Assessing the impact of discordant antibiotic treatment on adverse outcomes in community-onset UTI: a retrospective cohort study.

OBJECTIVES: To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI). METHODS: Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant.The primary outcome was the proportion of patients experiencing urinary infection-related hospital admission (UHA) within 30 days. Secondary outcomes were the proportion of patients experiencing reconsultation within 30 days, and the odds of UHA and reconsultation following discordant treatment, adjusting for sex, age, risk factors for complicated UTI, previous antibiotic treatment, recurrent UTI and comorbidities. RESULTS: A total of 11 963 UTI episodes in 8324 patients were included, and 1686 episodes (14.1%, 95% CI 13.5%-14.7%) were discordant. UHA occurred in 212/10 277 concordant episodes (2.1%, 95% CI 1.8%-2.4%) and 88/1686 discordant episodes (5.2%, 95% CI 4.2%-6.4%). Reconsultation occurred in 3961 concordant (38.5%, 95% CI 37.6%-39.5%) and 1472 discordant episodes (87.3%, 95% CI 85.6%-88.8%). Discordant treatment compared with concordant was associated with increased odds of UHA (adjusted OR 2.31, 95% CI 1.77-3.0, P < 0.001) and reconsultation (adjusted OR 11.25, 95% CI 9.66-13.11, P < 0.001) on multivariable analysis. Chronic kidney disease and diabetes mellitus were also independently associated with increased odds of UHA. CONCLUSIONS: One in seven COLUTI episodes in primary care were treated with discordant antibiotics. In higher risk patients requiring urine culture, empirical antibiotic choice optimization could meaningfully reduce adverse outcomes.

Long-term oral antibiotic use in people with acne vulgaris in UK primary care: a drug utilization study.

BACKGROUND: The inappropriate use of antibiotics is understood to contribute to antimicrobial resistance. Oral antibiotics are regularly used to treat moderate-to-severe acne vulgaris. In practice, we do not know the typical length of oral antibiotic treatment courses for acne in routine primary care and what proportion of people receive more than one course of treatment following a new acne diagnosis. OBJECTIVES: To describe how oral antibiotics are prescribed for acne over time in UK primary care. METHODS: We conducted a descriptive longitudinal drug utilization study using routinely collected primary care data from the Clinical Practice Research Datalink GOLD (2004-2019). We included individuals (8-50 years) with a new acne diagnosis recorded between 1 January 2004 and 31 July 2019. RESULTS: We identified 217 410 people with a new acne diagnosis. The median age was 17 years [interquartile range (IQR) 15-25] and median follow-up was 4.3 years (IQR 1.9-7.6). Among people with a new acne diagnosis, 96 703 (44.5%) received 248 560 prescriptions for long-term oral antibiotics during a median follow-up of 5.3 years (IQR 2.8-8.5). The median number of continuous courses of antibiotic therapy (≥ 28 days) per person was four (IQR 2-6). The majority (n = 59 010, 61.0%) of first oral antibiotic prescriptions in those with a recorded acne diagnosis were between the ages of 12 and 18. Most (n = 71 544, 74.0%) first courses for oral antibiotics were for between 28 and 90 days. The median duration of the first course of treatment was 56 days (IQR 50-93 days) and 18 127 (18.7%) of prescriptions of ≥ 28 days were for < 6 weeks. Among people who received a first course of oral antibiotic for ≥ 28 days, 56 261 (58.2%) received a second course after a treatment gap of ≥ 28 days. The median time between first and second courses was 135 days (IQR 67-302). The cumulative duration of exposure to oral antibiotics during follow-up was 255 days (8.5 months). CONCLUSIONS: Further work is needed to understand the consequences of using antibiotics for shorter periods than recommended. Suboptimal treatment duration may result in reduced clinical effectiveness or repeated exposures, potentially contributing to antimicrobial resistance.

Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of long-term care facilities in the VIVALDI study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations. OBJECTIVE: To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs. DESIGN: Prospective cohort study. SETTING: LTCFs for older people in England participating in the VIVALDI study. METHODS: Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1-3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds). RESULTS: A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45-75% reduction in risk relative to primary vaccination. CONCLUSIONS: Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination.

Factors influencing staff attitudes to COVID-19 vaccination in care homes in England: a qualitative study.

BACKGROUND: The COVID-19 pandemic disproportionately affected people living and working in UK care homes causing high mortality rates. Vaccinating staff members and residents is considered the most effective intervention to reduce infection and its transmission rates. However, uptake of the first dose of the COVID-19 vaccine in care homes was variable. We sought to investigate factors influencing uptake of COVID-19 vaccination in care home staff to inform strategies to increase vaccination uptake and inform future preparedness. METHODS: Twenty care home staff including managerial and administrative staff, nurses, healthcare practitioners and support staff from nine care homes across England participated in semi-structured telephone interviews (March-June 2021) exploring attitudes towards the COVID-19 vaccine and factors influencing uptake. We used thematic analysis to generate themes which were subsequently deductively mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. The Behavioural Change Wheel (BCW) was used to identify potential intervention strategies to address identified influences. RESULTS: Enablers to vaccine uptake included the willingness to protect care home residents, staff and family/friends from infection and the belief that vaccination provided a way back to normality (reflective motivation); convenience of vaccination and access to accurate information (physical opportunity); and a supporting social environment around them favouring vaccination (social opportunity). Barriers included fears about side-effects (automatic motivation); a lack of trust due to the quick release of the vaccine (reflective motivation); and feeling pressurised to accept vaccination if mandatory (automatic motivation). CONCLUSIONS: We identified influences on COVID-19 vaccine uptake by care home staff that can inform the implementation of future vaccination programmes. Strategies likely to support uptake include information campaigns and facilitating communication between staff and managers to openly discuss concerns regarding possible vaccination side effects. Freedom of choice played an important role in the decision to be vaccinated suggesting that the decision to mandate vaccination may have unintended behavioural consequences.

A qualitative interview study applying the COM-B model to explore how hospital-based trainers implement antimicrobial stewardship education and training in UK hospital-based care.

BACKGROUND: Antimicrobial resistance (AMR) is a major global health threat caused by the inappropriate use of antimicrobials in healthcare and other settings. Antimicrobial stewardship (AMS) is a broad multi-component health services intervention that promotes and monitors the judicious use of antimicrobials to preserve their future effectiveness. A main component of AMS is education and training (E&T). However, there are often discrepancies in how such interventions are implemented and delivered in hospital-based care. The aim of this study was to explore the factors influencing the implementation of AMS E&T in UK hospitals. METHODS: Semi-structured interviews were carried out with AMS E&T trainers in UK hospitals. The interview schedule was developed using the Capability, Opportunity, Motivation = Behaviour (COM-B) model. Participants were identified via professional networks and social media. Interviews were analysed using inductive thematic analysis, followed by deductive analysis using the COM-B model as a framework. RESULTS: A total of 34 participants (26 antimicrobial pharmacists, 3 nurses, 1 advanced clinical practitioner, 2 infectious disease consultants, 1 microbiologist and 1 clinical scientist). responsible for designing, implementing and evaluating AMS E&T in UK hospitals (five from Northern Ireland, four from Wales, two from Scotland and 23 from England) took part in virtual interviews. Key themes were: (1) The organisational context, including system-level barriers to AMS included competing organisational targets (Reflective motivation and physical opportunity) and the impact of the COVID-19 pandemic on activity (Physical opportunity); (2) Healthcare professionals' roles and the wider multi-disciplinary team, such that AMS roles were defined and addressed poorly in E&T (Social opportunity); and (3) The individual perception of the need for AMS E&T in hospital-based care, manifest in a perceived lack of conviction of the wider threat of AMR and the resulting need for AMS E&T (Reflective motivation). CONCLUSION: This study has identified factors influencing implementation of AMS E&T in UK hospitals and further identified where implemented, AMS E&T did not address real-world challenges. Current AMS E&T needs to be optimised to elicit practice change, with recommendations including training and engaging the wider work-force and drawing upon theoretically-informed intervention development frameworks to inform AMS E&T to better target AMS behaviour change.

Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).

General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.

COVID-19 prevalence and mortality in longer-term care facilities.

This essay considers the factors that have contributed to very high COVID-19 mortality in longer-term care facilities (LTCFs). We compare the demographic characteristics of LTCF residents with those of community-dwelling older adults, and then we review the evidence regarding prevalence and infection fatality rates (IFRs), including links to frailty and some comorbidities. Finally, we discuss policy measures that could foster the physical and mental health and well-being of LTCF residents in the present context and in potential future pandemics.

Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study.

BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41-4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.

Variation in approaches to antimicrobial use surveillance in high-income secondary care settings: a systematic review.

INTRODUCTION: In secondary care, antimicrobial use (AMU) must be monitored to reduce the risk of antimicrobial resistance and infection-related complications. However, there is variation in how hospitals address this challenge, partly driven by each site's level of digital maturity, expertise and resources available. This systematic review investigated approaches to measuring AMU to explore how these structural differences may present barriers to engagement with AMU surveillance. METHODS: We searched four digital databases and the websites of relevant organizations for studies in high-income, inpatient hospital settings that estimated AMU in adults. Excluded studies focused exclusively on antiviral or antifungal therapies. Data were extracted data on 12 fields (study description, data sources, data extraction methods and professionals involved in surveillance). Proportions were estimated with 95% CIs. RESULTS: We identified 145 reports of antimicrobial surveillance from Europe (63), North America (53), Oceania (14), Asia (13) and across more than continent (2) between 1977 and 2018. Of 145 studies, 47 carried out surveillance based on digital data sources. In regions with access to electronic patient records, 26/47 studies employed manual methods to extract the data. The majority of identified professionals involved in these studies were clinically trained (87/93). CONCLUSIONS: Even in regions with access to electronic datasets, hospitals rely on manual data extraction for this work. Data extraction is undertaken by healthcare professionals, who may have conflicting priorities. Reducing barriers to engagement in AMU surveillance requires investment in methods, resources and training so that hospitals can extract and analyse data already contained within electronic patient records.

Incidence, healthcare-seeking behaviours, antibiotic use and natural history of common infection syndromes in England: results from the Bug Watch community cohort study.

BACKGROUND: Better information on the typical course and management of acute common infections in the community could inform antibiotic stewardship campaigns. We aimed to investigate the incidence, management, and natural history of a range of infection syndromes (respiratory, gastrointestinal, mouth/dental, skin/soft tissue, urinary tract, and eye). METHODS: Bug Watch was an online prospective community cohort study of the general population in England (2018-2019) with weekly symptom reporting for 6 months. We combined symptom reports into infection syndromes, calculated incidence rates, described the proportion leading to healthcare-seeking behaviours and antibiotic use, and estimated duration and severity. RESULTS: The cohort comprised 873 individuals with 23,111 person-weeks follow-up. The mean age was 54 years and 528 (60%) were female. We identified 1422 infection syndromes, comprising 40,590 symptom reports. The incidence of respiratory tract infection syndromes was two per person year; for all other categories it was less than one. 194/1422 (14%) syndromes led to GP (or dentist) consultation and 136/1422 (10%) to antibiotic use. Symptoms usually resolved within a week and the third day was the most severe. CONCLUSIONS: Most people reported managing their symptoms without medical consultation. Interventions encouraging safe self-management across a range of acute infection syndromes could decrease pressure on primary healthcare services and support targets for reducing antibiotic prescribing.

COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).

BACKGROUND: epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic. METHODS: cohort study of 179 UK care homes with 9,339 residents and 11,604 staff. We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality and estimate attributable mortality. RESULTS: 2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff, respectively. Sixty-eight percent (121/179) of care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection.Out of 607 residents with confirmed infection, 217 died (case fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was twofold higher in care homes with outbreaks versus those without (adjusted hazard ratio: 2.2 [1.8; 2.6]). CONCLUSIONS: findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.

Changes in COVID-19 outbreak severity and duration in long-term care facilities following vaccine introduction, England, November 2020 to June 2021.

We describe the impact of changing epidemiology and vaccine introduction on characteristics of COVID-19 outbreaks in 330 long-term care facilities (LTCF) in England between November 2020 and June 2021. As vaccine coverage in LTCF increased and national incidence declined, the total number of outbreaks and outbreak severity decreased across the LTCF. The number of infected cases per outbreak decreased by 80.6%, while the proportion of outbreaks affecting staff only increased. Our study supports findings of vaccine effectiveness in LTCF.

Antibiotic Prescribing Before and After the Diagnosis of Comorbidity: A Cohort Study Using Primary Care Electronic Health Records.

BACKGROUND: Comorbidities such as diabetes and chronic obstructive pulmonary disease (COPD) increase patients' susceptibility to infections, but it is unclear how the onset of comorbidity impacts antibiotic use. We estimated rates of antibiotic use before and after diagnosis of comorbidity in primary care to identify opportunities for antibiotic stewardship. METHODS: We analyzed UK primary care records from the Clinical Practice Research Datalink. Adults registered between 2008-2015 without prior comorbidity diagnoses were eligible for inclusion. Monthly adjusted rates of antibiotic prescribing were estimated for patients with new-onset stroke, coronary heart disease, heart failure, peripheral arterial disease, asthma, chronic kidney disease, diabetes, or COPD in the 12 months before and after diagnosis and for controls without comorbidity. RESULTS: 106 540/1 071 943 (9.9%) eligible patients were diagnosed with comorbidity. Antibiotic prescribing rates increased 1.9- to 2.3-fold in the 4-9 months preceding diagnosis of asthma, heart failure, and COPD before declining to stable levels within 2 months after diagnosis. A less marked trend was seen for diabetes (rate ratio, 1.55; 95% confidence interval, 1.48-1.61). Prescribing rates for patients with vascular conditions increased immediately before diagnosis and remained 30%-39% higher than baseline afterwards. Rates of prescribing to controls increased by 17%-28% in the months just before and after consultation. CONCLUSIONS: Antibiotic prescribing increased rapidly before diagnosis of conditions that present with respiratory symptoms (COPD, heart failure, asthma) and declined afterward. Onset of respiratory symptoms may be misdiagnosed as infection. Earlier diagnosis of these comorbidities could reduce avoidable antibiotic prescribing.

Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England.

BACKGROUND: Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care. METHODS AND FINDINGS: We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI. CONCLUSIONS: In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.

Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study.

BACKGROUND: There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions. METHODS: We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses. RESULTS: The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90-1), compared to 0.79 (0.68-0.91) for WCC and 0.73 (0.61-0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90-0.99) and 0.86 (0.64-0.96), compared to 0.90 (0.80-0.94) and 0.66 (0.48-0.79) for WCC and 0.88 (0.69-0.95) and 0.60 (0.31-0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials. CONCLUSIONS: Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.

Correction to: Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study.

An amendment to this paper has been published and can be accessed via the original article.

Opportunities to reduce antibiotic prescribing for patients with COPD in primary care: a cohort study using electronic health records from the Clinical Practice Research Datalink (CPRD).

BACKGROUND: In primary care there is uncertainty about which patients with acute exacerbations of COPD (AECOPD) benefit from antibiotics. OBJECTIVES: To identify which types of COPD patients get the most antibiotics in primary care to support targeted antibiotic stewardship. METHODS: Observational study of COPD patients using a large English primary care database with 12 month follow-up. We estimated the incidence of and risk factors for antibiotic prescribing relative to the number of AECOPD during follow-up, considering COPD severity, smoking, obesity and comorbidity. RESULTS: From 157 practices, 19594 patients were diagnosed with COPD, representing 2.6% of patients and 11.5% of all prescribed antibiotics. Eight hundred and thirty-three (4.5%) patients with severe COPD and frequent AECOPD were prescribed six to nine prescriptions per year and accounted for 13.0% of antibiotics. Individuals with mild to moderate COPD and zero or one AECOPD received one to three prescriptions per year but accounted for 42.5% of all prescriptions. In addition to COPD severity, asthma, chronic heart disease, diabetes, heart failure and influenza vaccination were independently associated with increased antibiotic use. CONCLUSIONS: Patients with severe COPD have the highest rates of antibiotic prescribing but most antibiotics are prescribed for patients with mild to moderate COPD. Antibiotic stewardship should focus on the dual goals of safely reducing the volume of prescribing in patients with mild to moderate COPD, and optimizing prescribing in patients with severe disease who are at significant risk of drug resistance.

Interventions to improve appropriate antibiotic prescribing in long-term care facilities: a systematic review.

BACKGROUND: Overuse of antibiotics has contributed to antimicrobial resistance; a growing public health threat. In long-term care facilities, levels of inappropriate prescribing are as high as 75%. Numerous interventions targeting long-term care facilities' antimicrobial stewardship have been reported with varying, and largely unexplained, effects. Therefore, this review aimed to apply behavioural science frameworks to specify the component behaviour change techniques of stewardship interventions in long-term care facilities and identify those components associated with improved outcomes. METHOD: A systematic review (CRD42018103803) was conducted through electronic database searches. Two behavioural science frameworks, the Behaviour Change Wheel and Behaviour Change Technique Taxonomy were used to classify intervention descriptions into intervention types and component behaviour change techniques used. Study design and outcome heterogeneity prevented meta-analysis and meta-regression. Interventions were categorised as 'very promising' (all outcomes statistically significant), 'quite promising' (some outcomes statistically significant), or 'not promising' (no outcomes statistically significant). 'Promise ratios' (PR) were calculated for identified intervention types and behaviour change techniques by dividing the number of (very or quite) promising interventions featuring the intervention type or behaviour change technique by the number of interventions featuring the intervention type or behaviour change technique that were not promising. Promising intervention types and behaviour change techniques were defined as those with a PR ≥ 2. RESULTS: Twenty studies (of19 interventions) were included. Seven interventions (37%) were 'very promising', eight 'quite promising' (42%) and four 'not promising' (21%). Most promising intervention types were 'persuasion' (n = 12; promise ratio (PR) = 5.0), 'enablement' (n = 16; PR = 4.33) and 'education' (n = 19; PR = 3.75). Most promising behaviour change techniques were 'feedback on behaviour' (n = 9; PR = 8.0) and 'restructuring the social environment' (e.g. staff role changes; n = 8; PR = 7.0). CONCLUSION: Systematic identification of the active ingredients of antimicrobial stewardship in long-term care facilities was facilitated through the application of behavioural science frameworks. Incorporating environmental restructuring and performance feedback may be promising intervention strategies for antimicrobial stewardship interventions within long-term care facilities.

Antibiotic prescribing in UK care homes 2016-2017: retrospective cohort study of linked data.

BACKGROUND: Older people living in care homes are particularly susceptible to infections and antibiotics are therefore used frequently for this population. However, there is limited information on antibiotic prescribing in this setting. This study aimed to investigate the frequency, patterns and risk factors for antibiotic prescribing in a large chain of UK care homes. METHODS: Retrospective cohort study of administrative data from a large chain of UK care homes (resident and care home-level) linked to individual-level pharmacy data. Residents aged 65 years or older between 1 January 2016 and 31 December 2017 were included. Antibiotics were classified by type and as new or repeated prescriptions. Rates of antibiotic prescribing were calculated and modelled using multilevel negative binomial regression. RESULTS: 13,487 residents of 135 homes were included. The median age was 85; 63% residents were female. 28,689 antibiotic prescriptions were dispensed, the majority were penicillins (11,327, 39%), sulfonamides and trimethoprim (5818, 20%), or other antibacterials (4665, 16%). 8433 (30%) were repeat prescriptions. The crude rate of antibiotic prescriptions was 2.68 per resident year (95% confidence interval (CI) 2.64-2.71). Increased antibiotic prescribing was associated with residents requiring more medical assistance (adjusted incidence rate ratio for nursing opposed to residential care 1.21, 95% CI 1.13-1.30). Prescribing rates varied widely by care home but there were no significant associations with the care home-level characteristics available in routine data. CONCLUSIONS: Rates of antibiotic prescribing in care homes are high and there is substantial variation between homes. Further research is needed to understand the drivers of this variation to enable development of effective stewardship approaches that target the influences of prescribing.

Diagnostic uncertainty and urinary tract infection in the emergency department: a cohort study from a UK hospital.

BACKGROUND: Suspected urinary tract infection (UTI) syndromes are a common reason for empirical antibiotics to be prescribed in the Emergency Department (ED), but differentiating UTI from other conditions with a similar presentation is challenging. We investigated how often an ED diagnosis of UTI is confirmed clinically/microbiologically, and described conditions which present as UTI syndromes. METHODS: Observational study using electronic health records from patients who attended the ED with suspected UTI and had a urine sample submitted for culture. We compared the ED diagnosis to diagnosis at discharge from hospital (ICD-10 codes), and estimated the proportion of cases with clinical/microbiological evidence of UTI. RESULTS: Two hundred eighty nine patients had an ED diagnosis of UTI syndrome comprising: lower UTI (191), pyelonephritis (56) and urosepsis (42). In patients admitted to hospital with an ED diagnosis of lower UTI, pyelonephritis or urosepsis, clinical/microbiological evidence of UTI was lacking in 61/103, 33/54 and 31/42 cases respectively. The ED diagnosis was concordant with the main reason for admission in less than 40% of patients with UTI syndromes, and antibiotics were stopped within 72 h in 37/161 patients. CONCLUSIONS: Clinical/microbiological evidence of UTI was lacking in 60-70% of patients, suggesting scope to revise empirical prescribing decisions for UTI syndromes in light of microbial culture and clinical progression.