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抗菌药物耐药性是一项重大的全球公共卫生挑战,2019年估计有495万人的死亡与抗菌药物耐药性有关。2024年5月17日,世界卫生组织(WHO)发布最新细菌优先病原体预警清单《WHO Bacterial Priority Pathogens List(BPPL), 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance》,以下简称“2024 WHO BPPL” 。
2024 WHO BPPL是WHO在2017年预警清单的基础上制定的,旨在应对当前的挑战,并为决策者、国家卫生当局和参与研发和投资决策的其他人员提供基本指导。
2024年的WHO BPPL包括15个抗生素耐药病原体家族,这些病原体被分为关键(critical)、高(high)和中(medium)三个优先级类别。相比2017年的版本,此次更新将对一线抗生素耐药的革兰氏阴性菌,如鲍曼不动杆菌(Acinetobacter baumannii)和各种肠杆菌目病原体,以及耐利福平的结核分枝杆菌(rifampicin-resistant Mycobacterium tuberculosis)列为关键优先级,因它们转移耐药基因的能力、引起的感染和疾病的严重性和/或其在全球范围内造成重大负担。
关键、高度和中度优先级组的定义
1. 关键优先级组(Critical group):对公共卫生构成最严重威胁的抗生素耐药(Antibiotic resistant ,ABR)的细菌病原体,主要是基于治疗选择有限、高疾病负担(死亡率和发病率)、ABR呈上升趋势、对此很少有或没有正在开发的候选药物。关键优先级别组的病原体感染也可能特别难以预防,并具有高度传播性;在某些人群或地理区域,病原体可能具有全球性的耐药机制和/或多重耐药菌株。
2. 高度优先级组(High group):非常难以治疗、疾病负担(死亡率和发病率)显著、耐药性呈上升趋势的ABR细菌病原体,其特别难以预防,具有高度传播性,对此正在开发的潜在治疗方法很少。虽然这类病原体并非属于全球性关键问题,但对某些人群和特定地理区域可能至关重要。
3. 中度优先级组(Medium group):中等治疗难度、中等疾病负担(死亡率和发病率)和中等耐药性趋势相关的ABR细菌病原体,具有独特的可预防性或可传播性问题,以及相对较多的候选治疗方案。同样,虽然这类病原体在全球范围内可能不是至关重要的,但对某些人群和特定地理区域可能是至关重要的。
将沙门氏菌和志贺氏菌(Salmonella and Shigella)列为高优先级,反映了它们对现有治疗方法的耐药性不断增加,以及与这些病原体相关的高感染性。2024年BPPL中的其他高优先级病原体包括抗生素耐药的铜绿假单胞菌(Pseudomonas aeruginosa)和金黄色葡萄球菌(Staphylococcus aureus),因为它们在医疗环境中的高度威胁。高优先级类别还包括呈现多重耐药菌株的淋病奈瑟菌(Neisseria gonorrhoeae),其治疗选择受到限制。另一个具有公共卫生重要性的病原体是抗生素耐药的屎肠球菌(Enterococcus faecium),由于其能够在“同一健康”范围内传递耐药性而被重视。
2024BPPL将A组和B组链球菌、肺炎链球菌(Streptococcus pneumoniae)和流感嗜血杆菌(Haemophilus influenzae)纳入中等优先级类别,表明迫切需要解决其公共卫生影响,尤其是在资源有限的环境中其对弱势人群的影响。有关清单背后的理念、制定清单所使用的方法论以及主要发现的更多细节,可以在随附的报告中找到。
The 2024 WHO Bacterial Priority Pathogens List (WHO BPPL) is an important tool in the global fight against antimicrobial resistance. Building on the 2017 edition, the 2024 WHO BPPL updates and refines the prioritization of antibiotic-resistant bacterial pathogens to address the evolving challenges of antibiotic resistance. The list categorizes these pathogens into critical, high, and medium priority groups to inform research and development (R&D) and public health interventions.
The 2024 WHO BPPL covers 24 pathogens, spanning 15 families of antibiotic-resistant bacterial pathogens. Notable among these are Gram-negative bacteria resistant to last-resort antibiotics, drug-resistant mycobacterium tuberculosis, and other high-burden resistant pathogens such as Salmonella, Shigella, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Staphylococcus aureus. The inclusion of these pathogens in the list underscores their global impact in terms of burden, as well as issues related to transmissibility, treatability, and prevention options. It also reflects the R&D pipeline of new treatments and emerging resistance trends.
The WHO BPPL acts as a guide for prioritizing R&D and investments in AMR, emphasizing the need for regionally tailored strategies to effectively combat resistance. It targets developers of antibacterial medicines, academic and public research institutions, research funders, and public–private partnerships investing in AMR R&D, as well as policy-makers responsible for developing and implementing AMR policies and programs.
2024年WHO的细菌类重点病原体目录包括以下细菌:
1. 关键优先级组(Critical group)病原体(4):
肠杆菌科细菌(Enterobacterales),碳青霉烯类药物耐药;
肠杆菌科细菌(Enterobacterales),第三代头孢菌素耐药;
鲍曼不动杆菌(Acinetobacter baumannii),碳青霉烯类药物耐药;
结核分枝杆菌(Mycobacterium tuberculosis),利福平耐药(采用平行定制标准进行独立分析后纳入,随后应用经调整的多标准决策分析矩阵)
2. 高度优先级组(High group)病原体(7):
伤寒沙门氏菌(Salmonella Typhi),氟喹诺酮类药物耐药;
志贺氏菌属(Shigella spp.),氟喹诺酮类药物耐药;
屎肠球菌(Enterococcus faecium),万古霉素耐药;
铜绿假单胞菌(Pseudomonas aeruginosa),碳青霉烯类药物耐药;
非伤寒沙门氏菌(Non-typhoidal Salmonella),氟喹诺酮类药物耐药;
淋病奈瑟菌(Neisseria gonorrhoeae),三代头孢菌素和/或氟喹诺酮类耐药;
金黄色葡萄球菌(Staphylococcus aureus),耐甲氧西林。
3. 中度优先级组(Medium group)病原体(4):
A组链球菌(Group A streptococci),大环内酯类药物耐药;
肺炎链球菌(Streptococcus pneumoniae),大环内酯类药物耐药;
流感嗜血杆菌(Haemophilus influenzae),氨苄西林耐药;
B组链球菌(Group B streptococci),青霉素耐药。
Further details on the rationale behind the list, the methodologies used to develop the list and the key findings, can be found in the accompanying report.
参考资料:https://www.who.int/publications/i/item/9789240093461
以上链接可下载PDF文件:《WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance》
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