A dramatic rise in global antibiotic consumption has led public health experts to call for fresh strategies to rein in excessive use of the drugs, and for major investments to provide clean water, sanitation and vaccines in countries where infectious diseases are rife, reports The Guardian.
The unrestrained use of antibiotics is the main driver for the rise in drug-resistant infections which now kill more than half a million people a year worldwide, including 50,000 in Europe and the US combined. Left unchecked, the spread of drug resistance could claim millions of lives a year by 2050, according to a 2014 report for David Cameron, the former UK prime minister.
The report says despite efforts to encourage more prudent use of antibiotics, an international team of researchers found a 65% rise in worldwide consumption of the drugs from 2000 to 2015. The sharp upturn, revealed in sales figures from 76 countries, was driven almost entirely by rising use in poorer nations, a study has found.
“We saw a dramatic increase in antibiotic use globally and this is mostly from gains in low and middle-income countries where economic growth means they have greater access to the drugs,” said Eili Klein, an author on the study at the Centre for Disease Dynamics, Economics and Policy in Washington DC. “While it’s generally a positive that there’s better access to effective antibiotics in these countries, there’s the potential for serious problems down the road from overuse. We know there’s a lot of inappropriate use in high income countries, and many of these lower income countries do not have the same controls in place.”
The report says that Public Health England recently reported that at least a fifth of antibiotics prescribed by GPs in England for coughs and sore throats were unnecessary. A panel of experts convened by PHE found that while only 13% of people with a sore throat should get antibiotics, 59% did when they visited their GP.
The danger posed by drug-resistant infections is so serious that England’s chief medical officer, Dame Sally Davies, has added antimicrobial resistance to the UK’s national risk register of civil emergencies. Five years ago, she warned of an “apocalyptic scenario” where people die of common infections and simple operations because antibiotics no longer work.
“As access to antimicrobials improves it is inevitable that overall use will increase,” Davies is quoted in the report as saying. “It is crucial that we concentrate on appropriate use of quality-assured medicines in both humans and animals. The importance of clean water, sanitation and vaccination must not be forgotten to avoid infections occurring in the first place.”
The latest study by researchers at the Centre for Disease Dynamics, Economics and Policy in Washington DC, Johns Hopkins Bloomberg School of Public Health, the Institute of Integrative Biology – ETH Zürich, and Princeton University, found that on average poorer nations still use antibiotics far less intensely than richer ones. In low and middle-income nations, the number of “defined daily doses” handed out per 1,000 people rose 77% from 7.6 to 13.5 over the 16 years studied. But richer nations consume antibiotics at nearly twice that rate. According to the study, consumption rates in high income countries fell on average by a modest 4%, to 25.7 doses per 1,000 people.
Of particular concern, the report states, is the steep rise in global use of antibiotics of last resort, such as colistin, a drug that has been reintroduced despite being all but abandoned in the 1970s because of its toxicity. Colistin has been used to treat infections that cannot be shifted with other drugs, but in the past decade bacteria with colistin-resistant genes spread around the world after they emerged in a Chinese pig in the mid-2000s.
Klein and his co-authors criticise the global response to the public health crisis as “slow and inadequate”. They call for a “radical rethinking” of policies to reduce antibiotic consumption, and advocate major investments to boost hygiene, sanitation, and vaccinations in countries where antibiotic use is rocketing. Without fresh interventions to curb overuse, the number of antibiotics handed out globally could rise more than 200% by 2030, from 42bn doses per day in 2015 to 128bn, the researchers predict.
“In high income countries, the most important thing that reduced mortality from infectious disease in the 20th century was infrastructure,” Klein said. “Separating waste from drinking water and chlorinating it was one of the most important things we did.”
Beyond clean water supplies, Klein said vaccination programmes could also help to curb excessive antibiotic use, and so drug-resistant infections. While antibiotics are not effective against viruses, vaccines that protect against the flu and viruses that cause diarrhoeal disease would reduce the number of people being handed antibiotics unnecessarily. “The reality is that a lot of antibiotic overuse is for viral infections,” Klein said.
“Our modern medical system is built on effective antibiotics,” Klein added. “If our antibiotics stop working, if bacteria become resistant to most of them, medicine will be in trouble. The worry is that people don’t do anything about it.”
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.
Authors
Eili Y Klein, Thomas P Van Boeckel, Elena M Martinez, Suraj Pant, Sumanth Gandra, Simon A Levin, Herman Goossens, Ramanan Laxminarayan
Resistant infections already kill an estimated 5,000 people in Britain each year. And global deaths are projected to grow to 10m a year by 2030 – one every three seconds – unless urgent action is taken, say experts. The Daily Telegraph reports that the study authors say that economic growth is driving the trend in the developing world but conclude that the “decline of antibiotic effectiveness represents a major threat to human health.”
The report says the news comes at its own investigation into the sale of antibiotics in India has found: multinational pharmaceutical companies, including Abbott, Pfizer and GlaxoSmithKline (GSK), have fuelled the crisis by marketing antibiotics in India that were unapproved elsewhere in the world; any multinational companies are continuing to pay their sales teams bonuses for volume sales, despite international calls for them to desist from doing so; failures in Indian regulation, with antibiotics given macho marketing names, including Fighttox and Megamycin, and made widely available without adequate controls or prescriptions; and resistant superbugs bugs being brought back to UK through travel and tourism, leading to hundreds of new cases in UK hospitals.
The disclosures are likely to fuel fears about how common infections could become untreatable.
The study authors are quoted as saying: “As with climate change, there may be an unknown tipping point, and this could herald a future without effective antibiotics. Even in the absence of tipping points, the decline of antibiotic effectiveness represents a major threat to human health.” The report says UK doctors were at pains to stress that the issue of antibiotic resistance was not just a future problem but one which is already taking many British lives.
Bruce Keogh, the former national medical director of the NHS and now chair of Birmingham Women’s and Children’s NHS Foundation Trust said: “I’ve watched patients deteriorate in in front of my eyes because the germs are resistant. It’s a terrible thing for the patient and the family and all concerned. People think of this as a problem of the future but the reality is it is a problem now and it’s likely to get a lot worse in years to come.”
Ramanan Laxminarayan, an expert in antibiotic resistance and director of the Centre for Disease Dynamics, Economics and Policy in Washington DC, said multinational pharmaceutical companies had to take responsibility for the products they sold. "If pharmaceutical companies sell antibiotics as fixed-dose combinations (FDCs) where there is no clinical evidence for them and where there is likely to be antibiotic resistance there is no justification for it. It's no longer sufficient for companies to say it's okay because someone wants to buy my drug," he said.
He said pharmaceutical companies had put "tremendous pressure" on the Indian government which is trying to ban the use of FDCs there. "This is where they make their money – antibiotics are the most commonly sold drug around the world," he said. The report said its investigation had established that some of these products are still available for sale in India without a prescription, with some packets costing less than one pound for ten tablets.
Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh, said the rise in the use of antibiotics in developing countries like India presented a global threat as superbugs travel round the world once created.
He said: “You cannot restrict the problem to one country. Once resistance is established it will travel.”
Drug company Abbott said that the products listed in the study were medicines they acquired in 2010 and many were no longer sold in India. They said that “medicines still available in India all have proper approvals in place”. A spokesperson said that “Fixed-dose combination medicines were created to improve patient adherence and they are important options for doctors when considering the best treatment for their patients, but should only be taken when prescribed by a doctor. This is important particularly in antibiotics, where overuse can contribute to antibiotic resistance”.
A spokesperson for Pfizer said that they are "committed to helping the health care community confront the challenges of antimicrobial resistance" and that "all our current formulations marketed in India have the applicable regulatory licenses and approvals in place". They also said that they were one of four companies who had "moved to decouple antibiotic sales volumes from sales agents’ bonuses".
The report says Glaxo did not respond to questions.
[link url="https://www.theguardian.com/science/2018/mar/26/calls-to-rein-in-antibiotic-use-after-study-shows-65-increase-worldwide"]The Guardian report[/link]
[link url="https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf"]2014 study[/link]
[link url="http://www.pnas.org/content/early/2018/03/20/1717295115"]PNAS abstract[/link]
[link url="https://www.telegraph.co.uk/news/0/global-antibiotic-consumption-soars-feeding-spread-uk-super/"]The Daily Telegraph[/link]