When CDC researchers sequenced the genetic code of more than 8,000 drug-resistant bacteria samples collected across the United States, they expected to find a bewildering diversity—thousands of unrelated strains collaborating in chaos. Instead, they discovered something far more alarming: a masterclass in bacterial ruthlessness. A small handful of highly successful clones have orchestrated the dramatic 461% surge in NDM-CRE infections between 2019 and 2023, and understanding exactly how has opened a new path to fighting back.
NDM-CRE—shorthand for NDM-producing carbapenem-resistant Enterobacterales—represents one of medicine's most pressing headaches: bacteria that shrug off nearly all antibiotics. These infections, often acquired in healthcare settings, can be nearly untreatable. Public health officials have watched their prevalence climb at an alarming rate. But until now, the question of whether that rise reflected one dominant threat or a fragmented epidemic remained murky. This distinction matters profoundly for strategy. Fighting one well-adapted strain requires different tools than containing many scattered ones.
The answer came through a collaborative effort spanning all 50 states. Scientists from the CDC's Division of Healthcare Quality Promotion analyzed whole genome sequencing data generated by state and local public health laboratories through the Antimicrobial Resistance Laboratory Network. This decoding of 8,000 bacterial blueprints revealed that roughly 50% of NDM-CRE cases trace back to just one species: Klebsiella pneumoniae. Another 31% come from Escherichia coli. Both are notorious for sparking healthcare-associated outbreaks. Most critically, the infections cluster around a small number of "high-risk clones"—strains with a proven track record of spreading aggressively in hospital environments.
The researchers spotted something else: a newly emerged threat. In 2022, a previously unknown high-risk K. pneumoniae lineage called ST45 began circulating. What makes this discovery particularly important is that ST45 carries a plasmid—a mobile piece of DNA that bacteria can share like contraband—encoding drug resistance. That same plasmid had already been identified in other known dangerous strains, suggesting ST45 may have acquired its lethal genetic cargo by swapping DNA with established threats. The ability of bacteria to share resistance genes horizontally means new high-risk clones can emerge suddenly, turning yesterday's minor concern into today's crisis.
"The spread of these nearly untreatable bacteria is being driven by a small number of highly successful bacterial strains that have acquired NDM," said Richard Stanton, Ph.D., the study's corresponding author and a bioinformatician at the CDC. "New resistant strains can emerge quickly once they acquire these genes."
The implications reshape how public health officials should respond. Rather than chasing an overwhelming diversity of threats, surveillance efforts can now focus resources on the specific high-risk clones doing the most damage. Research into new treatments and diagnostics can target these priority strains. Genomic surveillance—the ongoing sequencing work that revealed these patterns—becomes less a luxury and more a necessity, allowing public health teams to spot dangerous new clones like ST45 before they proliferate beyond control.
The work also highlights why state and local collaboration matters. No single lab could have seen this pattern. Only by stitching together genetic data from coast to coast could the true architecture of the crisis become visible. Moving forward, that same network will keep watch, ready to catch the next dangerous strain before it becomes the next epidemic.