For more than a decade, carbapenem-resistant Enterobacterales (CRE) have been a persistent concern for hospitals and long-term-care facilities in the United States. After years of stable or declining rates, new data show an alarming resurgence driven by a particularly difficult-to-treat form: New Delhi metallo-β-lactamase-producing CRE (NDM-CRE).
A new analysis published by CDC scientists in Annals of Internal Medicine describes sharp increases in carbapenemase-producing CRE isolates collected through the CDC’s Antimicrobial Resistance Laboratory Network (AR Lab Network) in recent years. The study—Changes in Carbapenemase-Producing Carbapenem-Resistant Enterobacterales, 2019 to 2023—found a five-fold increase in NDM-CRE incidence across 29 states that mandate reporting of these pathogens. Early 2024 data suggest that NDM-CRE levels have remained at or above those seen in 2023.
Key Findings from the CDC Study
- NDM-CRE on the rise: In clinical cultures submitted to the AR Lab Network, the incidence of carbapenemase-producing CRE rose sharply between 2019 and 2023, largely because of NDM-CRE.
- Shifts in carbapenemase landscape: Historically, U.S. CRE were dominated by KPC (Klebsiella pneumoniae carbapenemase), for which some novel β-lactam/β-lactamase inhibitor combinations remain active. In contrast, NDM and other metallo-β-lactamases leave clinicians with very few reliable antibiotic options.
- OXA-48-like enzymes also climbing: A smaller, but notable, increase in OXA-48-like-producing CRE was observed.
- Public-health impact: The growing presence of these resistance mechanisms threatens to reverse recent progress in CRE containment and raises the risk of hard-to-control healthcare-associated outbreaks.
Why It Matters for U.S. and Global Health Security
Carbapenem-resistant organisms already carry high mortality rates in vulnerable patients. NDM-CRE amplifies this threat because it is resistant to many last-line therapies, such as most β-lactams and even some novel agents.
Increased prevalence of NDM-CRE jeopardizes routine hospital care—from organ transplants to chemotherapy—where highly effective antibiotics are essential. From a national health security perspective, these pathogens erode the resilience of the healthcare system, potentially compounding the impact of other emergencies such as influenza or pandemic threats. Their rapid international spread via patient transfers and global travel highlights the need for coordinated surveillance and infection-prevention efforts across borders.
Role of the AR Lab Network
The CDC AR Lab Network, comprising regional laboratories and public-health partners nationwide, has been pivotal in detecting the trend early and providing carbapenemase-gene testing to jurisdictions that lack in-house capacity.
These laboratories support rapid identification of resistant isolates, enabling timely infection-control interventions in hospitals and guiding clinicians toward effective treatment options. The AR Lab Network’s data feed directly into the national response strategy for antimicrobial resistance.
Guidance for Healthcare Providers
CDC urges hospitals, nursing homes, and outpatient facilities to take several critical steps:
- Confirm testing capacity: Ensure clinical laboratories can identify carbapenemase-producing CRE, including NDM and OXA-48-like genes, or arrange access to state public-health labs.
- Engage with local HAI/AR programs: Understand the resistance mechanisms circulating in their communities and coordinate containment measures.
- Implement robust infection-control protocols: Follow recommended precautions—including contact precautions, environmental cleaning, and inter-facility communication on patient transfer.
- Stewardship and early detection: Use appropriate empiric therapy, prioritize diagnostic testing, and promptly report confirmed cases to health departments.
Implications for Policy and Preparedness
The emerging dominance of NDM-CRE underscores the importance of sustained federal and state investments in antimicrobial-resistance surveillance and laboratory capacity, as well as innovation in drug development. Public-health authorities note that reversing this trend will require collaboration between healthcare facilities, public-health departments, industry, and policymakers.
Beyond hospitals, this issue highlights the fragility of the antibiotic pipeline and the urgent need for new therapeutic options and diagnostics that can keep pace with evolving resistance mechanisms.
Challenges Ahead
While the AR Lab Network’s early warning offers an opportunity to respond before NDM-CRE becomes entrenched nationwide, experts warn that containment will be difficult without consistent adherence to infection-control protocols, expanded laboratory testing, and data-driven stewardship of limited antibiotics.
The CDC stresses that heightened awareness among clinicians and ongoing investment in public-health infrastructure will be essential to prevent a rollback of hard-won gains in combating drug-resistant infections.
Rankin DA, Stahl A, Sabour S et al. Changes in Carbapenemase-Producing Carbapenem-Resistant Enterobacterales, 2019 to 2023. Annals of Internal Medicine, 23 September 2025.