Carbapenem-resistant Enterobacteriaceae Surveillance Research Articles

Active surveillance for carbapenem resistant enterobacteriaceae (CRE) using stool cultures as a method to decrease CRE infections in the pediatric intensive care unit (PICU)

BackgroundThe incidence of Carbapenem Resistant Enterobacteriaceae (CRE) infections is increasing worldwide. Due to dearth of alternative antibiotics, prevention of infection transmission is a part of CRE infection management strategy. Early detection of CRE by active surveillance coupled with contact isolation is much more appropriate compared to contact isolation upon receipt of routine cultures dictated by the patient's clinical condition. ObjectivesTo determine whether active CRE surveillance will decrease CRE infection rates in the Pediatric Intensive Care Unit (PICU). MethodsRetrospective observational study done in the 10-bed PICU of a tertiary care teaching children's hospital from July 2013 to June 2015. Rectal swabs for CRE were sent from all PICU patients except stable post-operative patients. Contact isolation precautions were followed for rectal swab positive patients. CRE colonization and infection rates were calculated and compared. ResultsTotal of 1262 rectal swabs were sent from 1022 patients. CRE colonization rate was 19.5%. Post intervention, ICU acquired CRE colonization decreased by 36% and ICU acquired CRE infection rates decreased by 100%, both showed significant decrease (p ​< ​0.0001). ConclusionActive CRE surveillance and institution of contact isolation in appropriate situations is helpful in decreasing CRE colonization and infection rates in the PICU.

Clonal dissemination of carbapenem-resistant Klebsiella pneumoniae ST16 co-producing NDM-1 and OXA-232 in Thailand.

Background Klebsiella pneumoniae ST258 and ST11 carrying blaKPC are among the most widespread carbapenem-resistant K. pneumoniae strains worldwide. Our carbapenem-resistant Enterobacteriaceae surveillance in Thailand revealed a nationwide dissemination of K. pneumoniae ST16 isolates carrying blaNDM-1 and blaOXA-232.ObjectivesTo analyse the genomic details of this nationwide dissemination by focusing on plasmids and virulence factors.MethodsUsing WGS data of 119 K. pneumoniae ST16 isolates carrying blaNDM-1 obtained in our previous surveillance study, clonality of chromosomes and plasmids of the isolates with carriage of virulence factors was evaluated.ResultsOf the 119 isolates, 111 carried plasmid pKP151_NDM1, and all 104 isolates harbouring blaOXA-232 carried plasmid pKP151_OXA232. These 104 K. pneumoniae ST16 isolates showing chromosomal clonality possessed both pKP151_NDM1 and pKP151_OXA232, demonstrating clonal dissemination of K. pneumoniae ST16 with these plasmids. The isolates had essentially similar virulence factors as those of K. pneumoniae ST16 clones carrying blaKPC, which were recently reported as highly invasive clones in Brazil.ConclusionsThe potential global dissemination of these invasive clones with resistance to several antibiotics highlights the importance of appropriate monitoring and strict standard precautions.

Molecular characterization of carbapenem-resistant Enterobacteriaceae and emergence of tigecycline non-susceptible strains in the Henan province in China: a multicentrer study.

Introduction Carbapenem-resistant Enterobacteriaceae (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries.Hypothesis/Gap Statement To better understand the epidemiological trends and characteristics of CRE in the Henan province.Aim We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China.Methodology A total of 305 CRE isolates were subjected to multiple tests, including in vitro antimicrobial susceptibility testing, PCR for carbapenemase genes bla KPC, bla NDM, bla IMP, bla VIM, bla OXA-48-like. Tigecycline-resistant genes ramR, oqxR, acrR, tetA, rpsJ, tetX, tetM, tetL were analysed in five tigecycline non-susceptible carbapenem-resistant Klebsiella pneumoniae isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant K. pneumoniae (CRKP).Results The most common CRE species were K. pneumoniae (234, 77 %), Escherichia coli (36, 12 %) and Enterobacter cloacae (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % bla KPC, 13 % bla NDM, 6 % bla IMP, and 1 % combined bla KPC/bla NDM genes. K. pneumoniae carbapenemase (KPC) was the predominant carbapenemase in K. pneumoniae (87 %), whereas NDM and IMP were frequent in E. coli (53 %) and E. cloacae (69 %), respectively. Mutations in the ramR, tetA, and rpsJ genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among K. pneumoniae strains.Conclusion A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant K. pneumonia isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.

1425. Impact of Social Determinants on Racial Differences in Carbapenem-Resistant Enterobacteriaceae Incidence, Atlanta, 2012-2018

BackgroundPublic 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).MethodsThe 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.ResultsAdjusting 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) ConclusionPoverty 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

Prevalence of carbapenem-resistant Enterobacteriaceae and emergence of high rectal colonization rates of blaOXA-181-positive isolates in patients admitted to two major hospital intensive care units in Kuwait.

BackgroundFecal colonization by carbapenem-resistant Enterobacteriaceae (CRE) can be the main reservoir for transmission of these resistant organisms especially in the Intensive Care Units (ICUs).AimThis study was conducted to evaluate the rate of rectal carriage and molecular characterization of CRE in patients hospitalized in the ICUs of 2 major hospitals (Adan and Mubarak Al Kabeer Hospitals) in Kuwait.Materials and methodsRectal swabs were collected from all patients at admission, 48 h after admission and once weekly from April 2017- March 2018. Initial CRE screening was carried out on MacConkey agar on which meropenem disc 10μg was placed. Identification of isolates was by API 20E. Susceptibility testing was performed using the E-test method. Polymerase chain reaction (PCR) was used to detect the carbapenemase-encoding genes. Clonal relationship was investigated by pulsed-field electrophoresis (PFGE). Genes of blaOXA-181 and blaNDM-5–carrying plasmids were detected in some strains.ResultsA total of 590 patients were recruited into the study. Of these, 58 were positive for CRE, giving a prevalence of 9.8%; 25/320 (7.8%) in Adan and 33/270 (12.2%) in Mubarak Al Kabeer Hospitals. All isolates were resistant to multiple antibiotics. Resistance rates to colistin and tigecycline were 17% and 83%, respectively. Single genes of blaOXA-181 were detected in isolates from 38 (65.5%) out of 58 patients and in 5 patients colonized by blaOXA-48-positive CRE. A combination of 2 genes was detected in 12 isolates; 5 blaKPC-2 and blaOXA-181, 4 blaVIM-1 and blaOXA-181, and 3 blaNDM-5 and blaOXA-181. PFGE showed an overall level of similarity of 38%. Southern hybridization studies localized the blaOXA-181 and blaNDM-5 genes to a large plasmid of 200kb in 3 K. pneumoniae isolates and a small plasmid of 80kb in 2 E. coli isolates, respectively.ConclusionThe prevalence of CRE colonization in the 2 hospital ICUs was relatively high and the emergence of blaOXA-181-mediated CRE is a cause for concern as there is the possibility of rapid horizontal spread among hospital patients in Kuwait. Active surveillance of CRE in the ICUs is highly recommended to stem its spread.

Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying bla IMP by whole-genome sequencing and Southern blotting. bla IMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of bla IMP-6 caused an outbreak likely through covert transmission of bla IMP-6 For stable carriage of bla IMP-6, they occasionally integrated bla IMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in bla IMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments.IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying bla IMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of bla IMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of bla IMP-6, stabilization of bla IMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in bla IMP-6.

Carbapenem-Resistant Enterobacteriaceae Resistant Only to Ertapenem: An Epidemiologically Distinct Cohort, Atlanta, 2016–2018

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 &lt; .01) and less commonly K. pneumoniae (21% vs 58%; P &lt; .01) than CRE-O. CRE-EO cases were more often women (65% vs 50%; P &lt; .01), had a lower Charlson comorbidity index (mean ± SD, 2.4±2.3 vs 3.0±2.6; P &lt; .01), and were less commonly at a long-term care facility (24% vs 31%) or hospital (15% vs 21%; P &lt; .01) in the 4 days prior to the CRE culture. CRE-EO were more susceptible to all antibiotics tested at the clinical laboratory (P &lt; .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 &lt; .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 &lt; .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

Molecular Epidemiology and Outcomes of Patients with Carbapenem-Resistant Enterobacteriaceae Bacteriuria, Atlanta 2012–2015

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

533. Impact of Different Definitions on Reported Rates of Carbapenem-Resistant Enterobacteriaceae (CRE)

BackgroundDifferent definitions exist for tracking and trending rates of hospital-acquired Carbapenem-resistant Enterobacteriaceae (CRE). National Health Safety Network (NHSN) allows for Laboratory Identified Event (LabID) and Healthcare-associated infection (HAI) surveillance reporting for CRE. Our facility developed an internal definition for CRE prior to release of the NHSN modules that differs from the CDC definitions in that patients colonized or infected with CRE identified on hospital day 1 or 2 who had a hospitalization within the past four weeks are considered community-onset healthcare facility acquired (COHCFA) and are included in our HA definition. In addition, by our definition once a patient develops CRE any subsequent positive cultures for the same organism are not considered new events.MethodsAll CRE cultures at our facility were reviewed by an infection preventionist and hospital epidemiologist who categorized each culture as hospital acquired by our internal HA definition, NHSN LabID definition and NHSN HAI definition. Results from each method of surveillance were compiled and compared as were trends of HA CRE over time by each definition.Results590 patients with 975 clinical cultures for Carbapenem-resistant Klebsiella spp., Enterobacter spp and E. coli were reviewed from January 2012 to March 2019. 297 cultures met our internal definition for HA CRE compared with 302 by NHSN LabID and 189 by NHSN HAI surveillance. Sixty-one (21%) of HA cases by our definition were COHCFA. 259 patients had multiple CRE cultures and 1 patient had 22 cultures with the same CRE organism between 2014 and 2019 and met for 5 lab ID events and 5 NHSN HAI events. All 3 tests agreed that a culture was HA in 140 instances (14%) and all 3 agreed that a culture was not HA in 589 instances (60%). At least one definition yielded a discordant result in 246 cultures (25%). Trends over time were compared between the definitions. While the number of HA cases varied based on the definition used, overall trends over time were similar regardless of the definition utilized. (Figure 2)ConclusionRegardless of the definition used for surveillance of CRE, trends over time are similar. Consideration should be given to monitoring COHCFA cases in addition to those acquired on or after hospital day 3. Disclosures All authors: No reported disclosures.

497. Changing Molecular Epidemiology of CRE from 2016–2018, Increase in the Unknown

BackgroundHistorically, endemic Klebsiella pneumoniae carbapenemase (KPC) has accounted for the majority of carbapenem-resistant Enterobacteriaceae (CRE) in Los Angeles County (LAC). The LAC Department of Public Health (DPH) initiated enhanced CRE surveillance in 2016 to determine CRE prevalence and track emerging non-KPC resistance mechanisms (IMP, NDM, OXA, and VIM) among CRE to describe characteristics and identify local epidemiology for novel multi-drug-resistant organism (N-MDRO) infection and colonization.MethodsCRE isolates were voluntarily submitted by local clinical laboratories for mechanism detection by LAC Public Health Laboratory via MALDI-TOF and Nanosphere BC-GN. Baseline isolates were collected in 2016. Results are then presented by year through 2018. For N-MDRO cases, LACDPH interviewed healthcare facility (HCF) staff and cases to obtain case characteristics. Data were analyzed via Microsoft Access and SAS.ResultsCRE surveillance isolates were voluntarily submitted by 31 labs representing 34% (34/96) LAC hospitals and 1 large regional lab serving 60% of skilled nursing facilities from January 2016 to December 2018. LACDPH tested 1438 CRE isolates during the study period, 1168 (81%) were carbapenemase producing (CP). The proportion of CP CRE and KPC CRE declined over the study period (Table 1). NDM was the most common non-KPC (n = 30) followed by OXA (n = 28). The proportion of CRE with no genotypic marker increased over the course of the study. Case characteristics were obtained from 41 non-KPC CP CRE cases; median age was 66 years (range: 6–94 years); 12 (29%) expired. Among the 41 cases, 20 (49%) had a central line; 11 (27%) had surgery; 14 (34%) had antibiotics in the 6 months prior to culture date. Of the 41 cases, 11 (27%) had international healthcare exposure within 12 months with an invasive procedure and/or antibiotics.ConclusionSurveillance in a large urban setting suggests the molecular epidemiology of CRE is changing, with declining prevalence of KPC, increasing metallo-β-lactamase CP, and large proportion of isolates without resistance markers detected. Given the worrisome trends in non-KPC CRE, more systematic surveillance is warranted, potentially using more robust molecular epidemiology. Disclosures All authors: No reported disclosures.

High prevalence of colonisation with carbapenem-resistant Enterobacteriaceae among patients admitted to Vietnamese hospitals: Risk factors and burden of disease

Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC). A point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome. A total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n = 805), Escherichia coli (n = 682) and Enterobacter spp. (n = 61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2% per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU, CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5·5, P<0·01) with CRE colonisation and HAI on admission. These data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients.

Impact of individualized active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.

Purpose: Active surveillance of carbapenem-resistant Enterobacteriaceae (CRE) may contribute to the decline of the infection rate. Individualized active surveillance of CRE could cost less than screening all patients. However, the impact of individualized active surveillance on the CRE infection rate in intensive care units (ICUs) has not been well described.Patients and methods: We retrospectively studied the clinical data of all patients admitted in the ICUs of a tertiary-care hospital in China from 2015 to 2017 during two periods, before and after the implementation of individualized active surveillance. During period 1 (January 2015–April 2016), no screening protocol was used. During period 2 (May 2016–December 2017), we implemented active CRE screening for selected patients according to their clinical characteristics. The trend of CRE rate infection was analyzed by a joinpoint regression model, and multivariate analysis was performed to analyze the association of active surveillance, Acute Physiology and Chronic Health Evaluation (APACHE) II score, prior antimicrobial use, length of mechanical ventilation (MV) before infection, and other risk factors with CRE infection rate.Results: A total of 5,372 patients were included. After assessing the patients’ clinical characteristics, 72.3% (3,882/5,372) were considered to be at high risk of CRE infection. During period 1, the infection percent of CRE increased by 13.04% every month (95% CI: 5.2–21.5). During period 2, the infection rate decreased (monthly percent change, −3.57%; 95% CI −6.9 to −0.1, P<0.05). Multivariate analysis showed that individualized active surveillance (odds ratio, 0.146; 95% CI, 0.061–0.347; P<0.001) was associated with a reduction of the CRE infection rate, whereas APACHE II score, prior antimicrobial use, and length of MV before infection were independent risk factors.Conclusion: Individualized active surveillance may be associated with a reduction of the overall CRE infection rate in ICUs.

Carbapenem-Resistant Enterobacteriaceae: Rapid Laboratory Diagnosis and Surveillance Culture for Infection Control

Carbapenem-resistant Enterobacteriaceae (CRE) are increasing rapidly worldwide and in South Korea, which is a major problem for patient treatment and infection control. CRE is mainly due to carbapenem-hydrolyzing β-lactamase, which spreads through genetic mobile elements. Therefore, the rapid detection of carbapenemase-producing CRE (CP-CRE) and carrier surveillance are very important for infection control. Most clinical microbiology laboratories use automated real-time PCR methods for the rapid detection of CP-CRE; in some cases, additional accurate molecular tests are necessary. For the surveillance of risk groups, the complementary use of liquid culture and real-time PCR methods is important, taking into consideration their advantages and disadvantages. Furthermore, the expansion of surveillance targets is also necessary. Keywords: Carbapenem-resistant Enterobacteriaceae; Carbapenemase; Laboratory diagnosis; Surveillance culture 중심 단어: 카바페넴 내성 ìž¥ë‚´ì„¸ê· ; 카바페넴 분해효소; ì‹ ì† 진단; 감시 배양

Evaluating Movement of Patients With Carbapenem-resistant Enterobacteriaceae Infections in the Greater Atlanta Metropolitan Area Using Social Network Analysis.

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. 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. 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. 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.

Surveillance-guided selective digestive decontamination of carbapenem-resistant Enterobacteriaceae in the intensive care unit: A cost-effectiveness analysis

Clinical findings have shown effectiveness and safety of selective digestive decontamination (SDD) for eradication of carbapenem-resistant Enterobacteriaceae (CRE) in high-risk carriers. We aimed to evaluate the cost-effectiveness of SDD guided by CRE surveillance in the intensive care unit (ICU). Outcomes of surveillance-guided SDD (test-guided SDD) and no screening (control) in the ICU were compared by Markov model simulations. Model outcomes were CRE infection and mortality rates, direct costs, and quality-adjusted life year (QALY) loss. Model inputs were estimated from clinical literature. Sensitivity analyses were conducted to examine the robustness of base case results. Test-guided SDD reduced infection (4.8% vs 5.0%) and mortality (1.8% vs 2.1%) rates at a higher cost ($1,102 vs $1,074) than the control group in base case analysis, respectively. Incremental cost per QALY saved (incremental cost-effectiveness ratio [ICER]) by the test-guided SDD group was $557 per QALY. Probabilistic sensitivity analysis showed that test-guided SDD was effective in saving QALYs in 100% of 10,000 Monte Carlo simulations, and cost-saving 59.1% of time. The remaining 40.9% of simulations found SDD to be effective at an additional cost, with ICERs accepted as cost-effective per the willingness-to-pay threshold. Surveillance-guided SDD appears to be cost-effective in reducing CRE infection and mortality with QALYs saved.

The association between infection control interventions and carbapenem-resistant Enterobacteriaceae incidence in an endemic hospital

Israel experienced a national outbreak of carbapenem-resistant Enterobacteriaceae (CRE) starting in 2006. To assess the association between infection control (IC) interventions implemented in a referral hospital in Israel and CRE incidence. Retrospective quasi-experimental study of prospectively collected data. CRE incidence, defined as the number of patients newly acquiring CRE in surveillance or clinical samples per 100,000 hospital-days, was plotted quarterly between 2005 and 2016. IC interventions were applied at different time-points throughout this period. Data were collected on IC staffing, number of rectal surveillance cultures, and carbapenem consumption. Autocorrelated segmented linear regression analysis was used to assess the time-points at which a significant change in the CRE incidence trend occurred, and the association between the timing of IC intervention implementation and observed CRE trends was assessed. Trends between time-points were expressed as quarterly percent change (QPC) with 95% confidence intervals (CIs). Between 2005 and 2008, CRE incidence increased significantly (QPC: 19.7%; CI: 11.5-28.4), reaching a peak of 186.6 new acquisitions per 100,000 hospital-days. From mid-2011 until the end of follow-up, there was a significantly decreasing incidence trend (QPC:-4.5; CI: -6.4 to -2.5). Cohorting of patients, screening of contacts and high-risk patients on admission were insufficient to control the epidemic. Improved hand hygiene compliance, cohorting with dedicated nursing staff, addition of regular screening in high-risk departments, and carbapenem restriction were required. Decreasing CRE incidence was observed with an infectious diseases/IC staffing of 1.2-1.5 per 100 beds and 20,000-36,000 yearly CRE surveillance samples. A multi-faceted hospital-wide intervention programme is required to control CRE in hospital settings.

Use of the Extensively Drug-resistant Organism (XDRO) Registry for Carbapenem-Resistant Enterobacteriaceae (CRE) Reporting and Initiation of Transmission Precautions — Chicago, Illinois, 2016

Background Carbapenem-resistant Enterobacteriaceae (CRE) are a group of multidrug-resistant bacteria that cause ~9,000 infections annually; ~50% of CRE bloodstream infections are fatal. The use of contact precautions (CP) for CRE patients can prevent transmission. To improve CRE surveillance and interfacility communication about positive patients, Illinois implemented the extensively drug-resistant organism (XDRO) registry in 2013. Healthcare facilities must report a patient’s first positive CRE culture per stay ≤7 days from culture confirmation. Facilities can query the registry at patient admission to identify CRE status and implement transmission precautions. We assessed facility timeliness of reporting and querying frequency and registry usefulness in identifying patients who should be on CP.Methods We analyzed Chicago XDRO data for November 2013–October 2016. Variables were facility type (hospital, long-term acute care hospital [LTACH], and skilled nursing facility [SNF]), culture date, and report date. Timeliness was time from culture collection to reporting. Nine facilities (2 hospitals, 4 LTACHs and 3 SNFs) completed a survey on querying frequency; all but 1 LTACH provided single day census and contact precaution lists. We compared these with the XDRO registry to identify CRE patients for whom querying would have initiated CP use.ResultsChicago facilities reported 2,469 CRE cases. Median timeliness varied by facility type (hospitals: 8 days; SNF: 10 days; and LTACH: 55 days). Of patients on CP for CRE but not reported to the registry, 11/12 (92%) were in LTACHs. Reported querying frequency was daily for 1 hospital and rarely for other facilities. Overall, 91 patients at 8 facilities were in the registry; of these, 0/1 (0%) hospital, 3/27 (11%) LTACH, and 28/63 (44%) SNF patients were not on CP.Conclusion Timeliness of reporting CRE patients to the XDRO registry varied by facility type and exceeded the 7-day timeframe. Routine registry querying can identify CRE patients who should be on CP. Querying was uncommon in surveyed facilities, identifying an opportunity to improve transmission precautions among CRE patients, particularly in SNFs. We recommend facilities report cases in a timely manner and query the registry at patient admission.Disclosures M. Y. Lin, CareFusion Foundation: Grant Investigator, Research grant

The Efficacy of the MicroScan®Walkaway System in Reporting Carbapenemase-Producing Enterobacteriaceae in Patients with Bacteremia, South Africa

Background: The emergence of Carbapenemase-producing Enterobacteriaceae (CPE) is a major public health problem worldwide. As Carbapenemase-production has emerged, treatment of infections has become more difficult leading to high mortality. Real time detection of the presence of these enzymes by in vitro susceptibility testing of these organisms is urgently needed to provide effective treatment and appropriate implementation of infection and prevention control measures. Automated phenotypic systems are widely used in clinical microbiology laboratories for bacterial identification and antimicrobial susceptibility testing. However, critical evaluation is needed to determine the accuracy of these systems. Objective: Our study was set out to evaluate whether the MicroScan® Walkaway system is a reliable method for predicting CPE in patients with a Carbapenem-resistant Enterobacteriaceae (CRE) infections. Methods: This was a cross-sectional study of CRE isolates from July 2015 to July 2016 received as part of an active CRE surveillance programme. Bacterial identification and antimicrobial susceptibility testing for Carbapenems were performed using the MALDI-ToF and MicroScan® Walkaway system, respectively. Genotypic testing was performed using the LightMix® modular Carbapenemase kits in a multiplex real-time PCR assay to confirm the presence of Carbapenemase genes. Results: During the study period, there were 219 CRE tested. Out of 219 CRE cases, Carbapenemase genes were detected in 173 (78.9%). The most prevalent gene was blaNDM (38.8%; n=85), followed by blaOXA-48 and variants (32.8%; n=72), blaVIM (6.9%; n=15) and blaGES (0.5%; n=1). The MicroScan® Walkaway system had the highest sensitivity with ertapenem (86.7%). Sensitivities for all other Carbapenems were similar, but below 65%. The positive predictive value for ertapenem was 78.9% and >80% for imipenem (86.2%), meropenem (81.3%) and doripenem (83.7%). Overall, testing for all Carbapenems had a sensitivity of 89%, positive predictive value of 79% and specificity of 10.9%, amongst them imipenem having the highest specificity at 60.9%. Conclusion: The MicroScan® Walkaway system is sensitive, but lacks specificity. However, it shows to be an efficient diagnostic adjunct to the LightMix® modular multiplex real-time PCR assay for predicting CPE in a patient with a CRE infection depending on the Carbapenem used.

Active surveillance of carbapenem-resistant Enterobacteriaceae in intensive care units: Is it cost-effective in a nonendemic region?

Carbapenem-resistant Enterobacteriaceae (CRE) cause significant morbidity and mortality in intensive care unit (ICU) settings. We examined potential cost-effectiveness of active CRE surveillance at ICUs in a nonendemic region from the perspective of a Hong Kong health care provider. A decision analytic model was designed to simulate outcomes of active CRE surveillance in ICUs. Outcome measures included CRE-associated direct medical cost, infection rate, mortality rate, quality-adjusted life year (QALY) loss, and incremental cost per QALY saved by active surveillance. Model inputs were derived from the literature. Sensitivity analyses evaluated the influence of uncertainty of model variables. In base-case analysis, the surveillance group was more costly ($1,260 vs $1,256) with lower CRE infection rate (5.670% vs 5.902%), CRE-associated mortality rate (2.139% vs 2.455%), and CRE-associated QALY loss (0.3335 vs 0.3827) than the control group. Incremental cost per QALY saved of active surveillance was $81 per QALY saved. One-way sensitivity analyses found base-case results to be robust to a variety of model inputs. In 10,000 Monte Carlo simulations, the surveillance group was the preferred option 99.98% of time. Active CRE surveillance in ICUs appears to be highly cost-effective to reduce CRE infection rate, mortality rate, and QALY loss in a low CRE burden region.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013.

Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. Demographics, comorbidities, health care exposures, and culture source and location. Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.