Metal Complexes against Multidrug-Resistant Bacteria: Recent Advances (2020-Present)

Abstract

The increasing prevalence of multidrug-resistant (MDR) bacterial infections worldwide represents a critical challenge to contemporary healthcare, with high mortality rates attributed primarily to biofilm formation and the widespread dissemination of antibiotic resistance genes. Metal complexes have emerged as promising candidates for combating resistant pathogens owing to their distinctive multi-target mechanisms. These compounds demonstrate dual functionality by effectively penetrating bacterial biofilms while simultaneously exerting antimicrobial effects through multiple pathways, including reactive oxygen species (ROS) production and interference with essential metal homeostasis. The growing inadequacy of conventional antibiotics against resistant infections necessitates the development of novel metal-based antimicrobial agents with low resistance propensity, high efficacy, and minimal toxicity profiles. The clinical validation of metallodrugs like auranofin provides a crucial foundation for designing next-generation anti-MDR therapeutics. Notably, complexes of gold (Au), silver (Ag), copper (Cu), gallium (Ga), iridium (Ir), and ruthenium (Ru) demonstrate multifaceted mechanisms of action through selective targeting of bacterial resistance mechanisms. These attributes provide a strategic framework for developing next-generation metal-based antibacterials. This review systematically summarizes recent advances (2020–present) in the design and application of these six metal complexes against MDR bacteria, emphasizing their structural motifs, antimicrobial potency, and mechanistic insights. The presented insights contribute novel approaches to combat the intensifying global challenge of antibiotic resistance.

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