Antibiotic Resistance: Revisiting Older Antibiotics for Modern Bacterial Challenges

ABSTRACT The growing challenge of antibiotic resistance necessitates a strategic re‐evaluation of older antibiotics as vital antimicrobial tools. This re‐assessment, while facing hurdles, reveals promising possibilities. Understanding bacterial resistance mechanisms is fundamental for effectively utilizing these legacy drugs. Older antibiotics typically have a narrower spectrum than modern ones, emphasizing careful antimicrobial stewardship to prevent overuse and further resistance. Strategies to improve their clinical value include combination therapies with newer antibiotics to overcome resistance and boost efficacy. Furthermore, repurposing and reformulating older antibiotics can enhance their activity against contemporary bacterial strains. Targeted treatment regimens focusing on specific clinical niches or bacterial species where older antibiotics remain effective, are crucial. Streptothricin F exemplifies this renewed potential, particularly against Gram‐negative bacteria, a recent research focus. Despite prior concerns about its limited spectrum and resistance potential, recent findings indicate streptothricin F's re‐emerging utility. This antibiotic's ability to target highly resistant Gram‐negative pathogens, such as carbapenem‐resistant Enterobacterales, highlights its potential as a valuable therapeutic option. This encouraging discovery underscores the need for further research into streptothricin F's role in combating drug‐resistant Gram‐negative pathogens, opening avenues for future investigation.