Vol. 25 No. 11 Page 34
Researchers identify a strain of drug-resistant bacteria.
Recently, a team of researchers from N.J. reported what is thought to be the first strain of Escherichia coli bacteria from a patient in the United States that is resistant to both broad spectrum carbapenem antibiotics and colistin. Their study findings, published in mBio, revealed that the strain carried the colistin-resistant gene mcr-1, as well as a carbapenemase gene called NDM-5.
Carbapenem and Colistin Resistance
Over the last 10 years, there has been an explosion of carbapenem resistance in Gram-negative bacteria, primarily affecting Enterobacteriaceae strains, senior study author, Barry N. Kreiswirth, Ph.D., told ADVANCE. Kreiswirth, who is the founding director of the Public Health Research Institute (PHRI) Tuberculosis Center at New Jersey Medical School, part of Rutgers University in Newark, N.J, went on to explain that beta-lactams, a class of drugs that includes carbapenems, are the most effective antibiotics and are typically used for serious infections–especially in immunosuppressed patients.
“The fact that we now have what are called carbapenemase-enzymes that actually degrade these drugs has created a big problem in treating these infections,” Kreiswirth said. “In fact, approximately 50% of seriously infected patients don’t survive because we don’t have effective antibiotics.”
One of the drugs used to treat carbapenem-resistant Gram-negative infection is colistin, an older antibiotic that has become a last resort for multi-drug resistant infections. “Colistin has now become almost a front-line drug when you get a carbapenem-resistant infection, so obviously, colistin resistance is a concern,” Kreiswirth explained.
Mobile colistin resistance was first reported in China in November 2015, in a gene called mcr-1. This gene exists on plasmids, which have the ability to transfer between and among various bacteria. “An mcr-1 plasmid can transfer from E. coli to Klebsiella to Enterobacter,” Kreiswirth said. “Therefore we now have a concern that we’re going to have colistin resistance spreading, and that’s going to be a concern, because in the U.S. we use colistin.”
The other important aspect of the finding, Kreiswirth said, is that this strain was discovered in a retrospective analysis. This means that mcr-1 was present in the U.S. earlier than was previously thought. This particular strain was isolated in 2014 from a patient with a complicated urinary tract infection, but wasn’t analyzed until 2016.
When mcr-1 was first discovered and published, Kreiswirth’s lab screened for the gene among their samples. “We and many other people around the world who had colistin resistant strains in their collection basically went back, pulled these strains out of our refrigerators, made DNA, and did PCR analysis to see if we had any strains that were mcr-1 positive,” he said.
Then, after performing PCR, they sequenced the entire gene “In our paper, we knew we had the right thing because not only did we get a PCR product, but when we sequenced it, it matched perfectly to the published sequence,” Kreiswirth explained.
Identifying a drug resistant organism in a retrospective screen simply confirms its presence, Kreiswirth said. “The important message that it sends going forward is that other labs can do the same thing—but more importantly, they can do surveillance for it in real-time, instead of retrospectively,” he said. “That’s sort of like saying that ‘we just had a fire,’ as opposed to trying to prevent the fire.”
As strains come through hospital laboratories, they can now screen for this gene—especially among strains that have been shown to be colistin-resistant. “A lot of this is research based, so eventually, the other significance of finding the mcr-1 gene is that diagnostic companies could actually try to incorporate screening for the mcr-1 gene even in commercial assays,” Kreiswirth said.
Labs may also need to screen for mcr-2, which was reported in Belgium nearly the same time that Kreiswirth and his team identified the multidrug-resistant E. coli. “All it says is that there’s a mechanism out there now to give you transmissible colistin resistance,” Kreiswirth explained, “and not surprisingly, these strains they found in Belgium were all from animals. It’s just a matter of time—especially if patients are treated with this drug—that if that resistance gene is around, it’ll get selected for and increase the amount of mcr-1, and presumably, mcr-2. So colistin resistance is now going to have to be screened a little differently because of the fact that we have these mobile elements.”
Currently, carbapenem resistance only affects certain regions in the U.S., and the regions that have this problem are routinely using colistin to treat their patients. According to Kreiswirth, it’s these areas that especially need surveillance for this multidrug-resistant E. coli strain. “The goal of public health and the goal of this is to try to prevent things from spreading out of control,” Kreiswirth explained, “and we have the opportunity now when we make these observations to integrate this into hospital routine.”
“The problem is, A, some hospitals say, ‘well we don’t have this problem, why should we bother?’ Which isn’t legitimate,” Kreiswirth continued. “And then B, the ones that do have this problem, the real question is, are they going to put in the resources and dollars, and who’s going to pay for it? It always comes back down to someone has to pay for additional testing.”
Currently, Kreiswirth’s lab is working with the hospital where the patient with the E. coli strain was treated to screen for that strain. “A lot of it has to do with logistics,” Kreiswirth said. “For me to help the hospital laboratories—as I’m not a hospital lab; I’m a research lab—I have to get the strains in real-time. So a lot of it is logistical, but we’re going to try to be proactive and screen for this.”
Among other antibiotic resistance research, Kreiswirth’s lab is also working to determine why certain bacteria become colistin resistant in the absence of an mcr-1 gene. “The public health significance is that they don’t spread their DNA,” Kreiswirth said. “That’s an individual patient who developed colistin resistance. And colistin resistance doesn’t spread except if that strain spreads. So that’s a different pathway to our research.”