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Table 1.  
Carbapenem-Resistant Enterobacteriaceae (CRE) Organisms and Carbapenemase-Producing Isolates by Emerging Infections Program Site, 2012-2013
Carbapenem-Resistant Enterobacteriaceae (CRE) Organisms and Carbapenemase-Producing Isolates by Emerging Infections Program Site, 2012-2013
Table 2.  
Carbapenem-Resistant Enterobacteriaceae (CRE) Cases and Individuals With CRE, Annual Crude Incidence, and Standardized Incidence Ratio by Emerging Infections Program Site, 2012-2013
Carbapenem-Resistant Enterobacteriaceae (CRE) Cases and Individuals With CRE, Annual Crude Incidence, and Standardized Incidence Ratio by Emerging Infections Program Site, 2012-2013
Table 3.  
Isolate Collection Location, Culture Source, Infection Type, and Prior Health Care Exposures Among Incident Carbapenem-Resistant Enterobacteriaceae Cases, 2012-2013
Isolate Collection Location, Culture Source, Infection Type, and Prior Health Care Exposures Among Incident Carbapenem-Resistant Enterobacteriaceae Cases, 2012-2013
Table 4.  
Demographic and Clinical Characteristics of Unique Individuals With Carbapenem-Resistant Enterobacteriaceae
Demographic and Clinical Characteristics of Unique Individuals With Carbapenem-Resistant Enterobacteriaceae
Table 5.  
Outcome of Carbapenem-Resistant Enterobacteriaceae Cases
Outcome of Carbapenem-Resistant Enterobacteriaceae Cases
Table 6.  
Antimicrobial Susceptibility of Carbapenem-Resistant Enterobacteriaceae Isolates Based on Testing by Local Clinical Laboratories
Antimicrobial Susceptibility of Carbapenem-Resistant Enterobacteriaceae Isolates Based on Testing by Local Clinical Laboratories
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Original Investigation
October 13, 2015

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013

Author Affiliations
  • 1Division of Healthcare Quality Promotion, US Centers for Disease Control and Prevention, Atlanta, Georgia
  • 2Emory University School of Medicine, Atlanta, Georgia
  • 3Georgia Emerging Infections Program, Decatur
  • 4Atlanta Research and Education Foundation, Decatur, Georgia
  • 5Atlanta Veterans Affairs Medical Center, Atlanta, Georgia
  • 6Maryland Department of Health and Mental Hygiene, Baltimore
  • 7Minnesota Department of Health, St Paul
  • 8Colorado Department of Public Health and Environment, Denver
  • 9New York Emerging Infections Program and University of Rochester Medical Center, Rochester
  • 10Oregon Health Authority, Portland
  • 11University of New Mexico, Albuquerque
JAMA. 2015;314(14):1479-1487. doi:10.1001/jama.2015.12480
Abstract

Importance  Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts.

Objective  To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas.

Design, Setting, and Participants  Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed.

Exposures  Demographics, comorbidities, health care exposures, and culture source and location.

Main Outcomes and Measures  Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics.

Results  Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100 000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase.

Conclusions and Relevance  In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100 000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

Introduction

Carbapenem-resistant Enterobacteriaceae (CRE) are a worldwide clinical and public health problem. These multidrug-resistant organisms cause infections associated with high mortality and limited treatment options, and are increasingly recognized as an important cause of health care–associated infections.15 In the United States, much of the initial dissemination of CRE can be attributed to organisms producing the Klebsiella pneumoniae carbapenemase, a type of β-lactamase enzyme that confers resistance to carbapenem antimicrobials.

Since the first case was reported in North Carolina in 2001, cases of K pneumoniae carbapenemase-producing CRE have been reported in almost every state and it remains the carbapenemase most commonly identified in isolates sent to the US Centers for Disease Control and Prevention (CDC).6 To date, 23 states have required some form of CRE reporting; however, requirements and definitions vary by state. The current US reporting requirements are available online.7

To describe CRE epidemiology in the catchment areas and inform prevention efforts, the CDC formally initiated population-based surveillance in 2012 in select US geographical areas using the Emerging Infections Program (EIP). This surveillance system provides the most extensive US population–based evaluation of CRE to date, allowing for the monitoring of the burden of disease over time, identification of risk factors, and characterization of strains. We present the population-based incidence of CRE and describe the clinical characteristics and resistance mechanism associated with a subset of isolates from the 7 participating communities.

Methods
Surveillance Population

The Multi-site Gram-negative Surveillance Initiative is an ongoing, population-based (ie, based on the entire population of the included catchment areas), active, laboratory-based surveillance system. Surveillance of CRE was initiated in January 2012 at 3 EIP sites (metropolitan areas in Georgia, Minnesota, and Oregon) and expanded in 2013 to 4 additional sites (metropolitan areas in Colorado, Maryland, New Mexico, and New York).

The total population in the 7 participating areas under surveillance in 2013 was an estimated 13.2 million8; this includes Atlanta, Georgia (estimated population, 3 864 091), Denver, Colorado (estimated population, 2 583 519), Baltimore, Maryland (estimated population, 1 917 263), Minneapolis/St Paul, Minnesota (estimated population, 1 725 492), Portland, Oregon (estimated population, 1 709 394), Rochester, New York (estimated population, 749 606), and Albuquerque, New Mexico (estimated population, 674 221).

The surveillance project was reviewed at the CDC by the National Center for Emerging and Zoonotic Diseases in accordance with institutional policy and was determined not to meet the regulatory definition of research (under 45 CFR §46.102[d]), and therefore it was not subject to institutional review board requirements. Similarly, the project was reviewed at each of the participating EIP sites in accordance with institutional policies. In places where institutional review board approval was sought, a formal waiver of informed consent was obtained.

Race and ethnicity were collected from the medical record and could have been defined by the case-patient or the facility. These variables were included to evaluate the need for and to allow for rate adjustment between sites.

Case Definitions and Ascertainment

A CRE case was defined as a carbapenem-nonsusceptible and extended-spectrum cephalosporin-resistant (ceftriaxone, ceftazidime, ceftizoxime, and cefotaxime) Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, K pneumoniae, or Klebsiella oxytoca isolate recovered from a body site that is normally sterile (eg, bloodstream) or urine from individuals residing in the surveillance area during January 2012-December 2013. Because the minimum inhibitory concentration for ertapenem against Enterobacteriaceae is lower than for the other carbapenems, ertapenem was excluded from this CRE definition to increase specificity for carbapenemase-producing CRE. Isolates were identified by local laboratories through a query of automated testing instruments based on the protocols of the laboratories9 and using the 2012 Clinical and Laboratory Standards Institute break points.10

An incident CRE case was defined as the first CRE isolate from a patient during a 30-day period that met the surveillance definition. All incident CRE cases underwent medical record review using a standardized abstraction form. Both inpatient and outpatient medical records were reviewed for patient demographics, underlying clinical comorbidities, location of culture collection, specimen source, associated infectious syndromes, relevant health care exposures (exposure to long-term acute care hospital was collected starting in 2013), and patient outcomes.

Information could not be identified for all variables because of the limitations of medical record review, therefore, denominators often varied for each of the variables. All-cause mortality was determined based on documentation in the medical record at the time of outpatient evaluation for outpatients, at discharge if hospitalized, or at the end of a 30-day period for individuals undergoing outpatient dialysis or residing in a long-term care facility or a long-term acute care hospital.

Isolate Collection and Evaluation

Laboratories serving the catchment areas were requested to submit CRE isolates to the CDC meeting the case definition for carbapenem-resistance mechanism testing. Isolates, particularly those from urinary sources, were difficult to acquire because they are often not saved. Due to this common practice limitation, an isolate was submitted for only the minority of cases. Polymerase chain reaction was performed by the CDC on submitted isolates for genes encoding K pneumoniae carbapenemase, New Delhi metallo-β-lactamase,11 and OXA-48-type enzymes.12

Isolates were evaluated for metallo-β-lactamase production using a broth microdilution screening method consisting of serial dilutions of imipenem with and without chelators at fixed concentrations. A decrease in the minimum inhibitory concentration of the drug by 2 or more doubling dilutions in the presence of chelators was considered a positive metallo-β-lactamase screening.11 Any isolate positive for metallo-β-lactamase but negative for New Delhi metallo-β-lactamase was further tested by polymerase chain reaction for genes encoding Verona integron–encoded metallo-β-lactamase and Imipenemase metallo-β-lactamase. The modified Hodge test was performed on all submitted isolates using both ertapenem and meropenem; a positive result for either carbapenem was considered indicative of carbapenemase production.

Statistical Analyses

Annual incidence rates for CRE cases and case-patients were calculated using the 2012 and 2013 US census estimates of the surveillance area population as the denominator. Standardized incidence ratio, which is an indirect standardization, was calculated to compare incident CRE rates among EIP sites. Standardized incidence ratio was used for this analysis because the relatively small number of CRE cases produced stratum-specific estimates (by age and race) that were too low to allow accurate direct standardization for disease rate comparison.13 Missing values for race were imputed based on the distribution of known race by age, sex, and surveillance site.

The standardized incidence ratio was calculated by dividing the number of observed cases by the number of predicted cases. The number of predicted cases was estimated from a multivariable negative binomial regression predicting CRE infection incidence, adjusted by age (0-18 years, 19-49 years, 50-64 years, and ≥65 years) and race (white and nonwhite), and constructed from CRE surveillance data during 2012-2013 using surveillance site US census data as the denominator.13

The CRE incidence estimates aggregated across all participating sites during this same period represent the population used to standardize CRE incidence (standard population). The 95% confidence intervals for the standardized incidence ratios were constructed using the site-specific predicted case counts from each EIP site. A standardized incidence ratio of less than 1.0 indicates fewer observed CRE cases than predicted compared with the standard population, whereas a ratio greater than 1.0 indicates more observed CRE cases than predicted compared with the standard population.

Descriptive analyses were performed to summarize specimen information, health care exposures, outcomes, and microbiological results of incident CRE cases; χ2 tests were used to compare groups when applicable. Demographic information, underlying comorbidities, and travel history of unique CRE case-patients were described for first incident CRE episode for the entire surveillance period. Charlson comorbidity index scores were calculated.

All statistical analyses were performed using SAS version 9.3 (SAS Institute Inc). A 2-sided P value of <.05 was considered statistically significant.

Results

During 2012-2013, 599 incident CRE cases were identified in 481 individuals across the 7 EIP sites. Of the 599 cases, 351 (58.6%; 95% CI, 54.6%-62.6%) were K pneumoniae; 89 (14.9%; 95% CI, 12.0%-17.7%), E coli; 79 (13.2%; 95% CI, 9.8%-15.2%), E cloacae; 75 (12.5%; 95% CI, 9.8%-15.2%), E aerogenes; and 5 (0.8%; 95% CI, 0.1%-1.6%), K oxytoca (Table 1). Most of the CRE cases were K pneumoniae in Georgia (235/356 [66.0%; 95% CI, 61.1%-71.0%]), Maryland (69/92 [75.0%; 95% CI, 66.0%-84.0%]), and New York (17/27 [63.0%; 95% CI, 43.5%-82.4%]), whereas most of the cases were E coli in New Mexico (3/6 [50.0%; 95% CI, 0%-100%]) and E aerogenes in Minnesota (29/79 [40.8%; 95% CI, 29.1%-52.6%]).

Of the 481 unique individuals with CRE, 409 (85.0%) had 1 incident CRE-positive culture and 72 (15.0%) had 2 or more incident cultures during the 2-year surveillance period (range, 2-6 episodes). Of the 72 individuals with more than 1 incident culture, 13 (18.1%) had more than 1 species reported.

Incidence Rates and Standardized Incidence Ratios

The overall crude annual CRE incidence across the EIP sites during the 2-year period was 2.93 (95% CI, 2.65-3.23) per 100 000 population. Site-specific crude incidence rates in 2012 ranged from 0.35 (95% CI, 0.14-0.74) per 100 000 population in Oregon to 4.58 (95% CI, 3.94-5.30) per 100 000 population in Georgia (Table 2). The site-specific crude incidence rates in 2013 ranged from 0.82 (95% CI, 0.47-1.34) per 100 000 population in Oregon to 4.80 (95% CI, 3.89-5.85) per 100 000 population in Maryland.

Significantly higher than predicted CRE standardized incidence ratios adjusted for age and race, which were independently associated with increased risk of CRE, for the 2-year period were observed for Georgia (P < .001), Maryland (P = .001), and New York (P = .048). Significantly lower than predicted standardized incidence ratios were observed for Colorado (P < .001), New Mexico (P = .01), and Oregon (P < .001).

Specimen Information and Prior Health Care Exposures of Incident CRE Cases

Data on the health care location of specimen collection (eg, outpatient, short-stay acute care), specimen source, and type of infection appear in Table 3. Although medical record review identified lower urinary tract infection (UTI) as the most commonly associated infection, only 102 of the 392 reported cases of UTI (26.0%; 95% CI, 21.7%-30.4%) met the revised McGeer criteria and the CDC National Healthcare Safety Network long-term care facility surveillance definition.14,15

Prior health care exposures were reported for individuals in 531 of 575 cases (92.3%; 95% CI, 90.2%-94.5%). Hospitalization during the prior year was the most common health care exposure overall and among both cases with a carbapenemase-producing CRE and those cases not linked to a carbapenemase-producing CRE.

Demographics and Clinical Information

Of 481 unique individuals with CRE, 284 were women (59.0%; 95% CI, 54.6%-63.5%); the median age was 66 years (range, <1-100 years; Table 4). Clinical characteristics were available for 454 unique individuals. Of these 454 individuals, 415 (91.4%; 95% CI, 88.8%-94.0%) had at least 1 underlying comorbid condition with a median Charlson comorbidity index of 2 (range, 0-12) and 39 (8.6%; 95% CI, 6.0%-11.2%) had no documented underlying condition. The most commonly reported conditions included diabetes (201 [44.3%; 95% CI, 39.7%-48.9%]) and neurological disorders (185; 40.7% [95% CI, 36.2%-45.3%]). Of the 185 individuals with neurological disorders, 107 (57.8%; 95% CI, 50.7%-65.0%) had an indwelling urinary catheter within 2 days prior to their initial positive culture. Two individuals were hospitalized outside the United States (India and Italy) during the 2 months prior to their positive culture.

Outcome of CRE Cases

Among 569 CRE cases with data available, 371 (65.2%; 95% CI, 61.3%-69.1%) were in individuals who were hospitalized at the time of or within 30 days after having a positive culture (Table 5), including at least 171 (46.1%; 95% CI, 41.5%-51.7%) whose cultures were initially collected outside a short-stay acute care setting. Among 322 cases in hospitalized individuals with data available, 180 (55.9%; 95% CI, 50.0%-60.8%) were discharged directly to either a long-term care facility (153; 47.5% [95% CI, 42.0%-53.0%]) or a long-term acute care hospital (27; 8.4% [95% CI, 5.3%-11.4%]). Of 566 cases, death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%); this included 25 (27.5%; 95% CI, 18.1%-36.8%) of 91 with sterile-site positive cultures compared with 26 (5.5%; 95% CI, 3.4%-7.5%) of 475 with only urine cultures (P < .001). Of the 25 individuals with a sterile-site positive culture who died, 20 (80.0%) had positive blood cultures.

Microbiological Results

Among cases with antimicrobial susceptibility results available from local clinical laboratories, 262 (88.8%; 95% CI, 85.2%-92.4%) were susceptible to tigecycline, 470 (81.7%; 95% CI, 78.6%-84.9%) to at least 1 aminoglycoside, 136 (25.3%; 95% CI, 21.7%-29.2%) to at least 1 fluoroquinolone, 68 (13.2%; 95% CI, 10.2%-16.1%) to piperacillin and tazobactam, and 19 (4.5%; 95% CI, 2.5%-6.5%) to aztreonam (Table 6).

Of the 188 CRE isolates submitted from the 6 EIP sites for carbapenemase testing (Table 1), K pneumoniae carbapenemase was the only one identified (90 [47.9%; 95% CI, 40.6%-55.1%]). It was most commonly found in K pneumoniae (69/87 [79.3%; 95% CI, 70.6%-88.0%]) and less commonly seen in other species (12/32 [37.5%; 95% CI, 19.8%-55.2%] in E cloacae complex; 7/32 [21.9%; 95% CI, 6.7%-37.0%] in E coli; and 2/37 [5.4%; 95% CI, 0%-13.0%] in E aerogenes).

Antimicrobial susceptibility results for carbapenemase-producing and non–carbapenemase-producing isolates and for sterile and nonsterile isolates appear in Table 6. A carbapenemase was detected in 15 of 25 (60.0%; 95% CI, 39.4%-80.6%) sterile-site isolates and 75 of 163 (46.0%; 95% CI, 38.3%-53.7%) urine isolates (P = .19). All 90 isolates for which a carbapenemase was detected were found to be positive using the modified Hodge test. There were 24 of 98 (24.5%; 95% CI, 15.8%-33.2%) non–carbapenemase-producing isolates found to be positive using the modified Hodge test.

Discussion

During this 2-year surveillance period, 599 incident CRE cases were reported across 7 EIP sites, resulting in an overall crude incidence of 2.93 per 100 000 population. This estimate is substantially lower than the incidence of infections due to other pathogens traditionally associated with health care exposures, including methicillin-resistant Staphylococcus aureus (25.1 per 100 000 population),16 invasive candidiasis (13.3-26.2 per 100 000),17 and Clostridium difficile (147.2 per 100 000).18 We found variation by site for the distribution of species, annual incidence, and the percentage of isolates that produced carbapenemase. Ninety-one percent of CRE cases were in individuals with preceding health care exposures and underlying comorbidities.

Although most cases were from cultures collected outside a short-stay acute care hospital, almost half were among individuals hospitalized within 30 days after their initial culture. The majority of hospitalized cases resulted in a discharge directly to a long-term care facility or long-term acute care hospital. Urine was the most common source of CRE, which likely accounted for the low overall mortality observed.

The variability in CRE incidence and the frequency with which different species are represented in EIP sites might reflect the degree to which carbapenemase-producing strains have emerged within and across regions of the United States. Carbapenemase-producing CRE carry antimicrobial resistance genes on mobile plasmids that can move between organisms, potentially facilitating a wider and more rapid spread, adding to the background of non–carbapenemase-producing CRE. Failure to address the spread of carbapenemase-producing CRE could lead to further increases in CRE incidence in areas in which they are already present and wider spread of CRE to areas that have not seen these organisms regularly.

Recommended control measures (eg, contact precautions) should be generally implemented to prevent further spread of all CRE, with more aggressive interventions used for carbapenemase-producing CRE (eg, surveillance cultures of hospitalized roommates).3,19 Regionwide control measures also have been recommended to achieve maximal benefit.19 Only half of all submitted CRE isolates meeting the case definition were found to possess a carbapenemase gene. The epidemiological significance of these cases of non–carbapenemase-producing CRE is less clear because they do not appear to have spread as rapidly during the last 15 years as cases of carbapenemase-producing CRE have. Continued multisite, population-based surveillance beyond the time frame provided in this report will be needed to better understand the relative contributions of carbapenemase-producing and non–carbapenemase-producing CRE to the spread of these organisms in the United States.

Although the majority of cases included in this report were identified from cultures collected in an outpatient setting (65.5%), more were actually collected in a short-stay acute care hospital (33.9%) than in a long-term care facility (26.9%) or a long-term acute care hospital (7.5%). The most common preceding health care exposure among cases was a prior short-stay acute care hospitalization (75.1%). Although previous studies have found a substantially higher incidence of CRE in certain postacute care settings, particularly in long-term acute care hospitals compared with short-stay acute care hospitals,2022 and have demonstrated the vital role of long-term acute care hospitals in the regional dissemination of CRE,23,24 our data suggest that short-stay acute care hospitals also have an important role in the regional epidemiology of CRE.

Approximately 8% of the cases were in individuals who did not have any documented relevant health care exposures prior to their positive CRE culture; however, the extent to which these cases represent community-associated CRE compared with undocumented health care exposures is not clear. The possible spread of CRE from health care settings into the community, as has been recognized with other resistant gram-negative bacilli,2528 is a concerning prospect requiring further evaluation.

Hospitalization around the time of the positive CRE culture was common among cases, with the majority among surviving individuals (55.9%), resulting in discharge directly to a long-term care facility or a long-term acute care hospital. This likely reflects the high prevalence of underlying comorbidities and older age among these individuals. The frequent movement of these individuals across the continuum of care underscores their important role in the interfacility spread of CRE,23,24,29 especially if CRE status is not communicated to accepting facilities as part of the transfer process.

This investigation had several limitations. First, because the definition for carbapenem nonsusceptibility did not include ertapenem, organisms that were nonsusceptible to only ertapenem were not captured.

Second, the case definition relied on susceptibility testing performed locally; it is possible that methods varied across laboratories. Results from the local laboratory rather than results from confirmatory susceptibility testing were used to determine inclusion in this project to allow for a more inclusive description of CRE epidemiology from the perspective of health care facilities and laboratories.

Third, because not all commercial laboratories serving the catchment areas participated, these results may underestimate the CRE burden. However, these laboratories frequently serve postacute care and outpatient settings. Therefore, cases identified by these commercial laboratories are often captured later by cultures from acute care hospitalizations performed at other participating laboratories in the catchment area.

Fourth, surveillance definitions are limited in their ability to differentiate urinary isolates that represent true infections from those that do not. Because many of the case-patients were elderly and had isolates collected outside short-stay acute care settings, we applied a recognized long-term care facility UTI surveillance definition to determine if the reported UTIs might be true infections.

Fifth, although a broad set of catchment areas are included in this surveillance system, it is not designed to be representative of the United States. In addition, isolates from only one-third of all cases were available for molecular characterization. Although attempts were made to systematically collect isolates, a nonrepresentative sample might have been selected at some sites.

In summary, the results of this investigation further inform local efforts to prevent CRE transmission. The low CRE incidence in the catchment areas, compared with other more established resistant organisms, highlights that CRE are emerging and suggests that control interventions implemented now could have a substantial effect.

The fact that heterogeneity exists (with respect to the incidence and the types of CRE found in these different surveillance areas) further highlights the need to understand the local epidemiology to tailor prevention efforts in individual regions of the United States. The frequency with which individuals with CRE are transferred between facilities emphasizes the need for regional control efforts in all the facilities. In addition, the finding that many CRE do not produce a carbapenemase suggests the potential need for a tiered response to these organisms as well as the need for more rapid and readily available laboratory tests to differentiate these strains.

Conclusions

In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100 000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

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Article Information

Corresponding Author: Alexander J. Kallen, MD, MPH, Division of Healthcare Quality Promotion, US Centers for Disease Control and Prevention, 1600 Clifton Rd, MS A-31, Atlanta, GA 30329 (akallen@cdc.gov).

Published Online: October 5, 2015. doi:10.1001/jama.2015.12480.

Author Contributions: Dr Guh and Ms Bulens had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Mu, Lynfield, Beldavs, Limbago, Kallen.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Guh, Mu, Kallen.

Critical revision of the manuscript for important intellectual content: Bulens, Jacob, Reno, Scott, Wilson, Vaeth, Lynfield, Shaw, Vagnone, Bamberg, Janelle, Dumyati, Concannon, Beldavs, Cunningham, Cassidy, Phipps, Kenslow, Travis, Lonsway, Rasheed, Limbago, Kallen.

Statistical analysis: Guh, Mu.

Obtained funding: Beldavs.

Administrative, technical, or material support: Bulens, Wilson, Lynfield, Shaw, Vagnone, Beldavs, Lonsway, Rasheed, Limbago.

Study supervision: Wilson, Lynfield, Dumyati, Beldavs, Phipps, Lonsway, Limbago, Kallen.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This work was supported by the Emerging Infections Program and the National Center for Emerging and Zoonotic Infectious Diseases at the US Centers for Disease Control and Prevention.

Role of the Funder/Sponsors: The funding source was the US federal government. Federal government employees led or participated in all aspects of the project, including design and conduct of the project; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of US Centers for Disease Control and Prevention.

Additional Contributions: We acknowledge the following: Karen Xavier, MT(ASCP) (Laboratory Services Division Public Health Microbiology Laboratory at the Colorado Department of Public Health and Environment, Denver); Wendy Baughman, MPH (Atlanta Research and Education Foundation, Decatur, Georgia); Chris Bowers, MPH, Calista Schenck, MLS(ASCP), Lewis Perry, RN, MPH, and Betsy R. Stein, RN, BSN (Georgia Emerging Infections Program, Decatur); Malorie Givan, MPH (Maryland Department of Health and Mental Hygiene, Baltimore; now with Johns Hopkins University); Jane Harper, BSN, MS, CIC, and Annastasia Gross, MT(ASCP) (Minnesota Department of Health, St Paul); Emily Hancock, MS (University of New Mexico, Albuquerque); and Gary Hollick, PhD, and Rebecca Tsay, MPH (New York Emerging Infections Program, University of Rochester Medical Center, Rochester). All contributed as part of their work on the Emerging Infections Program and were compensated for their efforts.

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