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The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

ObjectiveThe 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.MethodsDuring 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 Escherichia coli or Klebsiella pneumoniae/oxytoca 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.ResultsWe 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 E. coli. 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 blaCTX-M gene. Among ESBL-producing E. coli isolates, 52 (54%) were ST131; 44% of these cases were community associated.ConclusionsThe 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.

Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community.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 collected3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing.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.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: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.Funding: NoneDisclosures: None

Background: Certain nursing home (NH) resident care tasks have a higher risk for multidrug-resistant organisms (MDRO) transfer to healthcare personnel (HCP), which can result in transmission to residents if HCPs fail to perform recommended infection prevention practices. However, data on HCP-resident interactions are limited and do not account for intrafacility practice variation. Understanding differences in interactions, by HCP role and unit, is important for informing MDRO prevention strategies in NHs. Methods: In 2019, we conducted serial intercept interviews; each HCP was interviewed 6–7 times for the duration of a unit’s dayshift at 20 NHs in 7 states. The next day, staff on a second unit within the facility were interviewed during the dayshift. HCP on 38 units were interviewed to identify healthcare personnel (HCP)–resident care patterns. All unit staff were eligible for interviews, including certified nursing assistants (CNAs), nurses, physical or occupational therapists, physicians, midlevel practitioners, and respiratory therapists. HCP were asked to list which residents they had cared for (within resident rooms or common areas) since the prior interview. Respondents selected from 14 care tasks. We classified units into 1 of 4 types: long-term, mixed, short stay or rehabilitation, or ventilator or skilled nursing. Interactions were classified based on the risk of HCP contamination after task performance. We compared proportions of interactions associated with each HCP role and performed clustered linear regression to determine the effect of unit type and HCP role on the number of unique task types performed per interaction. Results: Intercept-interviews described 7,050 interactions and 13,843 care tasks. Except in ventilator or skilled nursing units, CNAs have the greatest proportion of care interactions (interfacility range, 50%–60%) (Fig. 1). In ventilator and skilled nursing units, interactions are evenly shared between CNAs and nurses (43% and 47%, respectively). On average, CNAs in ventilator and skilled nursing units perform the most unique task types (2.5 task types per interaction, Fig. 2) compared to other unit types (P < .05). Compared to CNAs, most other HCP types had significantly fewer task types (0.6–1.4 task types per interaction, P < .001). Across all facilities, 45.6% of interactions included tasks that were higher-risk for HCP contamination (eg, transferring, wound and device care, Fig. 3). Conclusions: Focusing infection prevention education efforts on CNAs may be most efficient for preventing MDRO transmission within NH because CNAs have the most HCP–resident interactions and complete more tasks per visit. Studies of HCP-resident interactions are critical to improving understanding of transmission mechanisms as well as target MDRO prevention interventions.Funding: Centers for Disease Control and Prevention (grant no. U01CK000555-01-00)Disclosures: Scott Fridkin, consulting fee, vaccine industry (spouse)

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 (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

The convergence of hypervirulence and multidrug resistance in Klebsiella pneumoniae is a significant concern. Here, we report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a U.S. surveillance collection of carbapenem-resistant (CR) K. pneumoniae isolates. We identified one hypermucoviscous isolate, which carried a gene encoding the KPC-3 carbapenemase, among numerous resistance genes. The strain further exhibited colistin heteroresistance undetected by diagnostics. This convergence of diverse resistance mechanisms and increased virulence underscores the need for enhanced K. pneumoniae surveillance.

Background. Clostridium difficile infection (CDI) incidence in hospitalized children has increased over the past decade and disease has been reported in the community. Therefore, population surveillance that includes nonhospitalized cases is important to accurately estimate the burden of CDI in children. We describe the epidemiology of CDI in the pediatric population of Monroe County, New York. Methods. Active, laboratory, and population-based surveillance for CDI has been ongoing in Monroe County through the Emerging Infections Program of the Centers for Disease Control and Prevention since 2010. Infants less than 12 months of age are excluded. Results. In 2010, the incidence of CDI in the pediatric population was 33.8 per 100 000 population, which increased to 45.8 in 2011and remained stable in 2012. Seventy-one percent of the CDI cases were communityassociated, 60% had an underlying medical condition, and 71% received antibiotics before their illness. The North American pulsed-field gel electrophoresis type 1 (NAP1) epidemic strain was identified in 27% of cultured stool specimens. Conclusions. Clostridium difficile infection has emerged as a disease affecting children in both the community and hospital settings, with a higher proportion of community illness in our population. The majority of children with CDI had chronic underlying conditions and prior antibiotic exposure. To prevent CDI in this population, the judicious use of antibiotics, especially in the outpatient setting, may be the best strategy. Further population-based studies are warranted to determine preventable risk factors for CDI in the pediatric population.

Background Pseudomonas aeruginosa is intrinsically resistant to many commonly used antimicrobials and carbapenems are often required to treat infections. We describe the epidemiology and crude incidence of carbapenem-resistant P. aeruginosa(CRPA) in the EIP catchment area. Methods From August 1, 2016 through July 31, 2017, we conducted laboratory- and population-based surveillance for CRPA in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. We defined an incident 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. A random sample of isolates was screened at CDC for carbapenemases using the modified carbapenem inactivation method (mCIM) and real-time PCR. Results During the 12-month period, we identified 3,042 incident cases among 2,154 patients. The crude incidence rate was 21.2 (95% CI, 20.4–21.9) per 100,000 persons and varied by site (range: 7.7 in Oregon to 31.1 in Maryland). The median age of patients was 64 years (range: Conclusion The burden of CRPA varied by EIP site. Most cases occurred in persons with healthcare exposures and underlying conditions. The majority of isolates were susceptible to at least one first-line antimicrobial. Carbapenemase producers were rare; a more specific phenotypic definition would greatly facilitate surveillance for these isolates. Disclosures All authors: No reported disclosures.

Background Carbapenemase-producing (CP-) carbapenem-resistant Enterobacteriaceae (CRE) have been almost exclusively linked to extensive healthcare exposure and are of significant concern due to limited treatment options and potential for plasmid-mediated spread of resistance. We report on CP-CRE in community-dwelling individuals. Methods We used 2012–2017 active, laboratory and population-based surveillance data for CRE from CDC’s Emerging Infections Program sites (9 sites by 2017). Cases were the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. from a normally sterile body specimen or urine in a surveillance site resident meeting a CRE phenotype (figure) in a 30 day period. Epidemiologic data were obtained from chart review. Cases were community-associated (CA) if not isolated after the first three days of a hospital stay; without inpatient healthcare, dialysis, or surgery in the year prior; and without indwelling medical devices within two days prior to culture. A convenience sample of isolates was tested at CDC by real-time PCR to detect blaKPC, blaNDM, blaOXA-48-like, blaVIM, or blaIMP. Results Of 4023 CRE cases, 699 (17%) were CA, from which 297 isolates were tested; 20 (7%) were CP-CRE, from 18 patients (2 had repeat isolation of the same gene/species). The median age was 68 years (range: 33–91), and 14 (78%) were female. Patients were from 7 sites (range: 1–4/site). Their CP-CRE (10 blaKPC, 6 blaNDM, and 2 blaOXA-48-like) were from three species (10 K. pneumoniae, 6 E. coli, 2 E. cloacae) and isolated from urine (n = 16) and blood (n = 2). Among those with CP-CRE from urine, 12 (75%) had clinical diagnoses of urinary tract infections and the rest had no infection documented. Overall, 7 (39%) were admitted to a hospital within 30 days of culture; none died during hospitalization. Most (n = 13; 72%) had underlying medical comorbidities, most commonly urinary tract abnormalities (n = 5; 28%) and diabetes mellitus (n = 5; 28%). Three (17%) had international travel within two months prior to culture. Conclusion CA CP-CRE were found in most surveillance sites but are rare, occurring primarily in older patients with underlying medical conditions. Patient interviews are planned to determine whether CA CP-CRE may be associated with distant or undocumented healthcare exposures. Disclosures All authors: No reported disclosures.

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.

Background Increases in the C. difficile infection (CDI) incidence, severity and mortality were reported in the early 2000s due to the emergence of the NAP1/027 strain. We evaluated the trends in incidence, mortality, hospitalization, and the prevalence of NAP1/027 strain in Monroe County, New York. Methods We conducted population and laboratory-based surveillance for CDI from 2011 to 2016 as part of the CDC Emerging Infections Program. An incident CDI case is defined as a positive C. difficile stool specimen from a resident of the county aged >1 year with no positive test in the prior 8 weeks. All the laboratories in our catchment area used nucleic acid amplification for diagnosis starting in 2011 as part of single or 2-step algorithm. A convenience sample of specimens were cultured and underwent molecular characterization. Mortality data was obtained via vital statistics databases and medical chart abstraction. Hospitalization within 2 days before to 7 days of diagnosis was collected. Results We identified 9189 incident CDI cases between 2011 and 2016. The CDI incidence decreased from 241 in 2011 to 175 cases per 100,000 persons in 2016, with the largest decrease among older adults aged ≥85 years. Similarly, the 30-day mortality rates decreased, with the largest decrease among persons aged ≥85 years: from 310 cases to 169 cases per 100,000 population (Figure 1). The percentage of isolates due to NAP1/027 decreased from 20.3% in 2011 to 6.5% in 2016. There was no decrease in the proportion of cases that died within 7 (range: 2% to 3%) and 30 days (range: 7% to 8%) and no decrease in the proportion of patients hospitalized after their CDI diagnosis (range: 34% to 40%). These findings are similar in persons aged ≥85 years. Conclusion From 2011 to 2016, the CDI incidence and mortality decreased concurrently with a decrease in the percentage of infections due to the NAP1/027 strain. Although NAP1/027 is known to be associated with more severe outcomes, we did not observe a reduction in the proportion of cases that died or the proportion of cases that were hospitalized. Figure 1. Incidence and Mortality Rates of CDI Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Background.Long-term care facility (LTCF) residents are at increased risk of Clostridium difficile infection (CDI). However, little is known about the incidence, recurrence, and severity of CDI in LTCFs or the extent to which acute care exposure contributes to CDI in LTCFs. We describe the epidemiology of CDI in a cohort of LTCF residents in Monroe County, New York, where recent estimates suggest a CDI incidence in hospitals of 9.2 cases per 10,000 patient-days.Design.Population-based surveillance study.Setting.Monroe County, New York.Patients.LTCF residents with onset of CDI while in the LTCF or less than 4 calendar-days after hospital admission from the LTCF from January 1 through December 31, 2010.Methods.We conducted surveillance for CDI in residents of 33 LTCFs. A CDI case was defined as a stool specimen positive for C. difficile obtained from a patient without a C. difficile-positive specimen in the previous 8 weeks; recurrence was defined as a stool specimen positive for C. difficile obtained between 2 and 8 weeks after the last C. difficile-positive stool specimen.Results.There were 425 LTCF-onset cases and 184 recurrences, which yielded an incidence of 2.3 cases per 10,000 resident-days (interquartile range [IQR], 1.2–3.3) and a recurrence rate of 1.0 case per 10,000 resident-days (IQR, 0.3–1.4). The cases occurred in 394 LTCF residents, and 52% of these residents developed CDI within 4 weeks after hospital discharge. Hospitalization for CDI occurred in 70 cases (16%). Of those cases that involved hospitalization for CDI, 70% were severe CDI, and 23% ended in death within 30 days after hospital admission.Conclusion.CDI incidence in Monroe County LTCFs is one-fourth the incidence among hospitalized patients. Approximately 50% of LTCF-onset cases occurred more than 4 weeks after hospital discharge, which emphasizes that prevention of CDI transmission should go beyond acute care settings.

 For each incident CDI case, (defined as positive C. difficile test in a resident of the county with no positive test in the prior 8 weeks), trained staff abstracted from the medical records data including demographic and clinical characteristics, exposure to antibiotic and acute care in the 12 weeks prior to CDI and hospitalization within 7 days of CDI. Recurrent cases were defined as patients with a positive C. difficile test within 2-8 weeks of initial positive test. Review of hospital onset cases was limited to 1:10 sampling.