Nichola R Naylor

A National Estimate of the Health and Cost Burden of Escherichia coli Bacteraemia in the Hospital Setting: The Importance of Antibiotic Resistance.

Background Antibiotic resistance poses a threat to public health and a burden to healthcare systems. Escherichia coli causes more bacteraemia cases in England than any other bacterial species, these infections, in part due to their high incidence, also pose a significant antibiotic resistance burden. The main aim of this study was to estimate the impact of E. coli bacteraemia on patient in-hospital mortality and length of stay. Secondarily, this study also aimed to estimate the effect of antibiotic resistance on these outcomes. Methods and Findings Case patients were adult E. coli bacteraemia patients infected between July 2011 and June 2012, as reported in an English national mandatory surveillance database, with susceptibility data taken from a national laboratory surveillance database. Control patients were all non-case, adult patients with an English hospital admission record. Case and control patient characteristics and admission information were taken from NHS Digital Datasets. ‘Resistance’ was defined as non-susceptible and intermediate isolates, whilst ‘susceptible’ was defined as susceptible and non-tested isolates. Time to in-hospital mortality and discharge was investigated through Cox proportional hazards models. To acquire estimates of excess length of stay, multistate models were constructed, with a unit bed day cost applied to estimate cost burden. The total number of case and control hospital spells was 14,051 and 8,919,275 respectively. Acquisition of E. coli bacteraemia was associated with a statistically significant increased daily risk of in-hospital mortality, especially for the first eight days of someone’s hospital admission [Hazard Ratio = 2.77 (95% confidence interval; 2.61-2.94)]. Antibiotic resistance did not seem to significantly increase this risk further, though did significantly reduce risk of experiencing a discharge event (dead or alive). E.coli bacteraemia was estimated to cost ₤14,340,900 over the study period (rounded to the nearest ₤100), with resistance associated with excess costs per infection of ₤220 - ₤420 dependent on resistance type, for those where a significant impact was found (rounded to the nearest ₤10). Conclusions E. coli bacteraemia places a significant burden on patient health and on the hospital sector in England. Resistance is an important factor on length of stay with regards to such infections.

Estimating the burden of antimicrobial resistance: a systematic literature review

BackgroundAccurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base.MethodsMEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD.ResultsOut of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to

Methods for estimating the burden of antimicrobial resistance: a systematic literature review protocol

1 billion per year, whilst economic burden ranged from

Quantifying drivers of antibiotic resistance in humans: a systematic review

21,832 per case to over

Comparison of national strategies to reduce meticillin-resistant Staphylococcus aureus infections in Japan and England

3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively.ConclusionsThis study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review.Trial registrationThis systematic review is registered with PROSPERO (PROSPERO CRD42016037510).

Bed utilisation and increased risk of Clostridium difficile infections in acute hospitals in England in 2013/2014

BackgroundEstimates of the burden of antimicrobial resistance (AMR) are needed to ascertain AMR impact, to evaluate interventions, and to allocate resources efficiently. Recent studies have estimated health, cost, and economic burden relating to AMR, with outcomes of interest ranging from drug-bug resistance impact on mortality in a hospital setting to total economic impact of AMR on the global economy. However, recent collation of this information has been largely informal, with no formal quality assessment of the current evidence base (e.g. with predefined checklists). This review therefore aims to establish what perspectives and resulting methodologies have been used in establishing the burden of AMR, whilst also ascertaining the quality of these studies.MethodsThe literature review will identify relevant literature using a systematic review methodology. MEDLINE, EMBASE, Scopus and EconLit will be searched utilising a predefined search string. Grey literature will be identified by searching within a predefined list of organisational websites. Independent screening of retrievals will be performed in a two-stage process (abstracts and full texts), utilising a pre-defined inclusion and exclusion criteria. Data will be extracted into a data extraction table and descriptive examination will be performed. Study quality will be assessed using the Newcastle-Ottawa scales and the Philips checklists where appropriate. A narrative synthesis of the results will be presented.DiscussionThis review will provide an overview of previous health, cost and economic definitions of burden and the resultant impact of these different definitions on the burden of AMR estimated. The review will also explore the methods that have been used to calculate this burden and discuss resulting study quality. This review can therefore act as a guide to methods for future research in this area.Systematic review registrationPROSPERO CRD42016037510

Potential impact of novel diagnostics and treatments on the burden of antibiotic resistant in Escherichia coli

Mitigating the risks of antibiotic resistance requires a horizon scan linking the quality with the quantity of data reported on drivers of antibiotic resistance in humans, arising from the human, animal, and environmental reservoirs. We did a systematic review using a One Health approach to survey the key drivers of antibiotic resistance in humans. Two sets of reviewers selected 565 studies from a total of 2819 titles and abstracts identified in Embase, MEDLINE, and Scopus (2005-18), and the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and WHO (One Health data). Study quality was assessed in accordance with Cochrane recommendations. Previous antibiotic exposure, underlying disease, and invasive procedures were the risk factors with most supporting evidence identified from the 88 risk factors retrieved. The odds ratios of antibiotic resistance were primarily reported to be between 2 and 4 for these risk factors when compared with their respective controls or baseline risk groups. Food-related transmission from the animal reservoir and water-related transmission from the environmental reservoir were frequently quantified. Uniformly quantifying relationships between risk factors will help researchers to better understand the process by which antibiotic resistance arises in human infections.

Trends in Secondary Care Costs for Treatment of Head and Neck Cancer in England

BACKGROUND National responses to healthcare-associated infections vary between high-income countries, but, when analysed for contextual comparability, interventions can be assessed for transferability. AIM To identify learning from country-level approaches to addressing meticillin-resistant Staphylococcus aureus (MRSA) in Japan and England. METHODS A longitudinal analysis (2000-2017), comparing epidemiological trends and policy interventions. Data from 441 textual sources concerning infection prevention and control (IPC), surveillance, and antimicrobial stewardship interventions were systematically coded for: (a) type: mandatory requirements, recommendations, or national campaigns; (b) method: restrictive, persuasive, structural in nature; (c) level of implementation: macro (national), meso (organizational), micro (individual) levels. Healthcare organizational structures and role of media were also assessed. FINDINGS In England significant reduction has been achieved in number of reported MRSA bloodstream infections. In Japan, in spite of reductions, MRSA remains a predominant infection. Both countries face new threats in the emergence of drug-resistant Escherichia coli. England has focused on national mandatory and structural interventions, supported by a combination of outcomes-based incentives and punitive mechanisms, and multi-disciplinary IPC hospital teams. Japan has focused on (non-mandatory) recommendations and primarily persuasive interventions, supported by process-based incentives, with voluntary surveillance. Areas for development in Japan include resourcing of dedicated data management support and implementation of national campaigns for healthcare professionals and the public. CONCLUSION Policy interventions need to be relevant to local epidemiological trends, while acceptable within the health system, culture, and public expectations. Cross-national learning can help inform the right mix of interventions to create sustainable and resilient systems for future infection and economic challenges.

Is antimicrobial stewardship cost-effective? A narrative review of the evidence

Background The study aimed to identify thresholds for hospital bed utilisation which are independently associated with significantly higher risks for Clostridium difficile infections (CDI) in acute hospitals in England. Method A retrospective analysis was carried out on reported data from the English National Health Service (NHS) for the financial year 2013/2014. Reported rates of CDI were used as a proxy for hospital infection rates in acute NHS hospital trusts. Multivariate linear regression was used to assess the relationship between bed utilisation values and CDI controlling for confounding factors. Hospitals were finally plotted in a Pabon Lasso graph according to their average bed occupancy rate (BOR) and bed turnover rate (BTR) per year to visualise the relationship between bed utilisation and CDI. Results Among English hospital NHS trusts, increasing BTR and decreasing BOR were associated with a decrease in CDI. However, this effect was not large, and patient mix had a larger impact on CDI rates than bed utilisation. Conclusions While policymakers and managers wishing to target healthcare providers with high CDI rates should look at bed utilisation measures, focusing on these alone is unlikely to have the desired impact. Instead, strategies to combat CDI must take a wider perspective on contributory factors at the institutional level.

Mapping national surveillance of surgical site infections in England: needs and priorities

The rising threat of antibiotic resistance in Europe and beyond is of increasing concern and is prompting renewed effort to better understand and mitigate their impact. Escherichia Coli blood stream infections are a more major concern in Europe given their incidence and severe associated outcomes. Additionally the level of 3rd generation cephalosporins and carbapenems resistance among those bacteraemia has significantly increased, limiting available treatment options. We estimated the current burden associated with E. coli blood stream infections in Europe at 17,000 (95%CI [8,000; 30,000]) excess deaths and 960,000 (95%CI [600,000; 1,450,000]) extra hospital bed days. From those, the contribution due to 3rd generation cephalosporins and carbapenems resistant strains reached 6,000 (95%CI [2,000; 12,000]) excess deaths, and 200,000 (95%CI [76,000; 420,000]) extra hospital bed stay. In the worst case scenario, we estimated the burden of E. coli blood stream infection in 2026 could increase over 4-fold, mostly resulting from an increase in the level of resistance rather than an increase in the incidence of blood stream infections. Finally, we estimated that the impact of combined novel diagnostics and treatments could substantially reduce the excess mortality by 18.5% to 55.5%, and length of stay by 13.2% to 75.6%.