Ashfield Tom, Cooray Mineli, Jimenez-Acha Isabel, Riaz Zeshan, Gifford Danna R, Lagator Mato
The Signpost, Winchester, Hampshire, UK.
School of Life Sciences, University of Warwick, Warwickshire, UK.
Microbiology (Reading). 2025 Feb;171(2). doi: 10.1099/mic.0.001534.
Antimicrobial resistance poses one of the greatest and most imminent threats to global health, environment and food security, for which an urgent response is mandated. Evolutionary approaches to tackling the crisis tend to focus on proximate issues including the mechanisms and pathways to resistance, with associated calls to action for infection control and antimicrobial stewardship. This is of clear benefit but overlooks the fundamental influence of policy and stakeholder decision-making on resistance evolution. In 1945, Fleming issued a stark warning on the irresponsible use of penicillin and its potential to cause death due to penicillin-resistant infections. Attention to resistance evolution theory and heeding Fleming's advice could have allowed for a vastly different reality. Embedding evolutionary theory within policy, industry and regulatory bodies is not only essential but is now a race against time. Hence, critical appraisal of historical behaviour and attitudes at a global scale can inform a paradigm of anticipatory and adaptive policy. To undertake this exercise, we focused on the largest group of antibiotics with the greatest clinical and economic footprint, the beta-lactams. We examined historical case studies that affected how beta-lactams were developed, produced, approved and utilized, in order to relate stakeholder decision-making to resistance evolution. We derive lessons from these observations and propose sustainable approaches to curb resistance evolution. We set a position that actively incorporates an evolutionary theory of antimicrobial resistance into decision-making within antimicrobial development, production and stewardship.
抗菌药物耐药性对全球健康、环境和粮食安全构成了最重大且最紧迫的威胁之一，因此必须做出紧急应对。应对这一危机的进化方法往往侧重于直接问题，包括耐药性的机制和途径，同时呼吁采取行动进行感染控制和抗菌药物管理。这显然有益，但却忽视了政策和利益相关者决策对耐药性进化的根本影响。1945年，弗莱明就青霉素的不当使用及其导致耐青霉素感染死亡的可能性发出了严厉警告。关注耐药性进化理论并听从弗莱明的建议，可能会带来截然不同的现实。将进化理论融入政策、行业和监管机构不仅至关重要，而且现在是一场与时间的赛跑。因此，在全球范围内对历史行为和态度进行批判性评估，可以为一种前瞻性和适应性政策范式提供参考。为了进行这项工作，我们聚焦于临床和经济影响最大的最大一类抗生素——β-内酰胺类抗生素。我们研究了影响β-内酰胺类抗生素研发、生产、批准和使用方式的历史案例研究，以便将利益相关者的决策与耐药性进化联系起来。我们从这些观察中吸取教训，并提出遏制耐药性进化的可持续方法。我们确立了一个立场，即在抗菌药物研发、生产和管理的决策过程中积极纳入抗菌药物耐药性的进化理论。
