Repurposed Drugs Boost Activity Against Resistant Pathogens

Commonly prescribed medications used to treat hypertension and depression may help improve the effectiveness of existing antimicrobial therapies against multidrug-resistant pathogens, according to a study. Researchers found that several combinations of repurposed non-antibiotic drugs enhanced the activity of ciprofloxacin and fluconazole against resistant bacterial and fungal isolates in vitro.

The rise of antimicrobial resistance (AMR) has intensified efforts to identify alternative treatment strategies without relying solely on the development of new antibiotics. Drug repurposing—the use of established medicines for new therapeutic purposes—has emerged as a promising approach, particularly because approved drugs already have well-characterised safety profiles and are widely available.

Researchers Tested Common Medicines as Adjuvants

The investigators evaluated three licensed non-antibiotic medications—amlodipine, fluoxetine, and escitalopram—against multidrug-resistant clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans.

The drugs were tested individually and in combination with the antibiotic ciprofloxacin or the antifungal fluconazole using multiple laboratory techniques, including minimum inhibitory concentration (MIC) testing and checkerboard assays to assess synergy.

The team also used molecular docking and computational modelling to explore potential interactions between the repurposed drugs and microbial targets, although these analyses were intended only to generate hypotheses rather than confirm mechanisms of action.

Drug Combinations Enhanced Antimicrobial Activity

Among the individual drugs, fluoxetine demonstrated the strongest antimicrobial activity across all three organisms tested.

Several combinations also produced synergistic effects, with selected triple-drug regimens reducing antimicrobial MIC values by between four- and 64-fold compared with antimicrobial therapy alone.

The greatest inhibitory effects were observed with ciprofloxacin plus fluoxetine and amlodipine against S. aureus, ciprofloxacin plus fluoxetine and escitalopram against P. aeruginosa, and ciprofloxacin combined with amlodipine and fluconazole against C. albicans.

The researchers note that antimicrobial enhancement varied depending on both the pathogen and the specific drug combination used.

Potential Strategy to Combat Antimicrobial Resistance

Because all three repurposed medications are already licensed for clinical use, the findings raise the possibility that they could eventually be investigated as adjuncts to existing antimicrobial therapies.

Such combination strategies may offer a practical means of improving treatment effectiveness while helping preserve the activity of current antibiotics and antifungals, particularly in settings where access to newer agents is limited.

However, the authors stress that the observed effects were demonstrated only under laboratory conditions.

Further Research Needed

The researchers conclude that selected combinations of repurposed drugs warrant further investigation as potential antimicrobial adjuvants. While checkerboard testing identified genuine synergistic interactions, they caution that diffusion assays should be regarded as preliminary screening methods.

Similarly, the computational modelling supported the experimental observations but did not establish how the drugs exerted their antimicrobial effects.

Further studies in animal models and clinical trials will be necessary to determine whether these combinations can safely and effectively improve outcomes for patients with multidrug-resistant bacterial and fungal infections.

Reference

Alkhawlani MA  et al. Repurposing amlodipine, fluoxetine, and escitalopram as non-antibiotic adjuvants: in vitro enhancement of ciprofloxacin and fluconazole activity against multidrug-resistant bacterial and candida clinical isolates. BMC Microbiol. 2026;DOI: 10.1186/s12866-026-05443-4.