New Frontiers for Old Medications: Repurposing Approved Drugs Against Gram-Negative Bacterial Infections

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Antimicrobial resistance (AMR) in Gram-negative bacteria is a critical global health threat.
• Traditional antibiotic development is insufficient to combat rapidly emerging resistant strains.
• Innovative therapeutic strategies are urgently needed to address multidrug-resistant Gram-negative infections.

Purpose of the Study:

• To review the potential of drug repurposing as a strategy against Gram-negative bacterial infections.
• To explore repurposed drugs with direct antibacterial activity or the ability to enhance existing antibiotic efficacy.
• To highlight the application of repurposed drugs against antibiotic-resistant bacteria relevant to biological warfare.

Main Methods:

• Literature review of clinically approved drugs with antibacterial properties or synergistic effects.
• Analysis of mechanisms of action for repurposed drugs, including direct antibacterial effects and host-directed therapies.
• Examination of repurposed drug applications against specific Gram-negative pathogens and potential biowarfare agents.

Main Results:

• Repurposed drugs exhibit diverse antibacterial mechanisms: membrane disruption, efflux pump inhibition, iron metabolism interference, quorum sensing suppression, and biofilm inhibition.
• Many repurposed agents show host-directed therapeutic effects, modulating inflammation, enhancing autophagy, or boosting innate immunity.
• Potential applications against antibiotic-resistant Gram-negative bacteria, including those relevant to biological warfare, were identified.

Conclusions:

• Drug repurposing presents a rapid, cost-effective approach to combat the AMR crisis.
• Combining repurposed drugs with conventional antibiotics or using them as host-directed therapies shows promise for treating multidrug-resistant Gram-negative infections.
• Further research and clinical validation are crucial to implement repurposed drugs effectively in clinical practice.