Alternative Approaches to Antibiotics: Phage Therapy, Antimicrobial Peptides, and Phytotherapeutics

Vollständiger Abstract

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Antibiotic resistance has emerged as a critical threat to global health, food security, and economic stability due to the overuse of antibiotics in human medicine and livestock production. This review examines the mechanisms of antibiotic action and resistance, clinical and environmental consequences of resistance, and evaluates current alternative strategies to conventional antibiotics. Bacteria develop resistance through enzymatic degradation, target modification, reduced membrane permeability, alternative metabolic pathways, and horizontal gene transfer. The misuse of antibiotics in animal breeding as growth promoters has further accelerated the spread of resistant and multidrug-resistant pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. To address this crisis, the review discusses three major alternatives: phage therapy, antimicrobial peptides (AMPs), and phytochemicals/plant extracts. Phage therapy offers highly specific bacterial lysis with minimal impact on microbiota, though challenges include narrow host range and phage resistance. AMPs exhibit broad-spectrum antimicrobial, antibiofilm, and immunomodulatory activities, with several FDA approved peptides already in clinical use, but limitations include high minimum inhibitory concentrations and potential toxicity. Plant-derived phytochemicals demonstrate antibacterial and efflux pump inhibitory effects and show synergistic potential when combined with antibiotics. The findings suggest that a multifaceted approach combining prudent antibiotic stewardship with investment in phage therapy, AMPs, and plant-based compounds is essential to mitigate resistance and ensure sustainable treatment options. Further in vivo studies and clinical trials are needed to optimize efficacy, safety, and large-scale application of these alternatives.