Highlights
- •Carbapenem-resistant Enterobacterales (CRE) are an important cause of multi drug-resistant infections and are primarily associated with exposure to health care, such as hospitalization or residence in a long-term care facility. CRE that harbor a carbapenemase enzyme have the potential to spread rapidly and are classified as an urgent public health threat by the CDC.
- •The Emerging Infections Programs tracks CRE through laboratory- and population-based surveillance, providing a unique system for identifying CRE in persons without health care exposures.
- •Through this surveillance program we found that 10% of all CRE occurred in persons without known health care risk factors. Some of these community-associated CRE harbored a carbapenemase enzyme and most were identified from urine cultures and occurred in older women and persons of White race.
- •These findings show that a small but notable proportion of CRE occur in persons without health care risk factors. Understanding populations at risk of community-associated CRE infections, as well as tracking the burden of CRE that is community-associated into the future, can inform CRE prevention strategies.
Abstract
Background
Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community.
Methods
Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing.
Results
We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene.
Conclusions
Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings.
Key Words
Background
Carbapenem-resistant Enterobacterales (CRE) are typically associated with health care settings and are the focus of targeted infection-control interventions because of CRE's capacity to cause difficult-to-treat infections and to spread rapidly.
1
, Centers for Disease Control and Prevention. Antibiotic resistant threats in the United States, 2019. Accessed January 22, 2021. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.
2
, World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Accessed July 29, 2021. https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf.
3
, 4
Of particular concern are CRE that produce carbapenemases, enzymes that inactivate most or all β-lactam antibiotics and are frequently encoded on mobile genetic elements such as plasmids that can be transmitted between organisms, facilitating spread.Centers for Disease Control and Prevention. Interim guidance for a public health response to contain novel or targeted multidrug-resistant organisms (MDROs). Updated 2019. Accessed February 25, 2019. https://www.cdc.gov/hai/pdfs/containment/Health-Response-Contain-MDRO-H.pdf.
5
The burden of CRE infections might be increasing among persons without health care exposure, both in the United States and abroad; however, as most United States CRE surveillance is hospital-based, robust ascertainment of prior health care exposures in patients with CRE and epidemiologic descriptions of CRE among persons without health care exposures are limited.6
, 7
, - See I
- Ansari U
- Reses H
- et al.
507. Epidemiology of community-associated carbapenemase- producing carbapenem-resistant enterobacteriacae identified from the emerging infections program, 2012–2017.
in: Presented at Infectious Diseases WEEK (ID WEEK), Washington, DC, October 2-9, 2019. Open Forum Infectious Diseases. Oxford University Press US,
2019
8
, Centers for Disease Control and Prevention. Healtcare-Assocaited Infections, Multidrug-resistant organisms (HAI MDRO) message mapping guide. Accessed April 16, 2021. https://ndc.services.cdc.gov/mmgpage/healthcare-associated-infections-multidrug-resistant-organisms-hai-mdro-message-mapping-guide/.
9
The Centers for Disease Control and Preventions' (CDC's) Emerging Infections Program (EIP) Health Care-Associated Infections–Community Interface Activity (HAIC) has conducted surveillance for CRE and other drug-resistant Gram-negative bacteria since 2012 through the Multi-site Gram-negative Surveillance Initiative (MuGSI). We analyzed MuGSI CRE surveillance data from 2012 to 2015 to compare the incidence and epidemiology of community-associated-CRE (CA-CRE) cases to CRE cases with health care risk factors, and to describe the molecular epidemiology of CRE isolated from CA-CRE cases.
Methods
Surveillance catchment area
Laboratory and population-based surveillance was conducted at 8 EIP sites in 2012-2015. Participating sites as of 2015 included Atlanta, Georgia (8 counties; estimated population: 3,991,607); Minneapolis and St. Paul, Minnesota (2 counties; estimated population: 1,761,282); and Portland, Oregon (3 counties; estimated population; 1,766,135), Denver, Colorado (5 counties; estimated population: 2,694,886), Baltimore, Maryland (4 counties; estimated population: 1,934,018), Albuquerque, New Mexico (1 county; estimated population: 676,685), Rochester, New York (1 county; estimated population: 749,600), Nashville, Tennessee (8 counties; estimated population: 1,653,871).
10
,Centers for Disease Control and Prevention. Multi-site gram-negative surveillance initiative. Accessed March 16, 2021. https://www.cdc.gov/hai/eip/mugsi.html.
11
The total population under surveillance in 2015 was approximately 15.2 million.United States Census Bureau. 2015 population estimates. Accessed June 27, 2016. http://quickfacts.census.gove/qfd/index.html.
11
United States Census Bureau. 2015 population estimates. Accessed June 27, 2016. http://quickfacts.census.gove/qfd/index.html.
Case definition and epidemiological classification
We defined a CRE case as the first isolation, in a 30-day period, from a catchment area resident, meeting the phenotypic case definition of carbapenem non-susceptible and third-generation cephalosporin-resistant Klebsiella pneumoniae, K. oxytoca, K. aerogenes (formerly Enterobacter aerogenes), Enterobacter cloacae complex, or Escherichia coli from a normally sterile body site or urine specimen. Antimicrobial resistance was defined according to the Clinical and Laboratory Standards Institute (CLSI) interpretive criteria.
12
Antimicrobial susceptibility testing results from the local clinical laboratory's primary testing method were used to identify isolates with carbapenem minimum inhibitory concentrations (MICs) ≥2 µg/mL to imipenem, meropenem, or doripenem (ertapenem was excluded) and with MICs indicating resistance to any third-generation cephalosporin tested (ceftazidime MIC ≥16 µg/mL; ceftriaxone or cefotaxime MIC ≥4 µg/mL).12
,13
Although this surveillance program is ongoing, the phenotypic case definition was changed in 2016, therefore our analysis is limited to data collected before 2016.14
Centers for Disease Control and Prevention. HAIC Viz Multi-site gram-negative surveillance initiative, carbapenen-resistant enterobacterales. Accessed September 14, 2021. https://www.cdc.gov/hai/eip/haicviz.html.
A case was defined as health care-associated (HCA) if it occurred in a patient with any of the following risk factors: (1) collection of the case-defining culture on or after day 3 of admission to a short stay acute care hospital (ACH); (2) admission to an ACH or long-term acute care hospital (LTACH), residence in a long-term care facility (LTCF) (including nursing home, skilled nursing facility, inpatient hospice or physical rehabilitation facility), or inpatient or outpatient surgery in the year prior to the date of culture; (3) undergoing chronic dialysis at time of culture; or (4) presence of a urinary catheter or another type of indwelling device at the time of or in the 2 calendar days before the date of incident culture. Cases in patients without any of these health care risk factors were classified as CA.
Case identification and data collection
To identify cases, reports of CRE isolates were actively collected from clinical laboratories serving the catchment area. Catchment area residency was determined using the patient address that accompanied isolate submission. A standardized case report form was used to collect patient demographics, clinical characteristics, underlying conditions, health care exposures and outcomes, location of specimen collection, and types of infections associated with the case-defining specimen. All inpatient (ACH and LTACH) and LTCF medical records from the year prior to the date of collection for the case-defining specimen were reviewed. In the outpatient setting, records from the 5 days prior to the date of collection for the case-defining specimen were reviewed; if no prior hospitalizations or surgeries were identified, then a full year of outpatient records was reviewed. Mortality was defined as death occurring within 30 days of the date of collection for the case-defining specimen, as documented in state death registries. A Charlson Comorbidity Index score (CCI) was calculated based on underlying conditions abstracted from the medical record.
15
,16
If the case-defining CRE was isolated from a urine culture, additional information was collected to apply a standardized definition for urinary tract infection (UTI).17
UTI was defined as a urine culture positive for ≥105 CFU/ml of a single species of CRE in a patient who had any one of the following criteria: (1) documentation of a urinary catheter in place in the 2 days before the date of collection for the case-defining urine specimen, (2) documented signs or symptoms consistent with UTI during the 2 calendar days before through the 2 calendar days after the date of collection for the case-defining urine specimen, or (3) positive blood culture with the same CRE species within 30 days of the date of collection for the case-defining urine specimen.Centers for Disease Control and Prevention. Urinary tract infectins (catheter-associated urinary tract infections [CAUTI] and non-catheter-associated urinary tract infections [UTI]) events. Accessed November 1, 2018. https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf.
17
,Centers for Disease Control and Prevention. Urinary tract infectins (catheter-associated urinary tract infections [CAUTI] and non-catheter-associated urinary tract infections [UTI]) events. Accessed November 1, 2018. https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf.
18
Analytic and statistical methods
Crude incidence rates were calculated by EIP site, year, and epidemiologic class using the annual case counts reported by each EIP site linked to the United States Census population for the areas under surveillance. These crude rates were expressed as the number of cases per 100,000 population, and 95% confidence intervals were calculated assuming a Poisson distribution.
19
Cases with missing values for race were imputed based on the distribution of known race among cases by age category, sex, EIP site, year of CRE specimen collection, and presence or absence of diabetes. Variables were selected for the imputation process to improve accuracy of the predicted race. Resulting imputed race categories were White, Black/African American, and other race which includes American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. Due to small numbers all non-White race categories, even after imputation, were collapsed into a single category for analysis. We performed descriptive analyses of demographics at the patient level. Health care exposures, outcomes, and isolate antibiotic susceptibility were analyzed at the case level. Analysis was limited to case report forms determined to be complete as of March 13, 2018. P-values for comparisons of categorical variables were calculated using the χ2test, or the Fisher's exact test for cell sizes less than 5. The Wilcoxon Rank Sum Test was used to test the difference between medians.20
Data management and analyses were conducted using SAS version 9.4 (SAS Institute Inc, Cary, North Carolina).SAS Institute. Scores for linear rank and one-way ANOVA Tests, Wilcoxon Scores. Accessed January 2, 2019. https://support.sas.com/documentation/cdl/en/statug/63033/HTML/default/viewer.htm#statug_npar1way_a0000000200.htm#statug.npar1way.npar1med.
Isolate collection, submission and evaluation
A convenience sample of isolates was submitted for further evaluation at CDC; the methods for isolate collection evolved during the project period, and these changes are documented in the Supplementary Material.
Isolates received at the CDC underwent the following testing: species identification using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF Biotyper 3.1, Bruker Daltonics, Billerica, MA), antimicrobial susceptibility testing using reference broth microdilution with a metallo-β-lactamase (MBL) screen; modified Hodge test to detect carbapenemase production (MHT; per CLSI the recommended phenotypic test for carbapenemase production at the time of isolate submission) and real-time polymerase chain reaction (PCR) testing for blaKPC, blaNDM and blaOXA-48-like genes.
12
,21
,22
If a CRE isolate was determined to harbor a carbapenemase-producing gene, it was classified as carbapenemase-producing (CP). Additional real-time PCR testing was conducted for blaVIM if the isolate was MBL screen positive and blaNDM negative.23
All isolates displaying a colistin MIC of ≥2 µg/mL were screened for plasmid-mediated colistin resistance genes (mcr-1 and mcr-2) by real-time PCR.24
Whole genome sequencing was conducted on CA-CRE isolates that were confirmed carbapenem non-susceptible and third-generation cephalosporin-resistant using reference broth microdilution at the CDC. Sequencing was performed using an Illumina MiSeq System (San Diego, CA). Sequences were analyzed using the CDC laboratory's in-house QuAISAR-H pipeline (Quality, Assembly, species Identification, Sequence typing, Annotation, Resistance mechanism for Health care pathogens).
25
QuAISAR-H performs a variety of functions, including cleaning, trimming, and assembling sequence data from each isolate. QuAISAR-H identified antibiotic resistance (AR) genes, including carbapenemase genes, beta-lactamase genes, and plasmid-mediated colistin resistance (mcr) genes, using a combined database of acquired antimicrobial resistance (AR) genes from ResFinder, ARG-ANNOT, and AMRFinderPlus; genes with 95% Identity and 100% Coverage threshold were reported.- Stanton RA
- Vlachos N.
- de Man T.J.B.
- Lawsin A.
- Halpin A.L.
Development and application of QuAISAR-H: A bioinformatics pipeline for short read sequences of health care-associated pathogens.
in: ASM Conference on Rapid Applied Microbial Next Generation Sequencing and Bioinformatic Pipelines, Tyson Falls2022
26
, 27
, 28
Multilocus sequence type (MLST) was determined using the publicly available schemes curated by pubMLST.29
,30
Whole genome sequence analyses were performed using the specified AR genes databases, listed above, current through December 27, 2019. All reported isolate results, generated at the CDC, are final as of August 7, 2020.Results
Cases and crude incidence rates
From January 1, 2012, through December 31, 2015, we identified a total of 1,585 incident cases. Among these, 1,499 cases in 1,194 case-patients are included in this analysis because the cases had complete medical record review, required for ascertainment of epidemiologic class. Among the cases, 1,350 (90%) were HCA-CRE and 149 (10%) were CA-CRE. The overall crude incidence of CRE across all the sites during the 4-year period was 2.96 (95% CI: 2.81, 3.11) cases per 100,000 population (Table 1). The crude incidence rates varied by EIP site, year, and epidemiological class (Table 1). Sites with the highest overall crude incidence of HCA-CRE, Maryland and Georgia, differed in epidmiological class from those with the highest overall crude incidence of CA-CRE, New Mexico and New York (Table 1).
Table 1Carbapenem-resistant Enterobacterales (CRE) crude incidence, by Emerging Infections Program site and epidemiological classification, 2012-2015, n = 1499
| EIP Site | Crude incidence rates per 100,000 population (95% confidence cnterval) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 2012 | 2013 | 2014 | 2015 | Overall | ||||||
| CA | HCA | CA | HCA | CA | HCA | CA | HCA | CA | HCA | |
| CO | 0.12 (0.02, 0.34) | 0.93 (0.60, 1.38) | 0.04 (0.00, 0.21) | 0.61 (0.35, 0.99) | 0.33 (0.15, 0.63) | 0.93 (0.60, 1.37) | 0.16 (0.09, 0.28) | 0.82 (0.63, 1.05) | ||
| GA | 0.21 (0.09, 0.41) | 4.16 (3.54, 4.86) | 0.13 (0.04, 0.30) | 4.11 (3.50, 4.81) | 0.20 (0.09, 0.40) | 3.90 (3.30, 4.57) | 0.13 (0.04, 0.29) | 3.43 (2.88, 4.06) | 0.17 (0.11, 0.24) | 3.90 (3.59, 4.22) |
| MD | 0.05 (0.00, 0.29) | 4.43 (3.54, 5.48) | 0.52 (0.25, 0.95) | 7.68 (6.49, 9.02) | 0.31 (0.11, 0.68) | 6.67 (5.57, 7.93) | 0.29 (0.17, 0.47) | 6.27 (5.64, 6.94) | ||
| MN | 0.29 (0.10, 0.68) | 1.53 (1.00, 2.23) | 0.35 (0.13, 0.76) | 1.85 (1.27, 2.62) | 0.23 (0.06, 0.59) | 2.18 (1.54, 2.99) | 0.40 (0.16, 0.82) | 2.55 (1.86, 2.42) | 0.32 (0.20, 0.48) | 2.03 (1.71, 2.40) |
| NM | 0.00 (0.00, 0.44) | 1.33 (0.61, 2.53) | 2.66 (1.58, 4.21) | 4.29 (2.87, 6.17) | 1.48 (0.71, 2.72) | 3.10 (1.92, 4.74) | 1.38 (0.92, 2.00) | 2.91 (2.22, 3.76) | ||
| NY | 0.93 (0.38, 1.92) | 2.53 (1.53, 3.96) | 1.33 (0.64, 2.45) | 4.80 (3.36, 6.65) | 0.80 (0.29, 1.74) | 1.73 (0.92, 2.97) | 1.02 (0.65, 1.53) | 3.02 (2.35, 3.83) | ||
| OR | 0.12 (0.01, 0.43) | 0.24 (0.06, 0.61) | 0.23 (0.06, 0.60) | 0.47 (0.20, 0.92) | 0.00 (0.00, 0.17) | 0.52 (0.24, 0.98) | 0.28 (0.09, 0.66) | 0.17 (0.04, 0.50) | 0.16 (0.08, 0.29) | 0.35 (0.22, 0.52) |
| TN | 0.31 (0.10, 0.72) | 0.68 (0.34, 1.22) | 0.24 (0.07, 0.62) | 0.73 (0.37, 1.27) | 0.27 (0.13, 0.52) | 0.70 (0.45, 1.05) | ||||
Overall | 0.21 (0.12, 0.34) | 2.62 (2.26, 3.02) | 0.20 (0.13, 0.29) | 2.54 (2.28, 2.83) | 0.37 (0.28, 0.48) | 2.93 (2.66, 3.22) | 0.34 (0.26, 0.45) | 2.53 (2.28, 2.79) | 0.29 (0.25, 0.35) | 2.66 (2.52, 2.81) |
CA, community-associated; HCA, health care-associated.
Organism, culture source and infection syndrome
K. pneumoniae was the most frequent organism among all cases (n = 800, 53%), followed by E. coli (n = 275, 18%). Overall, a higher proportion of HCA-CRE were K. pneumoniae compared to CA-CRE (772/1350 [58%] vs 28/149 [19%], respectively; P < .001), and a higher proportion of CA-CRE were E. coli compared to HCA-CRE (61/149 [40%] vs 214/1350 [16%], respectively; P < .001); however, at 2 sites, Minnesota and Oregon, the same organism predominated among both CA-CRE and HCA-CRE; in Minnesota, K. aerogenes (CA-CRE: 55%, HCA-CRE: 40%, overall: 42%), and in Oregon, E. cloacae complex (CA-CRE: 18%, HCA-CRE: 21%, overall: 20%).
Urine was the most common culture source among all CRE cases (n = 1,305, 87%) and was the source of 98% of all CA-CRE cases compared to 86% of HCA-CRE cases (P < .001). The most common infection syndrome associated with all cases, as documented in the medical record, was UTI (n = 1,024). Clinically documented UTIs were more commonly identified among CA-CRE cases than HCA-CRE cases (83% vs 67%, P < .001, Table 2). When applying a standardized UTI definition to cases where the isolate was from urine, 113 (9%) met the definition; the proportion of cases that met the UTI definition was similar among CA-CRE cases and HCA-CRE cases (16/146 [11%] vs 97/1159 [8%], P = .27).
16 HCA cases in which CRE was isolated from both blood and urine on the date of initial culture are included in the blood culture source category. Nine HCA cases had unknown hospital admission at the time of medical record review.
Table 2Organism type, culture source, infection syndrome, and outcomes among Carbapenem-resistant Enterobacterales (CRE) cases at Emerging Infections Program sites, by epidemiological class, 2012-2015, n = 1499
| Number of cases (%) | P value | |||
|---|---|---|---|---|
| All, n = 1499 | CA, n = 149 | HCA, n = 1350 | ||
| Organism type | ||||
| Klebsiella pneumoniae Escherichia coli Enterobacter cloacae Klebsiella aerogenes Klebsiella oxytoca | 800 (53.4) 275 (18.3) 208 (13.9) 191 (12.7) 25 (1.7) | 28 (18.8) 61 (40.9) 27 (18.1) 32 (21.5) 1 (0.7) | 772 (57.2) 214 (15.9) 181 (13.4) 159 (11.8) 21 (1.8) | .0008 .1142 <.0001 .5039 <.0001 |
| Culture Source | ||||
| Urine Blood Other normally sterile site | 1305 (87.1) 162 (10.8) 32 (2.1) | 146 (97.9) 3 (2.0) 0 (0.0) | 1159 (85.9) 159 (11.8) 32 (2.4) | <.0001 |
| Selected Infection Syndromes | ||||
| Urinary Tract Infection Bacteremia/Sepsis Septic Shock Pneumonia Pyelonephritis Vascular Graft Infection No infection syndrome documented | 1024 (63.7) 197 (13.1) 64 (4.3) 34 (2.3) 23 (1.5) 1 (0.1) 218 (14.5) | 123 (82.6) 4 (2.7) 0 (0.0) 0 (0.0) 4 (2.7) 1 (0.7) 19 (12.8) | 901 (66.7) 193 (14.3) 64 (4.7) 34 (2.5) 19 (1.4) 0 (0.0) 199 (14.7) | <.0001 <.0001 .0020 .0425 .2769 .0994 .5134 |
| Outcomes | ||||
| Hospitalized at the time of, or within 30 days after, the date of incident culture Admission to an intensive care unit on the day of, or within 7 days after, initial culture | 908/1490 (61.0) 316/908 (34.8) | 29/149 (19.5) 2/29 (6.9) | 879/1341 (65.6) 314/879 (35.7) | <.0001 .0006 |
| Died within 30 days of date of incident culture | 167/1499 (11.1) | 4/149 (2.7) | 163/1350 (12.1) | .0002 |
| Among cases with a sterile site culture Among cases with a urine culture | 58/167 (34.7) 109/167 (65.3) | 0/4 (0.0) 4/4 (100.0) | 58/163 (35.6) 105/163 (64.4) | .2992 |
CA, community-associated; HCA, health care-associated.
† Other normally sterile sites include internal body sites, bone, joint, peritoneal fluid and pleural fluid.
‡ Infection syndromes described in the table are limited to those associated with CA cases for the purpose of comparison between CA and HCA cases. Additional infection syndromes were reported among HCA cases.
§ Cases from urine compared to cases from normally sterile sites.
†† P-values for pair-wise comparison by epidemiologic class of proportion of cases that were each organism.
Demographics and clinical characteristics of case-patients
Among the 1,194 case-patients, the 139 CA-CRE case-patients were similar in age to the 1055 HCA-CRE case-patients (CA-CRE: median 64 years, interquartile range [IQR] 45-80; HCA-CRE: median 67 years, IQR 56-77; P = .098), but were more likely to be female (CA-CRE: 117/139 [84%]; HCA-CRE: 613/1055 [58%]; P < .001), of White race (CA-CRE: 102/139 [73%]; HCA-CRE: 539/1055 [51%,]; P < .001), and to have fewer comorbid conditions (CA-CRE: median 1 [assessed among 139 patients], IQR 0-2; HCA-CRE: median 3 [assessed among 1052 case-patients], IQR 1-4; P < .001) (Table S1 Supplementary Material).
Comorbid conditions could be assessed in 1,191 of the case-patients (see Table S1, Supplementary Material). Common comorbidities among CA-CRE and HCA-CRE case-patients included: diabetes (CA-CRE: 34/139 [24%]; HCA-CRE: 479/1052 [46%], P <.001), urinary tract problems/abnormalities (CA-CRE: 22/139 [16%]; HCA-CRE: 219/1052 [21%], P = .17), neurological conditions (including quadriplegia) (CA-CRE: 15/139 [11%]; HCA-CRE: 292/1052 [28%], P < .001,), and dementia (CA-CRE: 13/139 [9%]; HCA-CRE: 240/1,052 [23%], P < .001). The proportion of CA-CRE case-patients without documentation of an underlying medical condition (n = 51, 37%) was greater when compared to HCA patients (n = 36, 3%, P < .001).
Risk factors for infection and outcomes of cases
Culture sources, infection syndromes, and outcomes among cases are presented in Table 2. Overall, 15 cases occurred in 14 case-patients who had medical record notation of travel outside of the contiguous United States, Hawaii and/or Alaska in the 2 months before culture collection: these included 2 of 149 (1%) CA-CRE cases and 13 of 1350 (1%) HCA-CRE cases (Supplemental Material).
Antimicrobial susceptibility testing of incident case isolates at local clinical laboratories
Local clinical laboratory testing results for 12 non-carbapenem antibiotics are presented in Table 3. Among the 1,473 isolates that underwent testing for one or more common agents to treat UTI (ciprofloxacin, levofloxacin, ampicillin, nitrofurantoin, and trimethoprim-sulfamethoxazole), 664 (45%) were susceptible to at least one. This included 120 (81%) of 148 CA-CRE cases compared to 544 (41%) of 1325 HCA-CRE cases (P < .001).
EUCAST Version 8.0 clinical breakpoints were applied for colistin and tigecycline (http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_8.0_Breakpoint_Tables.pdf).
Table 3Antimicrobial susceptibility of Carbapenem-resistant Enterobacterales (CRE) isolates at local clinical laboratories, by epidemiological classification, 2012-2015, n = 1499
| Antimicrobial agent | Number susceptible/ Total number tested (%) | P-value | ||
|---|---|---|---|---|
| All, n = 1499 | CA, n = 149 | HCA, n = 1350 | ||
| Aminoglycosides | ||||
| Any tested | 1253/1473 (85.1) | 141/146 (96.6) | 1112/1327 (83.8) | <.0001 |
| Amikacin Gentamicin Tobramycin | 875/1286 (68.0) 973/1462 (66.6) 534/1325 (39.9) | 112/118 (94.9) 129/145 (89.0) 88/113 (77.9) | 763/1168 (65.3) 844/1317 (64.1) 436/1212 (36.0) | <.0001 <.0001 <.0001 |
| Fluoroquinolones | ||||
| Any tested | 454/1465 (31.0) | 102/145 (70.3) | 352/1320 (26.7) | <.0001 |
| Ciprofloxacin Levofloxacin | 391/1314 (29.8) 328/1133 (29.0) | 98/142 (69.0) 63/98 (64.3) | 293/1172 (25.0) 265/1035 (25.4) | <.0001 <.0001 |
| Other antimicrobials | ||||
| Ampicillin Aztreonam Colistin Piperacillin-tazobactam Nitrofurantoin Tigecycline Trimethoprim-sulfamethoxazole | 34/1295 (2.6) 87/1161 (7.5) 194/222 (87.4) 208/1397 (14.9) 90/377 (23.9) 188/657 (28.6) 463/1456 (31.8) | 22/121 (18.2) 35/105 (33.3) 2/2 (100.0) 57/138 (41.3) 23/39 (59.0) 11/28 (39.3) 80/144 (55.6) | 12/1174 (1.0) 52/1056 (4.9) 192/220 (87.3) 151/1259 (12.0) 67/338 (19.8) 177/629 (28.1) 383/1312 (29.2) | <.0001 <.0001 .5894 <.0001 <.0001 .2017 <.0001 |
CA, community-associated; HCA, health care-associated.
Characterization of isolates from community-associated CRE cases
Overall, 64 (43%) isolates from CA-CRE cases were submitted to the CDC for further characterization, from Minnesota (n = 18, 28%), New Mexico (n = 16, 24%), Colorado (n = 9, 14%), New York (n = 6, 9 %), Oregon (n = 6, 9%), Tennessee (n = 4, 6%), Georgia (n = 3, 5%), and Maryland (n = 2, 3%). Isolates were E. coli (n = 26, 41%), K. aerogenes (n = 18, 28%), E. cloacae complex (n = 14, 22%), and K. pneumoniae (n = 6, 9%). Five (8%) isolates had a carbapenemase identified by PCR: 3 KPC-K. pneumoniae, 1 KPC-E. cloacae complex, and 1 NDM-E. coli. Among the 64 isolates, 15 (23%) were MHT positive using ertapenem (K. aerogenes [n = 8], E. cloacae complex [n = 3], K. pneumoniae [n = 3], and E. coli [n = 1]) and 13 (20%) were MHT positive using meropenem (K. aerogenes [n = 6], K. pneumoniae [n = 3], E. cloacae complex [n = 3], and E. coli [n = 1]). Nine isolates had a colistin MIC ≥2 µg/ml and underwent PCR testing for mcr-1; all tested negative. Twelve CA-CRE isolates underwent WGS at CDC; 5 of 12 (42%) were CP positive and all sequenced isolates had unique MLST (Table 4).
None of the identified community-associated- K. aerogenes isolates that were sequenced met the phenotypic case definition after testing at CDC.
Table 4Multilocus sequence types, beta-lactamase genes identified, and antimicrobial resistance profiles of community-associated Carbapenem-resistant Enterobacterales isolates that underwent whole genome sequencing analysis at CDC, 2012-2015, n = 12
| Organism type | Carbapenemase gene variants | MLST | Non-carbapenemase beta-lactamase gene variants | Antimicrobial resistance profile ‡ Antimicrobials reported if the isolate tested resistant based on reference broth microdilution testing performed at CDC. Isolates were tested against the following unless noted: AMK, amikacin; AMC, amoxicillin-clavulanic acid; AMP, ampicillin; ATM, aztreonam; CFZ, cefazolin; FEP, cefepime; CTX, cefotaxime; CAZ, ceftazidime; FOX, cefoxitin; CRO, ceftriaxone; CIP, ciprofloxacin; CST, colistin; DOR, doripenem; ETP, ertapenem; GEN, gentamicin; IPM, imipenem; LVX, levofloxacin; MEM, meropenem; TZP, piperacillin-tazobactam; PMB, polymyxin B; TET, tetracycline; TGC, tigecycline; SXT, trimethoprim-sulfamethoxazole; TOB, tobramycin. Interpretations are based on the 2019 Clinical and Laboratory Standards Institute; CLSI, interpretative criteria. Performance standards for antimicrobial susceptibility testing: twenty-ninth informational supplement, M100-S29. Wayne [PA]: The Institute; 2019). |
|---|---|---|---|---|
| Enterobacter cloacae | None | Novel | ACT-70 | AMC, AMP, ATM, CFZ, FOX, TZP |
| complex (n = 6) | None | 108 | ACT-55 | AMP, ATM, CFZ, FOX, TZP |
| KPC-3 | 171 | ACT-45, OXA-9, SHV-12, TEM-1A | AMC, AMP, ATM, CFZ, FEP, FOX, CIP, LVX, TZP, SXT, TOB | |
| None | 45 | TEM-1B | AMC, AMP, ATM, CFZ, FOX, CST, TZP, PMB, SXT | |
| None | 365 | None | AMC, AMP, ATM, CFZ, FOX, CST, TZP, PMB | |
| None | 125 | ACT-28 | AMC, AMP, ATM, CFZ, FOX, CST, TZP, PMB | |
| Escherichia coli (n = 3) | NDM-1 | 5498 | TEM-1A | AMP, CFZ, FEP, FOX, CIP, GEN, LVX, TZP, TET, SXT, TOB |
| None | 167 | CTX-M-15, OXA-1 | AMP, ATM, CFZ, FEP, FOX, CIP, GEN, LVX, TET, SXT | |
| None | 131 | CTX-M-15, OXA-1, TEM-1B | AMC, AMP, ATM, CFZ, FEP, FOX, CIP, LVX, TZP, SXT, TOB | |
| Klebsiella pneumoniae (n = 3) | KPC-3 | 258 | SHV-11 | AMC, AMP, ATM, CFZ, CIP, LVX, TZP, SXT, TOB |
| KPC-3 | 1737 | LEN-17 | AMC, AMP, ATM, CFZ, FEP, CIP, LVX, TZP, SXT, TOB | |
| KPC-3 | 485 | SHV-27 | AMC, AMP, ATM, CFZ, FEP, CIP, LVX, TZP, SXT |
† Novel: This MLST sequence type is not in the Pasteur MLST database.
§ Isolate not tested against amoxicillin-clavulanic acid.
‡ Antimicrobials reported if the isolate tested resistant based on reference broth microdilution testing performed at CDC. Isolates were tested against the following unless noted: AMK, amikacin; AMC, amoxicillin-clavulanic acid; AMP, ampicillin; ATM, aztreonam; CFZ, cefazolin; FEP, cefepime; CTX, cefotaxime; CAZ, ceftazidime; FOX, cefoxitin; CRO, ceftriaxone; CIP, ciprofloxacin; CST, colistin; DOR, doripenem; ETP, ertapenem; GEN, gentamicin; IPM, imipenem; LVX, levofloxacin; MEM, meropenem; TZP, piperacillin-tazobactam; PMB, polymyxin B; TET, tetracycline; TGC, tigecycline; SXT, trimethoprim-sulfamethoxazole; TOB, tobramycin. Interpretations are based on the 2019 Clinical and Laboratory Standards Institute; CLSI, interpretative criteria. Performance standards for antimicrobial susceptibility testing: twenty-ninth informational supplement, M100-S29. Wayne [PA]: The Institute; 2019).
Epidemiology of carbapenemase-producing CA-CRE cases
Among the 12 CA-CRE cases with isolates that underwent WGS at CDC, 5 cases, representing 4 unique case-patients, harbored isolates that were CP. Of the CP-CA-CRE cases, 3 (60%) were from female patients, 4 (80%) were from individuals of White race, and the median case-patient age was 73 years (mean: 68, range: 52-84). Three cases had a documented urinary tract problem or abnormality, such as neurogenic bladder. The median CCI for the CP-CA-CRE cases was similar to the non-CP-CA-CRE cases (2 vs 1, respectively). Four CP-CA-CRE isolates (80%) were cultured from specimens collected in the outpatient setting, and one was collected in an emergency room; 2 (40%) cases were hospitalized. Three cases had documented diagnosis of UTI only, one had a bloodstream infection (BSI) only, and 1 patient had both a UTI and a BSI.
Discussion
Through population- and laboratory-based surveillance in 8 United States metropolitan areas during 2012-2015, we observed that 10% of CRE cases were CA, occurring in patients without known health care risk factors. We observed variation in HCA- and CA-CRE cases by geographic site, organism distribution, and case-patient demographics and risk factors. The twelve CA-CRE isolates that underwent molecular characterization at CDC had diverse MLSTs, and at least 1 carbapenemase gene was identified in 5 isolates.
Consistent with the current understanding of CRE epidemiology in the United States, we observed that a minority of CRE cases occurred in individuals without recent health care exposures.
9
The 10% of cases that were CA-CRE is near the upper boundary of the 5.6%-10.8% range identified among the 4 studies conducted in the United States and described in a scoping review of international studies assessing CRE in the community.9
A voluntary statewide surveillance program in Michigan (September 2012-February 2013), which defined community-onset CRE based on where the specimen was collected (ie, collected in the outpatient setting or within the first 3 days of hospitalization), was the source of the upper boundary published by Kelly et al.9
,31
Our program's estimate of CA-CRE incidence is likely near the upper boundary because it was based on active laboratory- and population-based surveillance that included commercial outpatient laboratories, rather than hospital-based cohorts that formed the population for 2 studies with lower estimates.9
,32
,33
Additionally, our surveillance system encompasses diverse geographies and included some areas with a high proportion of overall cases that were CA-CRE.- Thaden JT
- Lewis SS
- Hazen KC
- et al.
Rising rates of carbapenem-resistant enterobacteriaceae in community hospitals: a mixed-methods review of epidemiology and microbiology practices in a network of community hospitals in the southeastern United States.
Infect Control Hospital Epidemiol. 2014; 35: 978-983
Compared to HCA-CRE, CA-CRE identified in our surveillance were more likely to be E. coli, and cases were more likely to occur in female persons of White race with few documented underlying conditions. Our finding of E. coli as the most common cause of CA-CRE UTIs, and that the CA-CRE UTIs occured primarily in women, is consistent with published literature on community-acquired UTIs.
34
,35
Females outpatient settings who present with signs and symptoms of a UTI are likely treated empirically.36
,- Gupta K
- Hooton TM
- Naber KG
- et al.
International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.
Clin Infect Dis. 2011; 52: e103-e120
37
Our findings underscore the importance of using local epidemiology and patient risk factors (eg, age and sex) for decisions about testing and treatment.37
Fifty percent of females will develop a UTI at some point in their lifetime, regardless of their degree of exposure to the health care setting.34
,35
,38
Risk factors that predispose patients to UTIs include diabetes, neurological conditions that affect the urinary tract, and urinary tract problems or abnormalities, were frequently identified among our CA-CRE cases.34
,35
,37
,38
Additionally, menopause results in changes to the urobiome, putting post-menopausal females at higher risk for the development of a UTI.38
These data allow us to hypothesize that there could exist observed racial differences among patients with CA-CRE relative to HCA-CRE; these results were unexpected and merit further investigation. These differences may be due to unmeasured differences in health status, health care seeking behaviors, or provider laboratory test ordering practices. Unfortunately, due to small numbers we were not able to further assess differences among persons for whom race was reported to be non-White. Understanding racial and ethnic differences among patients who acquire multidrug-resistant organisms is complex, and the limited literature demonstrates a variety of causes for disparities. An analysis of patients with community-associated invasive methicillin-resistant Staphylococcus aureus, conducted within the EIP, found that patients of Black race had higher incidence of disease than patients of White race.
39
These differences were explained by socioeconomic characteristics as measured at the census tract level (eg, household income, proportion of expensive homes in a neighborhood, educational level, being in a medically underserved area).39
A review of studies addressing racial and ethnic disparities among patients with health care-associated Clostridioides difficile infection found predominance among patients of White race, and authors theorized that access to health care and thus antibiotics could be the reason for this difference.40
In an EIP study of CA-Clostridioides difficile infections (CA-CDI), communities with lower socioeconomic status, as measured at the census tract level, were found to have higher incidence of CA-CDI.41
Lastly, the Department of Veterans Affaris demonstrated that among a retrospective cohort of patients with CRE, more persons of White race were identified; however, among the subset with CP-CRE, patients were significantly more likely to be of African American or Black race.42
A carbapenemase gene was identified in 5 of the 12 CA-CRE isolates that underwent whole genome sequencing at the CDC, KPC being the most commonly identified gene (n = 4). In the United States, acquisition of CRE harboring carbapenemase enzymes is commonly linked to inpatient health care exposures, and among the carbapenemase KPC is the gene most commonly identified.
2
,World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Accessed July 29, 2021. https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf.
43
,- Sarah J
Janelle Alexander Kallen Tom de Man Brandi Limbago Maroya Walters Alison Halpin, Notes from the field New Delhi metallo-beta-lactamase-producing carbapenem-resistant enterobacteriaceae identified in patients without known health care risk factors- colorado, 2014-2016.
Morbidity Mortality Weekly Rep. 2016; 65: 1414-1415
44
This has been demonstrated in an earlier description of this surveillance system where all carbapenemase enzymes identified were KPC, and through national data where KPC was identified in 85% of tested isolates.Centers for Disease Control and Prevention. Antibiotic resistance and patient safety portal: carbapenem-resistant enterobacterales. Accessed January 7, 2022. https://arpsp.cdc.gov/profile/arln/cre.
44
,Centers for Disease Control and Prevention. Antibiotic resistance and patient safety portal: carbapenem-resistant enterobacterales. Accessed January 7, 2022. https://arpsp.cdc.gov/profile/arln/cre.
45
However, isolated cases of CP-CRE in persons without health care exposures have previously been reported in the United States, including in Colorado, where 6 NDM-producing CRE were identified in individuals without health care exposure in 2014-2016; cases were noted to have prior antibiotic use, international travel (without hospitalization) and/or exposure to family members with frequent health care exposures.43
,- Sarah J
Janelle Alexander Kallen Tom de Man Brandi Limbago Maroya Walters Alison Halpin, Notes from the field New Delhi metallo-beta-lactamase-producing carbapenem-resistant enterobacteriaceae identified in patients without known health care risk factors- colorado, 2014-2016.
Morbidity Mortality Weekly Rep. 2016; 65: 1414-1415
46
Internationally, isolation of CP-CRE from persons without health care exposure has been documented.9
,47
These findings suggest the importance of case investigations of United States CA-CP-CRE that include patient interviews to characterize risk factors that might not be well-documented in the medical record and to inform prevention efforts for CP-CRE transmission that could be occurring outside of health care settings traditionally associated with CRE acquisition.The limitations of this surveillance program have previously been described.
18
,45
These data describe cases that were collected from 2012 to 2015, and the epidemiology of CRE in the population under surveillance may have since changed, so findings may not reflect the current epidemiology of CRE; we have some indication that CA-CRE in this population has increased.7
Organisms that were not susceptible to ertapenem, but were susceptible to other carbapenems, were not included in our definition of CRE, as the current CDC CRE definition that includes ertapenem and excludes the third generation cephalosporins was not implemented until 2016.- See I
- Ansari U
- Reses H
- et al.
507. Epidemiology of community-associated carbapenemase- producing carbapenem-resistant enterobacteriacae identified from the emerging infections program, 2012–2017.
in: Presented at Infectious Diseases WEEK (ID WEEK), Washington, DC, October 2-9, 2019. Open Forum Infectious Diseases. Oxford University Press US,
2019
45
,46
,48
Additionally, our cases are based on the reported phenotype generated by the ATI used by participating clinical laboratories. These instruments are known to overcall carbapenem resistance, therefore our estimates of CRE could be inflated for both CA and HCA cases.49
, 50
, 51
Our rates of CA cases could have been underestimated because large private laboratories that mostly serve the outpatient setting did not participate uniformly across all sites.18
,45
Although the 15 million-person population under surveillance is large, the data demonstrate considerable heterogeneity by geographic region, and therefore caution should be used in extrapolating to other regions.18
,45
Our isolate collection is a convenience sample, and only about 10% of all cases that could have an isolate submitted, did. Additionally, isolate collection methods changed during the surveillance period. Despite this, case characteristics were similar between those with isolates that were eligible for shipment and those submitted to the CDC. Finally, data were retrospectively abstracted from medical records, and the quality and completeness of such records can vary between health care system and facility types, resulting in differences in reporting of some data elements. Despite expanded review of medical records for potential CA-CRE cases, it is possible that some health care exposures were missed, resulting in misclassification of HCA cases as CA.45
We used active, laboratory and population-based surveillance to compare the incidence and epidemiology of CA and HCA-CRE in the United States. Although the overall proportion of CRE in patients without health care risk factors was low, there was substantial site variation. Continued monitoring of CRE in the community is critical to inform prevention efforts, which are currently primarily targeted at health care settings, and understand populations at risk for CA-CRE infections.
2
,World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Accessed July 29, 2021. https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf.
52
Continued population-based surveillance of resistant gram-negative bacteria will further describe the intersection between health care and community settings and changes in the epidemiology of CA-CRE.Acknowledgments
We thank the Multi-site Gram-negative Surveillance Initiative (MuGSI) Information Technology Team for providing us with the MuGSI Data Management System which was used for the collection of the data analyzed in this manuscript. Additionally, authors wish to acknowledge the following contributors from the Centers for Disease Control and Prevention: Shelley S. Magill for her leadership and direction of the HAIC Program, Gwendolyn Hughes, Susannah McKay and Nicholas Vlachos for their editorial comments, and Alexander J. Kallen for conceptualizing and creating the MuGSI program. The Emerging Infections Program sites would like to acknowledge the following staff: Sarah Satola, GA EIP laboratory; Annastasia Gross, MN EIP.
Appendix. SUPPLEMENTARY MATERIALS
References
Centers for Disease Control and Prevention. Antibiotic resistant threats in the United States, 2019. Accessed January 22, 2021. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.
World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Accessed July 29, 2021. https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf.
- Multidrug-resistant bacteria in the community: trends and lessons learned.Infect Dis Clin North Am. 2016; 30: 377-390
Centers for Disease Control and Prevention. Interim guidance for a public health response to contain novel or targeted multidrug-resistant organisms (MDROs). Updated 2019. Accessed February 25, 2019. https://www.cdc.gov/hai/pdfs/containment/Health-Response-Contain-MDRO-H.pdf.
- The epidemiology of carbapenem-resistant enterobacteriaceae: the impact and evolution of a global menace.J Infect Dis. 2017; 215: S28-S36
Centers for Disease Control and Prevention. Multidrug-resistant organism & clostridioides difficile Infection (MDRO/CDI) module. 2021.
- 507. Epidemiology of community-associated carbapenemase- producing carbapenem-resistant enterobacteriacae identified from the emerging infections program, 2012–2017.in: Presented at Infectious Diseases WEEK (ID WEEK), Washington, DC, October 2-9, 2019. Open Forum Infectious Diseases. Oxford University Press US, 2019 (S246-S)
Centers for Disease Control and Prevention. Healtcare-Assocaited Infections, Multidrug-resistant organisms (HAI MDRO) message mapping guide. Accessed April 16, 2021. https://ndc.services.cdc.gov/mmgpage/healthcare-associated-infections-multidrug-resistant-organisms-hai-mdro-message-mapping-guide/.
- Carbapenem-resistant Enterobacteriaceae in the community: a scoping review.Int J Antimicrob Agents. 2017; 50: 127-134
Centers for Disease Control and Prevention. Multi-site gram-negative surveillance initiative. Accessed March 16, 2021. https://www.cdc.gov/hai/eip/mugsi.html.
United States Census Bureau. 2015 population estimates. Accessed June 27, 2016. http://quickfacts.census.gove/qfd/index.html.
- Performance Standards For Antimicrobial Susceptiblity Testing: Twenty-Third Informational Supplement, M100-S23.Wayne (PA): The Institute, 2013
- Querying automated antibiotic susceptibility testing instruments: a novel population-based active surveillance method for multidrug-resistant gram-negative bacilli.Infect Control Hospital Epidemiol. 2014; 35: 336-341
Centers for Disease Control and Prevention. HAIC Viz Multi-site gram-negative surveillance initiative, carbapenen-resistant enterobacterales. Accessed September 14, 2021. https://www.cdc.gov/hai/eip/haicviz.html.
- Utility of the chronic disease score and charlson comorbidity index as comorbidity measures for use in epidemiologic studies of antibiotic-resistant organisms.Am J Epidemiol. 2005; 161: 483-493
- Comorbidity risk-adjustment measures were developed and validated for studies of antibiotic-resistant infections.J Clin Epidemiol. 2006; 59: 1266-1273
Centers for Disease Control and Prevention. Urinary tract infectins (catheter-associated urinary tract infections [CAUTI] and non-catheter-associated urinary tract infections [UTI]) events. Accessed November 1, 2018. https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf.
- Carbapenem-nonsusceptible Acinetobacter baumannii, 8 US metropolitan areas, 2012–2015.Emerg Infect Dis. 2018; 24: 727
- Simple SAS macros for the calculation of exact binomial and Poisson confidence limits.Comput Biol Med. 1992; 22: 351-361
SAS Institute. Scores for linear rank and one-way ANOVA Tests, Wilcoxon Scores. Accessed January 2, 2019. https://support.sas.com/documentation/cdl/en/statug/63033/HTML/default/viewer.htm#statug_npar1way_a0000000200.htm#statug.npar1way.npar1med.
- New delhi metallo-beta-lactamase-producing enterobacteriaceae, United States.Emerg Infect Dis. 2013; 19: 870-878
- Phenotypic and genotypic characterization of enterobacteriaceae producing oxacillinase-48-like carbapenemases, United States.Emerg Infect Dis. 2018; 24: 700-709
- Evaluation of phenotypic screening methods to detect metallo-beta-lactamase production in Pseudomonas aeruginosa.in: American Society for Microbiology 115th General Meeting. 2015
- Development and validation of a clinical laboratory improvement amendments-compliant multiplex real-time PCR assay for detection of mcr genes.Microb Drug Resist. 2019; 25: 991-996
- Development and application of QuAISAR-H: A bioinformatics pipeline for short read sequences of health care-associated pathogens.in: ASM Conference on Rapid Applied Microbial Next Generation Sequencing and Bioinformatic Pipelines, Tyson Falls2022 (VA2018)
- Identification of acquired antimicrobial resistance genes.J Antimicrob Chemother. 2012; 67: 2640-2644
- ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes.Antimicrob Agents Chemother. 2014; 58: 212-220
- Validating the AMRFinder tool and resistance gene database by using antimicrobial resistance genotype-phenotype correlations in a collection of isolates.Antimicrob Agents Chemother. 2019; 63 (:e00483-19): e00483-19
Seemann T. Tseemann/mlst Github 2020.
- mlstdbNet – distributed multi-locus sequence typing (MLST) databases.BMC Bioinf. 2004; 5: 86
- Statewide surveillance of carbapenem-resistant enterobacteriaceae in Michigan.Infect Control Hospital Epidemiol. 2014; 35: 342-349
- Demographic and infection characteristics of patients with carbapenem-resistant Enterobacteriaceae in a community hospital: development of a bedside clinical score for risk assessment.Am J Infect Control. 2016; 44: 134-137
- Rising rates of carbapenem-resistant enterobacteriaceae in community hospitals: a mixed-methods review of epidemiology and microbiology practices in a network of community hospitals in the southeastern United States.Infect Control Hospital Epidemiol. 2014; 35: 978-983
- Community-acquired lower urinary tract infections: Etiology, antimicrobial resistance, and treatment results in female patients.J Global Infect Dis. 2018; 10: 129
- Clinical practice guidelines for the antibiotic treatment of community-acquired urinary tract infections.Infect Chemother. 2018; 50: 67-100
- International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.Clin Infect Dis. 2011; 52: e103-e120
- Diagnosis and treatment of urinary tract infections across age groups.Am J Obstet Gynecol. 2018; 219: 40-51
- The etiology and management of recurrent urinary tract infections in postmenopausal women.J Climacter. 2019; 22: 242-249
- Socioeconomic factors explain racial disparities in invasive community-associated methicillin-resistant Staphylococcus aureus disease rates.Clin Infect Dis. 2017; 64: 597-604
- Racial and ethnic disparities in health care–associated Clostridium difficile infections in the United States: State of the science.Am J Infect Control. 2016; 44: 91-96
- Association between socioeconomic status and incidence of community-associated clostridioides difficile infection — United States, 2014-2015.Clin Infect Dis. 2021; 73: 722-725
- Risk factors assocaited with carbapenemase-producting carbapenem-resistant enterobactereriaceae positive cultures in a cohort of US veterans.Clin Infect Dis. 2021; 73: 1370-1378
- Janelle Alexander Kallen Tom de Man Brandi Limbago Maroya Walters Alison Halpin, Notes from the field New Delhi metallo-beta-lactamase-producing carbapenem-resistant enterobacteriaceae identified in patients without known health care risk factors- colorado, 2014-2016.Morbidity Mortality Weekly Rep. 2016; 65: 1414-1415
Centers for Disease Control and Prevention. Antibiotic resistance and patient safety portal: carbapenem-resistant enterobacterales. Accessed January 7, 2022. https://arpsp.cdc.gov/profile/arln/cre.
- Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012-2013.J Am Med Associat. 2015; 314: 1479-1487
- Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort.Clin Ther. 2012; 34: 1314-1323
- The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide.Clin Microbiol Infect. 2014; 20: 821-830
- Improved phenotype-based definition for identifying carbapenemase producers among carbapenem-resistant Enterobacteriaceae.Emerg Infect Dis. 2015; 21: 1611
- Performance of Vitek 2 for antimicrobial susceptibility testing of Enterobacteriaceae with Vitek 2 (2009 FDA) and 2014 CLSI breakpoints.J Clin Microbiol. 2015; 53 (816-2): 816-823
- Performance evaluation of three automated identification systems in detecting carbapenem-resistant Enterobacteriaceae.Ann Clin Microbiol Antimicro. 2016; 15: 40
- Comparison of BD phoenix, vitek 2, and MicroScan automated systems for detection and inference of mechanisms responsible for carbapenem resistance in Enterobacteriaceae.J Clin Microbiol. 2010; 48: 2999-3002
- Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe.Clin Microbiol Infect. 2012; 18: 413-431
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Published online: July 27, 2022
Footnotes
Funding/support: The Health Care-Associated Infections Community Interface's Multi-Site Gram-negative Surveillance Initiative of the Emerging Infections Program is supported through the CDC's cooperative agreement, CDC-RFA-CK17-1701.
Conflict of Interest: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Included authors have nothing to disclose.
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