Interventions for rapid recognition and treatment of sepsis in the emergency department: a narrative review.

BACKGROUND: Sepsis is a major cause of morbidity and mortality worldwide. Early recognition and treatment of sepsis is associated with improved outcome. The emergency department (ED) is the department where patients with sepsis seek care. However, recognition of sepsis in the ED remains difficult. Different alert and triage systems, screening scores and intervention strategies have been developed to assist clinicians in early recognition of sepsis and to optimize management. OBJECTIVES: This narrative review describes currently applied interventions or interventions we can start using today, such as screening scores, (automated) triage systems, sepsis teams and clinical pathways in sepsis care; and it summarizes evidence for the effect of implementation of these interventions in the ED on patient management and outcomes. SOURCES: A systematic literature search was conducted in PubMed, resulting in 39 eligible studies. CONTENT: The main sepsis interventions in the ED are (automated) triage systems, sepsis teams and clinical pathways, the most integrative being a clinical pathway. Implementation of any of these interventions in sepsis care will generally lead to increased protocol adherence. Presumably increased adherence to sepsis guidelines and bundles will lead to better patient outcomes, but the level of evidence to support this improvement is low, whereas implementation of interventions is often complex and costly. No studies comparing different interventions were identified. Two essential factors for success of interventions in the ED are obtaining the support from all professionals and providing ongoing education. The vulnerability of these interventions lies in the lack of accurate tools to identify sepsis; diagnosing sepsis ultimately still relies on clinical assessments. A lack of specificity or sepsis alerts may lead to alert fatigue and/or overtreatment. IMPLICATIONS: The severity and poor outcome of sepsis as well as the frequency of its presentation in EDs make a structured, protocol-based approach towards these patients essential, preferably as part of a clinical pathway.

Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group.

BACKGROUND: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. METHODS: An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. RESULTS: We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. CONCLUSIONS: Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.

The quality of studies evaluating antimicrobial stewardship interventions: a systematic review.

BACKGROUND: Antimicrobial stewardship aims to optimize antibiotic use and minimize selection of antimicrobial resistance. The methodological quality of published studies in this field is unknown. AIMS: Our objective was to perform a comprehensive systematic review of antimicrobial stewardship research design and identify features which limit validity and translation of research findings into clinical practice. SOURCES: The following online database was searched: PubMed. STUDY ELIGIBILITY CRITERIA: Studies published between January 1950 and January 2017, evaluating any antimicrobial stewardship intervention in the community or hospital setting, without restriction on study design or outcome. CONTENT: We extracted data on pre-specified design quality features and factors that may influence design choices including (1) clinical setting, (2) age group studied, (3) when the study was conducted, (4) geographical region, and (5) financial support received. The initial search yielded 17 382 articles; 1008 were selected for full-text screening, of which 825 were included. Most studies (675/825, 82%) were non-experimental; 104 (15%) used interrupted time series analysis, 41 (6%) used external controls, and 19 (3%) used both. Studies in the community setting fulfilled a median of five out of 10 quality features (IQR 3-7) and 3 (IQR 2-4) in the hospital setting. Community setting studies (25%, 205/825) were significantly more likely to use randomization (OR 5.9; 95% CI 3.8-9.2), external controls (OR 5.6; 95% CI 3.6-8.5), and multiple centres (OR 10.5; 95% CI 7.1-15.7). From all studies, only 48% (398/825) reported clinical and 23% (190/825) reported microbiological outcomes. Quality did not improve over time. IMPLICATIONS: Overall quality of antimicrobial stewardship studies is low and has not improved over time. Most studies do not report clinical and microbiological outcome data. Studies conducted in the community setting were associated with better quality. These limitations should inform the design of future stewardship evaluations so that a robust evidence base can be built to guide clinical practice.

Relevance of healthcare-associated pneumonia for empirical antibiotic therapy in the Netherlands.

BACKGROUND: There is no consensus whether patients with healthcare-associated pneumonia (HCAP) should be considered as a patient with hospital-acquired pneumonia (HAP) and treated with broad-spectrum antibiotics, or as a patient with community-acquired pneumonia (CAP), and treated with narrow-spectrum antibiotics. HCAP research has focused mostly on the predictive value for non-susceptibility to broad-spectrum antibiotics and multi-drug resistant pathogens, in settings with moderate to high levels of antibiotic resistance. We investigated whether HCAP criteria predicts non-susceptibility to different empirical strategies, including narrow-spectrum antibiotics in the Dutch setting. METHODS: In a post hoc analysis of patients with moderate-severe CAP in seven Dutch hospitals, we compared in vitro antibiotic susceptibilities of definite and possible causative pathogens of CAP and HCAP to amoxicillin and broader antibiotic regimens. In a sensitivity analysis, pathogens with missing susceptibilities were assumed susceptible (best-case scenario) or non-susceptible (worst-case scenario). RESULTS: Among 2,283 patients with moderate-severe CAP, 23.1% (n = 527) were classified as HCAP. Non-susceptibility to amoxicillin ranged from 11.3% (95% CI 9.9-12.8%; best-case) to 14.4% (95% CI 12.8-16.1%; worst-case) in CAP patients and from 16.7% (95% CI 13.8-20.1%; best-case) to 19.7% (95% CI 16.6-23.3%; worst-case) in HCAP patients. The largest reduction in non-susceptibility was achieved by adding ciprofloxacin to amoxicillin treatment in both CAP patients (10% absolute risk reduction) and HCAP patients (11-16% reduction). CONCLUSIONS: In the Netherlands, HCAP criteria predict higher amoxicillin non-susceptibility in patients hospitalized with moderate-severe CAP. Although broadening the antibiotic spectrum of empiric treatment reduced the likelihood of non-susceptibility, absolute reductions of non-susceptibility in HCAP patients were too low to justify the universal use of broad-spectrum empirical therapy.No abstract available.

Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel method to compare strategies to optimize antibiotic use.

OBJECTIVES: The Response Adjusted for Days of Antibiotic Risk (RADAR) statistic was proposed to improve the efficiency of trials comparing antibiotic stewardship strategies to optimize antibiotic use. We studied the behaviour of RADAR in a non-inferiority trial in which a ß-lactam monotherapy strategy (n = 656) was non-inferior to fluoroquinolone monotherapy (n = 888) for patients with moderately severe community-acquired pneumonia. METHODS: Patients were ranked according to clinical outcome, using five or eight categories, and antibiotic use. RADAR was calculated as the probability that the ß-lactam group had a more favourable ranking than the fluoroquinolone group. To investigate the sensitivity of RADAR to detrimental clinical outcome we simulated increasing rates of 90-day mortality in the ß-lactam group and performed the RADAR and non-inferiority analysis. RESULTS: The RADAR of the ß-lactam group compared with the fluoroquinolone group was 60.3% (95% CI 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%) using eight clinical outcome categories, all in favour of ß-lactam. Sample sizes for RADAR were 38% (250/653) and 89% (580/653) of the non-inferiority sample size calculation, using five or eight clinical outcome categories, respectively. With simulated mortality rates, loss of non-inferiority of the ß-lactam group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the ß-lactam group lost superiority at a relative risk of mortality of 1.25 and 1.5, with eight and five clinical outcome categories, respectively. CONCLUSIONS: RADAR favoured ß-lactam over fluoroquinolone therapy for community-acquired pneumonia. Although RADAR required fewer patients than conventional non-inferiority analysis, the statistic was less sensitive to detrimental outcomes.

Predictors for individual patient antibiotic treatment effect in hospitalized community-acquired pneumonia patients.

OBJECTIVE: Our objective was to identify clinical predictors of antibiotic treatment effects in hospitalized patients with community-acquired pneumonia (CAP) who were not in the intensive care unit (ICU). METHODS: Post-hoc analysis of three prospective cohorts (from the Netherlands and Spain) of adult patients with CAP admitted to a non-ICU ward having received either ß-lactam monotherapy, ß-lactam + macrolide, or a fluoroquinolone-based therapy as empirical antibiotic treatment. We evaluated candidate clinical predictors of treatment effects in multiple mixed-effects models by including interactions of the predictors with empirical antibiotic choice and using 30-day mortality, ICU admission and length of hospital stay as outcomes. RESULTS: Among 8562 patients, empirical treatment was ß-lactam in 4399 (51.4%), fluoroquinolone in 3373 (39.4%), and ß-lactam + macrolide in 790 (9.2%). Older age (interaction OR 1.67, 95% CI 1.23-2.29, p 0.034) and current smoking (interaction OR 2.36, 95% CI 1.34-4.17, p 0.046) were associated with lower effectiveness of fluoroquinolone on 30-day mortality. Older age was also associated with lower effectiveness of ß-lactam + macrolide on length of hospital stay (interaction effect ratio 1.14, 95% CI 1.06-1.22, p 0.008). CONCLUSIONS: Older age and smoking could influence the response to specific antibiotic regimens. The effect modification of age and smoking should be considered hypothesis generating to be evaluated in future trials.