MIC distribution analysis identifies differences in AMR between population sub-groups.

Background: Phenotypic data, such as the minimum inhibitory concentrations (MICs) of bacterial isolates from clinical samples, are widely available through routine surveillance. MIC distributions inform antibiotic dosing in clinical care by determining cutoffs to define isolates as susceptible or resistant. However, differences in MIC distributions between patient sub-populations could indicate strain variation and hence differences in transmission, infection, or selection. Methods: The Vivli AMR register contains a wealth of MIC and metadata for a vast range of bacteria-antibiotic combinations. Using a generalisable methodology followed by multivariate regression, we explored MIC distribution variations across 4 bacteria, covering 7,135,070 samples, by key population sub-groups such as age, sex and infection type, and over time. Results: We found clear differences between MIC distributions across various patient sub-groups for a subset of bacteria-antibiotic pairings. For example, within Staphylococcus aureus, MIC distributions by age group and infection site displayed clear trends, especially for levofloxacin with higher resistance levels in older age groups (odds of 2.17 in those aged 85+ compared to 19-64), which appeared more often in men. This trend could reflect greater use of fluoroquinolones in adults than children but also reveals an increasing MIC level with age, suggesting either transmission differences or accumulation of resistance effects. We also observed high variations by WHO region, and over time, with the latter likely linked to changes in surveillance. Conclusions: We found that MIC distributions can be used to identify differences in AMR levels between population sub-groups. Our methodology could be used more widely to unveil hidden transmission sources and effects of antibiotic use in different patient sub-groups, highlighting opportunities to improve stewardship programmes and interventions, particularly at local scales.

Resistance of bacteria to antibiotics is a global problem and causes millions of deaths every year. How resistant an organism is to an antibiotic can be measured very easily and cheaply and can potentially provide a lot of information about bacterial evolution and how to use the right antibiotics to treat infections. We took multiple large, global collections of these measurements and combined them together. We then took this large dataset, and looked at whether any differences in the degree of resistance could be seen when you separated the bacteria by the background of the patient they came from. In other words, we looked at whether certain groups of patients had more or less resistant bacteria. For some very important bacterial species, we found that age played a strong role, with some bacteria from older people having more resistance against some antibiotics. Also, generally men had infections with bacteria with more resistance. The type of infection was also important, as was the region of the world that the patient was from, with South-East Asia generally having more risk of higher resistance. These results highlight that we can use this data to discover more subtle differences in the bacteria causing infections that different patients suffer from. This could help us to change how we use antibiotics, so that we can maximise their effectiveness for longer. Whilst these results were very interesting, the main thing that we hope to highlight is that this method could be used effectively in local hospitals, where resistance data is collected routinely and often, to try and help doctors to understand AMR in their settings, intervene to prevent spread and better prescribe antibiotics day-to-day.

Acceptability of the Venting Wisely pathway for use in critically ill adults with hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS): a qualitative study protocol.

INTRODUCTION: Hypoxaemic respiratory failure (HRF) affects nearly 15% of critically ill adults admitted to an intensive care unit (ICU). An evidence-based, stakeholder-informed multidisciplinary care pathway (Venting Wisely) was created to standardise the diagnosis and management of patients with HRF and acute respiratory distress syndrome. Successful adherence to the pathway requires a coordinated team-based approach by the clinician team. The overall aim of this study is to describe the acceptability of the Venting Wisely pathway among critical care clinicians. Specifically, this will allow us to (1) better understand the user's experience with the intervention and (2) determine if the intervention was delivered as intended. METHODS AND ANALYSIS: This qualitative study will conduct focus groups with nurse practitioners, physicians, registered nurses and registered respiratory therapists from 17 Alberta ICUs. We will use template analysis to describe the acceptability of a multicomponent care pathway according to seven constructs of acceptability: (1) affective attitude;,(2) burden, (3) ethicality, (4) intervention coherence, (5) opportunity costs, (6) perceived effectiveness and (7) self-efficacy. This study will contribute to a better understanding of the acceptability of the Venting Wisely pathway. Identification of areas of poor acceptability will be used to refine the pathway and implementation strategies as ways to improve adherence to the pathway and promote its sustainability. ETHICS AND DISSEMINATION: The study was approved by the University of Calgary Conjoint Health Research Ethics Board. The results will be submitted for publication in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04744298.

Designing a Behaviour Change Wheel guided implementation strategy for a hypoxaemic respiratory failure and ARDS care pathway that targets barriers.

BACKGROUND: A significant gap exists between ideal evidence-based practice and real-world application of evidence-informed therapies for patients with hypoxaemic respiratory failure (HRF) and acute respiratory distress syndrome (ARDS). Pathways can improve the quality of care provided by helping integrate and organise the use of evidence informed practices, but barriers exist that can influence their adoption and successful implementation. We sought to identify barriers to the implementation of a best practice care pathway for HRF and ARDS and design an implementation science-based strategy targeting these barriers that is tailored to the critical care setting. METHODS: The intervention assessed was a previously described multidisciplinary, evidence-based, stakeholder-informed, integrated care pathway for HRF and ARDS. A survey questionnaire (12 open text questions) was administered to intensive care unit (ICU) clinicians (physicians, nurses, respiratory therapists) in 17 adult ICUs across Alberta. The Behaviour Change Wheel, capability, opportunity, motivation - behaviour components, and Theoretical Domains Framework (TDF) were used to perform qualitative analysis on open text responses to identify barriers to the use of the pathway. Behaviour change technique (BCT) taxonomy, and Affordability, Practicality, Effectiveness and cost-effectiveness, Acceptability, Side effects and safety and Equity (APEASE) criteria were used to design an implementation science-based strategy specific to the critical care context. RESULTS: Survey responses (692) resulted in 16 belief statements and 9 themes with 9 relevant TDF domains. Differences in responses between clinician professional group and hospital setting were common. Based on intervention functions linked to each belief statement and its relevant TDF domain, 26 candidate BCTs were identified and evaluated using APEASE criteria. 23 BCTs were selected and grouped to form 8 key components of a final strategy: Audit and feedback, education, training, clinical decision support, site champions, reminders, implementation support and empowerment. The final strategy was described using the template for intervention description and replication framework. CONCLUSIONS: Barriers to a best practice care pathway were identified and were amenable to the design of an implementation science-based mitigation strategy. Future work will evaluate the ability of this strategy to improve quality of care by assessing clinician behaviour change via better adherence to evidence-based care.

Drivers of Antibiotic Use in Semi-Intensive Poultry Farms: Evidence from a Survey in Senegal.

Antimicrobial resistance (AMR), the capacity of microbial pathogens to survive in the presence of antimicrobials, is considered one of the greatest threats to human health worldwide and is growing rapidly in importance. AMR is thought to be driven in part by the use of antimicrobials (AMU) in livestock production. AMU reduction in agriculture is therefore important, but doing so may endanger farmers' livelihoods and hamper broader food security. Understanding the drivers for farmers' antibiotics use is essential for designing interventions which avoid harming agricultural output and to safeguard farmers' economic security. In this study, we analyse AMUSE survey data from poultry farmers in Senegal to explore the effects of vaccination, attitudes towards AMR, and biosecurity practices on: AMU, animal mortality, and farm productivity. We found that farmers with more "AMR-aware" attitudes may be less likely to use antibiotics in healthy birds. Stronger on-farm biosecurity was associated with less use of antibiotics in healthy birds, and in some specifications was linked to higher broiler productivity. Vaccination and AMU were both higher in farms with a higher disease prevalence, and both factors appeared conducive to higher broiler productivity. Overall, there is evidence that awareness raising and biosecurity improvements could encourage prudent use of antibiotics, and that biosecurity and vaccination could to some extent replace antibiotic use as productivity-enhancing and disease management tools in broiler farms. Finally, issues of farm antimicrobial stewardship must be considered at the structural level, with farm behaviours contingent on interaction with state and private stakeholders.

Protocol and statistical analysis plan for the identification and treatment of hypoxemic respiratory failure and acute respiratory distress syndrome with protection, paralysis, and proning: A type-1 hybrid stepped-wedge cluster randomised effectiveness-implementation study.

Objective: To describe a study protocol and statistical analysis plan (SAP) for the identification and treatment of hypoxemic respiratory failure (HRF) and acute respiratory distress syndrome (ARDS) with protection, paralysis, and proning (TheraPPP) study prior to completion of recruitment, electronic data retrieval, and analysis of any data. Design: TheraPPP is a stepped-wedge cluster randomised study evaluating a care pathway for HRF and ARDS patients. This is a type-1 hybrid effectiveness-implementation study design evaluating both intervention effectiveness and implementation; however primarily powered for the effectiveness outcome. Setting: Seventeen adult intensive care units (ICUs) across Alberta, Canada. Participants: We estimate a sample size of 18816 mechanically ventilated patients, with 11424 patients preimplementation and 7392 patients postimplementation. We estimate 2688 sustained ARDS patients within our study cohort. Intervention: An evidence-based, stakeholder-informed, multidisciplinary care pathway called Venting Wisely that standardises diagnosis and treatment of HRF and ARDS patients. Main outcome measures: The primary outcome is 28-day ventilator-free days (VFDs). The primary analysis will compare the mean 28-day VFDs preimplementation and postimplementation using a mixed-effects linear regression model. Prespecified subgroups include sex, age, HRF, ARDS, COVID-19, cardiac surgery, body mass index, height, illness acuity, and ICU volume. Results: This protocol and SAP are reported using the Standard Protocol Items: Recommendations for Interventional Trials guidance and the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. The study received ethics approval and was registered (ClinicalTrials.gov-NCT04744298) prior to patient enrolment. Conclusions: TheraPPP will evaluate the effectiveness and implementation of an HRF and ARDS care pathway.

Development and Content Validation of a Multidisciplinary Standardized Management Pathway for Hypoxemic Respiratory Failure and Acute Respiratory Distress Syndrome.

OBJECTIVES: Treatment of hypoxemic respiratory failure and acute respiratory distress syndrome is complex. Evidence-based therapies that can improve survival and guidelines advocating their use exist; however, implementation is inconsistent. Our objective was to develop and validate an evidence-based, stakeholder-informed standardized management pathway for hypoxemic respiratory failure and acute respiratory distress syndrome to improve adherence to best practice. DESIGN: A standardized management pathway was developed using a modified Delphi consensus process with a multidisciplinary group of ICU clinicians. The proposed pathway was externally validated with a survey involving multidisciplinary stakeholders and clinicians. SETTING: In-person meeting and web-based surveys of ICU clinicians from 17 adult ICUs in the province of Alberta, Canada. INTERVENTION: Not applicable. MEASUREMENTS AND MAIN RESULTS: The consensus panel was comprised of 30 ICU clinicians (4 nurses, 10 respiratory therapists, 15 intensivists, 1 nurse practitioner; median years of practice 17 [interquartile range, 13-21]). Ninety-one components were serially rated and revised over two rounds of online and one in-person review. The final pathway included 46 elements. For the validation survey, 692 responses (including 59% nurses, 33% respiratory therapists, 7% intensivists and 1% nurse practitioners) were received. Agreement of greater than 75% was achieved on 43 of 46 pathway elements. CONCLUSIONS: A 46-element evidence-informed hypoxemic respiratory failure and acute respiratory distress syndrome standardized management pathway was developed and demonstrated to have content validity.

Prone positioning for ARDS patients-tips for preparation and use during the COVID-19 pandemic.

Many patients with coronavirus disease (COVID-19) will develop acute respiratory distress syndrome (ARDS). Prone positioning is an important non-pharmacologic strategy that should be considered for all invasively ventilated patients with moderate to severe ARDS (including those with COVID-19). Prone positioning offers several physiologic and clinical benefits, including improving hypoxemia, matching ventilation with perfusion, reducing regional hyperinflation, and improving survival. To safely offer prone positioning, appropriate training, simulation, and health system planning should be undertaken. In this review, we offer ten tips, based on the Alberta provincial prone positioning strategy during COVID-19, to safely implement and improve the appropriate use of prone positioning. We provide special considerations for its use during the COVID-19 pandemic or future respiratory pandemics.

RéSUMé: De nombreux patients atteints de la maladie du coronavirus (COVID-19) développeront un syndrome de détresse respiratoire aiguë (SDRA, ARDS en anglais). Le positionnement ventral est une importante stratégie non pharmacologique qui devrait être envisagée pour tous les patients ventilés de manière invasive et souffrant d'un SDRA modéré à grave (y compris ceux atteints de la COVID-19). Le positionnement ventral offre plusieurs avantages physiologiques et cliniques, notamment l'amélioration de l'hypoxémie, une adéquation de la ventilation avec la perfusion, la réduction de l'hyperinflation régionale et l'amélioration de la survie. Pour offrir un positionnement ventral en toute sécurité, une formation, des simulations et une planification des ressources appropriées devraient être entreprises. Dans le cadre de ce compte rendu, nous proposons dix conseils, fondés sur la stratégie provinciale de positionnement ventral de l'Alberta au cours de la COVID-19, afin de mettre en œuvre et d'améliorer en toute sécurité l'utilisation appropriée du positionnement ventral. Nous décrivons des considérations particulières pour son utilisation pendant la pandémie de COVID-19 ou les futures pandémies respiratoires.

Standardized Management for Hypoxemic Respiratory Failure and ARDS: Systematic Review and Meta-analysis.

BACKGROUND: Treatment of hypoxemic respiratory failure (HRF) and ARDS is complex. Standardized management of HRF and ARDS may improve adherence to evidence-informed practice and improve outcomes. RESEARCH QUESTION: What is the effect of standardized treatment compared with usual care on survival of patients with HRF and ARDS? STUDY DESIGN AND METHODS: MEDLINE, EMBASE, Cochrane, CINAHL, Scopus, and Web-of-Science were searched (inception to 2018). Included studies were randomized clinical trials or quasi-experimental studies that examined the effect of standardized treatment (care-protocol, care-pathway, or bundle) compared with usual treatment among mechanically ventilated adult patients admitted to an ICU with HRF or ARDS. Study characteristics, pathway components, and patient outcomes were abstracted independently by two reviewers. RESULTS: From 15,932 unique citations, 14 studies were included in the systematic review (three randomized clinical trials and 11 quasi-experimental studies). Twelve studies (including 5,767 patients) were included in the meta-analysis. Standardized management of HRF was associated with a 23% relative reduction in mortality (relative risk, 0.77; 95% CI, 0.65-0.91; I2, 70%; P = .002). In studies targeting patients with ARDS (n = 8), a 21% pooled mortality reduction was observed (relative risk, 0.79; 95% CI, 0.71-0.88; I2, 3.1%). Standardized management was associated with increased 28-day ventilator-free days (weighted mean difference, 3.48 days; 95% CI, 2.43-4.54 days; P < .001). Standardized management was also associated with a reduction in tidal volume (weighted mean difference, -1.80 mL/kg predicted body weight; 95% CI, -2.80 to -0.80 mL/kg predicted body weight; P < .001). Meta-regression demonstrated that the reduction in mortality was associated with provision of lower tidal volume (P = .045). INTERPRETATION: When compared with usual treatment, standardized treatment of patients with HRF and ARDS is associated with increased ventilator-free days, lower tidal volume ventilation, and lower mortality. ICUs should consider the use of standardized treatment to improve the processes and outcomes of care for patients with HRF and ARDS. CLINICAL TRIAL REGISTRATION: PROSPERO; No.: CRD42019099921; URL: www.crd.york.ac.uk/prospero/.