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      Global increase and geographic convergence in antibiotic consumption between 2000 and 2015


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          Antibiotic resistance, driven by antibiotic consumption, is a growing global health threat. Our report on antibiotic use in 76 countries over 16 years provides an up-to-date comprehensive assessment of global trends in antibiotic consumption. We find 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. However, inequities in drug access persist, as many LMICs continue to be burdened with high rates of infectious disease-related mortality and low rates of antibiotic consumption. Our findings emphasize the need for global surveillance of antibiotic consumption to support policies to reduce antibiotic consumption and resistance while providing access to these lifesaving drugs.


          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.

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          Antibiotic resistance-the need for global solutions.

          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. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Extended-Spectrum β-Lactamases: a Clinical Update

            Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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              Dengue, Urbanization and Globalization: The Unholy Trinity of the 21st Century

              Dengue is the most important arboviral disease of humans with over half of the world’s population living in areas of risk. The frequency and magnitude of epidemic dengue have increased dramatically in the past 40 years as the viruses and the mosquito vectors have both expanded geographically in the tropical regions of the world. There are many factors that have contributed to this emergence of epidemic dengue, but only three have been the principal drivers: 1) urbanization, 2) globalization and 3) lack of effective mosquito control. The dengue viruses have fully adapted to a human-Aedes aegypti-human transmission cycle, in the large urban centers of the tropics, where crowded human populations live in intimate association with equally large mosquito populations. This setting provides the ideal home for maintenance of the viruses and the periodic generation of epidemic strains. These cities all have modern airports through which 10s of millions of passengers pass each year, providing the ideal mechanism for transportation of viruses to new cities, regions and continents where there is little or no effective mosquito control. The result is epidemic dengue. This paper discusses this unholy trinity of drivers, along with disease burden, prevention and control and prospects for the future.

                Author and article information

                Proc Natl Acad Sci U S A
                Proc. Natl. Acad. Sci. U.S.A
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                10 April 2018
                26 March 2018
                26 March 2018
                : 115
                : 15
                : E3463-E3470
                [1] aCenter for Disease Dynamics, Economics & Policy , Washington, DC 20005;
                [2] bDepartment of Emergency Medicine, Johns Hopkins School of Medicine , Baltimore, MD 21209;
                [3] cDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD 21205;
                [4] dInstitute of Integrative Biology , ETH Zürich, CH-8006 Zürich, Switzerland;
                [5] eDepartment of Ecology and Evolutionary Biology, Princeton University , Princeton, NJ 08544;
                [6] fPrinceton Environmental Institute, Princeton University , Princeton, NJ 08544;
                [7] gBeijer Institute of Ecological Economics , SE-104 05 Stockholm, Sweden;
                [8] hLaboratory of Medical Microbiology, Vaccine & Infectious Diseases Institute, University of Antwerp , 2610 Antwerp, Belgium;
                [9] iDepartment of Global Health, University of Washington , Seattle, WA 98104
                Author notes
                1To whom correspondence may be addressed. Email: klein@ 123456cddep.org or slevin@ 123456princeton.edu .

                Contributed by Simon A. Levin, February 23, 2018 (sent for review October 3, 2017; reviewed by Bruce R. Levin and Dominique L. Monnet)

                Author contributions: E.Y.K. and R.L. designed research; E.Y.K. performed research; E.Y.K., E.M.M., and S.P. analyzed data; and E.Y.K., T.P.V.B., E.M.M., S.G., S.A.L., H.G., and R.L. wrote the paper.

                Reviewers: B.R.L., Emory University; and D.L.M., European Centre for Disease Prevention and Control.

                Author information
                Copyright © 2018 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

                Page count
                Pages: 8
                Funded by: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) 100000865
                Award ID: OPP1112355
                Funded by: Princeton Environmental Institute, Princeton University (PEI) 100007084
                Award ID: N/A
                Funded by: ETH Zurich's Center for Adaptation to a Changing Environment
                Award ID: N/A
                Funded by: HHS | Centers for Disease Control and Prevention (CDC) 100000030
                Award ID: 16IPA1609425
                Funded by: HHS | Centers for Disease Control and Prevention (CDC) 100000030
                Award ID: 16IPA1609424
                PNAS Plus
                Biological Sciences
                Environmental Sciences
                PNAS Plus

                antimicrobial resistance,low-income countries,defined daily doses,antibiotic stewardship,antibiotics


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