Antibiotic-Free Strategies for Managing Antimicrobial-Resistant Infections

Antimicrobial resistance (AMR) presents a global health challenge that is projected to cause nearly 2 million deaths annually by 2050. With a growing ageing population and the rise of antibiotic-resistant strains globally, developing effective alternatives to combat infections while reducing AMR risks is critical. Over recent decades, antibiotic-free strategies have emerged as promising approaches, offering advantages over traditional antibiotics and reducing the likelihood of resistance. This review highlights antibiotic-free antimicrobial strategies for applications in chronic wound care, hard tissue repair, personal protective equipment, as well as hospital hygiene and infection control. We begin by outlining the broader AMR problem and then examine natural strategies—including the use of agents such as manuka honey—followed by synthetic approaches involving nanomaterials and metal–organic frameworks (MOFs), as well as biological and bioinspired antimicrobial strategies, involving antimicrobial peptides, antibodies, bacteriophages, extracellular vesicles, and macrocycles. Finally, we discuss innovations in artificial intelligence (AI)-assisted antimicrobial development and stimulus-responsive materials, before introducing a conceptual design framework for antibiotic-free antimicrobial materials. This review provides a comprehensive assessment of emerging antibiotic-free strategies to guide the development of next-generation antimicrobial solutions that reduce reliance on antibiotics and mitigate AMR in clinical and healthcare settings.