Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients, such as iron. Pathogens scavenge iron using siderophores, including enterobactin; however, this strategy is counteracted by host protein lipocalin-2, which sequesters iron-laden enterobactin. Although this iron competition occurs in the presence of gut bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron and sustains its resilience in the inflamed gut by utilizing siderophores produced by other bacteria, including Salmonella, via a secreted siderophore-binding lipoprotein XusB. Notably, XusB-bound enterobactin is less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella, allowing the pathogen to evade nutritional immunity. Because the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the host-pathogen interactions and nutritional immunity.

Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients such as iron. Pathogens scavenge iron using siderophores, which is counteracted by the host using lipocalin-2, a protein that sequesters iron-laden siderophores, including enterobactin. Although the host and pathogens compete for iron in the presence of gut commensal bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron in the inflamed gut by utilizing siderophores produced by other bacteria including Salmonella, via a secreted siderophore-binding lipoprotein termed XusB. Notably, XusB-bound siderophores are less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella , allowing the pathogen to evade nutritional immunity. As the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the interactions between pathogen and host nutritional immunity.

Redesign of computerized decision support to improve antimicrobial prescribing. A controlled before-and-after study.

OBJECTIVE: To determine the impact of the introduction of new pre-written orders for antimicrobials in a computerized provider order entry (CPOE) system on 1) accuracy of documented indications for antimicrobials in the CPOE system, 2) appropriateness of antimicrobial prescribing, and 3) compliance with the hospital's antimicrobial policy. Prescriber opinions of the new decision support were also explored to determine why the redesign was effective or ineffective in altering prescribing practices. METHODS: The study comprised two parts: a controlled pre-post study and qualitative interviews. The intervention involved the redesign of pre-written orders for half the antimicrobials so that approved indications were incorporated into pre-written orders. 555 antimicrobials prescribed before (September - October, 2013) and 534 antimicrobials prescribed after (March - April, 2015) the intervention on all general wards of a hospital were audited by study pharmacists. Eleven prescribers participated in semi-structured interviews. RESULTS: Redesign of computerized decision support did not result in more appropriate or compliant antimicrobial prescribing, nor did it improve accuracy of indication documentation in the CPOE system (Intervention antimicrobials: appropriateness 49% vs. 50%; compliance 44% vs. 42%; accuracy 58% vs. 38%; all p>0.05). Via our interviews with prescribers we identified five main reasons for this, primarily that indications entered into the CPOE system were not monitored or followed-up, and that the antimicrobial approval process did not align well with prescriber workflow. CONCLUSION: Redesign of pre-written orders to incorporate appropriate indications did not improve antimicrobial prescribing. Workarounds are likely when compliance with hospital policy creates additional work for prescribers or when system usability is poor. Implementation of IT, in the absence of support or follow-up, is unlikely to achieve all anticipated benefits.

Cost-effectiveness analysis of a hospital electronic medication management system.

OBJECTIVE: To conduct a cost-effectiveness analysis of a hospital electronic medication management system (eMMS). METHODS: We compared costs and benefits of paper-based prescribing with a commercial eMMS (CSC MedChart) on one cardiology ward in a major 326-bed teaching hospital, assuming a 15-year time horizon and a health system perspective. The eMMS implementation and operating costs were obtained from the study site. We used data on eMMS effectiveness in reducing potential adverse drug events (ADEs), and potential ADEs intercepted, based on review of 1 202 patient charts before (n = 801) and after (n = 401) eMMS. These were combined with published estimates of actual ADEs and their costs. RESULTS: The rate of potential ADEs following eMMS fell from 0.17 per admission to 0.05; a reduction of 71%. The annualized eMMS implementation, maintenance, and operating costs for the cardiology ward were A$61 741 (US$55 296). The estimated reduction in ADEs post eMMS was approximately 80 actual ADEs per year. The reduced costs associated with these ADEs were more than sufficient to offset the costs of the eMMS. Estimated savings resulting from eMMS implementation were A$63-66 (US$56-59) per admission (A$97 740-$102 000 per annum for this ward). Sensitivity analyses demonstrated results were robust when both eMMS effectiveness and costs of actual ADEs were varied substantially. CONCLUSION: The eMMS within this setting was more effective and less expensive than paper-based prescribing. Comparison with the few previous full economic evaluations available suggests a marked improvement in the cost-effectiveness of eMMS, largely driven by increased effectiveness of contemporary eMMs in reducing medication errors.

The safety of electronic prescribing: manifestations, mechanisms, and rates of system-related errors associated with two commercial systems in hospitals.

OBJECTIVES: To compare the manifestations, mechanisms, and rates of system-related errors associated with two electronic prescribing systems (e-PS). To determine if the rate of system-related prescribing errors is greater than the rate of errors prevented. METHODS: Audit of 629 inpatient admissions at two hospitals in Sydney, Australia using the CSC MedChart and Cerner Millennium e-PS. System related errors were classified by manifestation (eg, wrong dose), mechanism, and severity. A mechanism typology comprised errors made: selecting items from drop-down menus; constructing orders; editing orders; or failing to complete new e-PS tasks. Proportions and rates of errors by manifestation, mechanism, and e-PS were calculated. RESULTS: 42.4% (n=493) of 1164 prescribing errors were system-related (78/100 admissions). This result did not differ by e-PS (MedChart 42.6% (95% CI 39.1 to 46.1); Cerner 41.9% (37.1 to 46.8)). For 13.4% (n=66) of system-related errors there was evidence that the error was detected prior to study audit. 27.4% (n=135) of system-related errors manifested as timing errors and 22.5% (n=111) wrong drug strength errors. Selection errors accounted for 43.4% (34.2/100 admissions), editing errors 21.1% (16.5/100 admissions), and failure to complete new e-PS tasks 32.0% (32.0/100 admissions). MedChart generated more selection errors (OR=4.17; p=0.00002) but fewer new task failures (OR=0.37; p=0.003) relative to the Cerner e-PS. The two systems prevented significantly more errors than they generated (220/100 admissions (95% CI 180 to 261) vs 78 (95% CI 66 to 91)). CONCLUSIONS: System-related errors are frequent, yet few are detected. e-PS require new tasks of prescribers, creating additional cognitive load and error opportunities. Dual classification, by manifestation and mechanism, allowed identification of design features which increase risk and potential solutions. e-PS designs with fewer drop-down menu selections may reduce error risk.

Implementing electronic medication management at an Australian teaching hospital.

We describe the implementation of an electronic medication management system (eMMS) in an Australian teaching hospital, to inform future similar exercises. The success of eMMS implementation depends on: a positive workplace culture (leadership, teamwork and clinician ownership); acceptance of the major impact on work practices by all staff; timely system response to user feedback; training and support for clinicians; a usable system; adequate decision support.

The influence of computerized decision support on prescribing during ward-rounds: are the decision-makers targeted?

OBJECTIVE: To assess whether a low level of decision support within a hospital computerized provider order entry system has an observable influence on the medication ordering process on ward-rounds and to assess prescribers' views of the decision support features. METHODS: 14 specialty teams (46 doctors) were shadowed by the investigator while on their ward-rounds and 16 prescribers from these teams were interviewed. RESULTS: Senior doctors were highly influential in prescribing decisions during ward-rounds but rarely used the computerized provider order entry system. Junior doctors entered the majority of medication orders into the system, nearly always ignored computerized alerts and never raised their occurrence with other doctors on ward-rounds. Interviews with doctors revealed that some decision support features were valued but most were not perceived to be useful. DISCUSSION AND CONCLUSION: The computerized alerts failed to target the doctors who were making the prescribing decisions on ward-rounds. Senior doctors were the decision makers, yet the junior doctors who used the system received the alerts. As a result, the alert information was generally ignored and not incorporated into the decision-making processes on ward-rounds. The greatest value of decision support in this setting may be in non-ward-round situations where senior doctors are less influential. Identifying how prescribing systems are used during different clinical activities can guide the design of decision support that effectively supports users in different situations. If confirmed, the findings reported here present a specific focus and user group for designers of medication decision support.