Perspectives on Colistin—An Old Antibiotic with Renewed Relevance in Modern Medicine

Antibiotic resistance among bacteria represents a major challenge in modern medicine. The absence of antibiotics effective against multidrug-resistant pathogens triggers interest in reviving older antibiotics. This review aims to provide a focused and updated perspective on the reintroduction of polymyxin antibiotics, with a particular emphasis on colistin, a cyclic oligopeptide initially used in the 1950s and 1960s. We analyze colistin from multiple perspectives, including (i) its historical and contemporary clinical applications, (ii) pharmacokinetic and pharmacodynamic properties, and (iii) use in veterinary medicine and animal husbandry. Key unresolved issues are highlighted, such as colistin toxicity, challenges in susceptibility testing, the emergence of resistance, including the mcr gene variants, and inconsistent clinical evidence supporting combination therapy. By integrating historical background with current data, this review provides a comprehensive overview of the therapeutic relevance, limitations, and ongoing challenges associated with colistin in the era of multidrug-resistant Gram-negative infections.