Background: Carbapenemase genes in carbapenem-resistant Enterobacterales (CP-CRE) may be transmitted between patients and bacteria. Reported rates of carbapenemase genes vary widely, and it is unclear whether having a carbapenemase gene portends worse outcomes given that all patients with CRE infections have limited treatment options. Methods: Using active population- and laboratory-based active surveillance data collected by the US CDC-funded Georgia Emerging Infections Program from 2011 to 2020, we assessed the frequency of carbapenemase genes in a convenience sample of CRE isolates using whole-genome sequencing (WGS), and we investigated risk factors for carbapenemase positivity. Only the first isolate per patient in a 30-day period was included. We compared characteristics of patients with CP-CRE and non–CP-CRE. Using multivariable log binomial regression, we assessed the association of carbapenemase gene positivity and 90-day mortality. Results: Of 284 CRE isolates, 171 isolates (60.2%) possessed a carbapenemase gene (Table 1), and KPC-3 was the most common carbapenemase gene (80.7%), with only 7 isolates possessing NDM (Table 2). No isolates possessed >1 carbapenemase gene, and most isolates were from urine (82.4%) (Table 1). Carbapenemase gene positivity was associated with lower age, male sex, black race, infection with Klebsiella pneumoniae, polymicrobial infection, having an indwelling medical device, receiving chronic dialysis, and prior stay in a long-term acute-care hospital, long-term care facility, and/or prior hospitalization in the last year. The 90-day mortality rates were similar in patients with non–CP-CRE and CP-CRE: 24.8% versus 25.7% (P = .86). In multivariable analysis, carbapenemase gene presence was not associated with 90-day mortality (adjusted risk ratio, 0.82; 95% CI, 0.50–1.35) when adjusting for CCI, infection with Klebsiella pneumoniae, and chronic dialysis use. Conclusions: The frequency of CP-CRE among CRE was high in this study, but unlike prior studies, the 90-day mortality rates wer similar in patients with CP-CRE compared to non–CP-CRE. Our results provide novel associations (eg, lower age, male sex, infection with Klebsiella pneumoniae, and indwelling medical devices) that infection preventionists could use to target high-risk patients for screening or isolation prior to CP-CRE detection.

Disclosure: None

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

Stepwise non-pharmaceutical interventions and health system changes implemented as part of the COVID-19 response have had implications on the incidence, diagnosis, and reporting of other communicable diseases. Here, we established the impact of the COVID-19 outbreak response on gastrointestinal (GI) infection trends using routinely collected surveillance data from six national English laboratory, outbreak, and syndromic surveillance systems using key dates of governmental policy to assign phases for comparison between pandemic and historic data. Following decreases across all indicators during the first lockdown (March–May 2020), bacterial and parasitic pathogens associated with foodborne or environmental transmission routes recovered rapidly between June and September 2020, while those associated with travel and/or person-to-person transmission remained lower than expected for 2021. High out-of-season norovirus activity was observed with the easing of lockdown measures between June and October 2021, with this trend reflected in laboratory and outbreak systems and syndromic surveillance indicators. Above expected increases in emergency department (ED) attendances may have reflected changes in health-seeking behaviour and provision. Differential reductions across specific GI pathogens are indicative of the underlying routes of transmission. These results provide further insight into the drivers for transmission, which can help inform control measures for GI infections.

A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose–response and dietary modelling studies indicate dairy products, bread, hens’ eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for ‘real-world’ cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D’s importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

Background: Due to limited therapeutic options and potential for spread, carbapenem-resistant Enterobacteriaceae (CRE)-producing New Delhi metallo-β-lactamases (NDMs) are a public health priority. We investigated the epidemiology of NDM-producing CRE reported to the CDC to clarify its distribution and relative prevalence. Methods: The CDC’s Antibiotic Resistance Laboratory Network supports molecular testing of CRE for 5 carbapenemases nationally. Although KPC is the most common carbapenemase in the United States, non-KPC carbapenemases are a growing concern. We analyzed CRE with any of 4 non-KPC plasmid-mediated carbapenemases (NDM, VIM, IMP, or OXA-48 type) isolated from specimens collected from January 1, 2017, through June 30, 2019; only a patient’s first isolate per organism–carbapenemase combination was included. We excluded isolates from specimen sources associated with colonization screening (eg, perirectal). We compared the proportion of NDM-producing CRE to all non-KPC–producing CP-CRE between period A (January to June 2018) and period B (January to June 2019). Health departments and the CDC collected additional exposure and molecular information in selected states to better describe current NDM-producing CRE epidemiology. Results: Overall, 47 states reported 1,013 non–KPC-producing CP-CRE (range/state, 1–109 isolates; median, 11 isolates); 46 states reported 631 NDM-producing CRE (range/state, 1–84; median, 6). NDM-producing CRE increased quarterly from the third quarter of 2018 through the second quarter of 2019; CP-CRE isolates with other non-KPC carbapenemases remained stable (Fig. 1). In period A, 124 of 216 emerging CP-CRE had NDM (57.1%), compared with 255 of 359 emerging CP-CRE (71.0%) during period B (P = .1179). Among NDM-producing CRE, the proportion of Enterobacter spp increased from 10.5% in 2018 to 18.4% in 2019 (P = .0467) (Fig. 2). In total, 18 states reported more NDM-producing CRE in the first 6 months of 2019 than in all of 2018. Connecticut, Ohio, and Oregon were among states that conducted detailed investigations; these 3 states identified 24 NDM-producing CRE isolates from 23 patients in period B. Overall, 5 (21.7%) of 22 patients with history available traveled internationally ≤12 months prior to culture; 17 (73.9%) acquired NDM-producing CRE domestically. Among 15 isolates sequenced, 8 (53.3%) carried NDM-5 (6 E. coli, 1 Enterobacter spp and 1 Klebsiella spp) and 7 (46.7%) carried NDM-1 (6 Enterobacter spp and 1 Klebsiella spp). Species were diverse; no single strain type was shared by >2 isolates. Conclusions: Detection of NDM-producing CRE has increased across the AR Lab Network. Among states with detailed information available, domestic acquisition was common, and no single variant or strain predominated. Aggressive public health response and further understanding of current US NDM-CRE epidemiology are needed to prevent further spread.

Disclosures: None

Funding: None

Background: In April 2019, the Georgia Department of Public Health (DPH) initiated whole-genome sequencing (WGS) on NDM-producing Enterobacteriaceae identified since January 2018. The WGS data analyzed at CDC identified related Klebsiella pneumoniae isolates with hypervirulence markers from 2 patients. Carbapenemase-producing hypervirulent K. pneumoniae (CP-hvKP) are rarely reported in the United States, but they can to cause serious, highly resistant, invasive infections. We conducted an investigation to identify cases and prevent spread. Methods: We defined a case as NDM-producing K. pneumoniae with ≥4 hypervirulence markers identified by WGS, isolated from any specimen source from a Georgia patient. We reviewed the case patient’s medical history to identify potentially affected facilities. We also performed PCR-based colonization screening and retrospective and prospective laboratory-based surveillance. Finally, we assessed facility infection control practices. Results: Overall, 7 cases from 3 case patients (A, B, and C) were identified (Fig. 1). The index case specimen was collected from case-patient A at ventilator-capable skilled nursing facility 1 (vSNF1) in May 2018. Case-patient A had been hospitalized for 1 month in India before transfer to the United States. Case-patient B’s initial isolate was collected in January 2019 on admission to vSNF2 from a critical access hospital (CAH). The CAH laboratory retrospectively identified case-patient C, who overlapped with case-patient B at the CAH in October 2018. The CAH and the vSNF2 are geographically distant from vSNF1. Case-patients B and C had no known epidemiologic links to case-patient A. Colonization screening occurred at vSNF1 in May 2018, following detection of NDM-producing K. pneumoniae from case-patient A ∼1 year before determining that the isolate carried hypervirulence markers. Among 30 residents screened, 1 had NDM and several had other carbapenemases. Subsequent screening did not identify additional NDM. Colonization screening of 112 vSNF2 residents and 13 CAH patients in 2019 did not reveal additional case patients; case-patient B resided at vSNF2 at the time of screening and remained colonized. At all 3 facilities, the DPH assessed infection control practices, issued recommendations to resolve lapses, and monitored implementation. The DPH sequenced all 27 Georgia NDM–K. pneumoniae isolates identified since January 2018; all were different multilocus sequence types from the CP-hvKP isolates, and none possessed hypervirulence markers. Conclusions: We hypothesize that CP-hvKP was imported by a patient hospitalized in India and spread to 3 Georgia facilities in 2 distinct geographic regions through indirect patient transfers. Although a response to contain NDM at vSNF1 in 2018 likely limited CP-hvKP transmission, WGS identified hvKP and established the relatedness of isolates from distinct regions, thereby directing the DPH’s additional containment activities to halt transmission.

Funding: None

Disclosures: None

Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent a significant antibiotic resistance threat, in part because carbapenemase genes can spread on mobile genetic elements. Here, we describe the molecular epidemiology and outcomes of patients with CRE bacteriuria from the same city in a nonoutbreak setting. Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in Atlanta. We studied a cohort of patients with CRE (resistant to all tested third-generation cephalosporins and ≥1 carbapenem, excluding ertapenem) first identified in urine, and not in a prior or simultaneous sterile site, between 2012 and 2015. Whole-genome sequencing (WGS) was performed on a convenience sample. We obtained epidemiologic and outcome data through chart review and Georgia Vital Statistics records (90-day mortality). Using WGS, we created a core-genome alignment-based phylogenetic tree of the Klebsiella pneumoniae isolates and calculated the SNP difference between each sample. Using SAS version 9.4 software, we performed the Fisher exact test and univariable odds ratios (OR) with 95% CI to compare patient isolates with and without a carbapenemase gene. Results: Among 81 patients included, the median age was 68 (IQR, 57–74) years, and most were female (58%), black (60%), and resided in a long-term care facility 4 days prior to culture isolation (53%). Organisms isolated were K. pneumoniae (84%), Escherichia coli (7%), Enterobacter cloacae (7%), and Klebsiella oxytoca (1%). WGS identified at least 1 β-lactamase gene in 91% of the isolates; 85% contained a carbapenemase gene, the most frequent of which was blaKPC-3 (94%). Patients with CRE containing a carbapenemase gene were more likely to be black (OR, 3.7; 95% CI, 1.0–13.8) and to have K. pneumoniae (OR, 8.9; 95% CI, 2.2–35.0). Using a core-genome alignment of 3,708 genes (~63% of the complete genome), we identified a median of 67 (IQR, 23–3,881) SNP differences between each K. pneumoniae isolate. A phylogenetic tree identified clustering around carbapenemase gene and multilocus sequence type (84% were ST 258) but not based on referring laboratory or county of residence (Fig. 1). Although 7% of patients developed an invasive CRE infection within 1 year and 21% died within 90 days, having a carbapenemase gene was not associated with these outcomes. Conclusions: Molecular sequencing of a convenience sample of CRE bacteriuria support K. pneumoniae ST258 harboring blaKPC-3 being distributed throughout the Atlanta area, across the healthcare continuum. Overall mortality was high in this population, but the presence of carbapenemase genes was not associated with worse outcomes.

Funding: None

Disclosures: None

Disclosures: None

Funding: None

Background: Chlorhexidine bathing reduces bacterial skin colonization and prevents infections in specific patient populations. As chlorhexidine use becomes more widespread, concerns about bacterial tolerance to chlorhexidine have increased; however, testing for chlorhexidine minimum inhibitory concentrations (MICs) is challenging. We adapted a broth microdilution (BMD) method to determine whether chlorhexidine MICs changed over time among 4 important healthcare-associated pathogens. Methods: Antibiotic-resistant bacterial isolates (Staphylococcus aureus from 2005 to 2019 and Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex from 2011 to 2019) were collected through Emerging Infections Program surveillance in 2 sites (Georgia and Tennessee) or through public health reporting in 1 site (Orange County, California). A convenience sample of isolates were collected from facilities with varying amounts of chlorhexidine use. We performed BMD testing using laboratory-developed panels with chlorhexidine digluconate concentrations ranging from 0.125 to 64 μg/mL. After successfully establishing reproducibility with quality control organisms, 3 laboratories performed MIC testing. For each organism, epidemiological cutoff values (ECVs) were established using ECOFFinder. Results: Among 538 isolates tested (129 S. aureus, 158 E. coli, 142 K. pneumoniae, and 109 E. cloacae complex), S. aureus, E. coli, K. pneumoniae, and E. cloacae complex ECVs were 8, 4, 64, and 64 µg/mL, respectively (Table 1). Moreover, 14 isolates had an MIC above the ECV (12 E. coli and 2 E. cloacae complex). The MIC50 of each species is reported over time (Table 2). Conclusions: Using an adapted BMD method, we found that chlorhexidine MICs did not increase over time among a limited sample of S. aureus, E. coli, K. pneumoniae, and E. cloacae complex isolates. Although these results are reassuring, continued surveillance for elevated chlorhexidine MICs in isolates from patients with well-characterized chlorhexidine exposure is needed as chlorhexidine use increases.

Funding: None

Disclosures: None

The COVID-19 pandemic is exerting major pressures on society, health and social care services and science. Understanding the progression and current impact of the pandemic is fundamental to planning, management and mitigation of future impact on the population. Surveillance is the core function of any public health system, and a multi-component surveillance system for COVID-19 is essential to understand the burden across the different strata of any health system and the population. Many countries and public health bodies utilise ‘syndromic surveillance’ (using real-time, often non-specific symptom/preliminary diagnosis information collected during routine healthcare provision) to supplement public health surveillance programmes. The current COVID-19 pandemic has revealed a series of unprecedented challenges to syndromic surveillance including: the impact of media reporting during early stages of the pandemic; changes in healthcare-seeking behaviour resulting from government guidance on social distancing and accessing healthcare services; and changes in clinical coding and patient management systems. These have impacted on the presentation of syndromic outputs, with changes in denominators creating challenges for the interpretation of surveillance data. Monitoring changes in healthcare utilisation is key to interpreting COVID-19 surveillance data, which can then be used to better understand the impact of the pandemic on the population. Syndromic surveillance systems have had to adapt to encompass these changes, whilst also innovating by taking opportunities to work with data providers to establish new data feeds and develop new COVID-19 indicators. These developments are supporting the current public health response to COVID-19, and will also be instrumental in the continued and future fight against the disease.

Chickenpox is caused by varicella-zoster-virus (VZV) and is highly contagious. Immigration detention settings are a high-risk environment for primary VZV transmission, with large, rapidly-changing populations in close quarters, and higher susceptibility among non-UK-born individuals. During outbreaks, operational challenges occur in detention settings because of high-turnover and the potential need to implement population movement restriction for prolonged periods. Between December 2017 and February 2018, four cases of chickenpox were notified amongst 799 detainees in an immigration removal centre (IRC). Microbiological investigations included case confirmation by vesicular fluid polymerase chain reaction, and VZV serology for susceptibility testing. Control measures involved movement restrictions, isolation of cases, quarantining and cohorting of non-immune contacts and extending VZV immunity testing to the wider detainee population to support outbreak management. Immunity was tested for 301/532 (57%) detainees, of whom 24 (8%) were non-immune. The level of non-immunity was lower than expected based on the existing literature on VZV seroprevalence in detained populations in England. Serology results identified non-immune contacts who could be cohorted and, due to the lack of isolation capacity, allowed the placement of cases with immune detainees. The widespread immunity testing of all detainees was proving challenging to sustain because it required significant resources and was having a severe impact on operational capacity and the ability to maintain core business activities at the IRC. Therefore, mathematical modelling was used to assess the impact of scaling back mass immunity testing. Modelling demonstrated that interrupting testing posed a risk of one additional case compared to continuing with testing. As such, the decision was made to stop testing, and the outbreak was successfully controlled without excessive strain on resources. Operational challenges generated learning for future outbreaks, with implications for a local and national policy on IRC staff occupational health requirements, and proposed reception screening of detainees for VZV immunity.

Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.

In the present work, the microstructure and mechanical properties of Gilsocarbon graphite have been characterized over a range of length-scales. Optical imaging, combined with 3D X-ray computed tomography and 3D high-resolution tomography based on focus ion beam milling has been adopted for microstructural characterization. A range of small-scale mechanical testing approaches are applied including an in situ micro-cantilever technique based in a Dualbeam workstation. It was found that pores ranging in size from nanometers to tens of micrometers in diameter are present which modify the deformation and fracture characteristics of the material. This multi-scale mechanical testing approach revealed the significant change of mechanical properties, for example flexural strength, of this graphite over the length-scale from a micrometer to tens of centimeters. Such differences emphasize why input parameters to numerical models have to be undertaken at the appropriate length-scale to allow predictions of the deformation, fracture and the stochastic features of the strength of the graphite with the required confidence. Finally, the results from a multi-scale model demonstrated that these data derived from the micro-scale tests can be extrapolated, with high confidence, to large components with realistic dimensions.