Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

Abstract

Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.