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2019年全球细菌抗生素耐药性负担的系统分析
作者:小柯机器人 发布时间:2022/1/23 17:24:20

全球抗生素耐药协作组对2019年全球细菌抗生素耐药性负担进行了迄今为止最全面的系统分析。相关论文发表在2022年1月19日出版的《柳叶刀》杂志上。

抗生素耐药性(AMR)对世界各地的人类健康构成重大威胁。此前发表文献已估计了抗生素耐药性在特定地点对特定病原体-药物组合的发病率、死亡、住院时间和医疗成本的影响。据研究组所知,该研究工作提供了迄今为止最全面的AMR负担评估。

研究组估计了2019年204个国家和地区23种病原体和88种病原体-药物组合的细菌性AMR所致死亡和残疾调整生命年(DALYs)。他们从系统文献综述、医院系统、监测系统和其他来源获得数据,涵盖4.71亿份个人记录或分离群和7585个研究地点-年。

使用预测统计模型对所有地点的AMR负担进行估计,包括没有数据的地点。研究组的方法可分为五个主要部分:与感染有关的死亡人数,由特定感染综合征导致的感染性死亡的比例,由特定病原体导致的感染综合征死亡的比例,特定病原体对相关抗生素耐药的百分比,以及与这种耐药性相关的额外死亡风险或感染持续时间。

使用这五部分,研究组根据两个反事实估计疾病负担:AMR导致的死亡(基于一个替代方案,即所有耐药感染都被药敏感染取代),以及与AMR相关的死亡(基于一种替代方案,即所有耐药感染均被无感染所取代)。最终估计生成95%的不确定度区间(UIs),并交叉验证了模型的样本外预测有效性。研究组提供了全球和区域层面的汇总最终估算。

根据研究组的预测统计模型,2019年与细菌性AMR相关的死亡人数估计为495万,其中包括127万与细菌性AMR死亡人数。在区域水平上,研究组估计,在撒哈拉以南非洲西部,由于耐药而导致的全年龄死亡率最高,为每10万人死亡27.3人,在大洋洲最低,每10万人中有6.5人死亡。

2019年,与耐药性相关的下呼吸道感染死亡人数超过150万,使其成为最严重的感染综合征。与耐药性相关死亡的六种主要病原体(大肠杆菌,其次是金黄色葡萄球菌、肺炎克雷伯菌、肺炎链球菌、鲍曼不动杆菌和铜绿假单胞菌)共导致929000例AMR死亡,2019年与AMR相关的死亡人数为357万。

耐甲氧西林金黄色葡萄球菌的病原体-药物组合在2019年造成10万多例AMR死亡 ,另外6种病原体-药物组合分别导致5-10万例死亡:耐多药但不包括广泛耐药的结核病、耐第三代头孢菌素大肠杆菌、耐碳青霉烯类鲍曼尼菌、耐氟喹诺酮类大肠杆菌、耐碳青霉烯类肺炎克雷伯菌和耐第三代头孢菌素肺炎克雷伯菌。

据研究组所知,该研究首次全面评估了全球AMR负担,并对数据可用性进行了评估。AMR是世界范围内死亡的主要原因,在资源不足地区负担最高。了解AMR的负担以及导致AMR的主要病原体-药物组合,对于做出知情的、针对具体地区的政策决策至关重要,特别是关于感染预防和控制计划、基本抗生素的获取以及新疫苗和抗生素的研发。许多低收入地区中存在严重的数据缺口,亟需扩大微生物实验室能力和数据收集系统,以提高人们对这一重要人类健康威胁的认识。

附:英文原文

Title: Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

Author: Christopher JL Murray, Kevin Shunji Ikuta, Fablina Sharara, Lucien Swetschinski, Gisela Robles Aguilar, Authia Gray, Chieh Han, Catherine Bisignano, Puja Rao, Eve Wool, Sarah C Johnson, Annie J Browne, Michael Give Chipeta, Frederick Fell, Sean Hackett, Georgina Haines-Woodhouse, Bahar H Kashef Hamadani, Emmanuelle A P Kumaran, Barney McManigal, Ramesh Agarwal, Samuel Akech, Samuel Albertson, John Amuasi, Jason Andrews, Aleskandr Aravkin, Elizabeth Ashley, Freddie Bailey, Stephen Baker, Buddha Basnyat, Adrie Bekker, Rose Bender, Adhisivam Bethou, Julia Bielicki, Suppawat Boonkasidecha, James Bukosia, Cristina Carvalheiro, Carlos Castaeda-Orjuela, Vilada Chansamouth, Suman Chaurasia, Sara Chiurchiù, Fazle Chowdhury, Aislinn J Cook, Ben Cooper, Tim R Cressey, Elia Criollo-Mora, Matthew Cunningham, Saffiatou Darboe, Nicholas P J Day, Maia De Luca, Klara Dokova, Angela Dramowski, Susanna J Dunachie, Tim Eckmanns, Daniel Eibach, Amir Emami, Nicholas Feasey, Natasha Fisher-Pearson, Karen Forrest, Denise Garrett, Petra Gastmeier, Ababi Zergaw Giref, Rachel Claire Greer, Vikas Gupta, Sebastian Haller, Andrea Haselbeck, Simon I Hay, Marianne Holm, Susan Hopkins, Kenneth C Iregbu, Jan Jacobs, Daniel Jarovsky, Fatemeh Javanmardi, Meera Khorana, Niranjan Kissoon, Elsa Kobeissi, Tomislav Kostyanev, Fiorella Krapp, Ralf Krumkamp, Ajay Kumar, Hmwe Hmwe Kyu, Cherry Lim, Direk Limmathurotsakul, Michael James Loftus, Miles Lunn, Jianing Ma, Neema Mturi, Tatiana Munera-Huertas, Patrick Musicha, Marisa Marcia Mussi-Pinhata, Tomoka Nakamura, Ruchi Nanavati, Sushma Nangia, Paul Newton, Chanpheaktra Ngoun, Amanda Novotney, Davis Nwakanma, Christina W Obiero, Antonio Olivas-Martinez, Piero Olliaro, Ednah Ooko, Edgar Ortiz-Brizuela, Anton Yariv Peleg, Carlo Perrone, Nishad Plakkal, Alfredo Ponce-de-Leon, Mathieu Raad, Tanusha Ramdin, Amy Riddell, Tamalee Roberts, Julie Victoria Robotham, Anna Roca, Kristina E Rudd, Neal Russell, Jesse Schnall, John Anthony Gerard Scott, Madhusudhan Shivamallappa, Jose Sifuentes-Osornio, Nicolas Steenkeste, Andrew James Stewardson, Temenuga Stoeva, Nidanuch Tasak, Areerat Thaiprakong, Guy Thwaites, Claudia Turner, Paul Turner, H Rogier van Doorn, Sithembiso Velaphi, Avina Vongpradith, Huong Vu, Timothy Walsh, Seymour Waner, Tri Wangrangsimakul, Teresa Wozniak, Peng Zheng, Benn Sartorius, Alan D Lopez, Andy Stergachis, Catrin Moore, Christiane Dolecek, Mohsen Naghavi

Issue&Volume: 2022-01-19

Abstract:

Background

Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.

Methods

We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level.

Findings

On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929000 (660000–1270000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100000 deaths attributable to AMR in 2019, while six more each caused 50000–100000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.

Interpretation

To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat.

DOI: 10.1016/S0140-6736(21)02724-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext

 

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet