Researchers in Denmark announced Thursday that they had found several samples of E. coli bacteria that are resistant to the antibiotic of last resort, just two weeks after Chinese researchers revealed they had found a similarly resistant strain.
The announcement means the form of the bacteria has spread beyond just one region of the globe. To the surprise of scientists, it has also been circulating in the Scandinavian country for some time. The earliest of the Danish samples showing this resistance gene dates back to 2012.
Scientists at the Technical University of Denmark’s National Food Institute in Søborg and the State Serum Institute in Copenhagen discovered the presence of the new resistant bacteria by searching for it in a database containing the genetic sequences of about 3,000 E. coli samples. They ran the search after Chinese scientists last month reported finding a new colistin-resistent gene, mcr-1, in the journal Lancet Infectious Diseases.
Their search turned up six instances of bacteria carrying the mcr-1 gene.
“I was not surprised but I had really sincerely hoped not to see it,” Frank Aarestrup, head of the genomic epidemiology group at the National Food Institute, told STAT.
He suggested other researchers with similar databases should also look for mcr-1. “They should do it and they should do it now,” he said.
One of the Danish samples had been recovered from a man who had not traveled outside of the country. The other five were taken from poultry imported from Germany. Aarestrup said it’s not known at this point whether the poultry was produced in Germany or imported from a third country.
But that makes at least four countries where mcr-1 is known to have occurred. The Chinese report last month mentioned five entries of E. coli sequences from Malaysia in a European sequence database that contained mcr-1.
Lance Price, head of George Washington University’s Antibiotic Resistance Action Center, called the Danish discovery alarming and said countries around the world should institute a ban on agricultural use of colistin.
In China, the resistant bacteria were found in pigs, in pork meat, and in a few people.
“We must act swiftly to contain the spread of colistin-resistant bacteria, or we will face increasing numbers of untreatable infections,” Price said in a statement.
In an interview, he said the Danish finding was “a big shock” and “disheartening.” Price said his group looked through a database it had but found no sign of mcr-1. But those sequences, their most recent, were from 2012. He said it would be important to check the sequences of bacterial samples collected since then.
Colistin resistance has been seen before, but not in this form. What makes this situation unique — and unsettling — is that the gene that makes the bacteria colistin-resistant is contained in a plasmid, a mobile piece of DNA. Plasmids can easily move from one bacterium to another, both within a family of bacteria and to other families, as well. That means E. coli carrying mcr-1 can share it with other E. coli, as well as pass it to bacteria like Klebsiella pneumoniae.
That mobility suggests this form of resistance could disseminate widely and rapidly. “History shows that these mobile resistance genes can spread around the world quickly, silently riding in people, animals, and food,” Price said.
Aarestrup supported Price’s call for a ban on agricultural use of colistin, but also insisted more needs to be done. “We really need to drastically, drastically, drastically reduce the use of antibiotics,” he said, adding the reduction must occur both in agricultural and human use of the drugs.
Colistin is an old antibiotic that wasn’t much used for years because it can cause significant side effects. Newer, easier to tolerate antibiotics pushed it to the back of the shelf. But as more and more bacteria become resistant to an increasing number of drugs, old tools are finding their way to the front of the medicine cabinet again.
Both Aarestrup and Price warned that the world hasn’t grasped the severity of the threat posed by the rise of antibiotic resistance. Many procedures that are considered miracles of modern medicine — organ transplants, joint replacements to name a couple — will become too dangerous to perform if doctors cannot prevent post-operative infections or cure them if they arise.
Even things as simple as removing a tooth may require a discussion of whether it’s worth the risk, Aarestrup said grimly.