A pairwise approach to revitalize β-lactams for the treatment of TB.

The dual β-lactam approach has been successfully applied to overcome target redundancy in nontuberculous mycobacteria. Surprisingly, this approach has not been leveraged for despite the high conservation of peptidoglycan synthesis. Through a comprehensive screen of oral β-lactam pairs, we have discovered that cefuroxime strongly potentiates the bactericidal activity of tebipenem and sulopenem-advanced clinical candidates-and amoxicillin, at concentrations achieved clinically. β-lactam pairs thus have the potential to reduce TB treatment duration.