Experts have been warning for a while that the bell is tolling for the end of the antibiotic era, presaging a time when infections won’t be treatable with the drugs that have changed modern medicine. On Wednesday, that ominous knell got a little bit louder.
Chinese and British scientists reported that they have found a strain of Escherichia coli that is resistant to colistin, the antibiotic of last resort for gram-negative bacteria such as E. coli. The resistant bacteria were found in pigs, raw pork meat, and in a small number of people in China.
It’s not the first time colistin resistance has been spotted, but this time the phenomenon comes with a nasty twist. The resistance is conferred by a gene found on a plasmid, a portable piece of DNA. That’s alarming because plasmids can both transfer within a family of bugs and to other families of bacteria as well.
If the resistance spreads, it will seriously limit the treatment options available to doctors facing antibiotic-resistant infections, said Dr. Jean Patel, acting director of the office of antimicrobial resistance at the Centers for Disease Control and Prevention in Atlanta. Patel was not involved in the study.
The scientists — from the South China Agricultural University in Guangzhou, the China Agricultural University in Beijing, and other institutions — called the resistance gene mcr-1. Reporting in the journal Lancet Infectious Diseases, they described the emergence of mcr-1 as “the breach of the last group of antibiotics” by plasmid-mediated resistance.
The mcr-1 gene can move among E. coli bacteria, the scientists reported. But it can also go into other bacteria — Klebsiella pneumoniae and Pseudomonas aeruginosa — and give those bugs the capacity to resist colistin, too.
A member of the polymyxin class of antibiotics, colistin is an old drug that was rarely used for decades because there were other antibiotic options that have fewer side effects.
But as antibiotic resistance has increased, the drug has become a critical part of the armamentarium; in 2012 the World Health Organization designated it as critically important for human medicine.
Experts have insisted it should be preserved for people and should not be employed in agricultural operations, where vast quantities of antibiotics are fed to animals as growth promoters. And yet, in China, the drug is used more in animal production than it is on people, said Timothy Walsh, a medical microbiologist from Cardiff University in Wales, and one of the authors of this paper.
“We needed to have definitive borders between antibiotics that are used in human medicine and those that are used in the veterinary sector,” said Walsh, who was also involved in the discovery of another dangerous plasmid-mediated resistance gene, NDM-1. “That mantra should be universal and strictly adhered to.”
Walsh told STAT in an interview that he and his co-authors will meet next week with government officials to try to persuade China to ban agricultural use of colistin.
After finding the mcr-1 gene in one pig, the authors of the new study conducted a survey, finding the gene in 166 of 804 pigs tested at slaughterhouses and in 78 of 523 samples of raw meat. They also found it in E. coli bacteria isolated from a small number of hospitalized people in China; it was present in 1 percent of 1,322 samples they tested.
Dr. Amesh Adalja is a Pittsburgh-based infectious diseases physician who has seen one of his patients die because of a completely drug-resistant lung infection. He thinks doctors will have to get used to that sense of helplessness going forward. Adalja, a spokesperson for the Infectious Diseases Society of America, said the plasmid-mediated nature of mcr-1 is “particularly scary” because of the potential for spread.
But the CDC’s Patel cautioned that just because something has the potential to spread doesn’t always mean that it will. She noted that a few years ago, Staphylococcus aureus strains emerged that were resistant to the antibiotic vancomycin. In that case, too, the resistance was plasmid-mediated. Vancomycin is a mainstay in the treatment of staph infections, which are among the most common infections around. The discovery led to dire predictions. And they proved to be wrong.
“That’s our classic example where we were very, very concerned and then it didn’t spread,” said Patel. Nonetheless, she noted, the CDC will need to ramp up surveillance for mcr-1.