Repurposing an Anticonvulsant Drugagainst Pediatric Pathogens: Antibacterial,Antibiofilm, Antioxidant and SynergisticProperties of Gabapentin

Abstract

Aim: Multidrug-resistant bacterial infections present a significant challenge in pediatric cystic fibrosis (CF),
where Staphylococcus aureus and Pseudomonas aeruginosa commonly establish persistent airway colonization
through biofilm formation. Biofilms confer enhanced tolerance to antibiotics and host defences, complicating
infection management. So, the present study was aimed to investigate the antibacterial, antibiofilm, synergistic, and
antioxidant potential of gabapentin, a second-generation neuroleptic drug, against the mentioned CF-associated
pathogens. Materials and Methods: To find the antibacterial activity of the drug and its minimum inhibitory
concentrations, agar diffusion assays were performed. Crystal violet assays were conducted to understand the
biofilm prevention and eradication potentials of the drug. The synergic potential of the drug was analysed with
ampicillin and rifampicin. To study the anti-oxidant activities of the drug, DPPH assay and catalase assay were
performed. Results: The drug gabapentin shown promising antibacterial activities with minimum inhibitory
concentrations of 250 μg/mL for S. aureus and 125 μg/mL for P. aeruginosa. It also inhibited the bacterial
adhesion and early biofilm formation, and significantly disrupted mature biofilms, reducing S. aureus and P.
aeruginosa biofilm mass by up to 86% and 82%, respectively, at 3X MIC. It also showed synergistic interactions
with the tested antibiotics, ampicillin and rifampicin. Additionally, gabapentin exhibited notable antioxidant
activity. Conclusion: The above-mentioned results suggest that gabapentin has multifunctional potential as an
adjunctive therapeutic agent for managing biofilm-mediated, multidrug-resistant infections in paediatric cystic
fibrosis, offering a promising strategy to improve clinical outcomes.