Surge in NDM-producing superbug CRE linked to rising antibiotic resistance in U.S.

Health officials warn of a rapid and rising threat from drug-resistant bacteria that can kill thousands of Americans each year. A deadly “superbug” known as NDM-producing carbapenem-resistant Enterobacterales, or NDM-CRE, is spreading through U.S. healthcare facilities and is especially difficult to detect and treat. A government analysis published in the Annals of Internal Medicine shows that CRE infections overall rose about 18% from 2019 to 2023, while the most dangerous NDM-CRE subtype surged by 461%, meaning it became more than five times as widespread in the population studied. The findings come as clinicians and public health officials caution that the combination of greater bacterial spread and more vulnerable patients could erode progress against antibiotic resistance.

Carbapenem-resistant Enterobacterales, or CRE, are a family of common bacteria — including strains of E. coli and Klebsiella — that have developed resistance to carbapenem antibiotics, often used as a last line of defense. The most dangerous mechanism is the production of enzymes called carbapenemases, which cut apart antibiotics and render them ineffective. CRE bacteria often live quietly in the gut and other sites, but they can cause severe infections in the gut, urinary tract, lungs, or bloodstream, particularly in patients with weakened immune systems or who require invasive procedures. The NDM variant carries the New Delhi metallo-beta-lactamase gene, which acts as armor against many conventional antibiotics and can move between bacterial species, accelerating the spread of resistance across settings and regions. The gene’s spread is fueled by global travel, hospital transfers, and outbreaks in long-term-care facilities, where infection control can be challenging and surveillance testing is uneven.

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Experts say identifying NDM-CRE relies on specialized diagnostic tests that are not universally available in every hospital or clinic. Delays in pinpointing the exact carbapenemase class can lead to delays in providing targeted therapies, during which time the bacteria can continue to spread. Danielle Rankin, an epidemiologist in the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion, noted that the sharp rise in NDM-CRE signals a growing threat that limits treatment options for some of the most serious infections. She urged healthcare providers to have timely access to testing that helps direct appropriate, targeted therapies.

Looking at historical data, CRE infections were responsible for roughly 12,700 infections and about 1,100 deaths in 2020, according to the period’s latest published figures in 2022. The study covering 2019 to 2023 used state-level data from a growing network of reporting sites — 24 states in 2019 and 29 in 2021 — to model infection rates and identify trends. The authors stressed that not all states reported results, and large states such as California, Florida, New York, and Texas were missing from the national totals, suggesting the national figures likely understate the true burden.

In the study’s framing, CP-CRE, or carbapenemase-producing CRE, numbers also rose markedly, increasing by 69% over the period. Yet the underlying driver of that rise was the 461% escalation of NDM-CRE infections. In contrast, other drug-resistant Klebsiella strains showed a substantial but smaller 50% increase. The researchers highlighted that the diversity of carbapenemases now present among CRE complicates treatment because most FDA-approved agents active against CRE target specific carbapenemase classes. As a result, clinicians are urged to tailor therapy to the carbapenemase type, while acknowledging that routine carbapenemase testing is not universally available in clinical laboratories and public health labs may be slow to deliver results.

The study’s authors note that NDM-CRE can be particularly challenging to manage because it often resists newer antibiotics designed to combat CRE infections. By 2023, NDM had become as prevalent as KPC — previously the most common carbapenemase in the United States — and had become the leading carbapenemase detected in E. coli across the country. The broader public health picture remains dire: the CDC estimates more than 2.8 million antimicrobial-resistant infections occur in the United States each year, contributing to more than 35,000 deaths.

Public health experts say the rise of NDM-CRE and related resistant organisms threatens to undo progress made in reducing antibiotic resistance, a cornerstone of modern medicine. They emphasize that rapid, targeted testing and robust infection-control practices in hospitals and long-term care facilities are essential to slowing transmission. The trend also underscores the need for new antibiotics and diagnostic tools that can keep pace with evolving resistance patterns. In the meantime, clinicians face an expanding catalog of resistant organisms requiring different, specific antibiotics, complicating treatment decisions and potentially increasing the time to effective therapy for vulnerable patients.

Overall, the new findings underscore a shifting landscape in CRE epidemiology: while carbapenemase producers as a group remain a persistent threat, NDM-CRE’s explosive growth has pushed it to the forefront of concern for clinicians, laboratorians, and policymakers. As medical practice continues to save patients with complicated illnesses who require high-risk procedures, the challenge is to prevent infections in the first place and to accelerate detection and appropriate treatment when they occur. The study authors stressed that continued investment in laboratory capacity, surveillance, and infection-control infrastructure is critical to curbing the spread of these formidable organisms.