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  • Oxford University Press (OUP)  (56)
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  • Oxford University Press (OUP)  (56)
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  • 1
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. 12 ( 2019-12-01)
    Kurzfassung: The precise role of cytomegalovirus (CMV) in ulcerative colitis (UC) remains disputed. We evaluated the association of CMV-specific host immune responses and systemic or local viral replication with responses to systemic steroids in patients with moderate to severe UC. Methods Patients who were hospitalized for moderate to severe UC between April 2015 and June 2016 were enrolled. At baseline, all enrolled patients underwent CMV-specific enzyme-linked immunospot assays, quantitative polymerase chain reaction (qPCR) analysis of blood and colonic tissue for CMV viral load, histopathological testing for CMV in colonic tissue by hematoxylin and eosin staining, and immunohistochemical (IHC) analysis. Clinical responses to steroid therapy based on the Oxford index were assessed on day 3. Results Of the 80 patients evaluated, 28 (35.0%) had poor responses to steroid therapy on day 3 of intensive treatment. The presence of inclusion bodies (32.1%) and high-grade (≥3) positivity on IHC (50.0%), as well as colonic (mean 1440.4 copies/mg) and blood (mean, 3692.6 copies/mL) CMV viral load, were higher in steroid-refractory UC patients than the control group (13.5%, 1.9%, mean 429.2 copies/mg, and mean 231.2 copies/mL, respectively; P = .046, .009, .017, and .002, respectively). However, CMV-specific T-cell responses were not associated with steroid-refractory UC. Multivariate analysis revealed that a higher Mayo score (odds ratio [OR], 2.00; P = .002) and higher blood CMV viral load via qPCR analysis (OR, 3.58; P = .044) were independent risk factors for steroid-refractory UC. Conclusions In patients with moderate to severe UC, higher Mayo score and blood CMV expression determined by qPCR are independently associated with steroid refractoriness. ClinicalTrials.gov registration number NCT 02439372.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S249-S250
    Kurzfassung: Carbapenem-resistant Enterobacteriaceae (CRE) infection is an emerging clinical issue. One of the mechanisms of carbapenem-resistance is carbapenemase production. This study aimed to identify whether clinical outcomes differ by CRE resistance mechanism and to evaluate risk factors for mortality in patients with CRE bacteremia. Methods We conducted a retrospective cohort study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE and non-CP-CRE bacteremia during January 2011 to October 2018. Only monomicrobial Escherichia coli or Klebsiella pneumoniae bacteremia were included in the study. A modified carbapenem inactivation method was used for phenotypic detection of carbapenemase production. The presence of a variety of carbapenemase genes was evaluated by PCR with specific primers. Results Of 134 patients with monomicrobial CRE bacteremia, 48 (35.8%) were infected with CP-CRE, and 86 (64.1%) were infected with non-CP-CRE. The most common carbapenemase in CP-CRE isolates was KPC (66.7%), followed by NDM-1 (18.8%), OXA-48-like (10.4%), and VIM (4.1%). Baseline characteristics were similar between the two groups (Table 1). However, the CP-CRE group was significantly more likely to undergo removal of eradicable foci and to have meropenem MIC 〉 8 µg/mL. A total of 33 (24.6%) patients died within 14 days, including 9 (18.8%) in the CP-CRE group and 24 (27.9%) in the non-CP-CRE group. Deceased patients were more likely to have a higher Pitt bacteremia score, nosocomial acquisition, ineradicable or not-eradicated foci, immunosuppressant use, inappropriate definitive treatment (Table 2). Combination therapy for definitive treatment was associated with decreased mortality. In a multivariate analysis including carbapenemase production, a higher Pitt bacteremia score (aOR, 5.15), ineradicable or not-eradicated foci (aOR, 4.05) and combination therapy for definitive treatment (aOR, 0.35) were independent risk factors for mortality. Conclusion Our study suggests that carbapenemase production is not a mortality risk factor in CRE bacteremia and provides additional evidence for early source control and combination therapy. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S501-S502
    Kurzfassung: Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study. Methods Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. The study patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95). Conclusion The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Combining surveillance of the stool with other sites may be needed for detecting CPE. Disclosures All Authors: No reported disclosures
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S120-S121
    Kurzfassung: There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 9 ( 2021-09-01)
    Kurzfassung: ST72-SCCmecIV, a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain in Korea, originated in the community and has been spreading in health care settings. Herein, we describe the clinical and microbiological characteristics of patients with hospital-acquired MRSA bacteremia (MRSAB) caused by community-associated strains. Methods We analyzed hospital-acquired MRSAB cases caused by ST72-SCCmecIV using a prospective cohort of patients with SAB in a tertiary hospital in Korea from July 2008 to December 2018. We compared the clinical and microbiological characteristics of ST72-SCCmecIV with ST5-SCCmecII, a representative hospital-associated genotype strain. Results Of the 1782 S. aureus bacteremia (SAB) cases, 628 (35.2%) were hospital-acquired MRSAB. Of the 628 isolates, 431 (68.6%) were ST5-SCCmecII and 152 (24.2%) were ST72-SCCmecIV. Patients with ST72-SCCmecIV were younger than those with ST5-SCCmecII and less likely to have a history of recent surgery, antibiotic treatment, nasal MRSA colonization, and central venous catheter placement. Compared with ST5-SCCmecII, ST72-SCCmecIV isolates were more likely to have vancomycin MICs ≤1.0 mg/L (P & lt; .001). Osteoarticular infection as the site of infection (7.2% [11/152] vs 1.4% [6/431] ) was more common in patients with ST72-SCCmecIV. There were no significant differences in the rate of recurrence (≤90 days), persistent bacteremia (≥7 days), or 30- and 90-day mortality rates between the 2 groups. Conclusions Osteoarticular infections were more prevalent in ST72-SCCmecIV MRSAB. Mortality rates between the ST72-SCCmecIV and ST5-SCCmecII groups were not significantly different.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S86-S86
    Kurzfassung: Staphylococcus aureus can cause various types of infection, but involvement of biliary tract is rare. There were only few case reports and no clinical studies. We assessed the clinical characteristics and outcomes of S. aureus bacteremia from a biliary source (biliary SAB) in a large cohort of SAB patients and compared the cases with those of catheter-related SAB. Methods We performed a matched case–control study within a prospective observational cohort of patients with SAB at a 2,700-bed tertiary hospital. All adult patients with SAB were observed for 12 weeks from July 2008 to July 2018. Biliary SAB was defined as the case of S.aureus isolated from blood culture with appropriate clinical biliary infection symptoms (fever, abdominal pain, or jaundice) and signs (abdominal tenderness or liver enzyme elevation with obstructive pattern). Biliary SAB cases were matched 1:3 to control patients with catheter-related SAB based on age, gender, ward, and case year. Results A total of 1,818 patients with SAB were enrolled in the entire cohort, and 42 (2%) were biliary SAB. Among patients with biliary SAB, 32 (76%) had solid tumor involving pancreaticobiliary tract or liver, 30 (71%) had biliary drainage stent, 14 (33%) were biliary procedure-related infection, and 24 (57%) had recent broad-spectrum antibiotics exposure (Table 1). When biliary SAB patients were compared with 126 patients with catheter-related SAB, they were significantly more likely to have community-onset SAB, solid tumor, and lower APACHE II score; and less likely to have metastatic infection (P = 0.03) (Table 2). Biliary SAB, solid tumor, and a high Charlson comorbidity index were associated with 12-week mortality. In multivariate analysis, biliary SAB (aOR, 5.5; 95% CI, 2.47–12.25) and a high Charlson comorbidity index (aOR, 1.32; 95% CI, 1.12–1.54) were independent risk factors for 12-week mortality. Conclusion Biliary SAB was relatively rare and developed mainly in pancreaticobiliary cancer patients and in recent broad-spectrum antibiotic users. High mortality was probably attributable to underlying cancers. When biliary tract infection caused by S. aureus is clinically suspected, early aggressive treatment for SAB should be considered. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S95-S96
    Kurzfassung: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is an emerging clinical issue and shows high mortality rates. There are a few studies that have evaluated the microbiologic risk factors for mortality in CRAB bacteremia. Aim of this study is to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia. Methods Adult patients with monomicrobial CRAB bacteremia at a 2,700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled in the study. Risk factors for 30-day mortality were evaluated through a detailed clinical and microbiological analysis of study patients. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and genotyping by multilocus sequence typing (MLST). Results A total of 164 patients were enrolled and 90 (55%) died within 30 days. Of the 164 patients, 111 (68%) were male and median age was 66.5 years. The most common MLST genotype was ST191 (80 isolates, 49%), followed by ST451 (14%) and ST784 (13%), and 12 (7%) isolates were resistant to colistin (MIC ≥4 mg/L). Deceased patients were more likely to have hematologic malignancy, neutropenia, pneumonia, and primary bacteremia; less likely to have solid tumor, catheter-related infection, and biliary tract infection; more likely to have a high Pitt bacteremia score; and less likely to receive appropriate antibiotic treatment, colistin, and combination therapy with colistin and tigecycline, compared with surviving patients (Table 1). Genotype, colistin MIC, and colistin resistance were not associated with mortality (Figure 1 and 2). In multivariable analysis, neutropenia (aOR, 3.25; 95% CI, 1.18–8.95), catheter-related infection (aOR, 0.33; 95% CI, 0.11–0.99), biliary tract infection (aOR, 0.20; 95% CI, 0.04–0.99), a high Pitt bacteremia score (aOR,1.42; 95% CI, 1.20–1.67), and combination therapy with colistin and tigecycline (aOR, 0.36; 95% CI, 0.14–0.92) were independent risk factors for mortality (Table 2). Conclusion Clinical factors such as the site of infection, severity of bacteremia, and specific combination therapy rather than microbiologic factors contributed to mortality in CRAB bacteremia. Appropriate combination therapy may help improving outcomes in CRAB bacteremia. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S905-S906
    Kurzfassung: Agr is a key regulator that controls expression of secreted exoproteins and surface protein in Staphylococcus aureus. It has been reported that mixed status of two different phenotypes including agr functional and nonfunctional subpopulations can coexist in vitro and in vivo. However, data on the natural course and clinical implication of the mixed agr status is limited. We thus investigated the frequency and characteristics of the mixed agr in clinical settings. Methods We evaluated isogenic paired MRSA isolates collected from patients with persistent S. aureus bacteremia (SAB) between October 2010 and April 2016, and then prospectively performed surveillance for the presence of mixed agr function in MRSA isolates from patients with SAB between May 2016 and December 2017. The mixed agr status was evaluated by single colony evaluation on sheep blood agar plate containing RN4220 supernatant (β-hemolysin) (Figure 1). Cross-streaking with RN4220 and RNAIII measurement were performed to confirm the agr functionality of each of hemolytic and non-hemolytic colonies, separately. The expression levels of RNAIII, hla, and saeS/saeR were measured by real-time reverse transcription polymerase chain reaction. Results A total of 161 first blood isolates were collected during study period, and 6 isolates (4%) displayed mixed phenotype by single colony test. The mixed hemolytic pattern was observed in 5 out of 52 ST72 isolates (10%) and 1 out of 82 ST5 isolates (1%) (Figure 1). No difference was found in the genotypes between hemolytic and non-hemolytic colonies from each isolate. Of the 6 isolates, three lost mixed hemolytic features in the follow-up blood cultures (Table 1). One ST72 and one ST5 isolate showed agr mixed pattern determined by different RNAIII levels, but remaining four ST72 isolates had mixed hemolytic pattern due to different expression of hla correlated with saeS/saeR expression (Figure 2). Conclusion The mixture of agr function status among the clinical blood isolates of MRSA was rarely observed and isolates displaying heterogeneous hemolytic phenotype were largely due to differential expression of α-hemolysin. Further investigation is needed to unveil the clinical significance of mixture of different hemolytic phenotypes. Disclosures All authors: No reported disclosures.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S135-S136
    Kurzfassung: Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB. Methods We reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated. Results Of the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI] , 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality. Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia Fig 1. Duration of Staphylococcus aureus bacteremia Conclusion In persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality. Disclosures All Authors: No reported disclosures
    Materialart: Online-Ressource
    ISSN: 2328-8957
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2020
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 15, No. 11 ( 2021-11-08), p. 1898-1907
    Kurzfassung: Genome-wide association studies [GWAS] of inflammatory bowel disease [IBD] in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify two new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional dataset of 1726 cases and 378 controls. Methods An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3195 cases and 4419 controls, followed by replication in an additional 1088 cases and 845 controls. Results The meta-analysis of Korean GWAS identified one novel locus for ulcerative colitis at rs76227733 on 10q24 [pcombined = 6.56 × 10–9] and two novel loci for Crohn’s disease [CD] at rs2240751 on 19p13 [pcombined = 3.03 × 10–8] and rs6936629 on 6q22 [pcombined = 3.63 × 10–8] . Pathway-based analysis of GWAS data using MAGMA showed that the MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14% of the variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population. Conclusions The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations.
    Materialart: Online-Ressource
    ISSN: 1873-9946 , 1876-4479
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2389631-0
    Standort Signatur Einschränkungen Verfügbarkeit
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