Current Issues

The global escalation of antimicrobial resistance (AMR) has emerged as a serious public health threat, limiting the effectiveness of current antibiotics and complicating the treatment of infectious diseases. Multidrug-resistant (MDR) organisms—such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli—have developed sophisticated defense mechanisms, including enzymatic inactivation of drugs, efflux pump overexpression, target site mutations, and robust biofilm formation. As the conventional antibiotic pipeline declines, phytochemicals—bioactive compounds derived from medicinal plants—have re-emerged as promising candidates due to their broad-spectrum antimicrobial properties and low propensity to induce resistance. Phytochemicals such as curcumin, berberine, quercetin, allicin, and eugenol act through diverse molecular mechanisms, including membrane disruption, inhibition of protein and nucleic acid synthesis, ROS generation, and quorum sensing suppression. Many of these compounds can dismantle biofilms and restore the activity of conventional antibiotics via synergistic interactions, offering a dual advantage in the treatment of resistant infections. The recent integration of these agents into advanced delivery systems, such as hydrogels, nanoemulsions, liposomes, microneedles, and stimuli-responsive nanocarriers, has significantly improved their stability, solubility, site-specific delivery, and controlled release, particularly for topical application against chronic wounds, skin infections, and device-associated biofilms. Despite these advances, the path to clinical translation is hindered by issues such as batch-to-batch variability, lack of standardized toxicity profiles, and regulatory ambiguity concerning natural compounds. Overcoming these barriers will require a multidisciplinary approach, incorporating modern pharmacological tools, in silico modeling, robust in vivo studies, and harmonized regulatory frameworks. This review aims to present a comprehensive overview of the antimicrobial potential of phytochemicals, their mechanisms of action, modern formulation approaches for topical delivery, and the key challenges limiting their therapeutic use against AMR-associated diseases.

Keyword: Phytochemicals; Antimicrobial resistance; Multidrug-resistant bacteria; Bioactive natural compounds; Topical drug delivery