Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing

Abstract

Since its emergence shortly after the discovery of penicillin, antibiotic resistance has escalated dramatically, posing a significant health threat and economic burden. Combating antibiotic resistance, especially in Gram-negative bacteria (GNB) and drug-resistant Mycobacterium tuberculosis, necessitates innovative research, substantial financial investment, and global cooperation to safeguard public health and develop sustainable solutions. Drug repositioning, or drug repurposing, involves identifying new therapeutic applications for existing drugs, utilizing their established safety profiles and pharmacological data to swiftly provide effective treatments against resistant pathogens. Several drugs, including otilonium bromide, penfluridol, eltrombopag, ibuprofen, and ceritinib, have demonstrated potent antibacterial activity against multidrug-resistant (MDR) bacteria. These drugs can disrupt biofilms, damage bacterial membranes, and inhibit bacterial growth. Furthermore, the combination of repurposed drugs with conventional antibiotics can reduce the required dosage of individual drugs, mitigate side effects, and delay the development of resistance, making it a promising strategy against MDR bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Despite its promise, drug repurposing faces challenges such as potential off-target effects, toxicity, and regulatory and intellectual property issues, necessitating rigorous evaluations and strategic solutions. This article aims to explore the potential of drug repurposing as a strategy to combat antibiotic resistance, examining its benefits, challenges, and future prospects. We address the legal, economic, and practical challenges associated with repurposing existing drugs, highlight successful examples, and propose solutions to enhance the efficacy and viability of this approach in combating MDR bacterial infections.