December 12, 2016 Liz Borkowski, MPH 0Comment

Last week, the journal Antibiotic Agents and Chemotherapy posted an accepted manuscript that contains some very bad news: an easy-to-spread gene that makes bacteria resistant to an important class of antibiotics has been found in samples from a US pig farm.

A team of researchers from Ohio State University, led by Thomas Wittum, collected samples from pigs and buildings at a pig facility over five months in 2015. They found that several of the samples contained carbapenem-resistant Enterobacteriaceae (CRE). Back in 2013, CDC Director Thomas Frieden held a press briefing on this “nightmare bacteria,” warning of the alarming increase in hospital-acquired infections resistant to this last-resort class of antibiotics. Enterobacteriaceae is a family of bacteria that includes E. coli. They’re often involved in foodborne illness outbreaks and in urinary tract infections.

Two aspects of this new finding are especially alarming. First, the researchers found the carbapenem-resistance factor, IMP, on a plasmid. Plasmids are highly mobile portions of DNA that transfer easily between different bacterial strains. So, a strain of E. coli that’s already resistant to a first- or second-line antibiotic could acquire  plasmid-borne resistance to a last-resort antibiotic relatively easily. This is why last year’s discovery of colistin-resistance gene mcr-1 on a plasmid was so alarming.

The other worrisome thing is that carbapenems aren’t approved for use in agriculture. Much of today’s antibiotic resistance has been traced to the routine use of antibiotics in livestock for growth promotion, but the facility where Wittum’s team found CRE doesn’t use carbapenems — so, the bacteria must have arrived or developed there through another route, possibly involving human-to-animal transmission.

Maryn McKenna at FERN’s AG Insider considers what the new findings might mean for public health:

[Wittum’s] team did not find any CRE in the finishing barn, where the pigs spend the last part of their lives before being sold, nor in any fecal samples taken from pigs in any of the barns. Since then, however, they have gone back, retested sows and piglets, and found them carrying IMP in their feces — which raises the possibility these highly-resistant organisms could move with pigs when they leave the farm, and could enter the food chain.

… “If they can find this in one farm, and not a huge farm, over and over, then there is probably more of this out there than we realize,” said Tara Smith, a molecular epidemiologist at Kent State University who was the first researcher to identify MRSA, drug-resistant staph, in pigs in the United States.

If carbapenem resistance is spreading in agriculture, she pointed out, we probably won’t know — because the limited testing of animals and meat that occurs in the United States looks for antibiotic resistance only in foodborne organisms such as salmonella and campylobacter. The organisms that Wittum and his co-authors recovered from the barns were random gut bacteria that linger on environmental surfaces: E. coli, citrobacter, morganella and providencia.

McKenna is my favorite source of writing on resistant bacteria (and you should read her whole FERN article about this new finding). When researchers began finding mcr-1 in samples around the world, she offered this helpful analogy:

It’s natural to imagine that antibiotic resistance proceeds step-wise; that in the leapfrog between bug and drug, bacteria gain resistance to one drug, and then the next toughest drug presented to them, and then a last-resort drug after that. But in the wild, the way bacteria accumulate resistance DNA is more like being dealt cards in a hand of poker: one might have a 3, a 5, and a Jack, while another has a King, a Queen and a 10.

In these papers published tonight, researchers are finding bacteria that already possess colistin resistance— call it the Ace—and are accumulating the rest of a winning hand. Only, what looks like winning would be losing, for us.

If CRE isn’t already in the US food supply, it’s probably only a matter of time before it is. This is how we get closer to a day when a strain of bacteria assembles a winning hand that makes it resistant to all antibiotics. At that point, we’ll have to face a post-antibiotics era, when a simple cut can prove fatal and medical procedures that are routine today (dialysis, hip replacements, etc.) become much more likely to kill us.

Related posts:
The more researchers look for colistin-resistant bacteria, the more they find (August 2016)
US researchers find bacteria resistant to last-resort drug (June 2016)
More bad news about the global spread of antibiotic-resistant bacteria (December 2015)
Findings from China show the post-antibiotics future approaching (November 2015)

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