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We conducted surveillance for carbapenem-resistant Enterobacterales (CRE) during 2016–2020 at 10 US sites and extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) during 2019–2020 at 6 US sites. Among 159 CRE cases in children (median age 5 years), CRE was isolated from urine for 131 (82.4%) and blood from 20 (12.6%). Annual CRE incidence rate (cases/100,000 population) was 0.47–0.87. Among 207 ESBL-E cases in children (median age 6 years), ESBL-E was isolated from urine of 196 (94.7%) and blood of 8 (3.9%). Annual ESBL-E incidence rate was 26.5 in 2019 and 19.63 in 2020. CRE and ESBL-E rates were >2-fold higher among infants than other age groups. Most CRE and ESBL-E cases were healthcare-associated community-onset (68 [43.0%] for CRE vs. 40 [23.7%] for ESBL-E) or community-associated (43 [27.2%] for CRE vs. 109 [64.5%] for ESBL-E). Programs to detect, prevent, and treat multidrug-resistant infections must include pediatric populations (particularly the youngest) and outpatient settings.

Background: Infections lead to high mortality among patients on chronic dialysis; knowledge of multi-drug resistant infections is limited. The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) in 10 U.S. sites and carbapenem-resistant Acinetobacter baumannii (CRAB) in 9 U.S. sites. We investigated clinical characteristics, healthcare exposures, and outcomes of CRE and CRAB cases in persons on chronic dialysis from 2016-2021. Methods: Among EIP catchment-area residents on chronic dialysis, we defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes (formerly Enterobacter aerogenes), Klebsiella oxytoca, Klebsiella pneumoniae, or Klebsiella variicola resistant to any carbapenem, from a normally sterile site or urine in a 30-day period. A CRAB case was defined as the first isolation of Acinetobacter baumannii complex resistant to any carbapenem (excluding ertapenem), from a normally sterile site or urine (or lower respiratory tract or wound since 2021) in a 30-day period. Medical records were reviewed. A case was considered colonized if the case culture had no associated infection type or colonization was documented in the medical record. Descriptive analyses, including analyses stratified by pathogen, were conducted. Results: Among 426 cases, 314 were CRE, and 112 were CRAB; most cases were male (235, 55.2%), Black (229, 53.8%), and 51-80 years old (320, 75.1%) (Table). An infection was associated with 363 (85.2%) case cultures; bloodstream infections (148; 40.8%), urinary tract infections (134; 36.9%), and pneumonia (17; 4.7%) were the most frequent. Overall, most cases had documented healthcare exposures (excluding outpatient dialysis) in the year before incident specimen collection, including: 366 (85.9%) hospitalizations, 235 (55.2%) surgeries, 209 (49.1%) long-term care facility stays, 54 (12.7%) long-term acute care facility stays. Additionally, 125 (29.3%) had an intensive care unit admission within the 7 days before incident specimen collection. Compared to CRE cases, a higher proportion of CRAB cases (a) had a long-term care facility stay (82/112 [73.2%] versus 127/314 [40.5%], P<.0001) or hospitalization (103/112 [92%] versus 263/314 [83.8%], P = .03) within the preceding year and (b) died within 30 days of incident specimen collection (40/112 [35.7%] versus 64/314 [20.4%], P = .001). Discussion: Among CRE and CRAB cases in persons on chronic dialysis, healthcare exposures were common, and mortality was high. Additional efforts to better describe the burden of these organisms and associated risk factors in the dialysis population are needed for tailoring infection prevention strategies to this vulnerable.

Background: The Centers for Disease Control and Prevention’s Emerging Infections Program conducts active laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) and extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E). To better understand the U.S. epidemiology of these organisms among children, we determined the incidence of pediatric CRE and ESBL-E cases and described their clinical characteristics. Methods: Surveillance was conducted among children <18 years of age for CRE from 2016–2020 in 10 sites, and for ESBL-E from 2019–2020 in 6 sites. Among catchment-area residents, an incident CRE case was defined as the first isolation of Escherichia coli , Enterobacter cloacae complex, Klebsiella aerogenes , K. oxytoca , or K. pneumoniae in a 30-day period resistant to ≥1 carbapenem from a normally sterile site or urine. An incident ESBL-E case was defined as the first isolation of E. coli, K. pneumoniae , or K. oxytoca in a 30-day period resistant to any third-generation cephalosporin and non-resistant to all carbapenems from a normally sterile site or urine. Case records were reviewed. Results: Among 159 CRE cases, 131 (82.9%) were isolated from urine and 19 (12.0%) from blood; median age was 5 years (IQR 1–10) and 94 (59.1%) were female. Combined CRE incidence rate per 100,000 population by year ranged from 0.47 to 0.87. Among 207 ESBL-E cases, 160 (94.7%) were isolated from urine and 6 (3.6%) from blood; median age was 6 years (IQR 2–15) and 165 (79.7%) were female. Annual ESBL incidence rate per 100,000 population was 26.5 in 2019 and 19.63 in 2020. Incidence rates of CRE and ESBL-E were >2-fold higher in infants (children <1 year) than other age groups. Among those with data available, CRE cases were more likely than ESBL-E cases to have underlying conditions (99/158 [62.7%] versus 59/169 [34.9%], P<0.0001), prior healthcare exposures (74/158 [46.8%] versus 38/169 [22.5%], P<0.0001), and be hospitalized for any reason around time of their culture collection (75/158 [47.5%] versus 38/169 [22.5%], P<0.0001); median duration of admission was 18 days [IQR 3–103] for CRE versus 10 days [IQR 4–43] for ESBL-E. Urinary tract infection was the most frequent infection for CRE (89/158 [56.3%]) and ESBL-E (125/169 [74.0%]) cases. Conclusion: CRE infections occurred less frequently than ESBL-infections in U.S. children but were more often associated with healthcare risk factors and hospitalization. Infants had highest incidence of CRE and ESBL-E. Continued surveillance, infection prevention and control efforts, and antibiotic stewardship outside and within pediatric care are needed Disclosure: None

The incidence of infections from extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites. During October-December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of or resistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates. We identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were . Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a gene. Among ESBL-producing isolates, 52 (54%) were ST131; 44% of these cases were community associated. The burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.

Background: Extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-Ent) have emerged as a significant antimicrobial-resistance threat in the community in recent years. To better characterize ESBL-Ent in the community, we examined associations between community-associated ESBL-Ent incidence rates and area-based socioeconomic status (SES) characteristics. Methods: Cases were identified through active, laboratory- and population-based surveillance for ESBL-Ent in 3 Emerging Infections Program (EIP) sites (New Mexico, New York, and Tennessee) from October through December 2017. We defined a case as first isolation of Escherichia coli , Klebsiella pneumoniae , or K. oxytoca from a normally sterile body specimen or urine in a surveillance-site resident, with resistance to ≥1 extended-spectrum cephalosporin and nonresistance to all carbapenems tested. Epidemiologic data were abstracted from medical records. Cases were considered community associated if no significant prior healthcare exposures (ie, inpatient healthcare facility stay, surgery, chronic dialysis, indwelling devices, or external catheters) were documented. Case residential addresses were geocoded and linked to US Census Bureau data to obtain census-tract level SES measures. Census tracts were dichotomized by the percentage living in rural areas (0–49% or ≥50%); census tracts were stratified into quartiles for all other characteristics. Incidence rate ratios (IRR) for each measure, controlling for EIP site, were calculated using Poisson regression. Results: Among 742 ESBL-Ent cases with medical records available, 355 (47.1%) were community associated; of these, 327 case addresses (92.1%) were successfully geocoded. The combined annualized 2017 incidence rate for community-associated ESBL-Ent was 83.2 cases per 100,000 persons. The highest incidence of community-associated ESBL-Ent was seen in census tracts with the lowest median income (IRR, 1.4; 95% CI, 1.0–2.0) and with the highest percentages of persons without health insurance (IRR, 1.3; 95% CI, 1.0–1.7), with <12th-grade education (IRR, 1.5; 95% CI, 1.1–2.1), living in urban areas (IRR, 1.5; 95% CI, 1.0–2.2), foreign-born (IRR, 1.4; 95% CI, 1.0–2.0), or speaking limited English (IRR, 1.5; 95% CI, 1.1–2.0). There were no significant differences across quartiles for population density, income inequality, the percentage of the population living below poverty, or the percentage of households with crowding (>1 occupant or room). Conclusions: Social determinants of health, such as coverage for healthcare, appear to be important contributors to community-associated ESBL-Ent transmission. Higher rates in areas with more foreign-born persons and persons with limited English proficiency suggest a role for recent travel in importation and spread in specific communities. These findings provide additional information about the epidemiology of ESBL-Ent in the community and have potential implications for control efforts. Funding: None Disclosures: None

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a major public health problem. Ceftazidime-avibactam (CZA) is a treatment option for CRE approved in 2015; however, it does not have activity against isolates with metallo-β-lactamases (MBLs). Emerging resistance to CZA is a cause for concern. Our objective was to describe the microbiologic and epidemiologic characteristics of CZA-resistant (CZA-R) CRE. Methods: From 2015 to 2017, 9 states participated in laboratory- and population-based surveillance for carbapenem-resistant Escherichia coli , Klebsiella pneumoniae , K. oxytoca , K. aerogenes , and Enterobacter cloacae complex isolates from a normally sterile site or urine. A convenience sample of isolates from this surveillance were sent to the CDC for antimicrobial susceptibility testing (AST) using reference broth microdilution (BMD) including an MBL screen, species confirmation with MALDI-TOF, and real-time PCR to detect bla KPC, bla NDM, and bla OXA-48–like genes. Additional AST by BMD was performed on CZA-R isolates using meropenem-vaborbactam (MEV), imipenem-relebactam (IMR), plazomicin (PLZ), and eravacycline (ERV). Epidemiologic data were obtained from a medical record review. Community-associated cases were defined as having no healthcare exposures in the year prior to culture, no devices in place 2 days prior to culture, and culture collected before calendar day 3 after hospital admission. Data were analyzed in 3 groups: CRE that were CZA-susceptible (CZA-S), CZA-R that were due to bla NDM, and CZA-R without bla NDM. Results: Among 606 confirmed CRE tested with CZA, 33 (5.4%) were CZA-R. Of the CZA-R isolates, 16 (48.5%) harbored a bla NDM gene, of which 2 coharbored bla NDM and bla OXA-48-like genes; 9 (27.3%) harbored only a bla KPC gene. Of the 17 CZA-R isolates without bla NDM, all were MBL screen negative. CZA-R due to bla NDM were more frequently community-associated (43.8%) than CZA-S or CZA-R without bla NDM (11.0% and 5.9%, respectively); a higher percentage of CZA-R cases due to bla NDM also had recent international travel (25%) compared to the other groups (1.8% and 5.9%, respectively). CZA-R without bla NDM were more susceptible to MEV (76%), IMR (71%), PLZ (88%), and ERV (65%) compared to CZA-R due to bla NDM (19%, 6%, 56%, and 44%, respectively). Conclusions: The emergence of CZA-R isolates without bla NDM are concerning; however, these isolates are more susceptible to newer antimicrobials than those with bla NDM. In addition to high rates of resistance to newer antimicrobials, isolates with bla NDM are more frequently community-associated than other CRE. This underscores the need for more aggressive measures to stop the spread of CRE. Funding: None Disclosures: None

Background: Extended-spectrum β-lactamase–producing (ESBL) Escherichia coli infection incidence is increasing in the United States. This increase may be due to the rapid expansion of ST131, which is now the predominant ESBL strain globally, often multidrug resistant, and has been shown to establish longer-term human colonization than other E. coli strains. We assessed potential risk factors that distinguish ST131 from other ESBL E. coli . Methods: From October 1 through December 31, 2017, 5 CDC Emerging Infections Program (EIP) sites pilot tested active, laboratory-based surveillance in selected counties in Colorado, Georgia, New Mexico, New York, and Tennessee. An E. coli case was defined as the first isolation from a normally sterile body site or urine in a surveillance area resident in a 30-day period resistant to 1 extended-spectrum cephalosporin antibiotic and susceptible or intermediate to all carbapenem antibiotics tested. Epidemiologic data were collected from case patients’ medical records. A convenience sample of 117 E. coli isolates from case patients was collected. All isolates underwent whole-genome sequencing to determine sequence type and the presence of ESBL genes. We compared ST131 E. coli epidemiology to other ESBL E. coli . Results: Among 117 E. coli isolates , 97 (83%) were ESBL producers. Of the 97 ESBL E. coli , 52 (54%) were ST131 (range, for 4 EIP sites submitting >10 isolates: 25%–88%; P < .001). Other common STs were ST38 (12%) and ST10 (5%). ST131 infections were more likely to be healthcare-associated than non-ST131 (56% vs 36%; P = .05) (Table 1). Among specific prior healthcare exposures, only residence in long-term care facilities (LTCFs) in the year before culture was more common among ST131 case patients (29% vs 11%; P = .03). Notably, 85% of ESBL E. coli collected from LTCF residents were ST131. ST131 E. coli were more common among patients with underlying medical conditions (81% vs 60%; P = .02). No statistically significant difference by sex, race, age, culture source, location of culture collection, and frequency of antibiotic use in the prior 30 days was observed. Conclusions: The prevalence of ST131 E. coli varies regionally. The association between ST131 and LTCFs suggests that these may be particularly important settings for ST131 acquisition. Improving infection control measures that limit ESBL transmission in these settings and preventing dissemination in facilities receiving patients from LTCFs may be necessary to contain ST131 spread. Funding: None Disclosures: None

Abstract Background We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. Methods An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). Results Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70–.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67–.84]) and CA (0.75 [.61–.92]) but not for HO CRE. Conclusions Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings. From 2016 to 2020, the adjusted overall incidence rate of carbapenem-resistant Enterobacterales (CRE) across 7 US sites declined; however, changes over time varied by epidemiologic class.