Infections caused by the most dangerous class of drug-resistant bacteria in the United States surged 69% between 2019 and 2023, and one strain carrying the NDM enzyme rose 461% over the same period. The findings, drawn from CDC Antimicrobial Resistance Laboratory Network clinical culture data and published in Annals of Internal Medicine, signal that antibiotic-resistant organisms are spreading faster through healthcare settings than at any point since the agency began tracking them. For patients in hospitals and long-term care facilities, the trend means a shrinking menu of effective treatments and a growing chance that a routine infection could turn fatal.
Why a 69% Rise in Carbapenemase-Producing CRE Demands Attention Now
Carbapenem-resistant Enterobacterales, or CRE, are gut bacteria that have evolved to defeat carbapenems, a class of antibiotics often described as the last reliable defense against severe infections. The new peer-reviewed analysis, led by Danielle Rankin at the CDC and summarized in a recent agency communication, found that age-adjusted incidence of carbapenemase-producing CRE climbed to an incidence rate ratio of 1.69 with a 95% confidence interval of 1.61 to 1.78 when comparing 2023 to 2019. That 69% increase is not a gradual drift. It represents a sharp acceleration concentrated in organisms that carry specific enzymes capable of destroying nearly every beta-lactam antibiotic on the market.
The strain that grew fastest carries the New Delhi metallo-beta-lactamase, or NDM, gene. NDM-producing CRE can resist virtually all standard antibiotic options, leaving clinicians with a handful of newer, expensive, and sometimes toxic alternatives. The 461% increase in NDM-CRE cases over four years is especially alarming because NDM genes sit on mobile genetic elements, meaning they can transfer between bacterial species inside a patient’s body or spread between patients through contaminated surfaces and hands. Once NDM enters a healthcare facility, containment becomes far harder than with other resistance mechanisms.
Roughly 12,700 CRE infections and approximately 1,100 deaths occurred in 2020 alone, according to CDC estimates. Those figures predate the steepest part of the current surge, which means the actual toll by 2023 was likely higher, though facility-level and state-level breakdowns have not been released in the published summaries. The burden falls disproportionately on people with serious underlying conditions, those who have recently had invasive procedures, and residents of long-term care facilities, where resistant bacteria can circulate for months or years.
CDC Laboratory Network Data and the Annals of Internal Medicine Study
The headline statistics come from clinical culture reports collected through the CDC’s AR Laboratory Network between January 2019 and December 2023. That network uses RT-PCR testing to identify specific carbapenemase genes, including KPC, NDM, VIM, OXA-48, and IMP. By screening isolates at the molecular level rather than relying solely on antibiotic susceptibility testing, the network can distinguish which resistance mechanism a bacterium carries and track how each one spreads over time.
The Annals of Internal Medicine analysis used these laboratory records to calculate age-adjusted incidence trends for each carbapenemase type. The 69% overall increase in carbapenemase-producing CRE and the 461% spike in NDM-CRE represent the two most striking findings. Rankin, the study’s lead author, stated that clinicians should test for carbapenemases to guide therapy and infection control, a recommendation that carries weight because treatment choices differ sharply depending on which enzyme a patient’s infection produces. A KPC-carrying organism, for instance, can often be treated with newer beta-lactam combinations, while an NDM-carrying organism may require older, more toxic drugs like colistin or newer agents with limited clinical track records.
The CDC’s Multi-site Gram-negative Surveillance Initiative, known as MuGSI, provides additional context by tracking CRE alongside other resistant gram-negative organisms through Emerging Infections Program sites. Together, the AR Lab Network and MuGSI form the backbone of national resistance monitoring. But neither system captures every case. Hospitals and labs that do not participate in these networks may harbor undetected clusters, and the published data do not include colonization cases where patients carry resistant bacteria without showing symptoms. That means the true reservoir of carbapenemase-producing organisms is almost certainly larger than the counts reported in the study.
Gaps in Screening, Prescribing Data, and Facility-Level Tracking
Several questions remain unanswered by the available evidence. The Annals study and CDC summaries report national aggregates but do not break down which states, hospital systems, or long-term care facilities are driving the sharpest increases. Without that granularity, infection preventionists at individual facilities cannot benchmark their own performance against the national trend or identify whether nearby institutions are experiencing outbreaks.
The published data also do not link the NDM surge to specific antibiotic prescribing patterns or to delays in colonization screening that occurred during the COVID-19 pandemic. Earlier federal efforts coordinated through the U.S. Department of Health and Human Services, detailed on the department’s public health pages, emphasized stewardship programs and infection-control investments, but the new resistance patterns raise questions about how consistently those measures were implemented. For example, it is unclear whether facilities with robust stewardship and active CRE screening saw smaller increases than those that scaled back surveillance during pandemic surges.
Another blind spot involves outpatient and post-acute care. Many patients who ultimately develop CRE infections first encounter the healthcare system in emergency departments, dialysis centers, or skilled nursing facilities. The current datasets focus primarily on laboratory-confirmed infections, offering little insight into how often high-risk patients are screened on admission or transferred with clear documentation of their colonization status. Without that information, it is difficult to design targeted interventions for the points in the care continuum where transmission may be most intense.
Implications for Hospitals, Long-Term Care, and Patients
For frontline clinicians, the rise in carbapenemase-producing CRE translates into more frequent encounters with infections that do not respond to standard therapy. Empiric treatment for sepsis, pneumonia, or complicated urinary tract infections increasingly has to account for local resistance patterns, and delays in selecting an effective regimen can worsen outcomes. When NDM or other metallo-beta-lactamases are involved, physicians may be forced to rely on drugs with significant kidney or neurological toxicity, accept lower cure rates, or pursue invasive procedures such as source-control surgery more aggressively.
Hospitals and long-term care facilities face mounting pressure to strengthen infection prevention. Core measures include rapid identification of patients carrying carbapenemase-producing CRE, strict adherence to hand hygiene, use of gowns and gloves for contact precautions, and environmental cleaning focused on high-touch surfaces. Cohorting colonized patients and dedicating staff to their care can reduce cross-transmission, but these strategies demand staffing flexibility and physical space that many facilities lack.
From a systems perspective, the surge in NDM-CRE underscores the importance of information sharing. When a patient colonized with a highly resistant organism is transferred from one facility to another without clear documentation, the receiving institution may unknowingly place them in a general ward, creating opportunities for silent spread. Regional collaboratives that standardize transfer forms, flag high-risk organisms, and coordinate outbreak responses can help close these gaps, but they depend on timely data and sustained funding.
What Comes Next for Resistance Surveillance and Control
The new findings are a warning that progress against antibiotic resistance is fragile. Even as some carbapenemase types, such as KPC, become more manageable thanks to targeted therapies and improved infection control, others like NDM are filling the ecological space. That dynamic suggests that surveillance systems must evolve from counting resistant infections to anticipating how resistance genes move across species, settings, and regions.
Experts involved in the Annals analysis argue that wider access to rapid molecular diagnostics is essential. If hospitals can identify carbapenemase genes within hours rather than days, they can tailor both treatment and isolation precautions more precisely. At the same time, stewardship programs need better data on how often last-line antibiotics are used, in which clinical scenarios, and with what outcomes. Linking prescribing information to resistance trends would help determine whether current practices are accelerating or slowing the spread of NDM and other high-risk enzymes.
For patients and families, the message is not that all hospital care has become unsafe, but that infection prevention basics matter more than ever. Asking staff about hand hygiene, understanding why contact precautions are used, and completing prescribed antibiotic courses remain practical steps individuals can take. Ultimately, however, reversing the trajectory of carbapenemase-producing CRE will require coordinated action across healthcare systems, public health agencies, and policymakers. The 69% rise in these organisms-and the 461% explosion of NDM-CRE-shows that without sustained attention, the era of reliably effective antibiotics could narrow far faster than expected.
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*This article was researched with the help of AI, with human editors creating the final content.
