, researchers have used antibiotic development timelines, but these are often contradictory or imprecise. We conducted a systematic literature review to produce an antibiotic timeline that incorporates the dates of discovery, first use, and initial reports of the emergence of resistance for the 38 classes of clinically used antibiotics. From our timeline, we derive lessons for identifying new antibiotics that are less prone to resistance. These include a required focus on molecules that exhibit multiple modes of action, possess unusually long 'resistance windows', or those that engage cellular targets whose molecular architectures are at least in part decoupled from evolutionary pressures. Our analysis also further highlights the importance of safeguarding antibiotics as a mechanism for mitigating the development of resistance. We have made our data and sources freely available so that the research community can adapt them to their own needs.