Because of recent concerns raised by the UK’s Health Security Agency (UKHSA),colleagues suggested that we republish a Commentary entitled, “Slowing the steep rise in antimicrobial resistance”, which features Nobel Laureate Roger Kornberg. Since it was first published it has received >15,000 openings. UKHSA warned of a “hidden pandemic” this winter because last year, in the UK, 1 in 5 infections were resistant to antibiotic. The organization feared that as COVID-19 restrictions are lifted social mixing is likely to spread infections some of which will be resistant to antibiotics.
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- Currently 700,000 people die each year from Antimicrobial Resistance (AMR) and this could rise to 10 milion by 2050
- AMR could make routine surgeries and childbirth as dangerous and lethal as in the pre-antibiotic era killing millions and costing trillions worldwide
- Doctors inappropriately prescribing antibiotics for minor aliments shorten the useful life of antibiotics threatening modern medicine as there is an antibiotic pipeline deficiency
- 90% of GPs feel pressured by patients to prescribe antibiotics
- 70% of GPs are unsure whether sore throat and respiratory infections are viral or bacterial resulting in 50% of sore throats receiving antibiotics
- Clinical diagnosis leads to 50% of patients with a sore throat being prescribed antibiotics without having Group A Streptococcal infection
- 30% of patients with pharyngitis will not be treated but will be infected with Group A Streptococci
- 24% of doctors say they lack easy-to-use diagnostic tools
- 10m prescriptions for antibiotics are handed out in England each year to patients who do not need them
- A Nobel Laureate has developed a new technology to provide rapid, accurate, cost-effective diagnosis of bacterial sore throat resulting in informed prescribing and reducing unnecessary antibiotic usage
Slowing the steep rise of antimicrobial resistance
Should we listen when a professor of medicine and a Nobel Laureate says that the technology already exists to develop a cheap hand held device, which can rapidly and accurately diagnose a bacterial sore throat?
Without such a device to determine whether minor ailments require antibiotics, doctors will continue to prescribe them, and thereby contribute to the steep rise in Antimicrobial Resistance (AMR). In 2016 the National Institute for Health and Care Excellence (NICE), the UK government's NHS watchdog, reported that as many as 10m prescriptions for antibiotics are handed out in England every year to patients who do not need them. According to a 2016 report on AMR, by 2050 a staggering, “10m people will die from AMR each year . . . . The world needs rapid diagnostics to improve our use of antibiotics,” says the report.
Sore throat
Acute throat infections are among the most common infectious diseases presented to primary healthcare and A&E departments and are frequently misdiagnosed. They are responsible for 2 to 4% of all primary care visits. Viruses cause 85% to 95% of throat infections in adults and children younger than 5. For those aged 5 to 15, viruses cause about 70% of throat infections, with the other 30% due to bacterial infections, mostly group A β-hemolytic streptococcus (GAS), which can cause 0.5m deaths a year. There are challenges in diagnosing GAS because its signs and symptoms are often indistinguishable from viral and other causes of sore throat.
If a doctor intends to treat suspected GAS pharyngitis, it is generally recommended that laboratory confirmation of the presence of GAS be sought to limit unnecessary antibiotic prescription. The gold standard laboratory investigation is of a bacterial culture of a throat swab. However, this is expensive, and there is a relatively long lag time between the collection of the specimen and final microbiological diagnosis: so doctors tend not to it.
Rapid antigen diagnostic tests (RADTs) are an alternative to the gold standard laboratory test for GAS. However, widespread use of RADTs has been hindered by low sensitivity for most commonly used RADTs (immunoassays). Reviews of RADTs performance have identified significant variability in the diagnostic accuracy, especially sensitivity, between different test methodologies.
Urgent need for rapid and accurate diagnostic test
A principal recommendation of a 2016 report on AMR is to ban doctors from prescribing antibiotics until they have carried out rapid tests to prove the infection is bacterial. The report also stresses that doctors need urgent help to temporise their use of antibiotics if AMR is to be reduced.
Notwithstanding, the AMR challenge is bigger than doctors overprescribing antibiotics. Farmers feed antibiotics to livestock and poultry, and spray them on crops to make our food supply ‘safer’. We dump antibiotics in rivers, and even paint them on the hulls of boats to prevent the build up of barnacles. However, it seems reasonable to suggest that successfully reducing doctors’ over prescribing antibiotics would represent a significant contribution to denting the burden of AMR. To do this, “We need a step change in the technology available . . . Governments of the richest countries should mandate now that, by 2020, all antibiotic prescriptions will need to be informed by up to date surveillance and a rapid diagnostic test,” urges the AMR report.
The technological ‘step change’, which the report says is essential, has already been achieved, says Roger Kornberg, Professor of Medicine at Stanford University and Nobel Laureate for Chemistry. “Advanced biosensor technology enables virtually instantaneous, extraordinarily sensitive, electronic detection of almost any biomarker (protein, nucleic acid, small molecule, etc.). With relatively modest resources it would only be a matter of months to develop a simple, affordable handheld device, which not only would tell you immediately and accurately whether a sore throat requires antibiotics or not, but would also tell you which antibiotics you require, and for how long you should take them,” says Kornberg. See videos below in which Kornberg describes how tried and tested biosensor technology could facilitate rapid and accurate diagnosis of a sore throat.
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Serious and growing threat
Each year, millions of people throughout the developed world present themselves to their doctors with minor ailments, such as a sore throat. 97% of these patients demand antibiotics although 90% of their ailments are viral and therefore do not require antibiotics. 90% of doctors, who do not have the means to rapidly and accurately determine whether a minor ailment requires antibiotics, feel pressured by patients to prescribe them.
A 2014 study of four million NHS patients from 537 GP practices in England found that more than 50% of those presenting with a minor ailment were prescribed antibiotics, despite warnings that the medication will not help, but increases their risk of developing resistance. The study, by scientists at Public Health England and University College London, published in the Journal of Antimicrobial Chemotherapy, found that antibiotic prescriptions for minor ailments increased by some 40% between 1999 and 2011. 70% of GPs surveyed said they prescribed antibiotics because they were unsure whether patients had viral or bacterial infections, and 24% of GPs said it was because of a lack of an easy-to-use, rapid and accurate diagnostic device.
Superbugs will kill millions and cost trillions
Concerned about the rising levels of drug resistance whereby microbes evolve to become immune to known drugs, in 2014 the UK Government, in collaboration with the Wellcome Trust, commissioned a review of the large and growing global burden of AMR. Jim O’Neill, a former Goldman Sachs chief economist who coined the phrase “BRICS”, was appointed to lead the endeavour and propose actions to tackle AMR. In 2015 O’Neill was elevated to the House of Lords, and appointed Secretary to the UK government’s Treasury.
During the 18 months it took O’Neill to complete his final report, one million people worldwide died from AMR. At least 25,000 people die each year in Europe from AMR. According to the Centers for Disease Control and Prevention (CDC), more than 2m people in the US become infected with resistant bacteria every year, and at least 23,000 of them die. According to O’Neill, “If we don't do something about antibiotic resistance, we will be heading towards a world with no-antibiotic treatments for those who need them.”
A threat to modern medicine
O’Neill’s findings are congruent with warnings from the World Health Organization (WHO), which suggests AMR is a crisis worse than the Aids epidemic – which has caused some 25m deaths worldwide – and threatens to turn the clock back on modern medicine. The misuse of antibiotics has created, “A problem so serious that it threatens the achievements of modern medicine. A post-antibiotic era, in which common infections and minor injuries can kill, far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century,” says a 2014 WHO report. “Superbugs risk making routine surgery potentially lethal, killing millions and costing the world economy US$100 trillion a year by the middle of the century,” says O’Neill.
These dire warnings are supported by a case study of AMR published in Antimicrobial Agents and Chemotherapy in 2016, which suggests that we might be closer to a "post-antibiotic era" than we think. A particular group of bacteria (Gram-negative) have become increasingly resistant to currently available antimicrobial drugs. Colistin is one of the only antibiotics that still show some effectiveness against such infections, but the study suggests that even Colistin may no longer be effective.
Takeaways
AMR is widely recognized as a serious and growing worldwide threat to human health. New forms of AMR continue to arise and spread, leaving doctors with few weapons to bring potentially life-threatening infections under control. The injudicious use of antimicrobials, and the proliferation of AMR pathogens are compounded by the inability to rapidly and accurately diagnose minor ailments such as sore throats. Professor Kornberg has an answer.
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