Background We investigated hospitalized carbapenem-resistant Enterobacterales (CRE) and extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) cases with and without COVID-19, as identified through Emerging Infections Program surveillance in 10 sites from 2020 to 2022.Methods We defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K oxytoca, K pneumoniae, or K variicola resistant to any carbapenem. We defined an ESBL-E case as the first isolation of E coli, K pneumoniae, or K oxytoca resistant to any third-generation cephalosporin and nonresistant to all carbapenems tested. Specimens were drawn from a normally sterile site or urine among hospitalized residents of the surveillance area in a 30-day period. We defined COVID-19 as a positive SARS-CoV-2 test result (SC2+) within 14 days before CRE or ESBL-E specimen collection and performed multivariable logistic regression analyses.Results Of 1595 CRE and 1866 ESBL-E hospitalized cases, 38 (2.4%) and 60 (3.2%), respectively, had a SC2+. Among these cases, a SC2+ was associated with intensive care unit admission (adjusted odds ratio [aOR], 1.69 [95% CI, 1.14-2.50]; aOR, 1.48 [95% CI, 1.03-2.12]) and 30-day mortality (aOR, 1.79 [95% CI, 1.22-2.64]; aOR, 1.94 [95% CI, 1.39-2.70]).Conclusions CRE and ESBL-E infections among hospitalized patients with preceding COVID-19 were uncommon but had worse outcomes when compared with cases without COVID-19. COVID-19 prevention in patients at risk of CRE and ESBL-E infections is needed, as well as continued infection control measures and antibiotic stewardship for patients with COVID-19. From 2020 to 2022, hospitalized carbapenem-resistant Enterobacterales and extended-spectrum beta-lactamase-producing Enterobacterales cases with preceding COVID-19 were rare but associated with worse outcomes when compared with cases without COVID-19, with significantly higher rates of intensive care unit admission and 30-day mortality, even after adjusting for potential confounders.

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:Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step toward informing better infection prevention and control practices and improving public health response. METHODS:Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1 to December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS:Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS:Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

We conducted surveillance for carbapenem-resistant Enterobacterales (CRE) during 2016-2020 at 10 US sites and extended-spectrum beta-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 ESBLE 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 ES- BL-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: 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 thirdgeneration 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.

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 neededDisclosure: None

Abstract Background Preventing CRE spread is a U.S. public health priority. We described changes in 2016─2020 CRE incidence rates in 7 U.S. sites that conduct population-based CRE surveillance for the Centers for Disease Control and Prevention’s Emerging Infections Program. Methods An incident CRE case from 2016 onwards was defined as the 1st 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 to classify cases as hospital-onset (HO) if the culture was obtained >3 days after hospital admission; healthcare-associated, community-onset (HACO) if the culture was obtained in a non-hospital setting or < 3 days after hospital admission in a person with healthcare exposures in the prior year; and community-associated (CA) if there were no healthcare risk factors. 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 (RR) and 95% confidence intervals (CI). We also repeated the analysis using a pre-2016 CRE surveillance case definition that was more specific for carbapenemase-producing CRE and required carbapenem nonsusceptibility (excluding ertapenem) and third-generation cephalosporin resistance. Results Of 4996 CRE cases, 62% were HACO, 25% 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 (Figure 1). Compared to 2016, the adjusted overall CRE incidence rate declined since 2018, with a decrease of 24% (RR 0.76; 95% CI: 0.70−0.83) in 2020 (Figure 2). HACO and CA CRE rates significantly decreased in 2020, but the HO rate did not. Similar trends were seen using the other case definition, except the decline in CA CRE rate since 2016 was not significant (Figure 3).Figure 1.Crude CRE incidence rates, overall and by epidemiologic class, 2016─2020**Current CRE surveillance case definition (from 2016 onwards) applied to all yearsFigure 2.Adjusted rate ratios with 95% confidence intervals comparing annual 2017-2020 CRE incidence rates to the 2016 CRE incidence rate, using the current surveillance case definition* * Current CRE surveillance case definition (from 2016 onwards) applied to all years starting in 2016Figure 3.Adjusted rate ratios with 95% confidence intervals comparing annual 2017-2020 CRE incidence rates to the 2016 CRE incidence rate, using pre-2016 surveillance case definition* * Pre-2016 CRE surveillance case definition applied to all years starting in 2016 Conclusion Adjusted CRE incidence rates declined from 2016 to 2020 using current and prior case definitions but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support Rebecca Tsay, MPH, CDC: Grant/Research Support

Background We described changes in 20162020 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 20162020 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.

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.

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of blaKPC-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. ABSTRACT Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of blaKPC-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention’s Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of blaKPC-carrying Klebsiella pneumoniae ST258, and clonal expansion of blaKPC-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of blaKPC-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of blaKPC plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions.

Abstract Background Reports have shown increases in carbapenem-resistant Acinetobacter baumannii complex (CRAB) infections during the COVID-19 pandemic. To describe the effect of SARS-CoV-2 (SC2) infection on CRAB infection epidemiology, we analyzed data from the Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) population-based CRAB surveillance in 9 U.S. sites. Methods: In 2020–22, among surveillance-area residents, an incident CRAB case was defined as the 1st isolation of A. baumannii complex resistant to ≥1 carbapenem (excluding ertapenem) from a normally sterile site or urine (or lower respiratory tract or wound, as of 2021) in a 30-day period. We included cases that underwent chart review. Cases with a culture collected ≥3 days after hospitalization were considered hospital-onset (HO); all others were community-onset (CO). Cases with a SC2+ test ≤14 days before the incident CRAB culture were compared to other CRAB cases. Results Of 406 CRAB cases representing 344 patients, 26 (6%) cases in 24 patients were SC2+. SC2+ case-patients were more likely to be female than other CRAB case-patients (58% vs 34%, p=0.02); there were no significant differences in race/ethnicity or age distribution. SC2+ cases were more likely to be obese (42% vs. 23%, p=0.03), have bacteremia (23% vs. 10%, p=0.05), and to have died (39% vs. 16%, p=0.003). SC2+ cases were also more likely to require hospitalization (100% vs. 75%, p=0.005) and have HO CRAB (58% vs 29%, p=0.003). Median hospital length of stay was longer in SC2+ cases (19 days, interquartile range [IQR] 8–30) than in other CRAB cases (14 days, IQR 7–26, p=0.42), but there were no significant differences in the percentages with intensive care unit stays or mechanical ventilation in the 7 days before CRAB culture. Culture sources and infection types in SC2+ cases vs. other CRAB cases are shown in the Table. Conclusion A small minority of CRAB patients were infected with SC2+ in the 14 days before CRAB infection but these patients had epidemiological and clinical features that were distinct from other CRAB patients, including higher mortality. Infection control and clinical measures are needed to protect SC2+ patients from secondary bacterial infection and mitigate poor outcomes in those with SC2 and CRAB infection. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support Rebecca Tsay, MPH, CDC: Grant/Research Support

Abstract Background The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts active laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE), extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E), and carbapenem-resistant Acinetobacter baumannii (CRAB) in 10 U.S. sites. To describe the impact of the COVID-19 pandemic on the epidemiology of these antibiotic-resistant gram-negative bacteria (AR-GNB), we assessed characteristics of AR-GNB patients with and without a prior SARS-CoV-2 positive (SC2+) viral test. Methods In 2020 among EIP catchment-area residents, an incident CRAB or CRE case was defined as the first isolation of A. baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K. oxytoca, K. pneumonia, or K. variicola in a 30-day period resistant to ≥1 carbapenem (excluding ertapenem for CRAB) from a normally sterile site or urine. An incident ESBL-E case was defined as the first isolation of E. coli, K. pneumonia, 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. Patient charts were reviewed. Results Of 3904 AR-GNB cases with data available, 163 (4%) had a prior SC2+ test (85 ESBL-E, 70 CRE, and 8 CRAB). Median time from the most recent SC2+ test to AR-GNB culture date was 20 days (IQR 1–48 days). AR-GNB cases with a SC2+ test versus those without were more likely to be Black, non-Hispanic than another race/ethnicity (31% vs 15%; P< 0.0001), aged ≥65 years (62% vs 52%; P=0.0139), and to have prior healthcare exposures (63% vs 49%; P=0.0003) and indwelling devices (51% vs 28%; P< 0.0001). They were also more likely to have bacteremia (24% vs 11%; P< 0.0001), pneumonia (6% vs 1%; P< 0.0001) and be hospitalized around the time of their AR-GNB culture (67% vs 36%; P< 0.0001); median time from SC2+ test to hospital admission was 0.5 day (IQR 0–29.5 days). Conclusion AR-GNB infections preceded by a SC2+ test were rare but more severe and associated with more healthcare risk factors. This underscores the need for continued infection prevention and control practices and monitoring of these infections during the COVID-19 pandemic. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.Funding: NoneDisclosures: None

Background: Nursing homes (NHs) provide care in a congregate setting for residents at high risk of severe outcomes from SARS-CoV-2 infection. In spring 2020, NHs were implementing new guidance to minimize SARS-CoV-2 spread among residents and staff. Objective: To assess whether telephone and video-based infection control assessment and response (TeleICAR) strategies could efficiently assess NH preparedness and help resolve gaps. Design: We incorporated Centers for Disease Control and Prevention COVID-19 guidance for NH into an assessment tool covering 6 domains: visitor restrictions; health care personnel COVID-19 training; resident education, monitoring, screening, and cohorting; personal protective equipment supply; core infection prevention and control (IPC); and communication to public health. We performed TeleICAR consultations on behalf of health departments. Adherence to each element was documented and recommendations provided to the facility. Setting and Participants: Health department-referred NHs that agreed to TeleICAR consultation. Methods: We assessed overall numbers and proportions of NH that had not implemented each infection control element (gap) and proportion of NH that reported making >= 1 change in practice following the assessment. Results: During April 13 to June 12, 2020, we completed TeleICAR consultations in 629 NHs across 19 states. Overall, 524 (83%) had >= 1 implementation gap identified; the median number of gaps was 2 (interquartile range: 1-4). The domains with the greatest number of facilities with gaps were core IPC practices (428/625; 68%) and COVID-19 education, monitoring, screening, and cohorting of residents (291/620; 47%). Conclusions and Implications: TeleICAR was an alternative to onsite infection control assessments that enabled public health to efficiently reach NHs across the United States early in the COVID-19 pandemic. Assessments identified widespread gaps in core IPC practices that put residents and staff at risk of infection. TeleICAR is an important strategy that leverages infection control expertise and can be useful in future efforts to improve NH IPC. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of blaKPC predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a serious threat to patient safety due to limited treatment options and propensity to spread in healthcare settings. Using Emerging Infections Program (EIP) data, we describe changes in CRAB incidence and epidemiology. Methods: During January 2012 to December 2018, 9 sites (Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee) participated in active laboratory- and population-based surveillance. An incident case was defined as the first isolation of A. baumannii complex, in a 30-day period, resistant to ≥1 carbapenem (excluding ertapenem) from a normally sterile site or urine of a surveillance area resident. Cases were considered hospital-onset (HO) if the culture was collected >3 days after hospital admission; all others were community-onset (CO). Cases were classified as device-associated (DA) if the patient had 1 or more medical devices (ie, urinary catheter, central venous catheter (CVC), endotracheal/nasotracheal tube, tracheostomy, or another indwelling device) present in the 2 days prior to culture collection. Temporal trends were estimated using generalized linear models adjusted for age, race, sex, and EIP site. Results: Overall, 984 incident CRAB cases were identified, representing 849 patients. Among these patients, 291 (34%) were women, 510 (61%) were nonwhite, and the median age was 62 years (mean, 59; range, 0–102). Among the cases, 226 (23%) were HO; 758 (77%) were CO; and 793 (81%) were DA. Overall incidence rates in 2012 and 2018 were 1.58 (95% CI, 1.29–1.90) and 0.60 (95% CI, 0.40–0.67) per 100,000 population, respectively. There was a 15% annual decrease in incidence (adjusted rate ratio [aRR] 0.85; 95% CI: 0.82-0.88, P < .0001). Decreases were observed among sterile site (aRR 0.88; 95% CI, 0.84–0.93) and urine cases (aRR 0.83; 95% CI, 0.80–0.87). Annual decreases occurred for HO cases (aRR, 0.78; 95% CI, 0.73–0.85) and CO cases (aRR, 0.86; 95% CI, 0.83–0.9). The DA cases decreased 16% annually overall (aRR, 0.84; 95% CI, 0.81–0.88). Decreases among cases in patients with CVC (aRR, 0.85; 95% CI, 0.80–0.90) and urinary catheters (aRR, 0.84; 95% CI, 0.80–0.88) were smaller than what was seen in patients with other indwelling devices (aRR, 0.81; 95% CI, 0.77–0.86). Discussion: Overall, from 2012 to 2018, the incidence of CRAB decreased >60%. Decreases were observed in all case groups, regardless of source, infection onset location, or types of devices. Smaller annual decreases in rates of CO-CRAB than HO-CRAB suggest that there may be opportunities to accelerate prevention outside the hospital to further reduce the incidence of these difficult-to-treat infections.Funding: NoneDisclosures: 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 blaKPC, blaNDM, and blaOXA-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 blaNDM, and CZA-R without blaNDM. Results: Among 606 confirmed CRE tested with CZA, 33 (5.4%) were CZA-R. Of the CZA-R isolates, 16 (48.5%) harbored a blaNDM gene, of which 2 coharbored blaNDM and blaOXA-48-like genes; 9 (27.3%) harbored only a blaKPC gene. Of the 17 CZA-R isolates without blaNDM, all were MBL screen negative. CZA-R due to blaNDM were more frequently community-associated (43.8%) than CZA-S or CZA-R without blaNDM (11.0% and 5.9%, respectively); a higher percentage of CZA-R cases due to blaNDM also had recent international travel (25%) compared to the other groups (1.8% and 5.9%, respectively). CZA-R without blaNDM were more susceptible to MEV (76%), IMR (71%), PLZ (88%), and ERV (65%) compared to CZA-R due to blaNDM (19%, 6%, 56%, and 44%, respectively). Conclusions: The emergence of CZA-R isolates without blaNDM are concerning; however, these isolates are more susceptible to newer antimicrobials than those with blaNDM. In addition to high rates of resistance to newer antimicrobials, isolates with blaNDM are more frequently community-associated than other CRE. This underscores the need for more aggressive measures to stop the spread of CRE.Funding: NoneDisclosures: None

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of healthcare-associated infections with limited treatment options and high mortality. To describe risk factors for mortality, we evaluated characteristics associated with 30-day mortality in patients with CRAB identified through the Emerging Infections Program (EIP). Methods: From January 2012 through December 2017, 8 EIP sites (CO, GA, MD, MN, NM, NY, OR, TN) participated in active, laboratory-, and population-based surveillance for CRAB. An incident case was defined as patient’s first isolation in a 30-day period of A. baumannii complex from sterile sites or urine with resistance to ≥1 carbapenem (excluding ertapenem). Medical records were abstracted. Patients were matched to state vital records to assess mortality within 30 days of incident culture collection. We developed 2 multivariable logistic regression models (1 for sterile site cases and 1 for urine cases) to evaluate characteristics associated with 30-day mortality. Results: We identified 744 patients contributing 863 cases, of which 185 of 863 cases (21.4%) died within 30 days of culture, including 113 of 257 cases (44.0%) isolated from a sterile site and 72 of 606 cases (11.9%) isolated from urine. Among 628 hospitalized cases, death occurred in 159 cases (25.3%). Among hospitalized fatal cases, death occurred after hospital discharge in 27 of 57 urine cases (47.4%) and 21 of 102 cases from sterile sites (20.6%). Among sterile site cases, female sex, intensive care unit (ICU) stay after culture, location in a healthcare facility, including a long-term care facility (LTCF), 3 days before culture, and diagnosis of septic shock were associated with increased odds of death in the model (Fig. 1). In urine cases, age 40–54 or ≥75 years, ICU stay after culture, presence of an indwelling device other than a urinary catheter or central line (eg, endotracheal tube), location in a LTCF 3 days before culture, diagnosis of septic shock, and Charlson comorbidity score ≥3 were associated with increased odds of mortality (Fig. 2). Conclusion: Overall 30-day mortality was high among patients with CRAB, including patients with CRAB isolated from urine. A substantial fraction of mortality occurred after discharge, especially among patients with urine cases. Although there were some differences in characteristics associated with mortality in patients with CRAB isolated from sterile sites versus urine, LTCF exposure and severe illness were associated with mortality in both patient groups. CRAB was associated with major mortality in these patients with evidence of healthcare experience and complex illness. More work is needed to determine whether prevention of CRAB infections would improve outcomes.Funding: NoneDisclosures: None

Abstract Background Pseudomonas aeruginosa is intrinsically resistant to many commonly used antimicrobials, and carbapenems are often required to treat infections. We describe the crude incidence, epidemiology, and molecular characteristics of carbapenem-resistant P. aeruginosa (CRPA) in the EIP catchment area. Methods From August 1, 2016 through July 31, 2018, we conducted laboratory- and population-based surveillance for CRPA in selected areas in eight sites. We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period. Patient charts were reviewed. Analysis excluded cystic fibrosis patients. A random sample of isolates was collected. Real-time PCR to detect carbapenemase genes and whole-genome sequencing are in progress. Results We identified 4,209 cases in 3373 patients. The annual incidence was 14.50 (95% CI, 14.07–14.94) per 100,000 persons and varied among sites from 4.89 in OR to 25.21 in NY. The median age of patients was 66 years (range: < 1–101), 42.1% were female, and nearly all (97.5%) had an underlying condition. Most cases were identified from urine (42.8%) and lower respiratory tract (35.7%) cultures. Nearly all (93.3%) occurred in patients with inpatient healthcare facility stay, surgery, chronic dialysis, or indwelling devices in the prior year; death occurred in 7.2%. Among 937 isolates tested, 847 (90.4%) underwent PCR; six (0.7%) harbored a carbapenemase, from four sites (CO, MD, NY, and OR): blaVIM (3), blaKPC (2), and blaIMP (1). Of 612 (65.3%) isolates sequenced, the most common ST types were ST235 (9.2%) and ST298 (4.9%). Conclusion Carbapenemases were rarely the cause of carbapenem resistance but were found at EIP sites with high and low CRPA incidence. The emergence of mobile carbapenemases in P. aeruginosa has the potential to increase the incidence of CRPA. Increased detection and early response to carbapenemase-producing CRPA is key to prevent further emergence. Disclosures All authors: No reported disclosures.

Abstract Background Carbapenem-nonsusceptible Acinetobacter spp. (CNAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are recognized causes of severe and difficult to treat healthcare-associated infections. This study estimated and compared the incidence of CNAB and CRPA among patients admitted to US acute care hospitals in 2012–2017. Methods We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of over 300 hospitals submitting data to the Premier Healthcare Database and Cerner Health Facts in 2012–2017. We included clinical cultures from any body site yielding Acinetobacter spp./P. aeruginosa non-susceptible/resistant to imipenem, meropenem, or doripenem. Cultures collected on days 1–3 of hospitalization were considered community-onset (CO) and cultures from later were hospital-onset (HO). Duplicate isolates identified within 14 days of an incident culture and surveillance cultures were excluded. For each year, a raking procedure generated weights to extrapolate the sample estimate to match the American Hospital Association distributions based on US census division, hospital bed capacity, teaching status, and urban designation. We compared estimated rates in 2017 vs. 2012 using weighted multivariable logistic regression adjusting for hospital characteristics and hospital-level clustering. Results In 2017, the estimated rates of HO and CO CNAB rates were 0.77 and 1.39/10,000 discharges, and HO and CO CRPA rates were 3.14 and 6.57, respectively. Compared with 2017, rates of HO CNAB decreased 49% (Odds Ratio (OR) 0.51; 95% CI: 0.34–0.75) and rates of CO CNAB decreased 29% (OR 0.71; 95% CI: 0.54–0.92). For CRPA, the incidence of HO decreased (OR 0.66; CI: 0.49–0.88) with no change in CO rates (OR 0.93; CI: 0.79–1.11). Assessment of cultures from sterile sites alone showed similar results, but they did not reach statistical significance, Figure 1. Conclusion We estimate significant national decreases in the rates of HO and CO CNAB, and HO CRPA. Risk factors and effective interventions to reduce CO CRPA might differ from CNAB and HO CRPA. Additional prevention strategies are needed to address CO CRPA. Disclosures All authors: No reported disclosures.