But NDM-CRE infections present an additional problem because the newer combination drugs that were developed to defeat other carbapenemase genes “don’t treat NDM-CRE pathogens,” Spellberg explained. In other words, NDM-CRE has outfoxed these newer antibiotics.
“For years, NDM-CRE infections put clinicians in a position where the best new weapons in the arsenal simply didn’t apply,” said Amesh Adalja, MD, an infectious disease physician and senior scholar at the Johns Hopkins Center for Health Security.
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Newer options are now available, Spellberg and Adalja said. But one of the CDC’s concerns is that physicians need to know that a patient has an NDM-CRE infection to provide the proper treatment, and many clinical laboratories lack the molecular testing required to detect them.
“Selecting the right treatment has never been more complicated, so it is vitally important that healthcare providers have access to testing to help them select the proper targeted therapies,” CDC epidemiologist Danielle Rankin, PhD, MPH, said when the agency released its report last September.
New research by Stanton and CDC colleagues indicates that the growth of NDM-CRE infections is being driven primarily by a handful of strains from three members of the CRE family: K pneumoniae, Escherichia coli, and Enterobacter cloacae complex.
Stanton said that knowing which strains are driving the increase is important because it “can help the public health community recognize that there may be increased risk of local spread when these high-risk strains are encountered.”
An extremely mobile gene
But the tricky thing about the NDM gene is that it’s almost always carried by small pieces of DNA called plasmids that can move between bacteria. Plasmids allow the sharing of resistance traits between many types of bacteria, both pathogenic and non-pathogenic. While antibiotic resistance traditionally develops from bacteria exposed to an antibiotic, bacteria can acquire the NDM gene via a plasmid (or any other resistance gene) and become resistant without ever having encountered an antibiotic.
“It’s by nature an extremely mobile gene, and it can spread amongst any compatible host species that can hold on to the plasmids that carry it,” said Nathan Raabe, PhD, MPH, a genomic epidemiologist researching plasmids at the University of Pittsburgh School of Medicine.
This makes NDM-CRE more threatening than just clonal spread of a single strain of resistant bacteria, added colleague Alex Sundermann, DrPH. “All the different bacteria just want to eat it up because they’ll survive better,” he said.
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And that can make it harder to detect and prevent hospital outbreaks, because when those outbreaks occur, most hospitals are looking for transmission of a particular pathogen between patients. But in a study published in 2024, Raabe, Sundermann, and colleagues described an outbreak of NDM-CRE at UPMC Presbyterian Hospital involving 15 patients and seven different bacterial species in which some of the transmission involved the sharing of an NDM-carrying plasmid between different pathogens.
“Sometimes we were just seeing the plasmid move, then be integrated into different species that caused an infection,” Raabe explained. But not many hospitals have the ability to track that type of spread in real time.
Wastewater surveillance
NDM-CRE are primarily a threat in hospitals, a reservoir of resistant bacteria. But while the CDC data indicate that NDM is becoming more of a familiar presence and risk in hospitals, new wastewater analysis from 163 US sites suggests that in some parts of the country, the gene is spreading in the community.
In a study published in Nature Communications in April, a team led by researchers at the University of California (UC), Berkeley, found that though NDM was undetected in some areas of the country, concentrations of the gene were higher in wastewater from communities with hospitals and nursing homes, particularly in southern and western states.