More Countries Are Seeing a Last-Ditch Antibiotic Failing

(This post has been updated; read to the end.)

More news is emerging about the dire new antibiotic resistance factor announced last month: MCR-1, a gene that disables the action of colistin, a very last-resort drug in human medicine. (If you’re just coming to this, my past posts are here and here.)

Quick recap: A gene conferring resistance to colistin was found in pigs, retail meat, and human patients in China; then it was spotted in Malaysia; then in Portugal. Then, in the next major development, researchers in Denmark announced they had identified the gene in one human patient and five samples of imported meat.

Here’s the newest news: The Danish researchers tell me that they have identified another patient who was infected with a bacterium bearing that same resistance factor. And Public Health England has announced that it has found the gene in 15 stored bacterial samples in its databases: 10 Salmonella bacteria and three E. coli that came from hospitalized patients, and two Salmonella on a single sample of imported poultry meat.

The news is both alarming—more instances of this gene that creates resistance to last-ditch drugs, and that can transfer easily between bacteria—and also puzzling. The British samples were taken between this year and 2012. The Danish samples announced 10 days ago date back to 2012, and the newly discovered one comes from 2011. So the gene has been circulating for several years, without causing any outbreaks.

Is that a bullet dodged? Perhaps. But researchers studying the new gene say it may be a slow-burning fuse.

In human medicine, colistin is a rarely used drug, a survivor from the earliest decades of antibiotic development that was left on the shelf for decades because it was toxic. But in veterinary medicine, colistin has had wide use, which is probably what caused this resistance factor to emerge. Now, with the loss of other antibiotics to resistance, colistin use in humans is climbing, and that could set the stage for this effectively untreatable resistance to bloom.

“This seems to have been around for five to six years,” Robert Skov, MD of the Statens Serum Institut in Copenhagen, and the senior author in the Danish team’s rapidly produced article on their discoveries, told me by phone. “One thing is for sure: We are using more and more colistin in humans due to the increase in [bacteria resistant to carbapenems, the next-to-last-resort drug], and thus we are probably selecting for this colistin resistance to emerge.”

How the gene—which resides on a plasmid, a mobile piece of DNA that can move between bacteria— is traveling the world is a puzzle. Skov said the Danish government has done an emergency survey of the country’s animal herds and found no trace of the gene. (Which, before now, no one would have been looking for.) The chicken meat in which the gene was found in Denmark was imported from Germany. The two people in whom the MCR gene has been found had not traveled to Asia. In Britain, three out of 10 patients had been to Asia, and the meat on which two MCR-bearing Salmonella strains were found was imported from elsewhere in Europe.

When NDM, the last last-resort resistance threat, began to spread across the world, it did so in the guts of patients who visited India, where it first emerged, and then traveled home to Europe and Britain. It’s possible a similar thing is happening with MCR. “We have five chicken isolates [bacterial samples] and one human isolate, and when we compare the plasmids in the chicken and human isolates and what has been published from China, the greatest resemblance to the Danish human isolate is the isolates from China and not from the German chicken,” Skov said. “This suggests it was brought, not by chicken, but by people coming from Asia to Denmark.”

In the past few days, I asked antibiotic resistance experts in various parts of the world whether they had seen MCR yet, and whether they were looking for it. All of them were looking; outside of Britain, none had discovered it yet in any national collections of bacterial isolates. (Or, given that disclosing a finding might keep them from publishing in major medical journals, were willing to admit to discovering it.)

Lance Price, PhD of the Antibiotic Resistance Action Center at George Washington University, told me that additional analysis of the isolates found in Denmark shows two troubling things. All of the bacteria in which the gene was found were unique—six different strains of E. coli—and the gene has found a home in two different plasmids. Together those suggests that it has no difficulty moving among bacteria and finding a comfortable home in them. “It’s real world, empiric evidence that this thing can spread very widely,” he said. “Its’s almost like it possesses a universal key.”

Price told me that one concern at this point will be which bacterial strains the gene jumps into: indolent ones that cause little disease, or fast-moving virulent ones that cause infections in many body systems and are already resistant to many other drugs. One of the Danish isolates that carries MCR, he said, is an E. coli of a type known as ST131—which in the United States is already multi-drug resistant and causes thousands of serious bladder and bloodstream infections every year. “At this point we don’t know what the denominator is going to be,” he said. “We don’t know how many different strains this is going to get into, and this underscores the possibility it will jump into something really bad.”

Update: On Dec. 17, Dutch authorities announced they too had identified MCR-1 in a bacterial collection in the Netherlands. The Central Veterinary Institute, housed at Wageningen University, said it found three bacterial isolates containing the MCR-1 gene in a collection of 3,274 Salmonella strains from 2014 and 2015. Two similar strains came from chicken meat that originated in the Netherlands, and a different strain from imported turkey. (It does not give the source of the turkey.) They are now undertaking a broader search through other bacterial collections.

There will no doubt be more such discoveries as other health authorities complete searches through whatever national collections they have. But as Lance Price says above, this is further evidence that this gene has great facility for jumping among different bacteria and bacterial species.

Meanwhile, if you’re interested in more on this, Price, Skov and I were on the NPR show On Point on Dec. 16On Point on Dec. 16, discussing MCR. Replay and podcast instructions at the link.