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

Глобальное бремя бактериальной устойчивости к противомикробным препаратам в 2019 году: систематический анализ
Elsa Kobeissi, Christopher J L Murray, Peng Zheng, Catherine Bisignano, Carlos A Castañeda-Orjuela, Клара Докова, Simon I Hay, Kevin S Ikuta, Alan D Lopez, Puja C Rao, Benn Sartorius, Paul Turner, Anton Y. Peleg, Timothy R. Walsh, Mohsen Naghavi, Avina Vongpradith, Niranjan Kissoon, Hmwe Hmwe Kyu, Ababi Zergaw Giref, Fablina Sharara, Lucien R Swetschinski, Gisela Robles Aguilar, Authia P Gray, Chieh Han, Eve E Wool, Sarah Charlotte Johnson, Annie J. Browne, Michael G. Chipeta, Frederick Fell, Sean Hackett, Georgina Haines–Woodhouse, Bahar H. Kashef Hamadani, Emmanuelle A. P. Kumaran, Barney McManigal, Sureeruk Achalapong, Ramesh Agarwal, Samuel Akech, Samuel B Albertson, John Amuasi, Jason R. Andrews, Aleskandr Aravkin, Elizabeth A. Ashley, François-Xavier Babin, Freddie Bailey, Stephen Baker, Buddha Basnyat, Adrie Bekker, Rose Bender, James A. Berkley, B. Adhisivam, Julia Bielicki, Suppawat Boonkasidecha, James Bukosia, Cristina Gardonyi Carvalheiro, Vilada Chansamouth, Suman Chaurasia, Sara Chiurchiù, Fazle Rabbi Chowdhury, Rafai Clotaire Donatien, Aislinn Cook, Ben S. Cooper, Tim R. Cressey, Elia Criollo-Mora, Matthew Cunningham, Saffiatou Darboe, Nicholas Day, Maia De Luca, Angela Dramowski, Susanna Dunachie, Thuy Duong Bich, Tim Eckmanns, Daniel Eibach, Amir Emami, Nicholas Feasey, Natasha Fisher-Pearson, Karen Forrest, Coralith Garcia, Denise O. Garrett, Petra Gastmeier, Rachel Greer, Vikas Gupta, Sebastian Haller, Andrea Haselbeck, Marianne Holm, Susan Hopkins, Yingfen Hsia, Kenneth Iregbu, Jan Jacobs, Daniel Jarovsky, Fatemeh Javanmardi, Adam Jenney, Meera Khorana, Suwimon Khusuwan, Tomislav Kostyanev, Fiorella Krapp, Ralf Krumkamp, Ajay Kumar, Cherry Lim, Kruy Lim, Direk Limmathurotsakul, Michael J. Loftus, Miles Lunn, Jianing Ma, Anand Manoharan, Florian Marks, Jürgen May, Mayfong Mayxay, Neema Mturi, Tatiana Múnera‐Huertas, Patrick Musicha, Lilian A Musila, Marisa Márcia Mussi‐Pinhata, Ravi Naidu, Tomoka Nakamura, Ruchi Nanavati, Sushma Nangia, Paul N. Newton, Chanpheaktra Ngoun, Amanda Novotney, Davis Nwakanma, Christina W. Obiero, Theresa J. Ochoa, Antonio Olivas‐Martínez, Piero Olliaro, Edna Ooko, Edgar Ortíz‐Brizuela, Pradthana Ounchanum, Gideok D Pak, José Luis Paredes, Carlo Perrone, Thong Phe, Koukeo Phommasone, Nishad Plakkal, Alfredo Ponce‐de‐León, Mathieu Raad, Tanusha Ramdin, Sayaphet Rattanavong, Amy Riddell, Tamalee Roberts, Julie V. Robotham, Anna Roca, Víctor Rosenthal, Kristina E. Rudd, Neal Russell, Hélio S. Sader, Weerawut Saengchan, Jesse Schnall, John A. Scott, Samroeng Seekaew, Mike Sharland, Madhusudhan Shivamallappa, José Sifuentes‐Osornio, Andrew J. H. Simpson, Nicolas Steenkeste, Andrew J. Stewardson, Temenuga Stoeva, Nidanuch Tasak, Areerat Thaiprakong, Guy Thwaites, Caroline Tigoi, Claudia Turner, H. Rogier van Doorn, Sithembiso Velaphi, Manivanh Vongsouvath, Huong T L Vu, Judd L. Walson, Seymour Waner, Tri Wangrangsimakul, Prapass Wannapinij, Teresa M. Wozniak, Tracey E M W Young Sharma, Kalvin Yu, Andy Stergachis, Catrin E. Moore, Christiane Dolecek
2022-01-19

antimicrobial resistancedisability-adjusted life-yearspathogen-drug combinationspredictive statistical modellingsystematic analysis
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 100 000 (20·9-35·3), and lowest in Australasia, at 6·5 deaths (4·3-9·4) per 100 000. 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 929 000 (660 000-1 270 000) 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 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000-100 000 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. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
1
Estimates integrate 471 million individual records or isolates and 7585 study-location-years from literature, hospital, surveillance, and other data sources.
2
Global and regional estimates quantify AMR-related deaths and disability-adjusted life-years using 95% uncertainty intervals derived from 1000 posterior draws.
3
Predictive statistical models generated AMR burden estimates for all locations, including settings without direct data, with cross-validation assessing out-of-sample predictive validity.
4
The analysis distinguishes deaths attributable to AMR from deaths associated with AMR using counterfactual scenarios replacing resistant infections with susceptible infections or no infection.
5
The study provides comprehensive 2019 estimates of bacterial antimicrobial-resistance burden across 204 countries and territories, covering 23 pathogens and 88 pathogen-drug combinations.

Bacterial antimicrobial resistance at the global level in 2019

The global burden of bacterial antimicrobial resistance, measured by attributable and associated deaths and disability-adjusted life-years (DALYs)

Publication Details
Publication Date
2022-01-19
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Authors
Elsa Kobeissi
Christopher J L Murray
Peng Zheng
Catherine Bisignano
Carlos A Castañeda-Orjuela
Клара Докова
Simon I Hay
Kevin S Ikuta
Alan D Lopez
Puja C Rao
Benn Sartorius
Paul Turner
Anton Y. Peleg
Timothy R. Walsh
Mohsen Naghavi
Avina Vongpradith
Niranjan Kissoon
Hmwe Hmwe Kyu
Ababi Zergaw Giref
Fablina Sharara
Lucien R Swetschinski
Gisela Robles Aguilar
Authia P Gray
Chieh Han
Eve E Wool
Sarah Charlotte Johnson
Annie J. Browne
Michael G. Chipeta
Frederick Fell
Sean Hackett
Georgina Haines–Woodhouse
Bahar H. Kashef Hamadani
Emmanuelle A. P. Kumaran
Barney McManigal
Sureeruk Achalapong
Ramesh Agarwal
Samuel Akech
Samuel B Albertson
John Amuasi
Jason R. Andrews
Aleskandr Aravkin
Elizabeth A. Ashley
François-Xavier Babin
Freddie Bailey
Stephen Baker
Buddha Basnyat
Adrie Bekker
Rose Bender
James A. Berkley
B. Adhisivam
Julia Bielicki
Suppawat Boonkasidecha
James Bukosia
Cristina Gardonyi Carvalheiro
Vilada Chansamouth
Suman Chaurasia
Sara Chiurchiù
Fazle Rabbi Chowdhury
Rafai Clotaire Donatien
Aislinn Cook
Ben S. Cooper
Tim R. Cressey
Elia Criollo-Mora
Matthew Cunningham
Saffiatou Darboe
Nicholas Day
Maia De Luca
Angela Dramowski
Susanna Dunachie
Thuy Duong Bich
Tim Eckmanns
Daniel Eibach
Amir Emami
Nicholas Feasey
Natasha Fisher-Pearson
Karen Forrest
Coralith Garcia
Denise O. Garrett
Petra Gastmeier
Rachel Greer
Vikas Gupta
Sebastian Haller
Andrea Haselbeck
Marianne Holm
Susan Hopkins
Yingfen Hsia
Kenneth Iregbu
Jan Jacobs
Daniel Jarovsky
Fatemeh Javanmardi
Adam Jenney
Meera Khorana
Suwimon Khusuwan
Tomislav Kostyanev
Fiorella Krapp
Ralf Krumkamp
Ajay Kumar
Cherry Lim
Kruy Lim
Direk Limmathurotsakul
Michael J. Loftus
Miles Lunn
Jianing Ma
Anand Manoharan
Florian Marks
Jürgen May
Mayfong Mayxay
Neema Mturi
Tatiana Múnera‐Huertas
Patrick Musicha
Lilian A Musila
Marisa Márcia Mussi‐Pinhata
Ravi Naidu
Tomoka Nakamura
Ruchi Nanavati
Sushma Nangia
Paul N. Newton
Chanpheaktra Ngoun
Amanda Novotney
Davis Nwakanma
Christina W. Obiero
Theresa J. Ochoa
Antonio Olivas‐Martínez
Piero Olliaro
Edna Ooko
Edgar Ortíz‐Brizuela
Pradthana Ounchanum
Gideok D Pak
José Luis Paredes
Carlo Perrone
Thong Phe
Koukeo Phommasone
Nishad Plakkal
Alfredo Ponce‐de‐León
Mathieu Raad
Tanusha Ramdin
Sayaphet Rattanavong
Amy Riddell
Tamalee Roberts
Julie V. Robotham
Anna Roca
Víctor Rosenthal
Kristina E. Rudd
Neal Russell
Hélio S. Sader
Weerawut Saengchan
Jesse Schnall
John A. Scott
Samroeng Seekaew
Mike Sharland
Madhusudhan Shivamallappa
José Sifuentes‐Osornio
Andrew J. H. Simpson
Nicolas Steenkeste
Andrew J. Stewardson
Temenuga Stoeva
Nidanuch Tasak
Areerat Thaiprakong
Guy Thwaites
Caroline Tigoi
Claudia Turner
H. Rogier van Doorn
Sithembiso Velaphi
Manivanh Vongsouvath
Huong T L Vu
Judd L. Walson
Seymour Waner
Tri Wangrangsimakul
Prapass Wannapinij
Teresa M. Wozniak
Tracey E M W Young Sharma
Kalvin Yu
Andy Stergachis
Catrin E. Moore
Christiane Dolecek
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