Anti-HCV Signal-to-Cutoff Ratio in Predicting Hepatitis C Viremia

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Multisite Evaluation of the BD Max Extended Enteric Bacterial Panel for Detection of Yersinia enterocolitica, Enterotoxigenic Escherichia coli, Vibrio, and Plesiomonas shigelloides from Stool Specimens.

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of Yersinia enterocolitica, enterotoxigenic Escherichia coli (ETEC), Vibrio, and Plesiomonas shigelloides The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was also used to confirm the historical results for the retrospective specimens and for discrepant result analysis. A total of 2,410 unformed, deidentified stool specimens were collected. The prevalence in the prospective samples as defined by the reference method was 1.2% ETEC, 0.1% Vibrio, 0% Y. enterocolitica, and 0% P. shigelloides Compared to the reference method, the positive percent agreement (PPA) (95% confidence interval [CI]), negative percent agreement (NPA) (95% CI), and kappa coefficient (95% CI) for the BD Max xEBP assay for all specimens combined were as follows: ETEC, 97.6% (87.4 to 99.6), 99.8% (99.5 to 99.9), and 0.93 (0.87 to 0.99); Vibrio, 100% (96.4 to 100), 99.7% (99.4 to 99.8), and 0.96 (0.93 to 0.99); Y. enterocolitica, 99.0% (94.8 to 99.8), 99.9% (99.8 to 99.9), and 0.99 (0.98 to 1); P. shigelloides, 100% (96.4 to 100), 99.8% (99.5 to 99.9), and 0.98 (0.95 to 1), respectively. In this multicenter study, the BD Max xEBP showed a high correlation (kappa, 0.97; 95% CI, 0.95 to 0.98) with the conventional methods for the detection of ETEC, Vibrio, Y. enterocolitica, and P. shigelloides in stool specimens from patients suspected of acute gastroenteritis, enteritis, or colitis

Impact of real-time antimicrobial stewardship team intervention versus conventional microbiology reporting on time to appropriate antimicrobial therapy in patients with Enterobacterales bacteremia

Scott C. King Alyssa B. Christensen, Brent W. Footer, Timothy G. Shan, Kim Health, Ivor Thomas, and Margret Oethinger Impact of real-time antimicrobial stewardship team intervention versus conventional microbiology reporting on time to appropriate antimicrobial therapy in patients with Enterobacterales bacteremia. Introduction: The benefit of rapid laboratory speciation combined with real time antimicrobial stewardship team (AMT) interventions has been shown to improve patient outcomes and decrease hospital costs. The Providence Oregon region conducts direct from blood culture matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) identification, which results in decreased time to organism identification. The MALDI-TOF identification has allowed the AMT to intervene earlier than a health system using standard MALDI identification or comparable methods. The purpose of this study is to assess the impact of real time notification plus AMT intervention on clinical outcomes in patients with Enterobacterales blood stream infections (BSI). Methods: This was an IRB approved, retrospective, multi-center, pre- and post- quasi-experimental study conducted at eight acute care hospitals in the Providence Health & Services Oregon region. Adult patients (\u3e18 years old) with a diagnosed BSI caused by an Enterobacterales species were included. The control group was from August 2018 to January 2019 and the intervention group was from February 2019 to June 2019. Patients were matched based on age, gender, and admission to the ICU. Exclusion criteria included polymicrobial infection, Pitt bacteremia score \u3e1, unable to take PO therapy, and patients discharged to hospice care. During the intervention period the AMT members received real-time alerts for all blood culture speciation via a paging system. These cases where then reviewed and recommendations were made to the primary care team based off an approved protocol. The primary outcome for the study was time to de-escalation of therapy. Secondary outcomes include hospital length of stay and total duration of therapy. Results: A total of 60 patients were include in this study: 30 patients in the pre-intervention group and 30 patients in the post-intervention group. The most common age group was patients 60-69 years of age (43% vs 43%). The most common causative organism for the BSI was found to be Escherichia coli (76.7% vs 50%). During the intervention period a decrease was noted in median time to de-escalation of therapy (2.7 days vs 1.8 days, p=0.0061) and length of stay (5.3 days vs 4.3 days, p=0.0475). There was no statistical difference in the total length of therapy (combined inpatient and outpatient duration) noted between the two groups (9 days vs 9.5 days, p=1). Conclusion: The results show a statistically significant decrease in both time to de-escalation and length of stay within the intervention group due to AMT recommendations. This is in line with previous studies and also highlights the benefit de-escalation could have on length of stay in the hospital. Studies with larger samples sizes should be considered to further explore these results. IRB Status: Approvedhttps://digitalcommons.psjhealth.org/pharmacy_PGY1/1009/thumbnail.jp

Escherichia coli mar and acrAB Mutants Display No Tolerance to Simple Alcohols

The inducible Mar phenotype of Escherichia coli is associated with increased tolerance to multiple hydrophobic antibiotics as well as some highly hydrophobic organic solvents such as cyclohexane, mediated mainly through the AcrAB/TolC efflux system. The influence of water miscible alcohols ethanol and 1-propanol on a Mar constitutive mutant and a mar deletion mutant of E. coli K-12, as well as the corresponding strains carrying the additional acrAB deletion, was investigated. In contrast to hydrophobic solvents, all strains were killed in exponential phase by 1-propanol and ethanol at rates comparable to the parent strain. Thus, the Mar phenotype does not protect E. coli from killing by these more polar solvents. Surprisingly, AcrAB does not contribute to an increased alcohol tolerance. In addition, sodium salicylate, at concentrations known to induce the mar operon, was unable to increase 1-propanol or ethanol tolerance. Rather, the toxicity of both solvents was increased in the presence of sodium salicylate. Collectively, the results imply that the resilience of E. coli to water miscible alcohols, in contrast to more hydrophobic solvents, does not depend upon the AcrAB/TolC efflux system, and suggests a lower limit for substrate molecular size and functionality. Implications for the application of microbiological systems in environments containing high contents of water miscible organic solvents, e.g., phage display screening, are discussed

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction

Background: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well- recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI.<br/> Objective: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. Patients/methods: Cases (n = 399) were recruited 3-9 months after their event; 413 controls were age- and sex-matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. Results: All routine fibrinogen assays showed high intercorrelations (r = 0.82-0.93) and significant (P lt 0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r = 0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P lt 0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. Conclusions: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies

Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice

We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte, Klebsiella pneumoniae 342. Although K. pneumoniae 342 is a member of the enteric bacteria, it serves as a model for studies of endophytic, plant-bacterial associations due to its efficient colonization of plant tissues (including maize and wheat, two of the most important crops in the world), while maintaining a mutualistic relationship that encompasses supplying organic nitrogen to the host plant. Genomic analysis examined K. pneumoniae 342 for the presence of previously identified genes from other bacteria involved in colonization of, or growth in, plants. From this set, approximately one-third were identified in K. pneumoniae 342, suggesting additional factors most likely contribute to its endophytic lifestyle. Comparative genome analyses were used to provide new insights into this question. Results included the identification of metabolic pathways and other features devoted to processing plant-derived cellulosic and aromatic compounds, and a robust complement of transport genes (15.4%), one of the highest percentages in bacterial genomes sequenced. Although virulence and antibiotic resistance genes were predicted, experiments conducted using mouse models showed pathogenicity to be attenuated in this strain. Comparative genomic analyses with the presumed human pathogen K. pneumoniae MGH78578 revealed that MGH78578 apparently cannot fix nitrogen, and the distribution of genes essential to surface attachment, secretion, transport, and regulation and signaling varied between each genome, which may indicate critical divergences between the strains that influence their preferred host ranges and lifestyles (endophytic plant associations for K. pneumoniae 342 and presumably human pathogenesis for MGH78578). Little genome information is available concerning endophytic bacteria. The K. pneumoniae 342 genome will drive new research into this less-understood, but important category of bacterial-plant host relationships, which could ultimately enhance growth and nutrition of important agricultural crops and development of plant-derived products and biofuels