New MCR-1 reports warn of untreatable infection threat

The newly identified MCR-1 resistance gene has been detected in six more countries, along with worrisome signs that it can appear alongside other resistance genes, which would make some infections untreatable, according to reports yesterday from several research groups.

At least 17 countries have now reported the MCR-1 gene, which disables the last-line antibiotic colistin, an older drug that isn't often used in humans but is commonly used for raising food animals.

The newest reports—based on studies of existing bacteria collections—place the gene in Germany, Vietnam, Cambodia, Japan, Switzerland, and Belgium.

The MCR-1 gene was first reported by Chinese researchers in the middle of November. Since then, scientists in other countries have been looking in lab sample archives to gather more clues about its spread. The new findings appear in eight separate reports in The Lancet Infectious Diseases and follow a similar gush of new findings published in the same journal on Dec 17.

Most of today's reports detail findings in livestock or their environments, but three detections involve humans: a German patient, a Cambodian child who was hospitalized in 2012, and an elderly Swiss man who had no history of travel abroad.

Multi-country findings in farm animals

In one of the reports, German researchers looked for the gene in a database of 577 whole-genome sequences collected from people, animals, and the environment in Germany since 2009. They found the MCR-1 gene in four Escherichia coli samples—three from swine and one from the wound of an infected human. One was from 2010, which the authors said shows that transmission of colistin resistance in Germany's animal population isn't a recent occurrence.

An alarming finding was that all of the colistin-resistant isolates they found were also resistant to either third-generation cephalosporins or carbapenems. "Our data suggest that the advent of untreatable infections has already arrived," the team wrote.

In another study, scientists screened 24 extended-spectrum beta lactamase (ESBL) E coli samples collected between 2014 and 2015 from Vietnamese farm animals and a swine slaughterhouse. The MCR-1 gene was found in 9 samples: 6 from farm pigs, 1 from a slaughterhouse pig, and 2 from the slaughterhouse environment.

To gauge the presence in humans, they looked at 112 ESBL E coli isolates from patients who were seen for urinary tract infections at three Hanoi hospitals in 2014 and 2015. None of those samples yielded the MCR-1 gene.

They said their findings show that the MCR-1 gene is common in E coli that harbors the ESBL drug-resistance mechanism, but so far they haven't found that the same combination has jumped to humans.

In Japan, researchers looked at a database of gram-negative bacteria isolates from hospitalized patients, animals, and the environment. They also looked at genomes from 9,308 E coli isolates collected between 2000 and 2014 from food animals. They found the MCR-1 gene in 5 animal gram-negative bacteria isolates and in 2 pig E coli isolates from 2008 and 2010.

Meanwhile, French researchers who explored samples collected from 2005 to the middle of 2014 for diarrhea surveillance in veal calves found the MCR-1 gene in 106 of 517 ESBL E coli isolates. It was detected at 94 widely distant farms, with the oldest from 2005, which the authors said suggests dissemination more than a decade ago with major spread in Europe.

Seven of their samples harbored both MCR-1 and ESBL genes. "Worryingly, we show that selection pressure with broad-spectrum cephalosporins may select for colistin resistance and vice-versa, further highlighting the likelihood of a pandemic spread of MCR-1," they wrote, adding that widespread use of tetracyclines and sulfonamides in animals may also contribute to the problem.

Taken with other reports, the findings support an urgent need limit the spread of MCR-1 by scaling back the massive use of colistin in animals, the French team said.

In Belgium, investigators combed through 105 colistin-resistant E coli isolates collected from 2011 and 2012 from piglets and calves from two different regions during passive surveillance of diarrhea. Thirteen of the samples were positive for MCR-1: 6 from calves and 7 from piglets.

Samples from humans

Aside from the German sample from a patient's wound, yesterday's reports also touch on detections in Cambodia and Switzerland.

The Cambodian finding came from screening of a database of 1,100 E coli and 550 Klebsiella pneumoniae sequences collected between 1967 and 2012 from Europe, North America, and Southeast Asia. The sole MCR-1 finding was from E coli collected from the feces of a Cambodian child who was hospitalized in 2012, which was 2 years before China's sample was obtained.

The authors noted that the sample, like those described in other studies, contained other resistance genes.

In a very recent human detection, researchers detected E coli that contained the MCR-1 gene, along with a florfenicol-resistance gene, in a urine sample from a Swiss man who was hospitalized in December 2015 with diverticulitis. The E coli isolate was resistant to several antibiotics, including colistin.

The authors said the source of the patient's strain is unclear, but an animal source is likely, given the detection of MCR-1 alongside the resistance gene for florfenicol, another drug used in animals.

They warned that the accumulation of multidrug resistance traits signals another step toward untreatable Enterobacteriaceae infections.

See also:

Jan 7 Lancet Infect Dis letter on MCR-1 in Germany

Jan 7 Lancet Infect Dis letter on MCR-1 in Vietnam

Jan 7 Lancet Infect Dis letter on MCR-1 in Japan

Jan 7 Lancet Infect Dis letter on MCR-1 in French veal calves

Jan 7 Lancet Infect Dis letter on MCR-1 in Belgium

Jan 7 Lancet Infect Dis letter on MCR-1 in Cambodian child

Jan 7 Lancet Infect Dis letter on MCR-1 in Swiss man

Jan 7 Lancet Infect Dis letter on possible genetic events producing MCR-1 gene

Dec 18, 2015, CIDRAP News story "More MCR-1 findings lead to calls to ban ag use of colistin"

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