An Assessment of Potential Unintended Consequences Following a National Antimicrobial Stewardship Program in England: An Interrupted Time Series Analysis.

BACKGROUND: The "Quality Premium" (QP) introduced in England in 2015 aimed to financially reward local healthcare commissioners for targeted reductions in primary care antibiotic prescribing. We aimed to evaluate possible unintended clinical outcomes related to this QP. METHODS: Using Clinical Practice Research Datalink and Hospital Episode Statistics datasets, we examined general practitioner (GP) consultations (visits) and emergency hospital admissions related to a series of predefined conditions of unintended consequences of reduced prescribing. Monthly age- and sex-standardized rates were calculated using a direct method of standardization. We used segmented regression analysis of interrupted time series to evaluate the impact of the QP on seasonally adjusted outcome rates. RESULTS: We identified 27334 GP consultations and >5 million emergency hospital admissions with predefined conditions. There was no evidence that the QP was associated with changes in GP consultation and hospital admission rates for the selected conditions combined. However, when each condition was considered separately, a significant increase in hospital admission rates was noted for quinsy, and significant decreases were seen for hospital-acquired pneumonia, scarlet fever, pyelonephritis, and complicated urinary tract conditions. A significant decrease in GP consultation rates was estimated for empyema and scarlet fever. No significant changes were observed for other conditions. CONCLUSIONS: Findings from this study show that overall there was no significant association between the intervention and unintended clinical consequences, with the exception of a few specific conditions, most of which could be explained through other parallel policy changes or should be interpreted with caution due to small numbers.

Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis.

Objectives: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs). Methods: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD) between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium. Results: Prescribing rates decreased over the 6 year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1000 RTI consultations) (P < 0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after 2 years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change 2 years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats. Conclusions: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients.

A standardized methodology for the surveillance of antimicrobial prescribing linked to clinical indications in primary care.

Background: A key component of strategies to reduce antimicrobial resistance is better antimicrobial prescribing. The majority of antibiotics are prescribed in primary care. While many existing surveillance systems can monitor trends in the quantities of antibiotics prescribed in this setting, it can be difficult to monitor the quality of prescribing as data on the condition for which prescriptions are issued are often not available. We devised a standardized methodology to facilitate the monitoring of condition-specific antibiotic prescribing in primary care. Methods: We used a large computerized general practitioner database to develop a standardized methodology for routine monitoring of antimicrobial prescribing linked to clinical indications in primary care in the UK. Outputs included prescribing rate by syndrome and percentages of consultations with antibiotic prescription, for recommended antibiotic, and of recommended treatment length. Results: The standardized methodology can monitor trends in proportions of common infections for which antibiotics were prescribed, the specific drugs prescribed and duration of treatment. These data can be used to help assess the appropriateness of antibiotic prescribing and to assess the impact of prescribing guidelines. Conclusions: We present a standardized methodology that could be applied to any suitable national or local database and adapted for use in other countries.

Investigating the burden of antibiotic resistance in ethnic minority groups in high-income countries: protocol for a systematic review and meta-analysis.

BACKGROUND: Antibiotic resistance (ABR) is an urgent problem globally, with overuse and misuse of antibiotics being one of the main drivers of antibiotic-resistant infections. There is increasing evidence that the burden of community-acquired infections such as urinary tract infections and bloodstream infections (both susceptible and resistant) may differ by ethnicity, although the reasons behind this relationship are not well defined. It has been demonstrated that socioeconomic status and ethnicity are often highly correlated with each other; however, it is not yet known whether accounting for deprivation completely explains any discrepancy seen in infection risk. There have currently been no systematic reviews summarising the evidence for the relationship between ethnicity and antibiotic resistance or prescribing. METHODS: This protocol will outline how we will conduct this systematic literature review and meta-analysis investigating whether there is an association between patient ethnicity and (1) risk of antibiotic-resistant infections or (2) levels of antibiotic prescribing in high-income countries. We will search PubMed/MEDLINE, EMBASE, Global Health, Scopus and CINAHL using MESH terms where applicable. Two reviewers will conduct title/abstract screening, data extraction and quality assessment independently. The Critical Appraisal Skills Programme (CASP) checklist will be used for cohort and case-control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials, if they are included. Meta-analyses will be performed by calculating the minority ethnic group to majority ethnic group odds ratios or risk ratios for each study and presenting an overall pooled odds ratio for the two outcomes. The Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach will be used to assess the overall quality of the body of evidence. DISCUSSION: In this systematic review and meta-analysis, we will aim to collate the available evidence of whether there is a difference in rates of AMR and/or antibiotic prescribing in minority vs. majority ethnic groups in high-income countries. Additionally, this review will highlight areas where more research needs to be conducted and may provide insight into what may cause differences in this relationship, should they be seen. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( CRD42016051533 ).

A Risk Assessment of Antibiotic Pan-Drug-Resistance in the UK: Bayesian Analysis of an Expert Elicitation Study.

To inform the UK antimicrobial resistance strategy, a risk assessment was undertaken of the likelihood, over a five-year time-frame, of the emergence and widespread dissemination of pan-drug-resistant (PDR) Gram-negative bacteria that would pose a major public health threat by compromising effective healthcare delivery. Subsequent impact over five- and 20-year time-frames was assessed in terms of morbidity and mortality attributable to PDR Gram-negative bacteraemia. A Bayesian approach, combining available data with expert prior opinion, was used to determine the probability of the emergence, persistence and spread of PDR bacteria. Overall probability was modelled using Monte Carlo simulation. Estimates of impact were also obtained using Bayesian methods. The estimated probability of widespread occurrence of PDR pathogens within five years was 0.2 (95% credibility interval (CrI): 0.07-0.37). Estimated annual numbers of PDR Gram-negative bacteraemias at five and 20 years were 6800 (95% CrI: 400-58,600) and 22,800 (95% CrI: 1500-160,000), respectively; corresponding estimates of excess deaths were 1900 (95% CrI: 0-23,000) and 6400 (95% CrI: 0-64,000). Over 20 years, cumulative estimates indicate 284,000 (95% CrI: 17,000-1,990,000) cases of PDR Gram-negative bacteraemia, leading to an estimated 79,000 (95% CrI: 0-821,000) deaths. This risk assessment reinforces the need for urgent national and international action to tackle antibiotic resistance.

Capacity of English NHS hospitals to monitor quality in infection prevention and control using a new European framework: a multilevel qualitative analysis.

OBJECTIVE: (1) To assess the extent to which current English national regulations/policies/guidelines and local hospital practices align with indicators suggested by a European review of effective strategies for infection prevention and control (IPC); (2) to examine the capacity of local hospitals to report on the indicators and current use of data to inform IPC management and practice. DESIGN: A national and local-level analysis of the 27 indicators was conducted. At the national level, documentary review of regulations/policies/guidelines was conducted. At the local level data collection comprised: (a) review of documentary sources from 14 hospitals, to determine the capacity to report performance against these indicators; (b) qualitative interviews with 3 senior managers from 5 hospitals and direct observation of hospital wards to find out if these indicators are used to improve IPC management and practice. SETTING: 2 acute English National Health Service (NHS) trusts and 1 NHS foundation trust (14 hospitals). PARTICIPANTS: 3 senior managers from 5 hospitals for qualitative interviews. PRIMARY AND SECONDARY OUTCOME MEASURES: As primary outcome measures, a 'Red-Amber-Green' (RAG) rating was developed reflecting how well the indicators were included in national documents or their availability at the local organisational level. The current use of the indicators to inform IPC management and practice was also assessed. The main secondary outcome measure is any inconsistency between national and local RAG rating results. RESULTS: National regulations/policies/guidelines largely cover the suggested European indicators. The ability of individual hospitals to report some of the indicators at ward level varies across staff groups, which may mask required improvements. A reactive use of staffing-related indicators was observed rather than the suggested prospective strategic approach for IPC management. CONCLUSIONS: For effective patient safety and infection prevention in English hospitals, routine and proactive approaches need to be developed. Our approach to evaluation can be extended to other country settings.

Improving feedback of surveillance data on antimicrobial consumption, resistance and stewardship in England: putting the data at your Fingertips.

The provision of better access to and use of surveillance data is a key component of the UK 5 Year Antimicrobial Resistance (AMR) Strategy. Since April 2016, PHE has made data on practice (infection prevention and control; antimicrobial stewardship) and outcome (prevalence of AMR, antibiotic use and healthcare-associated infections) available through Fingertips, a publicly accessible web tool (https://fingertips.phe.org.uk/profile/amr-local-indicators). Fingertips provides access to a wide range of public health data presented as thematic profiles, with the above data being available through the 'AMR local indicators' profile. Local data on a range of indicators can be viewed at the level of National Health Service acute trusts, Clinical Commissioning Groups or general practitioner practices, all of which can be compared with the corresponding aggregate values for England to allow benchmarking. The data can be viewed in a range of formats including an overview showing counts and rates, interactive maps, spine charts and graphs that show temporal trends over a range of time scales or allow correlations between pairs of indicators. The aim of the AMR local indicators profile on Fingertips is to support the development of local action plans to optimize antibiotic prescribing and reduce AMR and healthcare-associated infections. Provision of access to relevant information in an easy to use format will help local stakeholders, including healthcare staff, commissioners, Directors of Public Health, academics and the public, to benchmark relevant local AMR data and to monitor the impact of local initiatives to tackle AMR over time.

Selecting appropriate empirical antibiotic regimens for paediatric bloodstream infections: application of a Bayesian decision model to local and pooled antimicrobial resistance surveillance data.

OBJECTIVES: The objective of this study was to evaluate the ability of weighted-incidence syndromic combination antibiograms (WISCAs) to inform the selection of empirical antibiotic regimens for suspected paediatric bloodstream infections (BSIs) by comparing WISCAs derived using data from single hospitals and from a multicentre surveillance dataset. METHODS: WISCAs were developed by estimating the coverage of five empirical antibiotic regimens for childhood BSI using a Bayesian decision tree. The study used microbiological data on ∼2000 bloodstream isolates collected over 2 years from 19 European hospitals. We evaluated the ability of a WISCA to show differences in regimen coverage at two exemplar hospitals. For each, a WISCA was first calculated using only their local data; a second WISCA was calculated using pooled data from all 19 hospitals. RESULTS: The estimated coverage of the five regimens was 72%-86% for Hospital 1 and 79%-94% for Hospital 2, based on their own data. In both cases, the best regimens could not be definitively identified because the differences in coverage were not statistically significant. For Hospital 1, coverage estimates derived using pooled data gave sufficient precision to reveal clinically important differences among regimens, including high coverage provided by a narrow-spectrum antibiotic combination. For Hospital 2, the hospital and pooled data showed signs of heterogeneity and the use of pooled data was judged not to be appropriate. CONCLUSIONS: The Bayesian WISCA provides a useful approach to pooling information from different sources to guide empirical therapy and could increase confidence in the selection of narrow-spectrum regimens.

Systematic analysis of funding awarded for antimicrobial resistance research to institutions in the UK, 1997-2010.

OBJECTIVES: To assess the level of research funding awarded to UK institutions specifically for antimicrobial resistance-related research and how closely the topics funded relate to the clinical and public health burden of resistance. METHODS: Databases and web sites were systematically searched for information on how infectious disease research studies were funded for the period 1997-2010. Studies specifically related to antimicrobial resistance, including bacteriology, virology, mycology and parasitology research, were identified and categorized in terms of funding by pathogen and disease and by a research and development value chain describing the type of science. RESULTS: The overall dataset included 6165 studies receiving a total investment of £2.6 billion, of which £102 million was directed towards antimicrobial resistance research (5.5% of total studies, 3.9% of total spend). Of 337 resistance-related projects, 175 studies focused on bacteriology (40.2% of total resistance-related spending), 42 focused on antiviral resistance (17.2% of funding) and 51 focused on parasitology (27.4% of funding). Mean annual funding ranged from £1.9 million in 1997 to £22.1 million in 2009. CONCLUSIONS: Despite the fact that the emergence of antimicrobial resistance threatens our future ability to treat many infections, the proportion of the UK infection-research spend targeting this important area is small. There are encouraging signs of increased investment in this area, but it is important that this is sustained and targeted at areas of projected greatest burden. Two areas of particular concern requiring more investment are tuberculosis and multidrug-resistant Gram-negative bacteria.