Antimicrobial Resistance: from Evolution to Clinical Impact and Strategies forCombating Drug-Resistant Infections

Abstract

Antimicrobial resistance has emerged as a major global health threat, challenging the effective prevention and treatment of infectious diseases. Its evolution spans from the pre-antibiotic era through the early and golden era of antibiotic discovery to the present phase, characterized by a high prevalence of resistance and a limited pipeline of new agents. This review presents a comprehensive overview of epidemiology and the global burden of antimicrobial resistance, projecting its increasing impact on healthcare systems. It discusses common pathogens associated with resistance and key mechanisms involved, including enzymatic drug inactivation, target modification, decreased permeability, efflux pumps, and biofilm formation. The major clinical implications of antimicrobial resistance, such as treatment failure, increased morbidity and mortality, and prolonged hospitalization, are also discussed. Furthermore, the review examines major risk factors that contribute to the emergence and spread of resistance, such as irrational use of antibiotics, inadequate infection control, and lack of awareness. Strategies to combat antimicrobial resistance, such as international initiatives, national policies and committees, and interventions at the community and patient levels, are discussed. The role of pharmacists in antimicrobial stewardship, patient education, and optimization of therapy is also highlighted. Recent advances in antimicrobial research have presented innovative approaches to mitigate the increasing antimicrobial resistance, which comprise nanotechnology-based antimicrobial development, computational methods, including in silico modelling and fragment-based drug design, and drug repurposing. These approaches offer potential for the discovery of novel therapeutic agents with improved stability, efficacy, and reduced resistance development.