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A dangerous type of superbug has more tricks up its sleeves than we may be giving it credit for, a new study suggests.

The researchers found that this class of bacteria, CREs — that’s short for carbapenem-resistant Enterobacteriaceae — has more ways to evade antibiotics than have been currently identified, and that these bugs share their tricks readily across the families of bacteria that make up this grouping.

Further, the authors suggest these bacteria may be spreading more stealthily than existing surveillance can detect.


“You know the phrase ‘Shutting the stable door after the horse has bolted?’ The horse has not only bolted, the horse has had a lot of ponies, and they’re eating all our carrots,” said Bill Hanage, an infectious diseases epidemiologist at the Harvard T.H. Chan School of Public Health and senior author of the study.

Hanage and colleagues from Harvard and the Broad Institute of MIT and Harvard took an in-depth look at CREs recovered from patients in three Boston hospitals and a hospital in Irvine, Calif. Their findings are published this week in the Proceedings of the National Academy of Sciences.


Dr. Tom Frieden, director of the Centers for Disease Control and Prevention, has dubbed CREs “nightmare bacteria.”  That’s because they are resistant to many, and sometimes most, antibiotics, including carbapenems, an important class of last-resort drugs.

They also have the capacity to transfer resistance genes from one family to the next — for instance from E. coli bacteria to Klebsiella pneumoniae. Think of it as gangs in a neighborhood teaching each other all their worst tricks.

According to CDC estimates, CREs cause 9,300 infections a year in the US and 600 deaths. They vary in their ability to fend off antibiotics; a report last week revealed a woman in Nevada died last September from a CRE infection that could not be treated with the antibiotics available in the United States.

“People are obviously concerned about CREs for very good reasons, as we see in the case of this lady who died in Nevada. They are very worrisome bacteria,” Hanage said.

The superbugs are growing in number and strength. Hyacinth Empinado/STAT

He and his coauthors wanted to take a closer look these bugs, so they studied the genetic sequences of 263 bacteria retrieved from the blood, urine, wounds, and respiratory tracts of patients in the four hospitals.

They were looking for, among other things, whether these resistant bacteria were spreading from patient to patient in a hospital. If they were, the genetic sequences of two patients infected in the same hospital around the same time would look quite similar.

Hanage said they didn’t find a lot of evidence of transmission, but they did see “a riot of diversity.” There were more specific families of bacteria represented among the CREs than they had expected. And there were additional surprises.

A number of genes are known to give bacteria resistance to carbapenems. In fact, the names of those genes make up a veritable alphabet soup: KPC, OXA, NDM, VIM. But some of the bacteria didn’t carry those signature genes — and yet, they could not be vanquished by carbapenem drugs. Hanage said they still haven’t figured out what in their genes allows these bacteria to resist the drugs. “There are many different ways in which they can be resistant,” he said.

An infection control expert at the CDC agreed. Dr. Alex Kallen wouldn’t comment specifically on the study — CDC scientists generally don’t comment on research they have not contributed to — but he suggested these bacteria have oodles of ways to overcome drugs.

“There are probably hundreds of different mechanism combinations,” said Kallen, a medical officer in the CDC’s division of health care quality promotion.

The fact that there wasn’t much evidence of transmission within hospitals raises other questions. How are the bacteria spreading? Are healthy people carrying them and transmitting them to others? Hanage said surveillance for these bacteria needs to be broadened.

“While the typical focus has been on treating sick patients with CRE-related infections, our new findings suggest that CRE is spreading beyond the obvious cases of disease. We need to look harder for this unobserved transmission within our communities and health care facilities if we want to stamp it out,” he said.

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