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New Resistance Gene Found in Multidrug-Resistant Pathogen

Infection experts warn of more U.S. ‘superbug’ cases in coming months

A team of Italian investigators has discovered a new variant of an emerging antibiotic resistance mechanism. The new variant, dubbed mcr-1.2, confers resistance to colistin, a last-resort antibiotic against multidrug-resistant gram-negative pathogens. The research was published online in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

“This is a particularly worrisome development for the future of antimicrobial therapy,” said corresponding author Gian Maria Rossolini, MD, of Florence Careggi University Hospital, Florence. More worrying is that the new resistance mechanism was discovered on a multidrug-resistant strain of Klebsiella pneumoniae, she added. That bacterium was isolated from a rectal swab of a child hospitalized with leukemia.

The investigators found the bacterium to be resistant to an unusual combination of antibiotics, said Rossolini. Noticing an odd resistance profile, first author Vincenzo Di Pilato, PhD, reanalyzed the genome data from the bacterium and discovered the new gene, which is a variant on the colistin-resistant gene mcr-1.

The mcr-1 gene was first reported in China in late 2015. Since then it has been found in several countries worldwide, mostly in Escherichia coli.

Like mcr-1, mcr-1.2 is carried on a plasmid. Plasmids are small pieces of genetic material that exist independently of chromosomal DNA, but which are replicated every time the bacterium divides. They are pieces of genetic material that can be transferred from one bacterium to another, and even from one species of bacterium to another.

This is the first time an mcr-type gene has been found on a “high risk” clone of K. pneumoniae. “‘High risk’ means that these multidrug-resistant clones retain a remarkable ability to disseminate in the clinical setting and to cause infections,” Rossolini explained.

In related news, infectious disease experts in the United States say they expect more cases of “superbug” infections in coming months. In May, U.S. Army scientists reported finding E. coli bacteria that harbored the mcr-1 gene in a urine sample from a Pennsylvania woman being treated for a urinary tract infection. Then, on July 11, researchers confirmed preliminary findings that E. coli organisms carrying the same mcr-1 gene were found in a stored bacterial sample from a New York patient who had been treated for an infection last year, as well as in patient samples from nine other countries.

The report came from a global effort called the SENTRY Antimicrobial Surveillance Program, led by JMI Laboratories in North Liberty, Iowa.

“You can be sure [mcr-1] is already in the guts of people throughout the United States and will continue to spread,” Dr. Brad Spellberg, professor of medicine at the University of Southern California, told the Reuters news service. 

Dr. David Van Duin, an infectious disease expert at the University of North Carolina in Chapel Hill, said he expects more documented U.S. cases of mcr-1 in coming months because it is already here and will spread from abroad.

The concern of many disease experts is that mcr-1 could soon show up in bacteria that are also resistant to carbapenems, one of the few remaining dependable classes of antibiotics. In that event, with colistin no longer a last-ditch option, some patients would have to rely on their immune systems to fight off infection.

“Within the next two to three years, it’s going to be fairly routine for infections to occur in the United States for which we have no [effective] drugs available,” said Dr. Gautam Dantas, associate professor of pathology at the Washington University Medical Center in St. Louis, Missouri.

Sources: American Society for Microbiology; July 11, 2016; Antimicrobial Agents and Chemotherapy; July 11, 2016; and Reuters; July 11, 2016.

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