- Email: [email protected]
No place to hide
analysis drug resistance
No place to hide IN DECEMBER, bacteria carrying a gene that allows them to resist the antibiotic colistin were found in Denmark and China. The discovery meant that some types of bacteria now have the potential to become “pan-resistant”, with genes that defeat all our antibiotics. The shock this news caused rippled across the world, including on social networks like Reddit. This is a snapshot edited for clarity: GermTheory I’m a microbiologist working in antibiotic discovery. That news has really made a lot of people in the field nervous. Finie I just sent two more carbapenemresistant E. coli samples to the state lab. It’s only Monday. We’ve seen a huge increase in them over the past year. H3OFoxtrot Please tell me what state you’re working in so I can avoid it.
HawkinsDB You can run, but you can’t hide. It’s across the glooooooobe. In the end when they study why we all died it won’t be because of nuclear wars or global warming. It will be from something like these, the bugs that finally got us all.
Antibiotic resistance is at its worst in south Asia, so for those of us in the US and particularly northern Europe, it’s easy to think of it as a distant problem in the hospitals of India. It’s hard to imagine that our hospitals could soon be brought to their knees: routine operations too dangerous to carry out, people made infertile by untreatable super-gonorrhoea, organ recipients at grave risk of death because of their weakened immune systems. Yet while northern European countries, including the UK, have low levels of resistant strains, such infections kill more than
50,000 people across the continent and in the US every year. By 2050, annual deaths are expected to reach 317,000 in North America, and 390,000 in Europe, while the toll is expected to top 4 million in Asia and Africa. As the Reddit exchange shows, for those confronting the threat of a post-antibiotic world, the reality is truly concerning. On page 17 we talk to five people, including Reddit microbiologist GermTheory, about their experiences on the front line. There is some hope, with public awareness rising and governments gearing up to take action. In 2014, the UK public voted for antimicrobial resistance to be the subject of a £10 million research competition, the Longitude prize. The same year, the UK government asked economist Jim O’Neill to lead a review and make international recommendations on how to speed up the discovery
Christian Adams/Getty
We are seeing the first glimpses of a post-antibiotic world, says Penny Sarchet
of new antibiotics. “This is not some distant threat but something happening right now,” the UK prime minister, David Cameron, said at the time. So far, O’Neill’s team has called for better regulation of antibiotic sales, for limits to their use in
THE BACTERIA WE SHOULD FEAR THE MOST Most worrying is resistance to antibiotics of last resort, like carbapenems and vancomycin, which are only given when other drugs have failed Enterococcus faecium
enterococcus faecalis
Klebsiella pneumoniae
pseudomonas aeruginosa
Staphylococcus aureus
SOURCE Found in soil and water INFECTS Wounds and blood. Can cause pneumonia RESISTANCE In Serbia, 93% samples tested were resistant to carbapenems; South Africa, 74%; US, 43%
SOURCE Carried in the gut INFECTS Blood and urinary tract RESISTANCE Widespread resistance to aminopenicillins in US, UK and Australia. In US, 76% resistance to vancomycin
SOURCE Carried in the gut INFECTS Heart, brain and spinal cord, urinary tract RESISTANCE In Slovakia, 96% resistance to gentamicin; Norway, 72%; US, 34%
SOURCE Carried in the gut INFECTS Wounds and blood. Can cause meningitis RESISTANCE In Greece, 60% resistance to carbapenems; India 57%; Italy 36%
SOURCE Widespread INFECTS Ears, skin, blood RESISTANCE In Romania and Slovakia, 53% resistance to carbapenems; South Africa, 40%; US, 25%; France, 22%
SOURCE Carried in people’s noses INFECTS Blood, heart, bones. Can cause pneumonia RESISTANCE In the US, 44% resistance to oxacillin (resulting in MRSA); Canada, 16%; UK, 14%
Photos from SPL/Alamy
Acinetobacter baumannii
Data from Centre for Disease Dynamics, Economics and Policy
16 | NewScientist | 30 April 2016
Dispatches from the front line KENNETH SMITH, AKA germtheory microbiologist, us I work on the early stages of antimicrobial discovery. I focus on Enterobacteriaceae, a family of bacteria that have evolved resistance to antibiotics called carbapenems. These drugs used to be a last line of defence, and it is probably this type of bacteria that also recently developed resistance to colistin. My goal is to identify compounds that can work as “antibiotic resistance breakers”, restoring the efficacy of existing antibiotics. Seeing new resistance mechanisms is very concerning but honestly, it’s not surprising. The problem of resistance has been building for decades – only now are we really forced to pay attention given the rise of essentially untreatable –Too dangerous too attempt?- infections.
agriculture, and made recommendations on how to speed up the development of tests that can tell if a person needs an antibiotic, like those being designed for the Longitude prize. The team is due to give its final recommendations next month. But even these won’t be enough. “What we lack are bright, new ideas,” says Richard James, a microbiologist at the University of Nottingham, UK. But we have a few tricks up our sleeves. Two new
“I am more scared by antibiotic resistance than climate change – it is more likely to kill my family” antibiotics were discovered last year, which may help against tuberculosis and gram positive bacteria, the type that includes MRSA. And molecules that can restore the power of antibiotics against resistant organisms – known as antibiotic resistance breakers – are helping to extend the lifetime of some drugs. But if we continue misusing antibiotics, resistance will
continue to evolve, even for new drugs. Refining how antibiotics are prescribed isn’t enough – we need to reduce the global threat from agriculture. Last year, 63,000 tonnes of antibiotics were fed to livestock to increase their size or protect them from infections. A 2006 ruling banning the use of antibiotics as growth promoters in Europe seems to have had little impact, says Mark Woolhouse at the University of Edinburgh, UK. We still don’t understand how dangerous such practices are to human health, but using antibiotics in industrial quantities should give bacteria ample chance to develop resistance. The gene that gave bacteria resistance to colistin probably evolved in a pig farm in China, for example. “I once said I was more concerned about antimicrobial resistance than I am about climate change, and I stand by that,” says Woolhouse. “I am worried that my family might be killed by antimicrobial resistance. I don’t have the same concern when it comes to climate change.” n
maureen baker family doctor, uk Things have changed. Doctors are very aware of a responsibility to prescribe antimicrobials appropriately. I prescribe antibiotics to no more than two or three people a day, out of about 40 patients. Patients are aware of the issue but sometimes come in geared up for battle. They say they wouldn’t normally ask but they are going on holiday, or a parent wants a prescription for their child for over Christmas or an exam. But if a young child is unwell with a high temperature and chest symptoms, it gets really difficult. It’s probably a viral illness but if it’s bacterial, failing to prescribe antibiotics could be bad. Diagnostic tools would help. JOSIE GARRETT tuberculosis PATIENT, UK I contracted TB in 2014 from my boyfriend. He was coughing up blood and lost a lot of weight. I knew TB was a huge issue globally, but at the time I had no idea that it was a problem in the UK. We both had the type that is resistant to isoniazid, which meant
that treatment took much longer – two years for me, rather than the six months it usually takes. At first, I was taking 11 pills a day, and one drug kept giving me hepatitis. ravi vermer engineer and entrepreneur, US I’m developing a device that can distinguish between types of bacterial infections, and tell them apart from ones caused by viruses. New diagnostic tools are desperately needed – today’s blood culture method dates back to the 1890s. If you are trying to identify one bacterium in 1 millilitre of blood, it makes up only one trillionth of that sample. My team has found a way to amplify this signal a million times using a type of spectroscopy. In preliminary tests, our machine could detect 23 different microorganisms, and we are now testing patient samples at a hospital in Leeds, UK. We entered the Longitude prize for diagnostic tests last year, and are planning to enter again now that our machine is cheaper, and we have reduced the test time to 5 minutes. mike brown hospital consultant, uk At the University College London Hospital for Tropical Diseases we look after people who have acquired infections in London or while travelling abroad, as well as people who have picked up hospital-acquired infections. We have seen an increase in resistant infections. It’s worrying for us but even more so for the countries the people have visited, which have less access to the expensive antimicrobials. We spend a lot of time thinking about whether our seriously ill patients are at risk of having a resistant infection. If they are, they need to start on broad-spectrum antibiotics while we wait for lab reports but the more we do that, the more we will escalate the problem.
As told to Penny Sarchet 30 April 2016 | NewScientist | 17
No place to hide IN DECEMBER, bacteria carrying a gene that allows them to resist the antibiotic colistin were found in Denmark and China. The discovery meant that some types of bacteria now have the potential to become “pan-resistant”, with genes that defeat all our antibiotics. The shock this news caused rippled across the world, including on social networks like Reddit. This is a snapshot edited for clarity: GermTheory I’m a microbiologist working in antibiotic discovery. That news has really made a lot of people in the field nervous. Finie I just sent two more carbapenemresistant E. coli samples to the state lab. It’s only Monday. We’ve seen a huge increase in them over the past year. H3OFoxtrot Please tell me what state you’re working in so I can avoid it.
HawkinsDB You can run, but you can’t hide. It’s across the glooooooobe. In the end when they study why we all died it won’t be because of nuclear wars or global warming. It will be from something like these, the bugs that finally got us all.
Antibiotic resistance is at its worst in south Asia, so for those of us in the US and particularly northern Europe, it’s easy to think of it as a distant problem in the hospitals of India. It’s hard to imagine that our hospitals could soon be brought to their knees: routine operations too dangerous to carry out, people made infertile by untreatable super-gonorrhoea, organ recipients at grave risk of death because of their weakened immune systems. Yet while northern European countries, including the UK, have low levels of resistant strains, such infections kill more than
50,000 people across the continent and in the US every year. By 2050, annual deaths are expected to reach 317,000 in North America, and 390,000 in Europe, while the toll is expected to top 4 million in Asia and Africa. As the Reddit exchange shows, for those confronting the threat of a post-antibiotic world, the reality is truly concerning. On page 17 we talk to five people, including Reddit microbiologist GermTheory, about their experiences on the front line. There is some hope, with public awareness rising and governments gearing up to take action. In 2014, the UK public voted for antimicrobial resistance to be the subject of a £10 million research competition, the Longitude prize. The same year, the UK government asked economist Jim O’Neill to lead a review and make international recommendations on how to speed up the discovery
Christian Adams/Getty
We are seeing the first glimpses of a post-antibiotic world, says Penny Sarchet
of new antibiotics. “This is not some distant threat but something happening right now,” the UK prime minister, David Cameron, said at the time. So far, O’Neill’s team has called for better regulation of antibiotic sales, for limits to their use in
THE BACTERIA WE SHOULD FEAR THE MOST Most worrying is resistance to antibiotics of last resort, like carbapenems and vancomycin, which are only given when other drugs have failed Enterococcus faecium
enterococcus faecalis
Klebsiella pneumoniae
pseudomonas aeruginosa
Staphylococcus aureus
SOURCE Found in soil and water INFECTS Wounds and blood. Can cause pneumonia RESISTANCE In Serbia, 93% samples tested were resistant to carbapenems; South Africa, 74%; US, 43%
SOURCE Carried in the gut INFECTS Blood and urinary tract RESISTANCE Widespread resistance to aminopenicillins in US, UK and Australia. In US, 76% resistance to vancomycin
SOURCE Carried in the gut INFECTS Heart, brain and spinal cord, urinary tract RESISTANCE In Slovakia, 96% resistance to gentamicin; Norway, 72%; US, 34%
SOURCE Carried in the gut INFECTS Wounds and blood. Can cause meningitis RESISTANCE In Greece, 60% resistance to carbapenems; India 57%; Italy 36%
SOURCE Widespread INFECTS Ears, skin, blood RESISTANCE In Romania and Slovakia, 53% resistance to carbapenems; South Africa, 40%; US, 25%; France, 22%
SOURCE Carried in people’s noses INFECTS Blood, heart, bones. Can cause pneumonia RESISTANCE In the US, 44% resistance to oxacillin (resulting in MRSA); Canada, 16%; UK, 14%
Photos from SPL/Alamy
Acinetobacter baumannii
Data from Centre for Disease Dynamics, Economics and Policy
16 | NewScientist | 30 April 2016
Dispatches from the front line KENNETH SMITH, AKA germtheory microbiologist, us I work on the early stages of antimicrobial discovery. I focus on Enterobacteriaceae, a family of bacteria that have evolved resistance to antibiotics called carbapenems. These drugs used to be a last line of defence, and it is probably this type of bacteria that also recently developed resistance to colistin. My goal is to identify compounds that can work as “antibiotic resistance breakers”, restoring the efficacy of existing antibiotics. Seeing new resistance mechanisms is very concerning but honestly, it’s not surprising. The problem of resistance has been building for decades – only now are we really forced to pay attention given the rise of essentially untreatable –Too dangerous too attempt?- infections.
agriculture, and made recommendations on how to speed up the development of tests that can tell if a person needs an antibiotic, like those being designed for the Longitude prize. The team is due to give its final recommendations next month. But even these won’t be enough. “What we lack are bright, new ideas,” says Richard James, a microbiologist at the University of Nottingham, UK. But we have a few tricks up our sleeves. Two new
“I am more scared by antibiotic resistance than climate change – it is more likely to kill my family” antibiotics were discovered last year, which may help against tuberculosis and gram positive bacteria, the type that includes MRSA. And molecules that can restore the power of antibiotics against resistant organisms – known as antibiotic resistance breakers – are helping to extend the lifetime of some drugs. But if we continue misusing antibiotics, resistance will
continue to evolve, even for new drugs. Refining how antibiotics are prescribed isn’t enough – we need to reduce the global threat from agriculture. Last year, 63,000 tonnes of antibiotics were fed to livestock to increase their size or protect them from infections. A 2006 ruling banning the use of antibiotics as growth promoters in Europe seems to have had little impact, says Mark Woolhouse at the University of Edinburgh, UK. We still don’t understand how dangerous such practices are to human health, but using antibiotics in industrial quantities should give bacteria ample chance to develop resistance. The gene that gave bacteria resistance to colistin probably evolved in a pig farm in China, for example. “I once said I was more concerned about antimicrobial resistance than I am about climate change, and I stand by that,” says Woolhouse. “I am worried that my family might be killed by antimicrobial resistance. I don’t have the same concern when it comes to climate change.” n
maureen baker family doctor, uk Things have changed. Doctors are very aware of a responsibility to prescribe antimicrobials appropriately. I prescribe antibiotics to no more than two or three people a day, out of about 40 patients. Patients are aware of the issue but sometimes come in geared up for battle. They say they wouldn’t normally ask but they are going on holiday, or a parent wants a prescription for their child for over Christmas or an exam. But if a young child is unwell with a high temperature and chest symptoms, it gets really difficult. It’s probably a viral illness but if it’s bacterial, failing to prescribe antibiotics could be bad. Diagnostic tools would help. JOSIE GARRETT tuberculosis PATIENT, UK I contracted TB in 2014 from my boyfriend. He was coughing up blood and lost a lot of weight. I knew TB was a huge issue globally, but at the time I had no idea that it was a problem in the UK. We both had the type that is resistant to isoniazid, which meant
that treatment took much longer – two years for me, rather than the six months it usually takes. At first, I was taking 11 pills a day, and one drug kept giving me hepatitis. ravi vermer engineer and entrepreneur, US I’m developing a device that can distinguish between types of bacterial infections, and tell them apart from ones caused by viruses. New diagnostic tools are desperately needed – today’s blood culture method dates back to the 1890s. If you are trying to identify one bacterium in 1 millilitre of blood, it makes up only one trillionth of that sample. My team has found a way to amplify this signal a million times using a type of spectroscopy. In preliminary tests, our machine could detect 23 different microorganisms, and we are now testing patient samples at a hospital in Leeds, UK. We entered the Longitude prize for diagnostic tests last year, and are planning to enter again now that our machine is cheaper, and we have reduced the test time to 5 minutes. mike brown hospital consultant, uk At the University College London Hospital for Tropical Diseases we look after people who have acquired infections in London or while travelling abroad, as well as people who have picked up hospital-acquired infections. We have seen an increase in resistant infections. It’s worrying for us but even more so for the countries the people have visited, which have less access to the expensive antimicrobials. We spend a lot of time thinking about whether our seriously ill patients are at risk of having a resistant infection. If they are, they need to start on broad-spectrum antibiotics while we wait for lab reports but the more we do that, the more we will escalate the problem.
As told to Penny Sarchet 30 April 2016 | NewScientist | 17