In a well-publicized case in 2016 that alerted many Americans to the rising threat of drug-resistant bacterial infections, the Centers for Disease Control and Prevention (CDC) and health officials in Nevada reported a bacterial infection in a 70-year-old woman that was resistant to all 26 of the antibiotics available to her doctors. 

The woman ultimately died from the infection, which was caused by Klebsiella pneumoniae, an opportunistic pathogen that infects the lungs, urinary tract, bloodstream, and wounds. What made the infection unique was that it carried an enzyme-encoded gene—New Delhi metallo-beta-lactamase, or NDM—that makes bacteria resistant to carbapenems, a class of last-resort antibiotics that physicians reach for when infections don’t respond to first- and second-line treatment options. 

NDM is one of several resistance genes that bacteria have acquired in their never-ending battle to defeat antibiotics. At the time, bacteria carrying NDM were fairly rare in the United States. In fact, investigators believed the woman likely acquired the infection in India, where the NDM gene was first detected. She had been travelling (and was hospitalized) in India prior to returning to Nevada. 

But that’s no longer the case. In a report published last September, the CDC said surveillance data from labs across the country showed that the incidence of carbapenem-resistant Enterobacterales (CRE, the family of pathogens that includes K pneumoniae) infections carrying NDM genes rose 461% from 2019 through 2023. And CDC officials are worried about the implications.

“The rapid increase is a major concern for CDC due to the implications for treating serious CRE infections and potential for NDM to spread outside of healthcare,” Richard Stanton, PhD, a bioinformatician with the CDC’s Division of Healthcare Quality Promotion, told CIDRAP News.

Dubbed a “nightmare bacteria,” all CRE infections present a challenge for physicians because they tend to target already sick hospital patients and limit treatment options. And they can be deadly, with a mortality rate that ranges from 30% to 50%. In a 2019 report, the CDC labeled CRE an “urgent threat.”

“CRE is a concern, period,” said Brad Spellberg, MD, chief medical officer at the Los Angeles General Medical Center.

NDM is one member of an alphabet soup of carbapenemase genes that CRE pathogens have acquired  to evade carbapenems. K pneumoniae carbapenemase (KPC) and Verona Integron-encoded metallo-beta-lactamase (VIM) are other commonly found pathogens that dwell in US hospitals. Carbapenemase genes often carry resistance mechanisms for other antibiotics, too, making the pathogens that carry them even harder to treat.