It was bound to happen -- a gene that confers resistance to a last-resort antibiotic has been detected in the U.S.
The gene -- dubbed mcr-1 -- deceases the sensitivity of bacteria to colistin, which is used as a last resort for treating multi-drug resistant infections. It has been found mainly in Escherichia coli, but has also been seen in other Enterobacteriaceae on every continent.
But until now, the gene had not been seen in the U.S.
That changed in late April, when a 49-year-old woman was seen in a Pennsylvania clinic with symptoms indicating a urinary tract infection, according to Patrick McGann, PhD, of the Walter Reed Army Institute of Research in Silver Spring, Md, and colleagues.
The Army institute, starting early this month, had begun testing all extended-spectrum beta-lactamase (ESBL)-producing E.coli clinical isolates for resistance to colistin. A sample from the Pennsylvania women, dubbed MRSN 388634, was among the first six to be tested, McGann and colleagues reported online in Antimicrobial Agents and Chemotherapy.
It was also the only one to show resistance to colistin, with a minimum inhibitory concentration (MIC) of four micrograms per milliliter. The MIC is the lowest concentration of a drug that will inhibit the growth of bacteria after overnight incubation; the MIC of the Pennsylvania isolate was more than 16 times that of the other samples tested, McGann and colleagues reported.
"It's hard to imagine worse news for public health in the United States," commented Lance Price, PhD, of George Washington University in Washington, DC.
He noted that infectious diseases physicians increasingly use colistin as the last-ditch defense against carbapenem-resistant Enterobacteriaceae (CRE), including E. coli.
"Colistin is the last drug that works against many of these bacteria, so we may soon be facing a world where CRE infections are untreatable," Price said in a statement.
"History shows that mobile resistance genes can spread quickly around the world, silently riding in people, animals, and food," Price said. "We're watching this scenario play out in real time."
One important factor driving antibiotic resistance is overuse of the drugs, especially in agricultural settings, he said, calling for a global agreement to stop such use.
But the news was not unexpected, other experts said, because mcr-1 is contained in a plasmid -- a short circular piece of DNA that can easily be transferred from one bacterium to another.
"The U.S. was actually an anomaly in not finding it until now," commented Gerry Wright, PhD, of McMaster University in Hamilton, Ont.
"I expect it's been around for some time, just not detected," he said in a statement.
The Pennsylvania patient reported that she had not recently traveled outside the country, Wright noted, and because of that "you can predict with certainty that mcr-1 is established in the USA."
Nonetheless, the finding is "extremely concerning," commented Nirav Patel, MD, of Saint Louis University.
"The use of colistin in the U.S. is relatively low, and thus it is concerning that even in this environment, the resistance gene has been identified," Patel said in a statement.
"Unfortunately, this revelation is likely to herald further cases," he added, "and it will only be a matter of time when a patient gets a truly serious infection for which we have no viable antibiotics."
"I don't even know what we would use to treat an infection if it was colistin-resistant," said Nasia Safdar, MD, PhD, of the University of Wisconsin School of Medicine and Public Health in Madison.
Indeed, she said in a statement, "It wouldn't be a stretch to say that we are towards the end of effective antimicrobial therapy for antibiotic resistant bacteria."
In the Pennsylvania case, the E.coli carried 15 resistance genes on two plasmids, but remained susceptible to carbapenem antibiotics, McGann and colleagues reported. Since the initial tests, they noted, a further 20 isolates have been tested for colistin resistance; all were sensitive to the drug.
The study had support from the U.S. Army Medical Command, the Global Emerging Infections Surveillance and Response System, and the Defence Medical Research and Development Program.
All authors and commenters said they had no conflicts of interest.
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