Infectious Disease Updates
November 1, 2025 6 minutes read
By Carol A. Kemper, MD, FIDSA
Emerging Carbapenemase Resistance in Enterobacterales
Source: Devinney K, Burton N, Alroy KA, et al. Notes from the field: Increase in New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales — New York City, 2019-2024. MMWR Morb Mortal Wkly Rep. 2025;74(23):401-403.
The emergence of carbapenem resistance in the Enterobacterales and other gram-negative organisms due to carbapenemase enzymes is alarming. Both New Delhi metallo-beta-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC) break down the carbapenem ring structures (which differ from ertapenem and meropenem vs. imipenem), making them ineffective, resulting in an infection with a high degree of mortality. Once confined to outbreaks in the Northeastern United States, KPC since has spread throughout the United States, especially in long-term care facilities (LTCFs). In contrast, NDM previously was reported largely in travelers and recent immigrants, predominantly with overnight stays in a hospital facility outside of the United States. Of the two, NDM is the more difficult to treat and confers resistance to antibiotics commonly used to treat KPC-containing organisms, e.g., ceftazidime- avibactam.
Recent data suggest a shift in this epidemiology between the two carbapenemases. In New York City, the prevalence of NDM, relative to KPC, has been increasing steadily, and the number of NDM cases surpassed that of KPC for the first time in 2024. From 2019 to 2024, a total of 7,114 carbapenem-resistant Enterobacterales (CRE) cases were reported in New York City. Of these, 3,293 (46%) had carbapenemase test results. While the number of KPC cases per year remained relatively stable (277-332 annually), the number of NDM cases steadily increased from 58 in 2019 to 388 in 2024. Two-thirds of these (68%) were due to NDM-containing Klebsiella pneumoniae and nearly half (43%) were urinary isolates.
This development is nothing short of frightening and parallels our own hospital’s experience in Silicon Valley. Since 2021, our facility has identified about two to 10 patients per year with carbapenemase-producing organisms (CPO), either based on the results of peri-rectal screening in high-risk travelers or clinical culture specimens. Some of these patients have become “frequent fliers,” and their charts are flagged and well-known to us. Others have been a surprise, such as a local resident who traveled to South Africa for safari and required critical care for a week in a South African hospital, and brought home with him KPC Klebsiella pneumoniae and Candida auris.
However, in just the past week, seven patients with CPO colonization and/or infection were seen at our facility — five were from skilled nursing facilities (SNFs) or LTCFs, and one was hospitalized in India, and five had NDM-containing organisms (three E. coli, one K. pneumoniae, and one carbapenem-resistant Acinetobacter baumannii [CRAB]). In an effort to identify and contain the spread of these organisms, we now have earmarked eight different “at-risk” LTCFs and ventilator-SNFs in our area, and immediately isolate and perform peri-rectal CRE screening (using exclusion culture media) on any admission from these facilities. Patients are not cleared from isolation until their screening test and clinical cultures are negative for CPO.
Information in this Morbidity and Mortality Weekly Report (MMWR) regarding residence or location was not available, but based on addresses, approximately 30% of cases occurred in residents of LTCFs. This MMWR report cautiously states, “The increase in the proportion of NDM-positive CRE among persons without known LTCF exposure suggests the possibility of community transmission beyond health care settings.” That statement seems a stretch, but regardless of where transmission is occurring, the threat is immediate. A recent Centers for Disease Control and Prevention press release reported a 460% increase in NDM-containing CRE between 2019 and 2023.1 This includes persons with active infection (pneumonia, bloodstream infection, urinary tract infection, and wound infection) and does not appear to include persons colonized with CPO based on the results of peri-rectal screening.
Not all states require carbapenemase testing of CRE, and reporting requirements vary between states. Just as public health dollars are being curtailed, CRE screening of at-risk persons and carbapenemase testing for all CRE isolates by clinical laboratories with enhanced reporting and notification is urgently required. Targeting LTCFs with colonized/infected residents and providing them with the necessary education and resources to improve their infection prevention and antimicrobial stewardship practices is essential.
Reference
1. Centers for Disease Control and Prevention. CDC report finds sharp rise in dangerous drug-resistant bacteria. Sept. 23, 2025. https://www.cdc.gov/media/releases/2025/2025-cdc-report-finds-sharp-rise-in-dangerous-drug-resistant-bacteria.html
Jamestown Canyon Virus Common in Northern Minnesota and Wisconsin
Source: Sutter RA, Calvert AE, Grimm K, et al. Jamestown Canyon virus seroprevalence in endemic regions and implications for diagnostic testing. Clin Infect Dis. 2025;81(2):397-402.
Jamestown Canyon virus (JCV) is one of several arboviruses causing neuroinvasive disease in the United States. It was first isolated in Jamestown Canyon near Boulder, CO, in 1961, and falls into the California serogroup of Orthobunyaviruses (OBV). It has been isolated from several different mosquito species throughout the United States, but it predominantly causes disease in Minnesota and Wisconsin. JCV may cause asymptomatic infection, a febrile illness, or meningitis and/or encephalitis exclusively in humans, largely in adults, and does not appear to cause congenital infection. From 2011-2022, a total of 282 cases of JCV infection were reported to the Centers for Disease Control and Prevention (CDC), including 187 (66%) causing neuroinvasive disease. Nearly three-fourths of these were reported from Minnesota and Wisconsin, where the infection appears endemic. One of the difficulties in determining causality with JCV is serological cross reactivity with La Crosse virus (LACV), another California-serogroup encephalitis OBV.
To determine seroprevalence of JCV infection in regions endemic for this viral infection, the authors chose 14 counties in Wisconsin, Minnesota, and Massachusetts, each with two or more reported human disease cases in 2019, or one case reported in 2019 and one or more cases in 2011-2018. A total of 355 blood specimens banked by the American Red Cross in these counties from 2019-2020 were tested for both JCV and LACV neutralizing antibody and JCV immunoglobulin M (IgM) antibodies (Ab). A 90% plaque reduction neutralizing assay at 1:10 dilution was used, and any cross reactivity between the two viruses was further tested with serial dilutions to determine a four-fold or greater difference in titers.
Sixty-four specimens (18%) tested positive for JCV and two specimens were indeterminate between JCV and LACV; 38/64 also tested positive for JCV-specific IgM antibody. Seroprevalence by neutralizing antibody assay was highest for seven Minnesota counties (18.8%) and four Wisconsin counties (18%), and lowest for three counties in Massachusetts (16.8%). Seroprevalence by IgM Ab was highest in Minnesota (13.5%) and lower for Wisconsin and Massachusetts (7.6% to 9.3%). There was an association between older age and higher seroprevalence, suggesting that infection with JCV is not only fairly common in these endemic areas but also results in fairly long-lasting neutralizing antibodies. Other seroprevalence data suggest that a related OBV, Snowshoe Hare virus, may result in IgM antibodies for a year or more, and possibly up to five years. This makes determination of causality in symptomatic cases more challenging — and clinicians must consider not only the clinical presentation, but the locality, and, when possible, obtain acute and convalescent serum to confirm recent infection.
There are 214 recognized named OBV. A recent causality study examined the literature for the strength of support for OBV central nervous system (CNS) disease, identifying 27 viruses causing CNS disease in vertebrates.1 Seven OBV viruses were linked to disease in humans and other vertebrates, 12 in humans alone, and eight in non-human vertebrates alone (e.g., ruminants, dogs and foxes, horses, bats). The authors found strong evidence for eight OBV causing human CNS disease, including two from the California serogroup (JCV and LACV); although, even at that, case-control studies are lacking for these infections.
In contrast, only moderate evidence was found for eight other OBV as a cause of CNS disease in humans, including two other California group-viruses, Inkoo virus and Snowshoe Hare virus. These two viruses have been purported to cause human CNS disease based on seroprevalence data but have never been found in the CNS. Only weak evidence was found to support California encephalitis virus as a cause of human CNS infection.
OBV CNS disease in humans predominately occurs in adults and less commonly in children, and only two OBV viruses have been associated with prenatal congenital human infection (Cache Valley virus and Tensaw virus). However, prenatal disease in non-human vertebrates is an important cause of congenital abnormalities, as occurred with the Schmallenberg virus outbreak in Europe in 2011, which caused fetal loss and significant fetal deformities in cows, sheep, and goats and affected more than 5,000 farms.
Carol A. Kemper, MD, FIDSA, is Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation.
Reference
1. Dante Edridge AW, van der Hoek L. Emerging orthobunyaviruses associated with CNS disease. PLoS Negl Trop Dis. 2020;14(10):e0008856.
Emerging Carbapenemase Resistance in Enterobacterales; Jamestown Canyon Virus Common in Northern Minnesota and Wisconsin
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