Antimicrobial Resistance Collaborators.
Lancet (London, England). Date of publication 2022 Jan 18;volume ():.
1. Lancet. 2022 Jan 18. pii: S0140-6736(21)02724-0. doi:
10.1016/S0140-6736(21)02724-0. [Epub ahead of print]
Global burden of bacterial antimicrobial resistance in 2019: a systematic
analysis.
Antimicrobial Resistance Collaborators.
Collaborators: Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G,
Gray A, Han C, Bisignano C, Rao P, Wool E, Johnson SC, Browne AJ, Chipeta MG,
Fell F, Hackett S, Haines-Woodhouse G, Kashef Hamadani BH, Kumaran EAP, McManigal
B, Agarwal R, Akech S, Albertson S, Amuasi J, Andrews J, Aravkin A, Ashley E,
Bailey F, Baker S, Basnyat B, Bekker A, Bender R, Bethou A, Bielicki J,
Boonkasidecha S, Bukosia J, Carvalheiro C, Castañeda-Orjuela C, Chansamouth V,
Chaurasia S, Chiurchiù S, Chowdhury F, Cook AJ, Cooper B, Cressey TR,
Criollo-Mora E, Cunningham M, Darboe S, Day NPJ, De Luca M, Dokova K, Dramowski
A, Dunachie SJ, Eckmanns T, Eibach D, Emami A, Feasey N, Fisher-Pearson N,
Forrest K, Garrett D, Gastmeier P, Giref AZ, Greer RC, Gupta V, Haller S,
Haselbeck A, Hay SI, Holm M, Hopkins S, Iregbu KC, Jacobs J, Jarovsky D,
Javanmardi F, Khorana M, Kissoon N, Kobeissi E, Kostyanev T, Krapp F, Krumkamp R,
Kumar A, Kyu HH, Lim C, Limmathurotsakul D, Loftus MJ, Lunn M, Ma J, Mturi N,
Munera-Huertas T, Musicha P, Mussi-Pinhata MM, Nakamura T, Nanavati R, Nangia S,
Newton P, Ngoun C, Novotney A, Nwakanma D, Obiero CW, Olivas-Martinez A, Olliaro
P, Ooko E, Ortiz-Brizuela E, Peleg AY, Perrone C, Plakkal N, Ponce-de-Leon A,
Raad M, Ramdin T, Riddell A, Roberts T, Robotham JV, Roca A, Rudd KE, Russell N,
Schnall J, Scott JAG, Shivamallappa M, Sifuentes-Osornio J, Steenkeste N,
Stewardson AJ, Stoeva T, Tasak N, Thaiprakong A, Thwaites G, Turner C, Turner P,
van Doorn HR, Velaphi S, Vongpradith A, Vu H, Walsh T, Waner S, Wangrangsimakul
T, Wozniak T, Zheng P, Sartorius B, Lopez AD, Stergachis A, Moore C, Dolecek C,
Naghavi M.
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-resistantE 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.
Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights
reserved.
DOI: 10.1016/S0140-6736(21)02724-0
PMID: 35065702
Conflict of interest statement: Declaration of interests E Ashley reports that
Lao-Oxford-Mahosot Hospital—Wellcome Trust Research Unit received financial
support from the Global Research on Antimicrobial Resistance Project (GRAM) to
extract and prepare data for the present manuscript. J Bielicki reports grants
from the European and Developing Countries Clinical Trials Partnership, Horizon
2020, and Swiss National Science Foundation, and a contract from the National
Institute for Health Research (NIHR), outside of the submitted work; and
consulting fees from Shionogi and Sandoz and speaking fees from Pfizer and
Sandoz, outside the submitted work. C Carvalheiro reports financial support for
the present manuscript from the Global Antibiotic Research and Development
Partnership, who provided payments to Fundação de Apoio ao Ensino, Pesquisa e
Assistência of the Clinical Hospital of the Faculty of Medicine of Ribeirão
Preto, University of São Paulo, Brazil. S Dunachie reports financial support for
the present manuscript from UL Flemming Fund at the Department of Health and
Social Care, the Bill & Melinda Gates Foundation, and the Wellcome Trust; a paid
membership role for the Wellcome Trust Vaccines Advisory Selection Panel Vaccines
and AMR in November, 2019; and an unpaid role as an expert adviser to WHO's
Global Antimicrobrial Resistance Surveillance System, from November, 2018
onwards, outside the submitted work. A Haselbeck reports support for the present
manuscript from the Bill & Melinda Gates Foundation (OPP1205877). C Lim was
supported by the Wellcome Trust Training Fellowship between September, 2017 and
March 2020 (206736/Z/17/Z), outside the submitted work. M Mussi-Pinhata reports
support for the present manuscript from research from grant funding from
Fondazione PENTA—Onlus and the Clinical Trial Manager Global Antibiotic R&D
Partnership (GARDP). P Newton reports support for the present manuscript from
research grant funding from the Wellcome Trust. J Robotham is a member of the UK
Government Advisory Committee on Antimicrobial Prescribing Resistance and
Healthcare Associated Infections, outside the submitted work. J Scott reports
that the London School of Hygiene & Tropical Medicine (LSHTM) received financial
support from Emory University to support CHAMPS projects in Ethiopia for the
present manuscript; reports a paid fellowship from the Wellcome Trust, research
grants from Gavi, the Vaccine Alliance, and NIHR paid to LSHTM, and an African
research leader fellowship paid to LSHTM by the Medical Research Council, outside
the submitted work; and reports being a member of the data safety and monitoring
board for PATH Vaccines Solutions for SII PCV10 in The Gambia. J
Sifuentes-Osornio reports financial support from Oxford University for the
present manuscript; research grants from Oxford, CONACYT, Sanofi, and Novartis,
outside of the study; consulting fees from Senosiain and speaker fees from Merck,
outside of the study; and membership of the Sanofi advisory board of COVID-19
Vaccine Development, which is currently in progress, outside of the study. A J
Stewardson reports grants or contracts from Merck, Sharp, & Dohme paid to Monash
University, Melbourne, outside of the study. P Turner reports grants, consulting
fees, and support for attending meetings or travel from Wellcome Trust, outside
the study. H van Doorn reports grants or contracts from the University of Oxford
and is the principal investigator for the Fleming Fund pilot grant; and he is a
board member of Wellcome Trust's Surveillance and Epidemiology of Drug Resistant
Infections. T Walsh reports financial support from the Bill & Melinda Gates
Foundation for the BARNARDS (neonatal sepsis and mortality) study for the present
manuscript. All other authors declare no competing interests.
