**5. Conclusions**

The retreat of the pharmaceutical sector from new antibiotic development has exacerbated the challenge of widespread resistance and signals a critical need for innovation. Repurposing drugs are an increasingly common practice in the pharmaceutical industry where an already existing drug is applied in a new, previously unknown, way. This is advantageous mainly because these drugs are already cleared for human use and thus may skip straight to phase II clinical trials which presents considerably less risk and costs compared to developing new drugs. They could represent a promising approach to enrich the therapeutic arsenal against Gramnegative critical-priority pathogens.

Some drugs indicated for human and veterinary use have been developed in combination with antibiotics; almost of them with polymyxins. They have yielded promising data in preclinical studies, specifically those with activity against biofilm formation and quorum sensing. However, additional relevant issues are required such as new formulations to increase their bioavailability and ADMET tests if the administration route is changed. Other drugs indicated for human use who have showed good activity against these pathogens in preclinical studies can be tested in advanced clinical trials. Early and late stages clinical trials with four repurposing drugs to treat cystic fibrosis and bronchiectasis by *P. aeruginosa*, and endotexemia by *E. coli* have provided promising results. Nevertheless, further clinical studies with extended clinical indications are needed to address the urgent demand for new treatments targeting infections caused by Gram-negative critical-priority pathogens.
