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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 (

Objective:To describe the epidemiology of carbapenem-resistant Enterobacterales (CRE) bacteriuria and to determine whether urinary catheters increase the risk of subsequent CRE bacteremia.Design:Using active population- and laboratory-based surveillance we described a cohort of patients with incident CRE bacteriuria and identified risk factors for developing CRE bacteremia within 1 year.Setting:The study was conducted among the 8 counties of Georgia Health District 3 (HD3) in Atlanta, Georgia.Patients:Residents of HD3 with CRE first identified in urine between 2012 and 2017.Results:We identified 464 patients with CRE bacteriuria (mean yearly incidence, 1.96 cases per 100,000 population). Of 425 with chart review, most had a urinary catheter (56%), and many resided in long-term care facilities (48%), had a Charlson comorbidity index >3 (38%) or a decubitus ulcer (37%). 21 patients (5%) developed CRE bacteremia with the same organism within 1 year. Risk factors for subsequent bacteremia included presence of a urinary catheter (odds ratio [OR], 8.0; 95% confidence interval [CI], 1.8–34.9), central venous catheter (OR, 4.3; 95% CI, 1.7–10.6) or another indwelling device (OR, 4.3; 95% CI, 1.6–11.4), urine culture obtained as an inpatient (OR, 5.7; 95% CI, 1.3–25.9), and being in the ICU in the week prior to urine culture (OR, 2.9; 95% CI, 1.1–7.8). In a multivariable analysis, urinary catheter increased the risk of CRE bacteremia (OR, 5.3; 95% CI, 1.2–23.6).Conclusions:In patients with CRE bacteriuria, urinary catheters increase the risk of CRE bacteremia. Future interventions should aim to reduce inappropriate insertion and early removal of urinary catheters.

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.

Colistin is a last-resort antibiotic for multidrug-resistant gram-negative infections. Recently, the ninth allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of clinical isolates collected between 2012-2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of mcr-9 positive and negative CRE cases were then compared. Among 235 sequenced CRE genomes, thirteen (6%) were found to harbor mcr-9, all of which were Enterobacter cloacae complex. The median MIC, rates of heteroresistance and inducible resistance to colistin were similar between mcr-9 positive and negative isolates. However, rates of resistance were higher among mcr-9 positive isolates across most antibiotic classes. All cases had significant healthcare exposures. The 90-day mortality was similarly high in both mcr-9 positive (31%) and negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geo-temporal clustering. mcr-9 positive isolates had a significantly higher number of median [range] AMR genes (16 [4-22] vs. 6 [2-15]; p mcr-9 negative isolates. Pan genome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes but continued genomic surveillance to monitor for emergence of AMR genes is warranted.

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

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July-October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcare facility inpatient stays in the prior year. Genes encoding carbapenemases were identified in 3 (2.3%) of 129 isolates tested. The burden of CRPA was high at facilities under surveillance, but carbapenemase-producing CRPA were rare.

Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy., Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States.

In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012-2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A. baumannii cultured from urine or normally sterile sites and to describe the demographic and clinical characteristics of patients and cases. We identified 621 cases in 537 patients; crude annual incidence was 1.2 cases/100,000 persons. Among 598 cases for which complete data were available, 528 (88.3%) occurred among patients with exposure to a healthcare facility during the preceding year; 506 (84.6%) patients had an indwelling device. Although incidence was lower than for other healthcare-associated pathogens, cases were associated with substantial illness and death.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (

Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) often results from multiple mechanisms, creating unique phenotypic patterns of resistance including retaining susceptibility to traditional antipseudomonal β-lactams: cefepime (FEP), ceftazidime (CAZ) and piperacillin-tazobactam (TZP). Outcomes of patients with CRPA susceptible to FEP, CAZ and TZP are unclear. Methods The Georgia Emerging Infections Programed performs active, population-based surveillance for CRPA (minimum inhibitory concentration [MIC] ≥ 8 µg/mL for doripenem, imipenem or meropenem) isolated from sterile sites, urine, lower respiratory tracts and wounds in metropolitan Atlanta. We created a retrospective cohort of adults without cystic fibrosis with their first episode of CRPA while hospitalized or hospitalized within 1 week, from 8/2016 – 7/2018. We compared patients with CRPA that remained susceptible to FEP, CAZ and TZP (“susceptible CRPA”) to those that were not (“resistant CRPA”) including multivariable logistic regression for 30-day mortality. Results Among 643 patients, 638 had susceptibility results available for FEP, CAZ or TZP. 60% were male, median age was 65 years, and median Charlson comorbidity index was 2 (Table 1). Most (66%) resided in a hospital or long-term care facility 4 days prior to culture. The most common source was urine (38%). Non-susceptibility to multiple antibiotic classes was common: 523 (81%) for 3 classes and 214 (33%) for 5 classes (Table 2). 220 (34%) patients had susceptible CRPA and compared to patients with resistant CRPA, were more likely to have lived in a private residence, have a community-associated infection, and less likely to be in the ICU previously (Table 1). Patients with susceptible CRPA had a similar crude 30-day mortality (16% vs 12%, p = 0.15) to those with resistant CRPA, but in a multivariable analysis had an increased 30-day mortality (OR 1.9; 95% CI 1.1–3.2). Table 1 (Part 1/2): Characteristics and outcomes of hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) in metropolitan Atlanta, stratified by antipseudomonal β-lactam susceptibility Table 1 (Part 2/2): Characteristics and outcomes of hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) in metropolitan Atlanta, stratified by antipseudomonal β-lactam susceptibility Table 2: Antibacterial susceptibility results for hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa in metropolitan Atlanta Conclusion Over 1/3 of hospitalized patients with CRPA retained susceptibility to other antipseudomonal β-lactams, but had an increased mortality compared to CRPA resistant to other β-lactams. Further research into mechanisms of resistance or antibiotics received might help explain this unexpected finding. Disclosures Jessica Howard-Anderson, MD, Antibacterial Resistance Leadership Group (ARLG) (Other Financial or Material Support, The ARLG fellowship provides salary support for ID fellowship and mentored research training)

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 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

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

Background: Carbapenem-resistant Enterobacteriaceae (CRE), particularly carbapenemase-producing (CP) CRE, pose a major public health threat. In 2016, the phenotypic definition of CRE expanded to include ertapenem resistance to improve sensitivity for detecting CP-CRE. We compared characteristics of CRE resistant to ertapenem only (CRE-EO) to CRE resistant to ≥1 other carbapenem (CRE-O). Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in metropolitan Atlanta. CRE cases were defined as any Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, Enterobacter cloacae complex, or Enterobacter aerogenes resistant to ≥1 carbapenem by the clinical laboratory and isolated from urine or a sterile site between 2016 and 2018. Data were extracted from retrospective chart review and 90-day mortality from Georgia vital statistics for 2016–2017. Polymerase chain reaction (PCR) for carbapenemase genes was performed on a convenience sample of isolates by the CDC or Georgia Public Health Laboratory. We compared characteristics of CRE-EO cases to CRE-O cases using χ2 tests or t tests. Results: Among 927 CRE isolates, 553 (60%) were CRE-EO. CRE-EO were less frequently isolated from blood (5% vs 12%; P < .01) and less commonly K. pneumoniae (21% vs 58%; P < .01) than CRE-O. CRE-EO cases were more often women (65% vs 50%; P < .01), had a lower Charlson comorbidity index (mean ± SD, 2.4±2.3 vs 3.0±2.6; P < .01), and were less commonly at a long-term care facility (24% vs 31%) or hospital (15% vs 21%; P < .01) in the 4 days prior to the CRE culture. CRE-EO were more susceptible to all antibiotics tested at the clinical laboratory (P < .01) except for tigecycline (P = 1.0) (Table 1). Of the 300 (32%) isolates tested for carbapenemase genes, 98 (33%) were positive (7% CRE-EO vs 62% CRE-O; P < .01). Of the CP isolates, we identified blaKPC in 93 cases (95%), blaNDM in 3 cases (3%), blaOXA-48-like in 2 cases (2%). CRE-EO cases had lower 90-day mortality (13% vs 21%; P < .01). Conclusions: CRE-EO are epidemiologically distinct from CRE-O and are less likely to harbor carbapenemase genes. CRE-EO may require less intensive infection prevention interventions and have more therapeutic options.Funding: NoneDisclosures: None

Background Public health prioritizes addressing social determinants of health to promote health equity. We hypothesized that social determinants of health, including poverty, are associated with racial disparity in the incidence of carbapenem-resistant Enterobacteriaceae (CRE). Methods The Georgia Emerging Infections Program conducted CDC-funded, active population-based CRE surveillance in metropolitan Atlanta (2017 population: 3.9 million) from 2012-2018. CRE cases were defined as Atlanta residents with a urine or normally sterile specimen growing E. coli, Klebsiella spp., or Enterobacter spp. resistant to ≥ 1 carbapenems (excluding ertapenem) and all third generation cephalosporins tested. Poverty, education and insurance levels by census tract of residence were obtained from the US Census Bureau’s 2017 American Community Survey. Race and end-stage renal disease (ESRD) were determined from chart review, and primary care provider (PCP) shortage area was obtained from the Health Resources and Services Administration. Age-adjusted incidence rate ratios were individually calculated using direct age standardization. Covariates were considered for inclusion in a multivariable Poisson regression model for the expected rate of CRE. Results Adjusting for age, CRE incidence was three times higher in blacks than whites. Higher CRE incidence was also observed among cases assigned > 40% below poverty level, > 15% below high school education, > 10% uninsured, and in a PCP shortage area (Table 1). CRE incidence was 58 times higher among ESRD cases than non-ESRD cases. In the multivariable model (Figure 1) addition of education, poverty or ESRD (p< 0.001), but not PCP access (p = 0.61) and insurance status (p=0.19), significantly reduced the racial difference in CRE incidence compared to race and age alone. Although controlling for age and either education, poverty level or ESRD reduced CRE among blacks, CRE incidence in blacks remained double that of whites. Figure 1. Comparison of race CRE incidence rate ratio adjusting for age alone (red line) to adjusting for age and individual social determinants (blue bars)” Table 1. Social Determinants Distribution and Age-Adjusted CRE Incidence Rate Ratio (N = 378) Conclusion Poverty level, ESRD and education only partially account for the racial differences seen in CRE incidence. While ESRD suggests a possible biologic component, persistent racial differences indicate the need for targeted public health interventions to address social determinants of health. Disclosures All Authors: No reported disclosures

Background Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat with potential for rapid spread. We evaluated the role of Medicare patient movement between facilities to model the spread of CRE within a region. Methods Through population-based CRE surveillance in the 8-county Atlanta (GA) metropolitan area, all Escherichia coli, Enterobacter spp., or Klebsiella spp. resistant to ≥1 carbapenem were reported from residents. CRE was attributed to a facility based on timing of culture and facility exposures. Centrality metrics were calculated from 2016 Medicare data and compared to CRE-transfer derived centrality metrics by Spearman correlation. Results During 2016, 283 incident CRE cases with concurrent or prior year facility stays were identified; cases were attributed mostly to acute care hospitals (ACHs; 141, 50%) and skilled nursing facilities (SNFs; 113, 40%), and less frequently to long-term acute care hospitals (LTACHs; 29, 10%). Attribution was widespread, originating at 17 of 20 ACHs (85%), 7 of 8 (88%) LTACHs, but only 35 of 65 (54%) SNFs. Betweenness of Medicare patient transfers strongly correlated with betweenness of CRE case-transfer data in ACHs (r = 0.75; P < .01) and LTACHs (r = 0.77; P = .03), but not in SNFs (r = 0.02; P = 0.85). We noted 6 SNFs with high CRE-derived betweenness but low Medicare-derived betweenness. Conclusions CRE infections originate from almost all ACHs and half of SNFs. We identified a subset of SNFs central to the CRE transfer network but not the Medicare transfer network; other factors may explain CRE patient movement in these facilities.

Background Patients with carbapenem-resistant Enterobacteriaceae (CRE) bacteriuria have better outcomes than patients with an invasive CRE infection, but patients with bacteriuria may subsequently develop an invasive infection (“progression”). We sought to evaluate risk factors, particularly urinary catheters, for progression from CRE bacteriuria to an invasive CRE infection within one year. Methods We used population-based active surveillance data from the Georgia Emerging Infections Program to identify patients in metropolitan Atlanta with CRE in urine, but not in a concomitant or previous sterile site between August 1, 2011 and July 31, 2017. CRE was defined as an isolate resistant to tested third-generation cephalosporins and a minimum inhibitory concentration of ≥4 µg/mL for meropenem, doripenem or imipenem. We then assessed if these patients developed an invasive CRE infection (positive sterile site culture) with the same organism between one day and one year later. Demographics, culture site, comorbidities, and risk factors were obtained by chart review. Univariable analyses and multivariable logistic regression with progression as the outcome were performed in SAS 9.4. Results We identified 551 patients with CRE bacteriuria in 6 years, with an annual incidence of 1.1 cases/100,000 population. Many patients previously resided in long-term care facilities (48%), had a Charlson comorbidity index (CCI) >3 (38%), a central venous catheter (CVC, 34%) or a decubitus ulcer (27%, Table 1). Twenty-five patients (5%) progressed from CRE bacteriuria to an invasive CRE infection within one year (median 34 days). Predictors of progression in univariable analyses included the presence of a urinary catheter (OR 6.4 [95% CI: 1.9–21.6]), decubitus ulcer, CVC or other indwelling device, Klebsiella pneumoniae, black race, CCI >3, and ICU stay after urine culture was obtained (Table 2). In a multivariable analysis, urinary catheter (OR 4.6 [95% CI: 1.3–16.1]) predicted progression as well as K. pneumoniae, CCI >3 and CVC. Conclusion Progression from CRE bacteriuria to an invasive CRE infection is rare but clinically significant and is associated with urinary catheters. Future interventions should target urinary catheter removal, where possible, in patients with CRE bacteriuria. Disclosures All authors: No reported disclosures.

Background Patients with end-stage renal disease (ESRD) have higher risks for resistant organisms including carbapenem-resistant Enterobacteriaceae (CRE). To explore the effect of ESRD on CRE, we compared characteristics of CRE cases with and without ESRD in a population-based cohort. Methods The Georgia Emerging Infections Program has performed active laboratory- and population-based surveillance for CRE in metropolitan Atlanta (4.1 million in 2017) since 2012. CRE cases are defined by isolation from a sterile body site or urine of E. coli, K. pneumoniae, K. oxytoca, K. aerogenes, or E. cloacae. From 2012 to 2015, cultures were resistant to all third-generation cephalosporins tested and non-susceptible to ≥1 carbapenem (excluding ertapenem). After 2016, cultures were resistant to ≥1 carbapenems. Epidemiologic data including ESRD were collected via medical chart review. ESRD population data were obtained from the US Renal Data System. Georgia vital records data were used to determine 90-day mortality rates. Prevalence estimates were calculated. Comparisons used a χ 2 test. Results Of 1,511 CRE cases, 136 (9%) were on current chronic dialysis, 128 (94%) of which were on hemodialysis (HD) and 5 (4%) were on peritoneal dialysis. Among CRE cases with HD, 94 (73%) had a catheter and 30 (23%) had an arteriovenous fistula or graft. CRE cases with ESRD were more likely to be male (58% vs. 40%), black (76% vs. 38%), and have diabetes (67% vs. 38%), congestive heart failure (25% vs. 17%), or peripheral arterial disease (12% vs. 4%). CRE cases with ESRD had more hospitalizations within 30 days of the culture date (77% vs. 47%), ICU admissions prior to (29% vs. 7%) or after the culture date (43% vs. 14%) and discharges to LTCFs (35% vs. 15%) after hospitalization. CRE cases with ESRD and bacteremia were more likely to have been hospitalized >3 days before the culture compared with CRE cases with ESRD and positive cultures from other body sites (52% vs. 24%). The 90-day mortality rate per 100,000 population was higher among CRE cases with ESRD (100.9 cases) than without ESRD (1.0 cases). Conclusion Among a population-based cohort of patients with CRE infections, ESRD comprised ~10% but had markedly mortality, suggesting that future interventions should target ESRD. Disclosures All authors: No reported disclosures.

In this study, a 5.9-inch foldable active-matrix organic light emitting diode (AMOLED) display was developed. A folding test was performed repeatedly. The display survived the folding test (100,000 folds) with a curvature radius of 2 mm. To protect an organic light emitting diode (OLED) against moisture, inorganic passivation layers are provided on the upper and lower sides of the flexible display. Using our transfer technology, high density passivation layers can be obtained. The measured water vapor transmission rate of the layer is 7 × 10−6 g/m2⋅day or less, which improves OLED reliability. With these techniques, we have developed a book-type display, which is repeatedly foldable like a book, and a tri-fold display including a display area, which is foldable in three.

Colloidal quantum dots (QDs) combined with a graphene charge transducer promise to provide a photoconducting platform with high quantum efficiency and large intrinsic gain, yet compatible with cost-efficient polymer substrates. The response time in these devices is limited, however, and fast switching is only possible by sacrificing the high sensitivity. Furthermore, tuning the QD size toward infrared absorption using conventional organic capping ligands progressively reduces the device performance characteristics. Here we demonstrate methods to couple large QDs (>6 nm in diameter) with organometal halide perovskites, enabling hybrid graphene phototransistor arrays on plastic foils that simultaneously exhibit a specific detectivity of 5 × 1012 Jones and high video-frame-rate performance. PbI2 and CH3NH3I co-mediated ligand exchange in PbS QDs improves surface passivation and facilitates electronic transport, yielding faster charge recovery, whereas PbS QDs embedded into a CH3NH3PbI3 matrix produce spatial...

In this study, white organic electroluminescent devices with microcavity structures were developed. A flexible high-resolution active-matrix organic light-emitting diode display with low power consumption using red, green, blue, and white sub-pixels formed by a color-filter method was fabricated. In addition, a side-roll touch display was developed in combination with a capacitive flexible touch screen.

We discuss the steps for obtaining a curved touch-enabled display by using a c-axis aligned crystalline oxide semiconductor, OLEDs, a flexible-display technology, and a capacitive touch screen. This result is a side-roll display in which the front and side surfaces are a single curved surface with a 4 mm radius.

A folding screen type OLED display was developed (Fig. 1) to demonstrate the application of a flexible display. The display surface can be bent with a curvature radius of 4 mm To protect an OLED against moisture, inorganic passivation layers are provided on the upper and lower sides of the flexible display. Using our transfer technology, dense passivation layers can be obtained The measured water vapor transmission rate of the layer is 7 × 10−6 g/m2.day or less, which improves OLED reliability.

In this study, a 5.9-inch foldable Book-Type AMOLED display was developed. A folding test was performed repeatedly. The display survived the folding test (100,000 folds) with a curvature radius of 2 mm.

In this study, white organic EL devices with microcavity structures were developed. A flexible high-resolution AMOLED display with low power consumption using RGBW sub-pixels formed by a color filter method was fabricated. In addition, side-roll and top-roll panels with bezels that are not viewable from the front were also developed using the flexible AMOLED display.

Background Carbapenem-resistant Enterobacteriacae (CRE) are an urgent US public health threat. CDC reported CRE incidence to be 2.93/100,000 population in 2012–2013 in selected sites but changed the CRE surveillance case definition in 2016 to improve sensitivity for detecting carbapenemase-producing (CP) CRE. We describe CRE epidemiology before and after the change. Methods Eight CDC Emerging Infections Program sites (CO, GA, MD, MN, NM, NY, OR, TN) conducted active, population-based CRE surveillance in selected counties. A case was defined as having an isolate of E. coli, Enterobacter, or Klebsiella meeting a susceptibility phenotype (figure) at a clinical laboratory from urine or a normally sterile body site in a surveillance area resident in a 30-day period. We collected data from medical records and defined cases as community-associated (CA) if no healthcare risk factors were documented. A convenience sample of isolates were tested for carbapenemase genes at CDC by real-time PCR. We calculated incidence rates (per 100,000 population) by using US Census data. Case epidemiology and the proportion of CP-CRE isolates in 2015 versus 2016 were compared. Results In total, 442 incident CRE cases were reported in 2015, and 1,149 cases were reported in 2016. Most isolates were cultured from urine: 87% in 2015 and 92% in 2016 (P < .001). The crude overall pooled mean incidence in 2015 was 2.9 (range by site: 0.45–7.19) and in 2016 was 7.48 (range: 3.13–15.95). The most common CRE genus was Klebsiella (51%) in 2015, and in 2016 was Enterobacter (41%, P < 0.001). Of the subset of CRE isolates tested at CDC, 109/227 (48%) were CP-CRE in 2015 and 109/551 (20%) were CP-CRE in 2016. In 2015, 52/442 (12%) of cases were CA CRE, and in 2016, 267/1,149 (23%) were CA CRE (P < 0.001). In 2016, 3/111 (2.7%) of CA CRE isolates tested were CP-CRE. Conclusion A large increase in reported CRE incidence was observed after the change in the case definition. The new case definition includes a substantially larger number of Enterobacter cases. A decrease in CP-CRE prevalence appears to be driven by an increase in non-CP-CRE cases. Although CP-CRE in the community still appear to be rare, a substantial proportion of phenotypic CRE appear to be CA, and CDC is undertaking efforts to further investigate CA CRE, including CP-CRE. Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

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.

IntroductionPyoderma gangrenosum (PG) is a rare relapsing autoimmuneinflammatory disorder resulting in skin necrosis and ulcera-tion. It can be idiopathic or associated with other conditions.Sterile pustular lesions can occur 24 –48 h following cutane-ous trauma in up to 30 % of patients with PG. Blobnet firstdescribed this process in 1937 that he termed pathergy [1].Lack of surgical awareness and a striking clinical similaritybetween pathergy and wound sepsis make both delayed diag-nosisandfailuretoinitiatecorrecttreatmentlikelytooccur.PGcan be extremely difficult to treat, often requiring systemicimmunosuppression. Recurrent disease is common, but itsrelative rarity means that there is a lack of published evidenceregarding its treatment. None of the commonly used agentshave been formally assessed through a randomized controlledtrial. Many of the commonly used agents are associated withunpleasant and potentially serious side effects. Descriptions ofsurgical site pathergy following arthroplasty surgery are limit-ed. Only six cases following knee arthroplasty [ 2–7]andtwofollowinghiparthroplasty[8,9]haveappearedintheliterature.Only one describes a case with a clear past history of PG [ 8].No reports have described the indication for prophylactic im-munosuppressionagainstpathergy,norwhichpharmacologicalregimen might optimally prevent this while minimizingdelayed wound healing. We describe the first reports of pro-phylacticpreoperativeimmunosuppressionintwopatientswitha known history of PG undergoing elective total knee replace-ment (TKR) surgery.Case reportsPatient 1A 76-year-old man with tricompartmental osteoarthritis waslisted for an elective right TKR. Preoperative assessmentrevealed a past history of contralateral lower limb PG thatoccurred following trauma (Fig. 1). This was initially resis-tant to high dose prednisolone and ciclosporin therapy buthealed 6 months following the administration of intravenousinfliximab. In the absence of formal guidance or evidence,the multidisciplinary team decided on a preoperative treat-ment protocol of prophylactic immunosuppression withprednisolone (60 mg daily for 14 days, commencing 5 daysprior to surgery and then reducing by 5 mg every 5 dayspostoperatively). This was on the basis that prednisolonewas felt to have the lowest risk side effect profile. A primarycemented right TKR was performed without complication.Standard intravenous antimicrobial prophylaxis was admin-istered. On day nine postsurgery, the surgical site appearedto have healed well with no evidence of pathergy. Thepatient was independently mobile and discharged.The patient returned on day 21 postsurgery with a swol-len right knee and a small amount of serous wound dis-charge. Clinically, the soft tissues were healthy, but a mildsystemic inflammatory response was present with a whitecell count (WCC) of 13.9×10

Melanoma is a rare form of skin cancer that is responsible for most skin cancer deaths globally. Tumors arising on the foot continue to be a particular challenge. Patients present later and lesions are frequently misdiagnosed, leading to more advanced disease with an overall poorer prognosis then melanoma elsewhere. In order to improve early recognition, this article reviews the clinical features of the disease along with published algorithms. Emerging assessment techniques such as dermoscopy are also discussed as tools to improve clinical decision making. Contemporary drug therapies in the treatment of advanced disease are also discussed.

We describe a fully programmable Electrostatic Tactile (ET) feedback system that delivers a range of tactile textures to a mobile display. The ET system is a robust, thin, and optically transparent structure that can be overlaid unobtrusively on top of a display screen. The system exploits the phenomenon of electrovibration to create a controllable frictional force between a user's fingertip and the surface. The system enables the realization of localized tactile information delivered to the user's skin directly, without moving parts. A tactile image is formed in accordance with the visual information displayed (virtual textures, tactile silhouettes, etc.). The magnitude and pattern of the frictional force on the display can be programmed to correspond to the images shown on the display and actual coordinates of the touch interaction in real time. This has been achieved using a variety of different materials, including those that are compatible with flexible devices.

We report the first successful application of an ordered bicontinuous double-gyroid vanadium pentoxide network in an electrochromic supercapacitor. The freestanding vanadia network was fabricated by electrodeposition into a voided block copolymer template that had self-assembled into the double-gyroid morphology. The highly ordered structure with 11.0 nm wide struts and a high specific surface to bulk volume ratio of 161.4 μm(-1) is ideal for fast and efficient lithium ion intercalation/extraction and faradaic surface reactions, which are essential for high energy and high power density electrochemical energy storage devices. Supercapacitors made from such gyroid-structured vanadia electrodes exhibit a high specific capacitance of 155 F g(-1) and show a strong electrochromic color change from green/gray to yellow, indicating the capacitor's charge condition. The nanostructuring approach and utilizing an electrode material that has intrinsic electrochemical color-change properties are concepts that can be readily extended to other electrochromic intercalation compounds.

Nature offers exciting examples for functional wetting properties based on superhydrophobicity, such as the self-cleaning surfaces on plant leaves and trapped air on immersed insect surfaces allowing underwater breathing. They inspire biomimetic approaches in science and technology. Superhydrophobicity relies on the Cassie wetting state where air is trapped within the surface topography. Pressure can trigger an irreversible transition from the Cassie state to the Wenzel state with no trapped air—this transition is usually detrimental for nonwetting functionality and is to be avoided. Here we present a new type of reversible, localized and instantaneous transition between two Cassie wetting states, enabled by two-level (dual-scale) topography of a superhydrophobic surface, that allows writing, erasing, rewriting and storing of optically displayed information in plastrons related to different length scales.