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Purpose. Results of a study to test the hypothesis that taking niacin simultaneously with different forms of aspirin would reduce the occurrence of niacin-induced flushing are reported. Methods. Traditionally, taking enteral absorbed aspirin 30 minutes before a niacin dose has been shown to reduce flushing by 30-50% relative to nonuse of aspirin. The objective of the study was to evaluate the efficacy of enteral absorbed and orally dissolved aspirin, taken at the same time as niacin, in reducing the frequency of moderate-to-severe flushing. In a prospective, double-blind, placebo-controlled crossover trial, healthy adult male and female volunteers were asked to take aspirin or a placebo (both agents were taken in both orally dissolved and swallowed formulations) immediately before niacin administration. Subjects then self-evaluated flushing symptoms on a validated scale. Results. Simultaneous administration of swallowed aspirin and niacin reduced moderate-to-severe flushing events by a mean of 36.1%, from 2.35 to 1.5 events per subject (p = 0.003), relative to event rates with use of niacin alone. In a subset of subjects who had experienced moderate-to-severe flushing symptoms despite taking swallowed aspirin, flushing in response to subsequent niacin use was decreased by 20.5% (p = 0.05) with coadministration of orally dissolved aspirin and by 18.0% with a regimen containing both orally dissolved and swallowed aspirin (p = 0.03). Conclusion. Novel regimens of niacin and aspirin, including orally dissolved aspirin, were effective in reducing niacin-induced flushing in a small sample of healthy adult volunteers. [ABSTRACT FROM AUTHOR]

This article focuses on the history of financialized management and its connections to shareholder value, which is often viewed as undermining patient strategies of investments. We argue that the rise of financialized management has in fact a long history that goes back to the conglomerate movement in 1960s America. As we show, the conglomerates pioneered the use of financial markets as a baseline for strategy, and the emphasis on financial transactions as an engine for growth. They developed key techniques--high leverage, share-price maximization and accounting manipulation--that later came to be associated with managerial strategies of the shareholder value era. This legacy has important implications for how we think about patient capital. It challenges the idea that patient capital consists foremost in shielding non-financial companies from capital markets and highlights the central role of management too often neglected in these debates. [ABSTRACT FROM AUTHOR]

Background Young people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWA) are at risk for HIV stigma. Methods The HIV/AIDS Stigma Instrument for PLWA was administered to 36 young PLWA across six clinics in Bandung, Indonesia, to assess the fear of contagion (FC), verbal abuse (VA), social isolation (SI), workplace stigma (WS), health care neglect (HCN) and negative self-perception (NSP). Results The median scores for FC, VA, SI, WS and HCN were all 0 while the median score for NSP was 4. In the last 3 months approximately 45% of surveyed PLWA felt they did not deserve to live and 64% felt completely worthless. Conclusions While these results are preliminary, access to mental health services should be a priority in the clinics that provide antiretroviral therapies. [ABSTRACT FROM AUTHOR]

Background. Patients with recurrent Clostridium difficile infection (CDI) have a ≥ 60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. Methods. Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 x 109 spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 x 108 spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. Results. Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. Conclusions. SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI. [ABSTRACT FROM AUTHOR]

Aims Evidence from randomized controlled trials (RCTs) evaluating possible benefits of endovascular therapy (EVT) for acute ischaemic stroke has shown conflicting results. The purpose of this meta-analysis was to systematically examine clinical outcomes in RCTs comparing the use of intravenous (IV) fibrinolysis alone to IV fibrinolysis plus EVT, for the treatment of acute ischaemic stroke. Methods and results We selected English language RCTs, comparing EVT plus IV tissue-type plasminogen activator (tPA) (if eligible) with IV tPA alone in eligible patients for the treatment of acute ischaemic stroke. The primary endpoint was good functional outcome [modified Rankin Scale (mRS) of 0-2]. Other major endpoints of interest were all-cause mortality and symptomatic intracerebral haemorrhage (sICH). The meta-analysis included 8 RCTs that randomized 2423 patients with large-vessel, anterior-circulation stroke. EVT significantly improved the rate of functional independence (90-day mRS of 0-2) when compared with IV fibrinolysis [odds ratio (OR) 1.73, 95% confidence interval (CI) 1.18-2.53, number needed to treat (NNT) =9.3]. The all-cause mortality was lower with EVT compared with the control group; however, the result did not reach statistical significance (OR 0.89, 95% CI 0.68-1.15). The rate of sICH was not higher with EVT (OR 1.07, 95% CI 0.73-1.56). Analyses from only the recent trials (reported in 2014-15) showed further benefit (OR of mRS 0-2: 2.42, 95% CI 1.91-3.08, NNT =5) with similar safety results. Conclusion In centres with advanced systems of stroke care, EVT significantly improved functional outcomes (without compromising safety) in patients with acute ischaemic stroke due to anterior circulation, large artery occlusion, compared with standard therapy. [ABSTRACT FROM AUTHOR]

We used an in silico approach to survey and compare microsatellites in transcript sequences of four sequenced members of genus Fusarium. G + C content of transcripts was found to be positively correlated with the frequency of SSRs. Our analysis revealed that, in all the four transcript sequences studied, the occurrence, relative abundance and density of microsatellites varied and was not influenced by transcript sizes. No correlation between relative abundance and transcript sizes was observed. The relative abundance and density of microsatellites were highest in the transcripts of Fusarium solani when compared with F. graminearum, F. verticillioides and F. oxysporum. The maximum frequency of SSRs among all four sequence sets was of trinucleotide repeats (67.8%), whereas the dinucleotide repeat represents <1%. Among all classes of repeats, 36.5% motifs were found conserved within Fusarium species. In order to study polymorphism within Fusarium isolates, 11 polymorphic genic-SSR markers were developed. Of the 11 markers, 5 were from F. oxysporum and remaining 6 belongs to F. solani. SSR markers from F. oxysporum were found to be more polymorphic (38%) as compared to F. solani (26%). Eleven polymorphic markers obtained in this study clearly demonstrate the utility of newly developed SSR markers in establishing genetic relationships among different isolates of Fusarium. [ABSTRACT FROM AUTHOR]

Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance. Fecal microbiota transplantation led to resolution of recurrent Clostridium difficile, significantly decreased recurrent UTI frequency, and improved antibiotic susceptibility profile of UTI-causing organisms. [ABSTRACT FROM AUTHOR]

The article focuses on Fecal Microbiota Transplantation. Topics discussed include Microbiota-based therapies are generally considered safe and are the cornerstone of management of patients with recurrent Clostridioides difficile infection, with high success rates to prevent future recurrences; and Health screening for stool donors who participate in studies and clinical practice of microbiome-based therapies have evolved.

Orphan nuclear receptors are potential therapeutic targets. The Orphan Nuclear Receptor Ligand Binding Database (ONRLDB) is an interactive, comprehensive and manually curated database of small molecule ligands targeting orphan nuclear receptors. Currently, ONRLDB consists of ∼11 000 ligands, of which ∼6500 are unique. All entries include information for the ligand, such as EC50 and IC50, number of aromatic rings and rotatable bonds, XlogP, hydrogen donor and acceptor count, molecular weight (MW) and structure. ONRLDB is a cross-platform database, where either the cognate small molecule modulators of a receptor or the cognate receptors to a ligand can be searched. The database can be searched using three methods: text search, advanced search or similarity search. Substructure search, cataloguing tools, and clustering tools can be used to perform advanced analysis of the ligand based on chemical similarity fingerprints, hierarchical clustering, binning partition and multidimensional scaling. These tools, together with the Tree function provided, deliver an interactive platform and a comprehensive resource for identification of common and unique scaffolds. As demonstrated, ONRLDB is designed to allow selection of ligands based on various properties and for designing novel ligands or to improve the existing ones. [ABSTRACT FROM AUTHOR]

In the article, the author discusses the developments in the study of microbiome-based therapies for the treatment of diseases associated with dysbiotic microbiome. Among the accomplishments is the use of fecal microbiota transplantation (FMT) to manage recurrent Clostridioides difficile infection. Also cited are how the use of antimicrobials increased the life expectancy of humans and the evolution of pathobionts to develop resistance to antibiotics.

Objectives A vast number of blinding diseases have genetic aetiologies and may be treated by molecular based therapies such as antisense oligonucleotides or short interfering RNA. However, treatment success of ocular gene therapy is highly dependent on efficient delivery of such molecules. Key findings The majority of clinical studies for ocular gene therapy utilize viral vectors. While these have proven highly efficient, they show limited loading capacity and pose significant safety risks owing to their oncogenic and immunogenic effects. Non-viral gene carriers have emerged as a promising alternative with dendrimers providing great potential for gene therapy because of their size, shape and high density of modifiable surface groups. However, while dendrimers have been used extensively for drug and gene delivery to other organs, only a few studies have been reported on the eye. Summary This review focuses on the development of dendrimers for gene delivery with special emphasis on ocular gene therapy. Different synthesis approaches and types of dendrimers are discussed. Ocular gene therapy targets are highlighted with an overview of current clinical studies. The use of dendrimers in ocular gene delivery in comparison to liposomes and nanoparticles is also discussed. Finally, future prospects of tailored multifunctional dendrimers for ocular gene therapy are highlighted. [ABSTRACT FROM AUTHOR]

Chandipura virus ( CHPV), alike other pathogens, exploits the cellular infrastructure of their hosts through complex network of interactions for successful infection. CHPV being a recently emerged pediatric encephalitic virus, the mechanisms involved in the establishment of viral persistence are still ill defined. Because the protein interface between CHPV and its host provides one means by which the virus invades and seize control of their human host machinery, the authors in this study have employed computational methods to create a network of putative protein-protein interactions between CHPV and its human host to shed light on the hitherto less-known CHPV biology. On the basis of the 2105 potential interactions predicted among 1650 human proteins and the five proteins of CHPV, the authors decipher the probable mode by which the virus manipulates the biological pathways of its host toward its own end and replicates while evading the immune system. Identification of such conserved set of putative interactions that allow the virus to take control of the host has the potential to deepen our understanding of the virus-specific remodeling processes of the host cell and illuminate new arenas of disease intervention. [ABSTRACT FROM AUTHOR]

Audio and visual modalities are two common output channels in the user interfaces embedded in today's mobile devices. However, these user interfaces are typically centered on the visual modality as the primary output channel, with audio output serving a secondary role. This paper argues for an increased need for shared input multimodal user interfaces for mobile devices. A shared input multimodal interface can be operated independently using a specific output modality, leaving users to choose the preferred method of interaction in different scenarios. We evaluate the value of a shared input multimodal menu system both in a single-task desktop setting and in a dynamic dual-task setting, in which the user was required to interact with the shared input multimodal menu system while driving a simulated vehicle. Results indicate that users were faster at locating a target item in the menu when visual feedback was provided in the single-task desktop setting, but in the dual-task driving setting, visual output presented a significant source of visual distraction that interfered with driving performance. In contrast, auditory output mitigated some of the risk associated with menu selection while driving. A shared input multimodal interface allows users to take advantage of multiple feedback modalities properly, providing a better overall experience. [ABSTRACT FROM AUTHOR]

Clostridium difficile incidence in children increased significantly from 1991 through 2009. The majority of cases were community-acquired. Severe infection was more common in hospital-acquired than community-acquired cases. There were fewer treatment failures with vancomycin compared to metronidazole.Background. The incidence of Clostridium difficile infection (CDI) is increasing, even in populations previously thought to be at low risk, including children. Most incidence studies have included only hospitalized patients and are thus potentially influenced by referral or hospitalization biases.Methods. We performed a population-based study of CDI in pediatric residents (aged 0–18 years) of Olmsted County, Minnesota, from 1991 through 2009 to assess the incidence, severity, treatment response, and outcomes of CDI.Results. We identified 92 patients with CDI, with a median age of 2.3 years (range, 1 month–17.6 years). The majority of cases (75%) were community-acquired. The overall age- and sex-adjusted CDI incidence was 13.8 per 100 000 persons, which increased 12.5-fold, from 2.6 (1991–1997) to 32.6 per 100 000 (2004–2009), over the study period (P < .0001). The incidence of community-acquired CDI was 10.3 per 100 000 persons and increased 10.5-fold, from 2.2 (1991–1997) to 23.4 per 100 000 (2004–2009) (P < .0001). Severe, severe-complicated, and recurrent CDI occurred in 9%, 3%, and 20% of patients, respectively. The initial treatment in 82% of patients was metronidazole, and 18% experienced treatment failure. In contrast, the initial treatment in 8% of patients was vancomycin and none of them failed therapy.Conclusions. In this population-based cohort, CDI incidence in children increased significantly from 1991 through 2009. Given that the majority of cases were community-acquired, estimates of the incidence of CDI that include only hospitalized children may significantly underestimate the burden of disease in children. [ABSTRACT FROM AUTHOR]

Background. Mycobacterium tuberculosis, the causative agent of tuberculosis, has a remarkable ability to usurp its host's innate immune response, killing millions of infected people annually. One approach to manage infection is prevention through the use of natural agents. In this regard, stem bromelain (SBM), a pharmacologically active member of the sulfhydryl proteolytic enzyme family, obtained from Ananas comosus and possessing a remarkable ability to induce the innate and acquired immune systems, is important.Methods. We evaluated SBM's ability to induce apoptosis and free-radical generation in macrophages. We also studied antimycobacterial properties of SBM and its effect on foamy macrophages.Results. SBM treatment of peritoneal macrophages resulted in the upregulation of proapoptotic proteins and downregulation of antiapoptotic proteins. Additionally, SBM treatment activated macrophages, curtailed the levels of free glutathione, and augmented the production of hydrogen peroxide, superoxide anion, peroxynitrite, and nitric oxide. SBM cleaves CD36 and reduced the formation of foam cells, the hallmark of M. tuberculosis infection. These conditions created an environment for the increased clearance of M. tuberculosis.Conclusions. Together these data provide a mechanism for antimycobacterial activity of SBM and provide important insights for the use of cysteine proteases as immunomodulatory agents. [ABSTRACT FROM PUBLISHER]

Fusarium oxysporum is a ubiquitous species complex of soil-borne plant pathogens comprising of many different formae speciales, each characterized by a high degree of host specificity. In the present investigation, we surveyed microsatellites in the available express sequence tags and transcript sequences of three formae speciales of F. oxysporum viz. melonis ( Fom), cucumerium ( Foc), and lycopersici ( Fol). The relative abundance and density of microsatellites were higher in Fom when compared with Foc and Fol. Thirty microsatellite primers were designed, ten from each forma specialis, for genetic characterization of F. oxysporum isolates belonging to five formae speciales. Of the 30 primers, only 14 showed amplification. A total of 28 alleles were amplified by 14 primers with an average of two alleles per marker. Eight markers showed 100% polymorphism. The markers were found to be more polymorphic (47%) in Fol as compared to Fom and Foc; however, polymorphic information content was the maximum (0.899) in Foc SSR-3. Nine polymorphic markers obtained in this study clearly demonstrate the utility of newly developed markers in establishing genetic relationships among different isolates of F. oxysporum. [ABSTRACT FROM AUTHOR]

An editorial is presented on Clostridium difficile infection (CDI). Topics include patients with diarrhoea and the positive test for C. difficile has presumed to have active infection, the diarrhoea does not respond to C. difficile treatment, does that mean the chosen agent being ineffective and an alternative treatment for CDI has initiated, and investigators have been searching for a test to make this distinction.

Background Ceftazidime–avibactam (CZA) is a novel cephalosporin/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) and multidrug-resistant (MDR) Pseudomonas aeruginosa (PA). Real-world experience with CZA for CRE infections is accumulating but data on its use for MDR PA infections remains limited. Methods Retrospective, multicenter cohort study describing the clinical characteristics and outcomes of patients treated with CZA (≥ 72 hours) for MDR PA infections between 2015 and 2018. Results Fifty-one patients were included. The median (IQR) age was 61 (43, 71) years. Most patients had MDR risk factors including recent hospitalization (74.5%), recent antimicrobial exposure (84.3%), and/or previous infection or colonization with an MDR pathogen (58.8%). The median Charlson Comorbidity score was 4 (2, 6) and the median APACHE II score was 20 (12, 29). Infections were predominantly (68.6%) hospital-acquired and 52.9% of patients were in the ICU at infection onset. The common sources were respiratory tract (60.8%), osteoarticular (11.8%) and skin and soft tissue (11.8%). Two patients had positive blood cultures. PA antibiotic susceptibilities were as follows: ceftazidime 52.6% (n = 51), CZA 92.0% (n = 25), ciprofloxacin 10% (n = 30), meropenem 19.6% (n = 46), piperacillin–tazobactam 30.4% (n = 4) and tobramycin 72.9% (n = 48). Most (60.8%) infections were polymicrobial including 15 (29.4) CRE co-infections. CZA was started 97 (50, 170) hours after culture collection and continued for 9 (7, 14) days. Only 8 patients (15.7%) received active antibiotic therapy before CZA. Combination CZA therapy was used 35.3%, most often an aminoglycoside (8/18, 44.4%). Clinical cure or improvement was achieved in 40 patients (78.4%), and 42 (82.4%) were discharged alive. Among patients with repeat cultures (n = 11), CZA resistance development was not detected. Three patients (5.9%) experienced infection recurrence within 30 days of completing therapy. Conclusion The use of CZA was associated with high rates of favorable outcomes in complex patients with MDR PA infections. Future studies evaluating long-term outcomes and comparative studies are needed to more precisely define the role of CZA for MDR PA infections. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Acute infection with Epstein–Barr virus (EBV) causes fever, fatigue and pharyngitis. Renal involvement in systemic EBV infections typically manifests as acute tubular necrosis or tubulointerstitial nephritis. Rarely, EBV infection causes nephrotic syndrome due to minimal change disease. A 22-year-old male with infectious mononucleosis (IM) presented with nephrotic syndrome. Renal biopsy showed minimal change disease with diffuse foot process effacement of the podocytes. Treatment with methylprednisone led to rapid and complete clinical remission. Minimal change nephropathy is a very rare manifestation of EBV infection and should be considered in patients with IM and proteinuria. [ABSTRACT FROM PUBLISHER]

Background We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. Methods This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. Results In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115–4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180–0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia) Conclusions Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) cures ~90% of patients with recurrent Clostridioides difficile infection (rCDI). Ongoing or repeated exposure to risk factors, especially antibiotics (a modifiable risk factor but often necessary), may lead to future CDI. However, it is not known if FMT provides durable protection against future CDI despite subsequent antibiotic exposure. We studied the long-term durability of FMT against antibiotic exposure post-FMT. Methods A retrospective cohort study of patients undergoing FMT via colonoscopy for rCDI from Sep 2012 - Jun 2018 was performed. Patients were followed up for 1 year after FMT; data regarding future CDI episodes (watery diarrhea with positive stool test after interim symptom resolution), healthcare exposure, systemic non-CDI antibiotics and acid blocker therapy were collected. Primary outcome was 'durability' of response to FMT (defined as no CDI within 1 year post-FMT). Descriptive statistics, Chi square test, Wilcoxon test and multivariate logistic regression were used as appropriate. Results The study included 460 patients; median age 57 years (range 18–94 years), 65.2% (300) female. Overall 31.6% (144) received antibiotics; median number of courses of antibiotics, 2 (range 1–7). Of those who received antibiotics, the incidence of future CDI was 24.3% (n = 34), compared with 9% (n = 28) of those who did not receive antibiotics (P <.001). Median time to first CDI episode post-FMT was 103 (range 5–338) days. Incremental antibiotic courses did not lead to increased risk of future CDI (comparing 1, 2 or ≥3 courses, p =.68). In patients with antibiotic exposure, age and risk factors were similar in patients with and without future CDI (Table 1). Amongst those without antibiotic exposure, inflammatory bowel disease (IBD) predicted future CDI (p =.02). After controlling for risk factors and comorbidities, antibiotic use (p =.004) and IBD (p =.02) independently increased risk of future CDI. Conclusion The majority of patients with rCDI have a durable response to FMT despite ongoing risk factors. These data suggest that three-fourth of patients who receive antibiotics after FMT do not develop future CDI. IBD and antibiotic exposure independently increase the risk of future CDI. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone. Methods Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation. Results A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table: Conclusion Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Introduction: Measurement of coagulation assay is pivotal all across in different specialties in field of medicine. We compared prothrombin time, activated prothrombin time and fibrinogen from fresh blood samples drawn into glass vs. plastic tubes. There was a recent recall of glass tubes nationwide from a leading manufacture. This type of situation imposes difficult scenario and put labs in a dilemma whether to use plastic tubes in place of glass tubes. Also the literature is extremely sparse in reference to the use of plastic tubes and shows inconsistence results. Hence, there is a need for further studies. To handle this scenario of the recall, the quality assurance project was performed at CMC Philadelphia VA Medical Center. Method: We collected 65 venous blood samples into 4.5 mL glass tubes and 2.7 mL plastic tubes from mix population patients with and without anticoagulant therapy. After centrifugation we used Diagnostic Stago instrument with Stago reagents for this testing. Mean and standard deviation (SD) were used to verify the adequacy of the analytic ranges in the study and to summarize results. Results: In our results, there was no statistically significance difference observed in prothrombin time, activated partial thromboplastin time, and fibrinogen results. We used Bland-Altman plot for determination of results comparison. Bland-Altman plot shows good correlation between two methods, and their regression shows excellent correlation of r values between 0.98 and 1.00. There is no indication of bias between the methods. Conclusion: Our study shows that the plastic tubes can be safely and successfully used for the coagulation studies in place of glass tubes. [ABSTRACT FROM AUTHOR]

Background Data suggest that vancomycin + β-lactam combinations improve the clearance of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin. Methods This was a multicenter, retrospective cohort study of adults with MRSA BSIs from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance. Results Three hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271–0.741). This was driven by a reduction in BSI duration ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202–0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435–2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (hazard ratio [HR], 1.408; 95% CI, 1.125–1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040–1.536). Conclusions Concomitant empiric cefepime improved MRSA BSI clearance and may be useful as the β-lactam component of synergistic vancomycin + β-lactam regimens when empiric or directed gram-negative coverage is desired. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Current status of Clostridium difficile infection epidemiology," published in a previous issue of the periodical is presented.

The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled-library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols. In this study, we reanalyze 17 genome-scale knockout screens in human cell lines from three research groups, using three different genome-scale gRNA libraries. Using the Bayesian Analysis of Gene Essentiality algorithm to identify essential genes, we refine and expand our previously defined set of human core essential genes from 360 to 684 genes. We use this expanded set of reference core essential genes, CEG2, plus empirical data from six CRISPR knockout screens to guide the design of a sequence-optimized gRNA library, the Toronto KnockOut version 3.0 (TKOv3) library. We then demonstrate the high effectiveness of the library relative to reference sets of essential and nonessential genes, as well as other screens using similar approaches. The optimized TKOv3 library, combined with the CEG2 reference set, provide an efficient, highly optimized platform for performing and assessing gene knockout screens in human cell lines. [ABSTRACT FROM AUTHOR]