Forecasting Implementation, Adoption, and Evaluation Challenges for an Electronic Game-Based Antimicrobial Stewardship Intervention: Co-Design Workshop With Multidisciplinary Stakeholders.

BACKGROUND: Serious games have been proposed to address the lack of engagement and sustainability traditionally affecting interventions aiming to improve optimal antibiotic use among hospital prescribers. OBJECTIVE: The goal of the research was to forecast gaps in implementation, adoption and evaluation of game-based interventions, and co-design solutions with antimicrobial clinicians and digital and behavioral researchers. METHODS: A co-development workshop with clinicians and academics in serious games, antimicrobials, and behavioral sciences was organized to open the International Summit on Serious Health Games in London, United Kingdom, in March 2018. The workshop was announced on social media and online platforms. Attendees were asked to work in small groups provided with a laptop/tablet and the latest version of the game On call: Antibiotics. A workshop leader guided open group discussions around implementation, adoption, and evaluation threats and potential solutions. Workshop summary notes were collated by an observer. RESULTS: There were 29 participants attending the workshop. Anticipated challenges to resolve reflected implementation threats such as an inadequate organizational arrangement to scale and sustain the use of the game, requiring sufficient technical and educational support and a streamlined feedback mechanism that made best use of data arriving from the game. Adoption threats included collective perceptions that a game would be a ludic rather than professional tool and demanding efforts to integrate all available educational solutions so none are seen as inferior. Evaluation threats included the need to combine game metrics with organizational indicators such as antibiotic use, which may be difficult to enable. CONCLUSIONS: As with other technology-based interventions, deploying game-based solutions requires careful planning on how to engage and support clinicians in their use and how best to integrate the game and game outputs onto existing workflows. The ludic characteristics of the game may foster perceptions of unprofessionalism among gamers, which would need buffering from the organization.

Investigating the cultural and contextual determinants of antimicrobial stewardship programmes across low-, middle- and high-income countries-A qualitative study.

BACKGROUND: Most of the evidence on antimicrobial stewardship programmes (ASP) to help sustain the effectiveness of antimicrobials is generated in high income countries. We report a study investigating implementation of ASP in secondary care across low-, middle- and high-income countries. The objective of this study was to map the key contextual, including cultural, drivers of the development and implementation of ASP across different resource settings. MATERIALS AND METHODS: Healthcare professionals responsible for implementing ASP in hospitals in England, France, Norway, India, and Burkina Faso were invited to participate in face-to face interviews. Field notes from observations, documentary evidence, and interview transcripts were analysed using grounded theory approach. The key emerging categories were analysed iteratively using constant comparison, initial coding, going back the field for further data collection, and focused coding. Theoretical sampling was applied until the categories were saturated. Cross-validation and triangulation of the findings were achieved through the multiple data sources. RESULTS: 54 participants from 24 hospitals (England 9 participants/4 hospitals; Norway 13 participants/4 hospitals; France 9 participants/7 hospitals; India 13 participants/ 7 hospitals; Burkina Faso 8 participants/2 hospitals) were interviewed. Across Norway, France and England there was consistency in ASP structures. In India and Burkina Faso there were country level heterogeneity in ASP. State support for ASP was perceived as essential in countries where it is lacking (India, Burkina Faso), and where it was present, it was perceived as a barrier (England, France). Professional boundaries are one of the key cultural determinants dictating involvement in initiatives with doctors recognised as leaders in ASP. Nurse and pharmacist involvement was limited to England. The surgical specialty was identified as most difficult to engage with in each country. Despite challenges, one hospital in India provided the best example of interdisciplinary ASP, championed through organisational leadership. CONCLUSIONS: ASP initiatives in this study were restricted by professional boundaries and hierarchies, with lack of engagement with the wider healthcare workforce. There needs to be promotion of interdisciplinary team work including pharmacists and nurses, depending on the available healthcare workforce in different countries, in ASP. The surgical pathway remains a hard to reach, but critical target for ASP globally. There is a need to develop contextually driven ASP targeting the surgical pathway in different resource settings.

Closed-Loop Control for Precision Antimicrobial Delivery: An In Silico Proof-of-Concept.

OBJECTIVE: Inappropriate dosing of patients with antibiotics is a driver of antimicrobial resistance, toxicity, and poor outcomes of therapy. In this paper, we investigate, in silico, the hypothesis that the use of a closed-loop control system could improve the attainment of pharmacokinetic-pharmacodynamic targets for antimicrobial therapy, where wide variations in target attainment have been reported. This includes patients in critical care, patients with renal disease, and patients with obesity. METHODS: The presented in silico study focuses on vancomycin delivery, a first line therapy for Methicillin-resistant Staphylococcus aureus (MRSA) that has serious side effects, including nephrotoxicity. For this purpose, an in silico platform for the simulation of pharmacokinetics of vancomycin agents was developed including 24 virtual noncritically ill-adult subjects obtained from routinely collected data from two prospective audits of vancomycin therapy. Intraday variability on renal clearance, sensor error, and infusion constraints were taken into account. Proportional integral derivative (PID) controller was chosen because of its simplicity of implementation and satisfactory performance. RESULTS: Even though significant intraday variability and sensor error were considered in the simulations, by assuming a minimum inhibitory concentration of 1 mg/l for MRSA, the proposed controller was able to reach the well-established therapeutic target of 24-h area under curve to minimum inhibitory concentration ratio equal to 400 $\text{mg} \cdot \text{h}\text{/}\text{l}$ for all the studied subjects, while staying significantly below toxic levels. CONCLUSION: A PID controller has the potential to precisely deliver a vancomycin therapy in a noncritically ill-adult population. SIGNIFICANCE: Closed-loop control for precision Vancomycin delivery can potentially reduce toxicity and poor therapeutic outcomes, as well as reduce antimicrobial resistance.

Obtaining antibiotics online from within the UK: a cross-sectional study.

Background: Improved antibiotic stewardship (AS) and reduced prescribing in primary care, with a parallel increase in personal internet use, could lead citizens to obtain antibiotics from alternative sources online. Objectives: A cross-sectional analysis was performed to: (i) determine the quality and legality of online pharmacies selling antibiotics to the UK public; (ii) describe processes for obtaining antibiotics online from within the UK; and (iii) identify resulting AS and patient safety issues. Methods: Searches were conducted for 'buy antibiotics online' using Google and Yahoo. For each search engine, data from the first 10 web sites with unique URL addresses were reviewed. Analysis was conducted on evidence of appropriate pharmacy registration, prescription requirement, whether antibiotic choice was 'prescriber-driven' or 'consumer-driven', and whether specific information was required (allergies, comorbidities, pregnancy) or given (adverse effects) prior to purchase. Results: Twenty unique URL addresses were analysed in detail. Online pharmacies evidencing their location in the UK ( n = 5; 25%) required a prescription before antibiotic purchase, and were appropriately registered. Online pharmacies unclear about the location they were operating from ( n = 10; 50%) had variable prescription requirements, and no evidence of appropriate registration. Nine (45%) online pharmacies did not require a prescription prior to purchase. For 16 (80%) online pharmacies, decisions were initially consumer-driven for antibiotic choice, dose and quantity. Conclusions: Wide variation exists among online pharmacies in relation to antibiotic practices, highlighting considerable patient safety and AS issues. Improved education, legislation, regulation and new best practice stewardship guidelines are urgently needed for online antibiotic suppliers.

Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study.

BACKGROUND: The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions. METHODS: Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached. RESULTS: Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing 'optimal' care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort. CONCLUSION: Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers.

Information provision for antibacterial dosing in the obese patient: a sizeable absence?

BACKGROUND: Obesity is on course to overtake being underweight as a global disease burden. Obesity alters antibacterial pharmacokinetics (PK) and pharmacodynamics (PD). Historically, drug PK/PD parameters have not been studied in obese populations. This means dose recommendations risk being sub-therapeutic in a population at increased risk of infection. Suboptimal antibacterial prescribing is widely associated with treatment failure, worse clinical outcomes, unnecessary escalation to broad-spectrum therapy and the emergence of antimicrobial resistance (AMR). OBJECTIVES: To analyse current information provided by pharmaceutical companies, for the most commonly prescribed antibacterial agents in the UK, for evidence of dosing guidance for obese adults. METHODS: We analysed the manufacturers' Summary of Product Characteristics (SPC) for 42 of the most clinically important and frequently prescribed antibacterial agents dispensed across both primary and secondary care. The manufacturer's SPC was reviewed, and cross-referenced with the online British National Formulary, to assess dosing guidance for obese adults. RESULTS: No advice was provided to guide dosing for obese adults in 35 (83%) of 42 of the most clinically important and frequently prescribed antibacterial agents in the UK. Seven (17%) antibacterial agents (tigecycline, vancomycin, daptomycin, amikacin, gentamicin, tobramycin and teicoplanin) provided variable levels of advice. CONCLUSIONS: There is a paucity of advice and evidence in the UK to guide dosing common antibacterial agents in the obese. The literature on antibacterial PK/PD studies in obese populations remains scarce. In the face of the increasing risks of AMR combined with the global rise of obesity there is an urgent need to address this significant research gap.