CORRECTED September 30, 2025 // An earlier version of this article incorrectly stated the two drugs which are effective against NDM-CRE. The article has been updated to state aztreonam-avibactam and cefiderocol.

A monumental increase of more than 400% in infections from a dangerous drug-resistant bacteria known as New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) suggests a growing risk for life-threatening illnesses and deaths with limited treatment options, based on two recent reports.

New data in the Annals of Internal Medicine and the CDC’s Morbidity and Mortality Weekly Report (MMWR) show spikes in NDM-CRE, a type of gram-negative bacteria often treated with carbapenems.

The presence of NDM gives the bacteria its resistant bite because this enzyme is less common in the US than elsewhere in the world and is resistant to most available antibiotics, according to the researchers.

In a study published in the Annals of Internal Medicine, Danielle Rankin, PhD, a CDC epidemiologist, and colleagues outlined the trends in carbapenemase-producing CRE (CP-CRE) clinical isolates reported to the Antimicrobial Resistance Laboratory Network of the CDC from January 2019 through December 2023.

“The researchers found a dramatic increase in NDM-CRE of 461% in 5 years in the United States,” she said.

“CDC’s Antimicrobial Resistance Threats Report identifies carbapenem-resistant Enterobacterales as an urgent threat to human health in the United States, requiring aggressive public health action to prevent, detect, and control these pathogens to protect lives,” Rankin said in an interview.

NDM-CRE is particularly alarming because of its increasing prevalence in the US, its ability to cause infections that are difficult to treat, and its ability to defeat many types of antibiotics, Rankin said. “Monitoring the epidemiology of CRE and NDM-CRE is crucial, as it changes the way infections are treated and how we implement infection control measures in healthcare facilities,” she emphasized.

“Unfortunately, the rise in NDM-CRE increases the likelihood that the sickest patients, such as those in hospitals and long-term care facilities, may get these serious infections that have very few treatment options,” said Rankin. The bacteria are also at risk of spreading to people in the community, meaning that common infections, such as urinary tract infections, that are usually treated with oral antibiotics may be more likely to need intravenous antibiotics and may require hospitalization, she added.

While the NDM carbapenemase is recognized as the most globally widespread, the Klebsiella pneumoniae carbapenemase (KPC) has historically been the most common carbapenemase enzyme among CRE in the US, Rankin said.

The rise in NDM-CRE is concerning but not surprising, Rankin told Medscape Medical News. Antimicrobial-resistant infections surged in the US after the COVID-19 pandemic pushed healthcare to its breaking point, she said. Increases in NDM elsewhere in the world suggested that increases could appear in the US as well, she added.

For Clinical Practice

The takeaway for clinicians is that the recent increases in CP-CRE and NDM-CRE threaten to reverse years of stable declining CRE rates, Rankin said. “Understanding the specific carbapenem resistance mechanisms can help healthcare providers select the appropriate treatment for their patients with CP-CRE infections,” Rankin said. Most approved drugs used to treat CP-CRE infections target specific carbapenem resistance mechanisms. To date, only two beta-lactam-based agents are active against NDM-CRE: aztreonam-avibactam and cefiderocol, though susceptibility testing for these agents is not widely available.

“In addition, healthcare providers, laboratory professionals, and pharmacists should be aware of the increasing threat of NDM-CRE, and testing for NDM should be included in clinical laboratory workflows,” Rankin told Medscape Medical News. Identifying patients with highly resistant pathogens and adhering to good infection control practices are crucial for slowing the spread of CRE and other antibiotic-resistant germs, she added.

The Annals of Internal Medicine study included 29 states with mandated submission of CRE specimens; therefore, data were not available from every state, Rankin said. However, the data from the study cohort aligned with national trends in a sensitivity analysis, she said. “Additional research is needed on understanding the reasons for the increases in CP-CRE and on the development of antibiotic therapy and decolonization agents,” Rankin added.

New York City Sees Its Own Surge

Similarly, data published in the MMWR showed a significant increase in the number of NDM-CRE cases in New York City in recent years, from 58 in 2019 to 388 in 2024.

In 2024, the number of NDM-positive CRE cases surpassed the number of KPC-positive CRE cases, which remained relatively stable during the study period, according to a report by Katelynn Devinney, MPH, of the New York City Department of Health and Mental Hygiene, New York City, and colleagues.

Some resistance mechanisms, such as NDM, can be transferred across different bacterial species and can reduce the effectiveness of both carbapenem and non-carbapenem antibiotics, limiting treatment options, said an NYC Health Department spokesperson in an interview.

The researchers were surprised by the rate of increase and that NDM-CRE had become more common than KPC-CRE, which has been present in New York City for much longer and has had stable case counts for the past few years, the spokesperson added. Contributing factors to the increase remain unclear because data on how the infections were acquired are limited, the spokesperson said. “The NYC Health Department is exploring ways to enhance our understanding of CRE exposures, including through laboratory testing, and the study findings highlight the important of access to carbapenemase testing to help inform treatment decisions,” the spokesperson said.

In the meantime, “healthcare providers treating CRE in areas with higher NDM incidence should consider empiric therapy effective against NDM-CRE in the absence of susceptibility results, particularly for patients with severe CRE infection,” the spokesperson said. Looking ahead, routine whole genome sequencing of CRE isolates would provide valuable insight to understand transmission and detect clusters and outbreaks, the spokesperson added.

Why Tracking Is Important

Tracking the NDM-CRE is important, given the transmission in both healthcare settings and the community, said Gonzalo Bearman, MD, professor of medicine and chair of the Division of Infectious Diseases at Virginia Commonwealth University, Richmond, Virginia, in an interview.

“When someone is colonized and later infected with this pathogen, treatment options are limited and require restricted antibiotics, ones are usually prescribed only by infectious diseases specialist,” said Bearman, who was not involved in the studies.

The increase in NDM-CRE is not unexpected, given the significant rise in global travel following the COVID-19 pandemic, Bearman said. Other potential factors contributing to the increase include the ongoing indiscriminate use of antibiotics and the breakdown of many infection prevention practices during the pandemic period in hospitals and long-term care facilities, he added.

Expert consultation with an infectious disease specialist should be strongly encouraged for patients with suspected or proven CRE infections, Bearman told Medscape Medical News. Additional research is needed to better define the transmission mechanisms of the CRE, as well as infection prevention measures and optimal treatment strategies, Bearman said.

The studies received no outside funding apart from the CDC.

Bearman, Devinney, and Rankin reported having no relevant financial conflicts to disclose.