http://www.sciencedirect.com/science/article/pii/S1473309913703189
Antibiotic resistance—the need for global solutions
Center for Disease Dynamics, Economics & Policy1, Princeton University2, Public Health Foundation of India3, University of the Witwatersrand4, Aga Khan University5, University of Oxford6, Food and Drug Administration7, Institute of Tropical Medicine Antwerp8, Aberdeen Royal Infirmary9, University of Antwerp10, National Veterinary Institute11, Duke University12, Karolinska Institutet13, St. John's University of Tanzania14, University of Cuenca15, Wellcome Trust16, St George's, University of London17, McMaster University18, Uppsala University19
TL;DR: The global situation of antibiotic resistance, its major causes and consequences, and key areas in which action is urgently needed are described and identified.
Abstract: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.
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TL;DR: In this paper , the authors presented the most comprehensive estimates of AMR burden to date, which 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, proportionof infectious syndrome deaths attributed to a particular 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.
2,710 citations
TL;DR: The first global map (228 countries) of antibiotic consumption in livestock is presented and it is projected that antimicrobial consumption will rise by 67% by 2030, and nearly double in Brazil, Russia, India, China, and South Africa.
Abstract: Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg(-1), 148 mg⋅kg(-1), and 172 mg⋅kg(-1) for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.
2,371 citations
Cites background from "Antibiotic resistance—the need for ..."
...Given the potential costs of inaction, this study, among others, calls for urgent and concerted action in all countries, which is needed to limit the overuse and abuse of antimicrobials in food animal production (2, 18, 47)....
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...In the United States, antimicrobial use in food animals is estimated to account for ∼80% of the nation’s annual antimicrobial consumption (1), a significant fraction of which involves antimicrobials that are important in human medicine in the treatment of common infections and also necessary to perform medical procedures such as major surgeries, organ transplantation, and chemotherapy (2)....
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TL;DR: This study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data, and estimates aggregated to the global and regional level.
2,222 citations
TL;DR: To prevent a striking rise in resistance in low-income and middle-income countries with large populations and to preserve antibiotic efficacy worldwide, programmes that promote rational use through coordinated efforts by the international community should be a priority.
Abstract: Summary Background Antibiotic drug consumption is a major driver of antibiotic resistance. Variations in antibiotic resistance across countries are attributable, in part, to different volumes and patterns for antibiotic consumption. We aimed to assess variations in consumption to assist monitoring of the rise of resistance and development of rational-use policies and to provide a baseline for future assessment. Methods With use of sales data for retail and hospital pharmacies from the IMS Health MIDAS database, we reviewed trends for consumption of standard units of antibiotics between 2000 and 2010 for 71 countries. We used compound annual growth rates to assess temporal differences in consumption for each country and Fourier series and regression methods to assess seasonal differences in consumption in 63 of the countries. Findings Between 2000 and 2010, consumption of antibiotic drugs increased by 35% (from 52 057 163 835 standard units to 70 440 786 553). Brazil, Russia, India, China, and South Africa accounted for 76% of this increase. In most countries, antibiotic consumption varied significantly with season. There was increased consumption of carbapenems (45%) and polymixins (13%), two last-resort classes of antibiotic drugs. Interpretation The rise of antibiotic consumption and the increase in use of last-resort antibiotic drugs raises serious concerns for public health. Appropriate use of antibiotics in developing countries should be encouraged. However, to prevent a striking rise in resistance in low-income and middle-income countries with large populations and to preserve antibiotic efficacy worldwide, programmes that promote rational use through coordinated efforts by the international community should be a priority. Funding US Department of Homeland Security, Bill & Melinda Gates Foundation, US National Institutes of Health, Princeton Grand Challenges Program.
1,757 citations
TL;DR: It is found that the antibiotic consumption rate in low- and middle- income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries, and projected total global antibiotic consumption through 2030 was up to 200% higher than the 42 billion DDDs estimated in 2015.
Abstract: Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1–34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3–15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth (P = 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns.
1,745 citations
Cites background from "Antibiotic resistance—the need for ..."
...Given the urgency of the threat posed by rising AMR levels (2), and in the absence of global, publicly funded, harmonized surveillance data on antibiotic use, alternative sources of data on antibiotic use must be used to track antibiotic consumption patterns across countries....
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...However, although data on the burden of resistant bacterial infections is limited, both in HICs and especially in LMICs (2), the magnitude of the challenge posed by rising antibiotic resistance levels has become increasingly visible....
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References
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TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
11,809 citations
TL;DR: A review of antibiotic resistance development over the past half-century can be found in this article, with the oft-restated conclusion that it is time to act and to restore the therapeutic applications of antibiotics.
Abstract: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.
4,364 citations
Tufts Medical Center1, University of California, San Diego2, Boston Children's Hospital3, University of California, Los Angeles4, Los Angeles Biomedical Research Institute5, Providence Portland Medical Center6, United States Department of Veterans Affairs7, Case Western Reserve University8, University of Virginia9, Johns Hopkins University School of Medicine10
TL;DR: An update on potentially effective antibacterial drugs in the late-stage development pipeline is provided, in the hope of encouraging collaboration between industry, academia, the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention work productively together.
Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
4,256 citations
TL;DR: Invasive MRSA infection affects certain populations disproportionately and is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.
Abstract: ContextAs the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA infections in the US population is needed.ObjectivesTo describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infections in the United States in 2005.Design and SettingActive, population-based surveillance for invasive MRSA in 9 sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA were investigated and classified as either health care–associated (either hospital-onset or community-onset) or community-associated (patients without established health care risk factors for MRSA).Main Outcome MeasuresIncidence rates and estimated number of invasive MRSA infections and in-hospital deaths among patients with MRSA in the United States in 2005; interval estimates of incidence excluding 1 site that appeared to be an outlier with the highest incidence; molecular characterization of infecting strains.ResultsThere were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care–associated: 5250 (58.4%) were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234 (13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100 000 (interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years and older (127.7 per 100 000; interval estimate, 92.6-156.9), blacks (66.5 per 100 000; interval estimate, 43.5-63.1), and males (37.5 per 100 000; interval estimate, 26.8-39.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100 000 (interval estimate, 3.3-7.5). Molecular testing identified strains historically associated with community-associated disease outbreaks recovered from cultures in both hospital-onset and community-onset health care–associated infections in all surveillance areas.ConclusionsInvasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.
3,803 citations
TL;DR: The role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
Abstract: Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
3,556 citations