Current state of antimicrobial stewardship in children’s hospital emergency departments

BACKGROUND Antimicrobial stewardship programs (ASPs) effectively optimize antibiotic use for inpatients; however, the extent of emergency department (ED) involvement in ASPs has not been described. OBJECTIVE To determine current ED involvement in children's hospital ASPs and to assess beliefs and preferred methods of implementation for ED-based ASPs. METHODS A cross-sectional survey of 37 children's hospitals participating in the Sharing Antimicrobial Resistance Practices collaboration was conducted. Surveys were distributed to ASP leaders and ED medical directors at each institution. Items assessed included beliefs regarding ED antibiotic prescribing, ED prescribing resources, ASP methods used in the ED such as clinical decision support and clinical care guidelines, ED participation in ASP activities, and preferred methods for ED-based ASP implementation. RESULTS A total of 36 ASP leaders (97.3%) and 32 ED directors (86.5%) responded; the overall response rate was 91.9%. Most ASP leaders (97.8%) and ED directors (93.7%) agreed that creation of ED-based ASPs was necessary. ED resources for antibiotic prescribing were obtained via the Internet or electronic health records (EHRs) for 29 hospitals (81.3%). The main ASP activities for the ED included production of antibiograms (77.8%) and creation of clinical care guidelines for pneumonia (83.3%). The ED was represented on 3 hospital ASP committees (8.3%). No hospital ASPs actively monitored outpatient ED prescribing. Most ASP leaders (77.8%) and ED directors (81.3%) preferred implementation of ED-based ASPs using clinical decision support integrated into the EHR. CONCLUSIONS Although ED involvement in ASPs is limited, both ASP and ED leaders believe that ED-based ASPs are necessary. Many children's hospitals have the capability to implement ED-based ASPs via the preferred method: EHR clinical decision support. Infect Control Hosp Epidemiol 2017;38:469-475

The current state of antifungal stewardship among pediatric antimicrobial stewardship programs

OBJECTIVE: To characterize the current state of antifungal stewardship practices and perceptions of antifungal use among pediatric antimicrobial stewardship programs (ASPs). DESIGN: We developed and distributed an electronic survey, which included 17 closed-ended questions about institutional antifungal stewardship practices and perceptions, among pediatric ASPs. PARTICIPANTS: ASP physicians and pharmacists of 74 hospitals participating in the multicenter Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative. RESULTS: We sent surveys to 74 hospitals and received 68 unique responses, for a response rate of 92%. Overall, 63 of 68 the respondent ASPs (93%) reported that they conduct 1 or more antifungal stewardship activities. Of these 68 hospital ASPs, 43 (63%) perform prospective audit and feedback (PAF) of antifungals. The most common reasons reported for not performing PAF of antifungals were not enough time or resources (19 of 25, 76%) and minimal institutional antifungal use (6 of 25, 24%). Also, 52 hospitals (76%) require preauthorization for 1 or more antifungal agents. The most commonly restricted antifungals were isavuconazole (42 of 52 hospitals, 80%) and posaconazole (39 of 52 hospitals, 75%). Furthermore, 33 ASPs (48%) agreed or strongly agreed that antifungals are inappropriately used at their institution, and only 25 of 68 (37%) of ASPs felt very confident making recommendations about antifungals. CONCLUSIONS: Most pediatric ASPs steward antifungals, but the strategies employed are highly variable across surveyed institutions. Although nearly half of respondents identified inappropriate antifungal use as a problem at their institution, most ASPs do not feel confident making recommendations about antifungals. Future studies are needed to determine the rate of inappropriate antifungal use and the best antifungal stewardship strategies

Characteristics of antifungal utilization for hospitalized children in the United States

OBJECTIVE: To characterize antifungal prescribing patterns, including the indication for antifungal use, in hospitalized children across the United States. DESIGN: We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a cross-sectional point-prevalence survey conducted between June 2016 and December 2017. METHODS: Inpatients aged \u3c18 years with an active systemic antifungal order were included in the analysis. We classified antifungal prescribing by indication (ie, prophylaxis, empiric, targeted), and we compared the proportion of patients in each category based on patient and antifungal characteristics. RESULTS: Among 34,927 surveyed patients, 2,095 (6%) received at least 1 systemic antifungal and there were 2,207 antifungal prescriptions. Most patients had an underlying oncology or bone marrow transplant diagnosis (57%) or were premature (13%). The most prescribed antifungal was fluconazole (48%) and the most common indication for antifungal use was prophylaxis (64%). Of 2,095 patients receiving antifungals, 79 (4%) were prescribed \u3e1 antifungal, most often as targeted therapy (48%). The antifungal prescribing rate ranged from 13.6 to 131.2 antifungals per 1,000 patients across hospitals ( CONCLUSIONS: Most antifungal use in hospitalized children was for prophylaxis, and the rate of antifungal prescribing varied significantly across hospitals. Potential targets for antifungal stewardship efforts include high-risk, high-utilization populations, such as oncology and bone marrow transplant patients, and specific patterns of utilization, including prophylactic and combination antifungal therapy

A System for Performing High Throughput Assays of Synaptic Function

Unbiased, high-throughput screening has proven invaluable for dissecting complex biological processes. Application of this general approach to synaptic function would have a major impact on neuroscience research and drug discovery. However, existing techniques for studying synaptic physiology are labor intensive and low-throughput. Here, we describe a new high-throughput technology for performing assays of synaptic function in primary neurons cultured in microtiter plates. We show that this system can perform 96 synaptic vesicle cycling assays in parallel with high sensitivity, precision, uniformity, and reproducibility and can detect modulators of presynaptic function. By screening libraries of pharmacologically defined compounds on rat forebrain cultures, we have used this system to identify novel effects of compounds on specific aspects of presynaptic function. As a system for unbiased compound as well as genomic screening, this technology has significant applications for basic neuroscience research and for the discovery of novel, mechanism-based treatments for central nervous system disorders

All in the family: partisan disagreement and electoral mobilization in intimate networks—a spillover experiment

We advance the debate about the impact of political disagreement in social networks on electoral participation by addressing issues of causal inference common in network studies, focusing on voters' most important context of interpersonal influence: the household. We leverage a randomly assigned spillover experiment conducted in the United Kingdom, combined with a detailed database of pretreatment party preferences and public turnout records, to identify social influence within heterogeneous and homogeneous partisan households. Our results show that intrahousehold mobilization effects are larger as a result of campaign contact in heterogeneous than in homogeneous partisan households, and larger still when the partisan intensity of the message is exogenously increased, suggesting discussion rather than behavioral contagion as a mechanism. Our results qualify findings from influential observational studies and suggest that within intimate social networks, negative correlations between political heterogeneity and electoral participation are unlikely to result from political disagreement

Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration : A Randomized Phase 2 Trial

Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Apoptosis Is Essential for Neutrophil Functional Shutdown and Determines Tissue Damage in Experimental Pneumococcal Meningitis

During acute bacterial infections such as meningitis, neutrophils enter the tissue where they combat the infection before they undergo apoptosis and are taken up by macrophages. Neutrophils show pro-inflammatory activity and may contribute to tissue damage. In pneumococcal meningitis, neuronal damage despite adequate chemotherapy is a frequent clinical finding. This damage may be due to excessive neutrophil activity. We here show that transgenic expression of Bcl-2 in haematopoietic cells blocks the resolution of inflammation following antibiotic therapy in a mouse model of pneumococcal meningitis. The persistence of neutrophil brain infiltrates was accompanied by high levels of IL-1β and G-CSF as well as reduced levels of anti-inflammatory TGF-β. Significantly, Bcl-2-transgenic mice developed more severe disease that was dependent on neutrophils, characterized by pronounced vasogenic edema, vasculitis, brain haemorrhages and higher clinical scores. In vitro analysis of neutrophils demonstrated that apoptosis inhibition completely preserves neutrophil effector function and prevents internalization by macrophages. The inhibitor of cyclin-dependent kinases, roscovitine induced apoptosis in neutrophils in vitro and in vivo. In wild type mice treated with antibiotics, roscovitine significantly improved the resolution of the inflammation after pneumococcal infection and accelerated recovery. These results indicate that apoptosis is essential to turn off activated neutrophils and show that inflammatory activity and disease severity in a pyogenic infection can be modulated by targeting the apoptotic pathway in neutrophils