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Journal ArticleDOI

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

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.
Citations
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Journal ArticleDOI
TL;DR: Adsorption technologies are a low-cost alternative, easily used in developing countries where there is a dearth of advanced technologies, skilled personnel, and available capital, and adsorption appears to be the most broadly feasible pharmaceutical removal method.
Abstract: In the last few decades, pharmaceuticals, credited with saving millions of lives, have emerged as a new class of environmental contaminant. These compounds can have both chronic and acute harmful effects on natural flora and fauna. The presence of pharmaceutical contaminants in ground waters, surface waters (lakes, rivers, and streams), sea water, wastewater treatment plants (influents and effluents), soils, and sludges has been well doccumented. A range of methods including oxidation, photolysis, UV-degradation, nanofiltration, reverse osmosis, and adsorption has been used for their remediation from aqueous systems. Many methods have been commercially limited by toxic sludge generation, incomplete removal, high capital and operating costs, and the need for skilled operating and maintenance personnel. Adsorption technologies are a low-cost alternative, easily used in developing countries where there is a dearth of advanced technologies, skilled personnel, and available capital, and adsorption appears to be the most broadly feasible pharmaceutical removal method. Adsorption remediation methods are easily integrated with wastewater treatment plants (WWTPs). Herein, we have reviewed the literature (1990-2018) illustrating the rising environmental pharmaceutical contamination concerns as well as remediation efforts emphasizing adsorption.

1,170 citations

Journal ArticleDOI
TL;DR: The literature review, which included articles published after the year 2012, indicated that the multifactorial threat of antimicrobial resistance has resulted in different complex issues affecting countries across the globe.
Abstract: Antimicrobial resistance (AMR) has developed as one of the major urgent threats to public health causing serious issues to successful prevention and treatment of persistent diseases. In spite of different actions taken in recent decades to tackle this issue, the trends of global AMR demonstrate no signs of slowing down. Misusing and overusing different antibacterial agents in the health care setting as well as in the agricultural industry are considered the major reasons behind the emergence of antimicrobial resistance. In addition, the spontaneous evolution, mutation of bacteria, and passing the resistant genes through horizontal gene transfer are significant contributors to antimicrobial resistance. Many studies have demonstrated the disastrous financial consequences of AMR including extremely high healthcare costs due to an increase in hospital admissions and drug usage. The literature review, which included articles published after the year 2012, was performed using Scopus, PubMed and Google Scholar with the utilization of keyword searches. Results indicated that the multifactorial threat of antimicrobial resistance has resulted in different complex issues affecting countries across the globe. These impacts found in the sources are categorized into three different levels: patient, healthcare, and economic. Although gaps in knowledge about AMR and areas for improvement are obvious, there is not any clearly understood progress to put an end to the persistent trends of antimicrobial resistance.

614 citations

Journal ArticleDOI
TL;DR: The risk data indicate that selected antibiotics may pose a threat to aquatic environments, and Cyanobacteria were the most sensitive organisms when using standard ecotoxicological bioassays.

582 citations

Journal ArticleDOI
TL;DR: Important aspects of antibiotic pollution in fresh waters are highlighted: that concentrations of antibiotics in the environment are substantial, that micro-organisms are susceptible to this, that bacteria can evolve resistance in the environments, and that antibiotic pollution affects natural food webs while interacting with other stressors; which taken together poses a number of challenges for environmental scientists.

570 citations

Journal ArticleDOI
TL;DR: It is suggested that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR.
Abstract: Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.

540 citations

References
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Journal ArticleDOI
TL;DR: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance, in Enterobacteriaceae and emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.
Abstract: Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10 −1 to 10 −3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.

3,647 citations

Journal ArticleDOI
TL;DR: Extended-spectrum β-lactamases 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.
Abstract: 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.

3,308 citations

Journal ArticleDOI
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.

3,181 citations


"Global increase and geographic conv..." refers background in this paper

  • ...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....

    [...]

  • ...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....

    [...]

Journal ArticleDOI
TL;DR: Outpatient antibiotic use in 26 countries in Europe between Jan 1, 1997, and Dec 31, 2002 was investigated by calculating the number of defined daily doses (DDD) per 1000 inhabitants per day according to WHO anatomic therapeutic chemical classification and DDD measurement methodology, and the ecological association between antibiotic use and antibiotic resistance rates was assessed using Spearman's correlation coefficients.

2,894 citations


"Global increase and geographic conv..." refers background in this paper

  • ...The association between antibiotic consumption and resistance is well documented across spatial and temporal scales at individual hospitals (5), nursing homes (6), primary care facilities (7), and communities (8), as well as across countries (9)....

    [...]

Journal ArticleDOI
TL;DR: It is explained how, in principle, early warning systems could be established to detect the proximity of some tipping points, and critically evaluate potential policy-relevant tipping elements in the climate system under anthropogenic forcing.
Abstract: The term "tipping point" commonly refers to a critical threshold at which a tiny perturbation can qualitatively alter the state or development of a system. Here we introduce the term "tipping element" to describe large-scale components of the Earth system that may pass a tipping point. We critically evaluate potential policy-relevant tipping elements in the climate system under anthropogenic forcing, drawing on the pertinent literature and a recent international workshop to compile a short list, and we assess where their tipping points lie. An expert elicitation is used to help rank their sensitivity to global warming and the uncertainty about the underlying physical mechanisms. Then we explain how, in principle, early warning systems could be established to detect the proximity of some tipping points.

2,660 citations


"Global increase and geographic conv..." refers background in this paper

  • ...As with climate change, there may be an unknown tipping point (47), and this could herald a future without effective antibiotics....

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