Trends in and predictors of carbapenem consumption across North American hospitals: Results from a multicenter survey by the MAD-ID research network

This Special Issue is dedicated to the late Dr. Charles (Charlie) D. Hufford, former Professor of Pharmacognosy and Associate Dean for Research and Graduate Studies at University of Mississippi [...]

Clinical Outcomes in Patients with Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Bloodstream Infection

The prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections varies in the literature, a problem complicated by the lack of routine screening procedures; however, limited data suggest that hVISA has been associated with persistent bloodstream infections (BSI) and vancomycin failure, yet these studies have been confounded by design issues. We conducted this study to compare the characteristics of patients with BSI caused by hVISA with those with vancomycin-susceptible Staphylococcus aureus (VSSA) treated with vancomycin. This retrospective, multicenter matched (1:1) cohort study compared the clinical characteristics and outcomes of hVISA and VSSA. Patients with hVISA methicillin-resistant Staphylococcus aureus (MRSA) BSI from 2004 to 2012 were matched to VSSA-MRSA BSI patients. The primary outcome was failure of vancomycin treatment, defined as a composite of persistent bacteremia (≥7 days), persistent signs and symptoms, change of MRSA antibiotic, recurrent BSI, or MRSA-related mortality. We identified 122 matched cases. The overall vancomycin failure rate was 57% (82% hVISA versus 33% VSSA; P \u3c 0.001). The individual components of failure in hVISA versus VSSA were persistent bacteremia, 59% versus 21% (P \u3c 0.001); change in MRSA therapy, 54% versus 25% (P = 0.001); MRSA-related mortality, 21% versus 10% (P = 0.081); and recurrence of BSI, 26% versus 2% (P \u3c 0.001). Using logistic regression analysis and adjusting for covariates, hVISA (adjusted odds ratio [aOR], 11.1; 95% confidence interval [CI], 4.3 to 28.7) and intensive care unit (ICU) admission (aOR, 4.5; 95% CI, 1.8 to 11.6) were still independently associated with vancomycin failure. Relative to VSSA BSI, patients with hVISA were more likely to experience failure of vancomycin treatment, including persistent bacteremia and recurrence. Our results indicate that hVISA was responsible for considerable morbidity

APOE4 genotype exerts greater benefit in lowering plasma cholesterol and apolipoprotein B than wild type (E3/E3), after replacement of dietary saturated fats with low glycaemic index carbohydrates

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial ('RISCK' study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC -0.28 mmol/L p = 0.03; apo B -0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates

Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggests that daptomycin \u3e 6mg/kg/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (\u3e 6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two-hundred and forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by 49 (20%) Enterococcus faecalis and 21 (9%) Enterococcus spp., overall 204 (83%) were VRE. Enterococcal infections included bacteremia (173, 71%), intra-abdominal (35, 14%) and bone/joint (25, 10%). The median dose and duration of HD-daptomycin was 8.2 mg/kg/day (IQR 7.7-9.7) and 10 days (IQR 6-15), respectively. Overall clinical success rate was 89% (193/218) and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR 2-5). Thirty-day all cause mortality rate was 27% and 5 (2%) patients developed daptomycin nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult to treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections

AutoRoot: open-source software employing a novel image analysis approach to support fully-automated plant phenotyping

Background: Computer-based phenotyping of plants has risen in importance in recent years. Whilst much software has been written to aid phenotyping using image analysis, to date the vast majority has been only semi-automatic. However, such interaction is not desirable in high throughput approaches. Here, we present a system designed to analyse plant images in a completely automated manner, allowing genuine high throughput measurement of root traits. To do this we introduce a new set of proxy traits. Results: We test the system on a new, automated image capture system, the Microphenotron, which is able to image many 1000s of roots/h. A simple experiment is presented, treating the plants with differing chemical conditions to produce different phenotypes. The automated imaging setup and the new software tool was used to measure proxy traits in each well. A correlation matrix was calculated across automated and manual measures, as a validation. Some particular proxy measures are very highly correlated with the manual measures (e.g. proxy length to manual length, r2 > 0.9). This suggests that while the automated measures are not directly equivalent to classic manual measures, they can be used to indicate phenotypic differences (hence the term, proxy). In addition, the raw discriminative power of the new proxy traits was examined. Principal component analysis was calculated across all proxy measures over two phenotypically-different groups of plants. Many of the proxy traits can be used to separate the data in the two conditions. Conclusion: The new proxy traits proposed tend to correlate well with equivalent manual measures, where these exist. Additionally, the new measures display strong discriminative power. It is suggested that for particular phenotypic differences, different traits will be relevant, and not all will have meaningful manual equivalent measures. However, approaches such as PCA can be used to interrogate the resulting data to identify differences between datasets. Select images can then be carefully manually inspected if the nature of the precise differences is required. We suggest such flexible measurement approaches are necessary for fully automated, high throughput systems such as the Microphenotron

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy