Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Naghavi, Mohsen, Vollset, Stein Emil, Ikuta, Kevin S, Swetschinski, Lucien R, Gray, Authia P, Wool, Eve E, Robles Aguilar, Gisela, Mestrovic, Tomislav, Smith, Georgia, Han, Chieh, Hsu, Rebecca L, Chalek, Julian, Araki, Daniel T, Chung, Erin, Raggi, Catalina, Gershberg Hayoon, Anna, Davis Weaver, Nicole, Lindstedt, Paulina A, Smith, Amanda E, Altay, Umut, Bhattacharjee, Natalia V, Giannakis, Konstantinos, Fell, Frederick, McManigal, Barney, Ekapirat, Nattwut, Mendes, Jessica Andretta, Runghien, Tilleye, Srimokla, Oraya, Abdelkader, Atef, Abd-Elsalam, Sherief, Aboagye, Richard Gyan, Abolhassani, Hassan, Abualruz, Hasan, Abubakar, Usman, Abukhadijah, Hana J, Aburuz, Salahdein, Abu-Zaid, Ahmed, Achalapong, Sureerak, Addo, Isaac Yeboah, Adekanmbi, Victor, Adeyeoluwa, Temitayo Esther, Adnani, Qorinah Estiningtyas Sakilah, Adzigbli, Leticia Akua, Afzal, Muhammad Sohail, Afzal, Saira, Agodi, Antonella, Ahlstrom, Austin J, Ahmad, Aqeel, Ahmad, Sajjad, Ahmad, Tauseef, Ahmadi, Ali, Ahmed, Ayman, Ahmed, Haroon, Ahmed, Ibrar, Ahmed, Mohammed, Ahmed, Saeed, Ahmed, Syed Anees, Akkaif, Mohammed Ahmed, Al Awaidy, Salah, Al Thaher, Yazan, Alalalmeh, Samer O, AlBataineh, Mohammad T, Aldhaleei, Wafa A, Al-Gheethi, Adel Ali Saeed, Alhaji, Nma Bida, Ali, Abid, Ali, Liaqat, Ali, Syed Shujait, Ali, Waad, Allel, Kasim, Al-Marwani, Sabah, Alrawashdeh, Ahmad, Altaf, Awais, Al-Tammemi, Alaa B., Al-Tawfiq, Jaffar A, Alzoubi, Karem H, Al-Zyoud, Walid Adnan, Amos, Ben, Amuasi, John H, Ancuceanu, Robert, Andrews, Jason R, Anil, Abhishek, Anuoluwa, Iyadunni Adesola, Anvari, Saeid, Anyasodor, Anayochukwu Edward, Apostol, Geminn Louis Carace, Arabloo, Jalal, Arafat, Mosab, Aravkin, Aleksandr Y, Areda, Demelash, Aremu, Abdulfatai, Artamonov, Anton A, Ashley, Elizabeth A, Asika, Marvellous O, Athari, Seyyed Shamsadin, Atout, Maha Moh'd Wahbi, Awoke, Tewachew, Azadnajafabad, Sina, Azam, James Mba, Aziz, Shahkaar, Azzam, Ahmed Y., Babaei, Mahsa, Babin, Francois-Xavier, Badar, Muhammad, Baig, Atif Amin, Bajcetic, Milica, Baker, Stephen, Bardhan, Mainak, Barqawi, Hiba Jawdat, Basharat, Zarrin, Basiru, Afisu, Bastard, Mathieu, Basu, Saurav, Bayleyegn, Nebiyou Simegnew, Belete, Melaku Ashagrie, Bello, Olorunjuwon Omolaja, Beloukas, Apostolos, Berkley, James A, Bhagavathula, Akshaya Srikanth, Bhaskar, Sonu, Bhuyan, Soumitra S, Bielicki, Julia A, Briko, Nikolay Ivanovich, Brown, Colin Stewart, Browne, Annie J, Buonsenso, Danilo, Bustanji, Yasser, Carvalheiro, Cristina G, Castañeda-Orjuela, Carlos A, Cenderadewi, Muthia, Chadwick, Joshua, Chakraborty, Sandip, Chandika, Rama Mohan, Chandy, Sara, Chansamouth, Vilada, Chattu, Vijay Kumar, Chaudhary, Anis Ahmad, Ching, Patrick R, Chopra, Hitesh, Chowdhury, Fazle Rabbi, Chu, Dinh-Toi, Chutiyami, Muhammad, Cruz-Martins, Natalia, da Silva, Alanna Gomes, Dadras, Omid, Dai, Xiaochen, Darcho, Samuel D, Das, Saswati, De la Hoz, Fernando Pio, Dekker, Denise Myriam, Dhama, Kuldeep, Diaz, Daniel, Dickson, Benjamin Felix Rothschild, Djorie, Serge Ghislain, Dodangeh, Milad, Dohare, Sushil, Dokova, Klara Georgieva, Doshi, Ojas Prakashbhai, Dowou, Robert Kokou, Dsouza, Haneil Larson, Dunachie, Susanna J, Dziedzic, Arkadiusz Marian, Eckmanns, Tim, Ed-Dra, Abdelaziz, Eftekharimehrabad, Aziz, Ekundayo, Temitope Cyrus, El Sayed, Iman, Elhadi, Muhammed, El-Huneidi, Waseem, Elias, Christelle, Ellis, Sally J, Elsheikh, Randa, Elsohaby, Ibrahim, Eltaha, Chadi, Eshrati, Babak, Eslami, Majid, Eyre, David William, Fadaka, Adewale Oluwaseun, Fagbamigbe, Adeniyi Francis, Fahim, Ayesha, Fakhri-Demeshghieh, Aliasghar, Fasina, Folorunso Oludayo, Fasina, Modupe Margaret, Fatehizadeh, Ali, Feasey, Nicholas ORCID: https://orcid.org/0000-0003-4041-1405, Feizkhah, Alireza, Fekadu, Ginenus, Fischer, Florian, Fitriana, Ida, Forrest, Karen M, Fortuna Rodrigues, Celia, Fuller, John E, Gadanya, Muktar A, Gajdács, Márió, Gandhi, Aravind P, Garcia-Gallo, Esteban E, Garrett, Denise O, Gautam, Rupesh K, Gebregergis, Miglas Welay, Gebrehiwot, Mesfin, 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QuynhAnh P, Noman, Efaq Ali, Nwakanma, Davis C, O'Brien, Seamus, Ochoa, Theresa J, Odetokun, Ismail A, Ogundijo, Oluwaseun Adeolu, Ojo-Akosile, Tolulope R, Okeke, Sylvester Reuben, Okonji, Osaretin Christabel, Olagunju, Andrew T, Olivas-Martinez, Antonio, Olorukooba, Abdulhakeem Abayomi, Olwoch, Peter, Onyedibe, Kenneth Ikenna, Ortiz-Brizuela, Edgar, Osuolale, Olayinka, Ounchanum, Pradthana, Oyeyemi, Oyetunde T, P A, Mahesh Padukudru, Paredes, Jose L, Parikh, Romil R, Patel, Jay, Patil, Shankargouda, Pawar, Shrikant, Peleg, Anton Y, Peprah, Prince, Perdigão, João, Perrone, Carlo, Petcu, Ionela-Roxana, Phommasone, Koukeo, Piracha, Zahra Zahid, Poddighe, Dimitri, Pollard, Andrew J, Poluru, Ramesh, Ponce-De-Leon, Alfredo, Puvvula, Jagadeesh, Qamar, Farah Naz, Qasim, Nameer Hashim, Rafai, Clotaire Donatien, Raghav, Pankaja, Rahbarnia, Leila, Rahim, Fakher, Rahimi-Movaghar, Vafa, Rahman, Mosiur, Rahman, Muhammad Aziz, Ramadan, Hazem, Ramasamy, Shakthi Kumaran, Ramesh, Pushkal Sinduvadi, Ramteke, Pramod W, Rana, Rishabh Kumar, Rani, Usha, Rashidi, Mohammad-Mahdi, Rathish, Devarajan, Rattanavong, Sayaphet, Rawaf, Salman, Redwan, Elrashdy Moustafa Mohamed, Reyes, Luis Felipe, Roberts, Tamalee, Robotham, Julie V, Rosenthal, Victor Daniel, Ross, Allen Guy, Roy, Nitai, Rudd, Kristina E, Sabet, Cameron John, Saddik, Basema Ahmad, Saeb, Mohammad Reza, Saeed, Umar, Saeedi Moghaddam, Sahar, Saengchan, Weeravoot, Safaei, Mohsen, Saghazadeh, Amene, Saheb Sharif-Askari, Narjes, Sahebkar, Amirhossein, Sahoo, Soumya Swaroop, Sahu, Maitreyi, Saki, Morteza, Salam, Nasir, Saleem, Zikria, Saleh, Mohamed A, Samodra, Yoseph Leonardo, Samy, Abdallah M, Saravanan, Aswini, Satpathy, Maheswar, Schumacher, Austin E, Sedighi, Mansour, Seekaew, Samroeng, Shafie, Mahan, Shah, Pritik A, Shahid, Samiah, Shahwan, Moyad Jamal, Shakoor, Sadia, Shalev, Noga, Shamim, Muhammad Aaqib, Shamshirgaran, Mohammad Ali, Shamsi, Anas, Sharifan, Amin, Shastry, Rajesh P, Shetty, Mahabalesh, Shittu, Aminu, Shrestha, Sunil, Siddig, Emmanuel Edwar, Sideroglou, Theologia, Sifuentes-Osornio, Jose, Silva, Luís Manuel Lopes Rodrigues, Simões, Eric A F, Simpson, Andrew J H, Singh, Amit, Singh, Surjit, Sinto, Robert, Soliman, Sameh S M, Soraneh, Soroush, Stoesser, Nicole, Stoeva, Temenuga Zhekova, Swain, Chandan Kumar, Szarpak, Lukasz, T Y, Sree Sudha, Tabatabai, Shima, Tabche, Celine, Taha, Zanan Mohammed-Ameen, Tan, Ker-Kan, Tasak, Nidanuch, Tat, Nathan Y, Thaiprakong, Areerat, Thangaraju, Pugazhenthan, Tigoi, Caroline Chepngeno, Tiwari, Krishna, Tovani-Palone, Marcos Roberto, Tran, Thang Huu, Tumurkhuu, Munkhtuya, Turner, Paul, Udoakang, Aniefiok John, Udoh, Arit, Ullah, Noor, Ullah, Saeed, Vaithinathan, Asokan Govindaraj, Valenti, Mario, Vos, Theo, Vu, Huong T L, Waheed, Yasir, Walker, Ann Sarah, Walson, Judd L, Wangrangsimakul, Tri, Weerakoon, Kosala Gayan, Wertheim, Heiman F L, Williams, Phoebe C M, Wolde, Asrat Arja, Wozniak, Teresa M, Wu, Felicia, Wu, Zenghong, Yadav, Mukesh Kumar Kumar, Yaghoubi, Sajad, Yahaya, Zwanden Sule, Yarahmadi, Amir, Yezli, Saber, Yismaw, Yazachew Engida, Yon, Dong Keon, Yuan, Chun-Wei, Yusuf, Hadiza, Zakham, Fathiah, Zamagni, Giulia, Zhang, Haijun, Zhang, Zhi-Jiang, Zielińska, Magdalena, Zumla, Alimuddin, Zyoud, Sa'ed H. H, Zyoud, Samer H, Hay, Simon I, Stergachis, Andy, Sartorius, Benn, Cooper, Ben S, Dolecek, Christiane and Murray, Christopher J L (2024) 'Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050'. Lancet, Vol 404, Issue 10459, pp. 1199-1226.

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Abstract

Background
Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts.
Methods
We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen–drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the 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 attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level.
Findings
In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000–372 000] and 57 200 attributable deaths [34 100–80 300] in 1990, to 550 000 associated deaths [500 000–600 000] and 130 000 attributable deaths [113 000–146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000–834 000) in 1990, to 1·03 million associated deaths (909 000–1·16 million) in 2021, and from 127 000 attributable deaths (82 100–171 000) in 1990, to 216 000 (168 000–264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56–2·26) deaths attributable to AMR and 8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2–69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5–89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (–6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8–102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08–13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths.
Interpretation
This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance.
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/S0140-6736(24)01867-1
Depositing User:	Amy Carroll
Date Deposited:	03 Dec 2024 07:10
Last Modified:	17 Dec 2024 14:42
URI:	https://archive.lstmed.ac.uk/id/eprint/25723

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