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ObjectiveTo describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children.DesignAnonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections.SettingPediatric intensive care units in Canada, Australia and New Zealand.ParticipantsPediatric intensivists, nurse practitioners, ID physicians and pharmacists.Main outcome measuresRecommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration.ResultsAmong 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4-6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8-4.4 days] for central vascular catheter-associated infections). Most clinicians (73-95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration.ConclusionsThe majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections.

Germin-like proteins (GLPs) are involved in biotic and abiotic stress tolerance in different plant species. Rice (Oryza sativa L.) genome contains about 40 GLP family member proteins in nine chromosomes. Although some of the rice GLP (OsGLP) promoters have been studied through in silico analysis as well as experimentally, studies regarding the distribution pattern of the biotic and abiotic stress associated transcription factor binding sites (TFbs) in the promoter regions of OsGLP genes have not been attempted thoroughly. Several transcription factors (TFs) namely NAC, WRKY, bHLH, bZIP, MYB and AP2/ERF act as major TFs concerned with biotic as well as abiotic stress responses across various plant species. In the present study the in silico analysis was carried out using the 1.5 kilobases (kb) promoter regions from 40 different OsGLP genes for the presence of NAC, WRKY, bHLH, bZIP, MYB and AP2/ERF TFbs in it. Among various OsGLP gene promoters, OsGLP8-11 was found to contain highest number of tested TFbs in the promoter region whereas the promoter region of OsGLP5-1 depicted least amount of TFbs. Phylogenetic study of promoter regions of different OsGLP genes revealed four different clades. Our analyses could reveal the evolutionary significance of different OsGLP gene promoters. It can be presumed from the present findings as well as previous reports that OsGLP gene duplications and subsequent variations in the TFbs in OsGLP gene promoter regions might be the consequences of neofunctionalization of OsGLP genes and their promoters for biotic and abiotic stress tolerance in rice.

BACKGROUND:A multidisciplinary approach has been recommended for the management of patients with infective endocarditis. We evaluated the impact of multidisciplinary case conferences on morbidity, mortality, and quality of care for these patients. METHODS:We conducted a quasi-experimental study of consecutive patients admitted for infective endocarditis before (2013/10/1-2015/10/12, n = 97) and after (2015/10/13-2017/11/30, n = 80) implementation of case conferences to discuss medical and surgical management. These occurred as face-to-face discussions or electronically (for non-complex patients), and included physicians from cardiac surgery, cardiology, critical care, infectious diseases and neurology. We assessed process-of-care and clinical outcomes, with the primary outcome being complications up to 90 days after hospital discharge. RESULTS:A case conference was held for 80/80 (100%) of patients in the post-intervention group. After the intervention, more patients received inpatient cardiology assessment (81.3% [post-intervention] vs. 63.9% [pre-intervention], p = 0.01), and more patients with definite infective endocarditis underwent cardiac surgery treatment (44.6% vs. 21.7%, p = 0.007). All pre-intervention and post-intervention patients received guideline-concordant antimicrobial therapy. There was no difference in rates of complications (40.0% vs. 51.5%, p = 0.13) or mortality up to 90 days after hospital discharge (26.3% vs. 17.5%, p = 0.20). In multivariable analyses, the intervention was not associated with differences in mortality (odds ratio 1.87, 95% confidence interval 0.88-3.99) or a composite measure of complications and mortality (odds ratio 0.86, 95% confidence interval 0.46-1.58). CONCLUSION:We successfully implemented a standardized multidisciplinary case conference protocol for patients with infective endocarditis. This intervention had no detectable effect on complications or mortality.

Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70-1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05-7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients.

Intake of saturated fat is a risk factor for ulcerative colitis (UC) and colon cancer. Changes in the microbiota have been implicated in the development of UC and colon cancer. The host and the microbiota generate metabolites that may contribute to or reflect disease pathogenesis. We used lipid class specific quantitative mass spectrometry to assess the phospholipid (PL) profile (phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], phosphatidylserine [PS]) of stool from mice fed a high fat (HFD) or control diet with or without induction of colitis-associated tumors using azoxymethane and dextran sodium sulfate. The microbiota was assessed using qPCR for several bacterial groups. Colitis-associated tumors were associated with reduced bulk PI and PE levels in control diet fed mice compared to untreated mice. Significant decreases in the relative quantities of several PC species were found in colitis-associated tumor bearing mice fed either diet. Statistical analysis of the PL profile revealed distinct clustering by treatment group. Partial least squares regression analysis found that the relative quantities of the PS class profile best predicted bacterial abundance of Clostridium leptum and Prevotella groups. Abundance of selected PL species correlated with bacterial group quantities. Thus, we have described that a HFD and colitis-associated tumors are associated with changes in phospholipids and may reflect host-microbial interactions and disease states.

Owing to its aggressiveness and the lack of effective therapies, pancreatic ductal adenocarcinoma has a dismal prognosis. New strategies to improve treatment and survival are therefore urgently required. Numerous fucosylated antigens in sera serve as tumor markers for cancer detection and evaluation of treatment efficacy. Increased expression of fucosyltransferases has also been reported for pancreatic cancer. These enzymes accelerate malignant transformation through fucosylation of sialylated precursors, suggesting a crucial requirement for fucose by pancreatic cancer cells. With this in mind, we developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specifically to cancer cells. L-fucose-bound liposomes containing Cy5.5 or Cisplatin were effectively delivered into CA19-9 expressing pancreatic cancer cells. Excess L-fucose decreased the efficiency of Cy5.5 introduction by L-fucose-bound liposomes, suggesting L-fucose-receptor-mediated delivery. Intravenously injected L-fucose-bound liposomes carrying Cisplatin were successfully delivered to pancreatic cancer cells, mediating efficient tumor growth inhibition as well as prolonging survival in mouse xenograft models. This modality represents a new strategy for pancreatic cancer cell-targeting therapy.