Emergence of colistin resistance represents ‘threatening development’
Last November, researchers in China announced an alarming discovery: They had detected the first transferable gene for resistance to colistin, an antibiotic that fell out of favor decades ago because of its toxicity, but has been increasingly used as a last resort to treat multidrug-resistant infections.
In the age of antibiotic overuse, the emergence of colistin resistance may have been inevitable, but the discovery of a gene that transferred that resistance to other bacteria still represented a “finding of global significance,” the researchers wrote.
Indeed, in less than 1 year since mcr-1 was first isolated in a strain of Escherichia coli from Chinese pigs, the plasmid-mediated gene has been detected worldwide in animals and people, including four human cases in the United States, all in E. coli isolates.
“The mcr-1 gene represents a very threatening development,” Amesh A. Adalja, MD, FACP, public health committee member for the Infectious Diseases Society of America, told Infectious Disease News. “What is particularly important to realize about mcr-1 is that it is transferrable from bacteria to bacteria, allowing it to disseminate among various bacterial species.”
US cases discovered
The researchers who discovered mcr-1 had been conducting a routine antimicrobial resistance surveillance project on Chinese food animals when they noted an increase in colistin resistance.
The gene was identified after a strain of E. coli isolated from pigs indicated that it could transfer its colistin resistance to other strains.
A retrospective study showed that the proportion of positive samples in retail meats and pigs at slaughter had increased each year from 2011 to 2014 in China. The researchers also detected mcr-1 in hospital patients.
“The emergence of mcr-1 heralds the breach of the last group of antibiotics,” they wrote.
Following the report, the CDC, FDA and Agriculture Department began searching for mcr-1 and have since found it in four humans and two pigs. In fact, mcr-1 has been in the U.S. since at least 2014, but was not identified in a patient here until May by Defense Department researchers who had only just begun looking for the plasmid-mediated gene. They found it in the first six E. coli isolates submitted to the clinical microbiology laboratory at Walter Reed National Military Medical Center.
The gene was detected in a culture taken from a female patient who was treated for a urinary tract infection in April at a Pennsylvania clinic. The patient had not traveled within the previous 5 months.
“The medicine cabinet is empty for some patients. It is the end of the road for antibiotics unless we act urgently,” CDC Director Thomas R. Frieden, MD, MPH, warned upon news of the discovery.
In truth, each of the four E. coli isolates harboring the mcr-1 gene that have been detected in U.S. patients have been susceptible to other antibiotics, but experts fear that the gene will eventually jump to a bacteria species that is already resistant to most drugs.
“The existence of mcr-1 reinforces the dire need to develop new solutions to antimicrobial resistance before it’s too late,” Adalja said.
Fears of panresistance
In addition to the Pennsylvania case, mcr-1 also has been detected in E. coli isolates taken from adults in New York and New Jersey and a child in Connecticut who may have acquired the gene while traveling in the Caribbean, researchers said.
The New York case, dating to May 2015, was discovered during a global antimicrobial surveillance project involving samples from 183 hospitals in North America, Europe, the Asia-Pacific region and Latin America. Some 19 E. coli isolates in 10 countries were found to harbor mcr-1, including five from Germany, four from Italy and three from Spain.
Of particular concern, the New Jersey case involved a patient who had an E. coli strain that was resistant to both colistin and broad-spectrum carbapenems — the first time such resistance was detected in the U.S. The strain came from the urine sample of a man, aged 76 years, who had recently emigrated from India but had been living in the U.S. continuously for 1 year with no recent history of travel. The sample was collected in August 2014 — the earliest appearance so far of mcr-1 in the U.S. By comparison, the first E. coli strain found by the researchers in China to harbor mcr-1 was recovered from a pig farm in Shanghai in July 2013.
The discovery of the multidrug-resistant case in New Jersey brought both good and bad news, according to one of the researchers who studied the case.
“The good news is that this did not cause a major outbreak of drug-resistant infection,” Barry N. Kreiswirth, PhD, director of the Public Health Research Institute Tuberculosis Center at Rutgers University, said in a news release. “The bad news is that since this occurred 2 years ago, there are clearly other strains out there we haven’t detected yet.”
More potential good news came from CDC researchers who investigated the Pennsylvania case and said that mcr-1 was not found among any of the 105 contacts of the patient who were screened, suggesting to them that the gene might not be easily transferred between a colonized patient and a healthy person.
While mcr-1 has been found in humans, food and food animals across the globe, scientists in China recently suggested yet another reservoir: companion animals such as dogs and cats. The scientists linked a human E. coli infection to dogs in the pet shop where the patient worked and said the discovery added “another layer of complexity to the rapidly evolving epidemiology of plasmid-mediated colistin resistance.” – by Gerard Gallagher
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Disclosures: Adalja reports being a Merck shareholder and part of Merck’s speakers bureau. Frieden is director of the CDC. Please see the full studies for a list of all authors’ relevant financial disclosures.