An Inevitable Invasion -- When a Last-Resort Antibiotic Is Not an Option: mcr-1 Plasmid-Driven Colistin Resistance

Paul G. Auwaerter, MD


June 21, 2016

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Editor's note: On June 13, 2016, the Centers for Disease Control and Prevention issued, via the Health Alert Network,
" Alert to U.S. Healthcare Facilities: First mcr-1 Gene in E. coli Bacteria found in a Human in the United States ."

This is Paul Auwaerter for Medscape Infectious Diseases, speaking from the Johns Hopkins University School of Medicine. A recent brief report[1] captured a lot of press and attention. What was believed to be a routine Escherichia coli urinary tract infection harbored a particular gene making it resistant to colistin, usually viewed as a last-resort antibiotic for the treatment of gram-negative infections.

This story has evolved rather quickly. A few months ago, a group of Chinese scientists found that many gram-negative bacteria (Enterobacteriaceae) harbor the plasmid gene mcr-1.[2] A plasmid enables bacteria to spread easily to other bacteria and generate resistance to colistin. Before now, these plasmids were more commonly found in pigs and other animals. Colistin is often used to treat pigs in Southeast Asia and China, but it has also been found in some human isolates.

A welter of publications followed, reporting the same colistin resistance profile and gene in Europe, Africa, and throughout Southeast Asia. As a commensal bacteria, it doesn't cause illness in humans [when residing in gut flora or colonizing skin and mucosal surfaces]. Mcr-1 colistin resistance has been found in non-ill nursing home residents in Italy,[3] and as far back as 2008, this resistance has been described in an isolate of Shigella, which usually is a cause of dysentery, in Vietnam.[4] So although just reported, colistin resistance has been developing for some time, perhaps silently, because such bacteria as E coli are rarely tested for colistin resistance.

The second aspect is that this gene has only just been described. However, it is important because, having plasmid as a basis, these bacteria can spread to a whole host of organisms. Everyone is waiting fearfully until mcr-1 is routinely found in acutely ill hospitalized patients who are already resistant to other antibiotics (eg, amikacin, aminoglycosides, or carbapenems).

Being plasmid-mediated is a concern especially as colistin use is the "canary in the coal mine" of gram-negative resistance. At Johns Hopkins, a decade and a half ago we might have used 10-15 courses of the drug each year, but now we are prescribing hundreds of courses of colistin annually. It's a concern that recognizes that extensive antibiotic use for growth production in industrialized animal raising is not without significant collateral damage or an impact on human health.

Already found here in the United States, we will look into this problem more extensively. I expect to see reports from more centers as they try to incorporate assessment of the resistance profiles of bacteria routinely into the care of their patients. Thanks for listening.


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