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《2024年世界卫生组织细菌重点病原体清单》:一项用于指导针对抗菌药物耐药性的研究、开发及公共卫生策略的优先级排序研究。

The WHO Bacterial Priority Pathogens List 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance.

作者信息

Sati Hatim, Carrara Elena, Savoldi Alessia, Hansen Paul, Garlasco Jacopo, Campagnaro Enrica, Boccia Simone, Castillo-Polo Juan Antonio, Magrini Eugenia, Garcia-Vello Pilar, Wool Eve, Gigante Valeria, Duffy Erin, Cassini Alessandro, Huttner Benedikt, Pardo Pilar Ramon, Naghavi Mohsen, Mirzayev Fuad, Zignol Matteo, Cameron Alexandra, Tacconelli Evelina

机构信息

Impact Initiatives and Research Coordination Unit, Division of Antimicrobial Resistance, World Health Organization, Geneva, Switzerland.

Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy.

出版信息

Lancet Infect Dis. 2025 Apr 11. doi: 10.1016/S1473-3099(25)00118-5.

Abstract

BACKGROUND

The 2017 WHO Bacterial Priority Pathogens List (BPPL) has been instrumental in guiding global policy, research and development, and investments to address the most urgent threats from antibiotic-resistant pathogens, and it is a key public health tool for the prevention and control of antimicrobial resistance (AMR). Since its release, at least 13 new antibiotics targeting bacterial priority pathogens have been approved. The 2024 WHO BPPL aims to refine and build on the previous list by incorporating new data and evidence, addressing previous limitations, and improving pathogen prioritisation to better guide global efforts in combating AMR.

METHODS

The 2024 WHO BPPL followed a similar approach to the first prioritisation exercise, using a multicriteria decision analysis framework. 24 antibiotic-resistant bacterial pathogens were scored based on eight criteria, including mortality, non-fatal burden, incidence, 10-year resistance trends, preventability, transmissibility, treatability, and antibacterial pipeline status. Pathogens were assessed on each of the criteria on the basis of available evidence and expert judgement. A preferences survey using a pairwise comparison was administered to 100 international experts (among whom 79 responded and 78 completed the survey) to determine the relative weights of the criteria. Applying these weights, the final ranking of pathogens was determined by calculating a total score in the range of 0-100% for each pathogen. Subgroup and sensitivity analyses were conducted to assess the impact of experts' consistency, background, and geographical origin on the stability of the rankings. An independent advisory group reviewed the final list, and pathogens were subsequently streamlined and grouped into three priority tiers based on a quartile scoring system: critical (highest quartile), high (middle quartiles), and medium (lowest quartile).

FINDINGS

The pathogens' total scores ranged from 84% for the top-ranked bacterium (carbapenem-resistant Klebsiella pneumoniae) to 28% for the bottom-ranked bacterium (penicillin-resistant group B streptococci). Antibiotic-resistant Gram-negative bacteria (including K pneumoniae, Acinetobacter spp, and Escherichia coli), as well as rifampicin-resistant Mycobacterium tuberculosis, were ranked in the highest quartile. Among the bacteria commonly responsible for community-acquired infections, the highest rankings were for fluoroquinolone-resistant Salmonella enterica serotype Typhi (72%), Shigella spp (70%), and Neisseria gonorrhoeae (64%). Other important pathogens on the list include Pseudomonas aeruginosa and Staphylococcus aureus. The results of the preferences survey showed a strong inter-rater agreement, with Spearman's rank correlation coefficient and Kendall's coefficient of concordance both at 0·9. The final ranking showed high stability, with clustering of the pathogens based on experts' backgrounds and origins not resulting in any substantial changes to the ranking.

INTERPRETATION

The 2024 WHO BPPL is a key tool for prioritising research and development investments and informing global public health policies to combat AMR. Gram-negative bacteria and rifampicin-resistant M tuberculosis remain critical priority pathogens, underscoring their persistent threat and the limitations of the current antibacterial pipeline. Focused efforts and sustained investments in novel antibacterials are needed to address AMR priority pathogens, which include high-burden antibiotic-resistant bacteria such as Salmonella and Shigella spp, N gonorrhoeae, and S aureus. Beyond research and development, efforts to address these pathogens should also include expanding equitable access to existing drugs, enhancing vaccine coverage, and strengthening infection prevention and control measures.

FUNDING

This work is based on the development of the 2024 WHO BPPL, which was conducted by the WHO AMR Division through grants from the Government of Austria, the Government of Germany, the Government of Saudi Arabia, and the European Commission's Health Emergency Preparedness and Response Authority.

摘要

背景

2017年世界卫生组织细菌重点病原体清单(BPPL)在指导全球政策、研发及投资以应对抗生素耐药性病原体带来的最紧迫威胁方面发挥了重要作用,它是预防和控制抗菌药物耐药性(AMR)的关键公共卫生工具。自发布以来,至少有13种针对细菌重点病原体的新型抗生素已获批准。2024年世界卫生组织BPPL旨在通过纳入新数据和证据、解决先前的局限性并改进病原体优先级排序,在前一清单的基础上进行完善,以更好地指导全球抗击AMR的努力。

方法

2024年世界卫生组织BPPL采用了与首次优先级排序类似的方法,使用多标准决策分析框架。基于八个标准对24种耐药细菌病原体进行评分,包括死亡率、非致命负担、发病率、10年耐药趋势、可预防性、传播性、可治疗性和抗菌药物研发进展情况。根据现有证据和专家判断,对每种标准下的病原体进行评估。对100名国际专家进行了一项采用成对比较的偏好调查(其中79人回复,78人完成调查),以确定各标准的相对权重。应用这些权重,通过计算每种病原体在0 - 100%范围内的总分来确定病原体的最终排名。进行了亚组分析和敏感性分析,以评估专家的一致性、背景和地理来源对排名稳定性的影响。一个独立咨询小组审查了最终清单,随后根据四分位数评分系统将病原体精简并分为三个优先等级:危急(最高四分位数)、高(中间四分位数)和中(最低四分位数)。

结果

病原体的总分范围从排名第一的细菌(耐碳青霉烯类肺炎克雷伯菌)的84%到排名最后的细菌(耐青霉素B组链球菌)的28%。耐抗生素革兰氏阴性菌(包括肺炎克雷伯菌、不动杆菌属和大肠杆菌)以及耐利福平结核分枝杆菌被排在最高四分位数。在通常导致社区获得性感染的细菌中,排名最高的是耐氟喹诺酮类肠炎沙门氏菌血清型伤寒亚种(72%)、志贺氏菌属(70%)和淋病奈瑟菌(64%)。清单上的其他重要病原体包括铜绿假单胞菌和金黄色葡萄球菌。偏好调查结果显示评分者间一致性很强,斯皮尔曼等级相关系数和肯德尔和谐系数均为0.9。最终排名显示出高度稳定性,基于专家背景和来源对病原体进行聚类并未导致排名有任何实质性变化。

解读

2024年世界卫生组织BPPL是确定研发投资优先级和为全球抗击AMR的公共卫生政策提供信息的关键工具。革兰氏阴性菌和耐利福平结核分枝杆菌仍然是关键的优先病原体,突出了它们持续存在的威胁以及当前抗菌药物研发进展的局限性。需要集中努力并持续投资于新型抗菌药物,以应对AMR优先病原体,这些病原体包括负担沉重的耐药细菌,如沙门氏菌和志贺氏菌属、淋病奈瑟菌和金黄色葡萄球菌。除了研发之外,应对这些病原体的努力还应包括扩大现有药物的公平可及性、提高疫苗接种覆盖率以及加强感染预防和控制措施。

资金来源

这项工作基于2024年世界卫生组织BPPL的制定,该清单由世界卫生组织抗菌药物耐药性司通过奥地利政府、德国政府、沙特阿拉伯政府以及欧盟委员会卫生应急准备和响应局提供的赠款开展。

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