Dangerous bacteria called carbapenemase-producing Enterobacterales (CRE), which can resist strong antibiotics, are spreading in the U.S., with a resistance type called New Delhi metallo-β-lactamase (NDM) that is becoming more common than the older type, Klebsiella pneumoniae carbapenemase (KPC), in E. coli, according to a new study published in Annals of Internal Medicine.
CRE are bacteria that normally live in the human and animal gut but can cause serious infections when they spread outside the digestive tract. This bacteria is resistant to carbapenems, which is a class of powerful antibiotics that are typically reserved as a last line of defense, according to study authors.
Resistance is driven by enzymes called carbapenemases, which break down these antibiotics. The type of carbapenemase the bacteria carries is critical for treatment decisions. While KPC has historically been the most common carbapenemase in the U.S., NDM and other metallo-β-lactamases are more difficult to treat because fewer drugs are effective against them.
CRE is posing as a growing public health concern.
For example, in 2017, the CDC reported roughly 13,100 hospital infections and 1,100 deaths due to CRE in the U.S. A population-based survey in 2022 by the CDC also showed an incidence of 6.4 cases per 100,000 persons, a 4.9% increase over 2021, based on data from more than 23 million participants.
Recent CDC data also highlighted a dramatic rise in NDM-positive CRE. In New York City, cases increased from 58 in 2019 to 388 in 2024, surpassing KPC-positive cases. This shift brings to light an evolving resistance that complicates treatment and presents the need for ongoing surveillance, timely testing and targeted interventions.
The researchers of this new study aimed to examine trends in carbapenemase-producing CRE (CP-CRE) by analyzing clinical isolates reported to the CDC’s Antimicrobial Resistance Laboratory Network between January 2019 and December 2023.
The study included U.S. states that mandated submission of carbapenem-resistant Klebsiella, Escherichia coli (E. coli) and Enterobacter isolates before July 2020 and provided at least 36 months of data. CP-CRE were defined by detection of one or more carbapenemases (KPC, NDM, VIM, IMP, OXA-48-like) or confirmed carbapenemase activity.
Annual and state-specific incidence rates were calculated using isolate counts and U.S. Census data, with age-adjustment to the 2010 population. Temporal trends were also analyzed with Poisson regression, adjusting for age. Sensitivity analyses compared cohort estimates to national trends.
Results revealed that between 2019 and 2023, CP-CRE incidence increased significantly across the U.S. states included in the study.
It was found that age-adjusted CP-CRE incidence rose 69%, while NDM-CRE showed the most dramatic growth, increasing 461% over the five-year period. NDM-CRE rates also increased across nearly half of the states in the cohort and were detected in 27% of carbapenem-resistant E. coli, 24% of carbapenem-resistant Klebsiella spp. and 6% of carbapenem-resistant Enterobacter spp. by 2023.
In addition, OXA-48-like CRE also increased, though at a more gradual rate, while KPC-CRE initially decreased from 2019 to 2020 and then returned to near 2019 levels by 2023. Increases in CP-CRE and NDM-CRE were observed across all bacterial genera studied, including Klebsiella spp. These trends were consistent in national analyses and across sensitivity analyses, demonstrating a clear rise in less common carbapenemases, including NDM and OXA-48, which could complicate treatment and public health efforts.
Strengths of this study that support findings include its use of a large multi-state cohort with mandated CRE isolate submission over five years, allowing researchers to track trends in CP-CRE across diverse regions. The analysis also captured shifts in less common carbapenemases, including NDM and OXA-48, providing a look into emerging resistance patterns. Additional analyses showed that the trends in the study matched national data, confirming that the findings are reliable.
Limitations include the exclusion of highly populated states such as California, Florida, New York and Texas, although national trends suggest these exclusions didn’t affect overall conclusions. Some cases may have also been missed because labs did not send all samples, and some patients may have been counted more than once.
Study authors suggest that integrating carbapenemase testing into clinical workflows and understanding local CP-CRE epidemiology are critical to guiding timely appropriate treatment, especially given the limited availability of agents effective against NDM.