Background: Accurate 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. Methods: MEDLINE, 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. Results: Out 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 $1 billion per year, whilst economic burden ranged from $21,832 per case to over $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. Conclusions: This 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 registration: This systematic review is registered with PROSPERO (PROSPERO CRD42016037510).

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.

Antibiotic resistance poses a threat to public health and healthcare systems. Escherichia coli causes more bacteraemia episodes in England than any other bacterial species. This study aimed to estimate the burden of E. coli bacteraemia and associated antibiotic resistance in the secondary care setting. This was a retrospective cohort study, with E. coli bacteraemia as the main exposure of interest. Adult hospital in-patients, admitted to acute NHS hospitals between July 2011 and June 2012 were included. English national surveillance and administrative datasets were utilised. Cox proportional hazard, subdistribution hazard and multistate models were constructed to estimate rate of discharge, rate of in-hospital death and excess length of stay, with a unit bed day cost applied to the latter to estimate cost burden from the healthcare system perspective. 14,042 E. coli bacteraemia and 8,919,284 non-infected inpatient observations were included. E. coli bacteraemia was associated with an increased rate of in-hospital death across all models, with an adjusted subdistribution hazard ratio of 5.88 (95% CI: 5.62–6.15). Resistance was not found to be associated with in-hospital mortality once adjusting for patient and hospital covariates. However, resistance was found to be associated with an increased excess length of stay. This was especially true for third generation cephalosporin (1.58 days excess length of stay, 95% CI: 0.84–2.31) and piperacillin/tazobactam resistance (1.23 days (95% CI: 0.50–1.95)). The annual cost of E. coli bacteraemia was estimated to be £14,346,400 (2012 £), with third-generation cephalosporin resistance associated with excess costs per infection of £420 (95% CI: 220–630). E. coli bacteraemia places a statistically significant burden on patient health and the hospital sector in England. Resistance to front-line antibiotics increases length of stay; increasing the cost burden of such infections in the secondary care setting.

Zoonotic bacterial infections are a health hazard for people who are in regular contact with livestock at the farm level. Improved biosecurity can limit zoonotic pathogen transmission within farms. The aim of this review was to summarize the effectiveness of farm‐level biosecurity interventions in reducing bacterial transmission from animals to people who lived, worked in or visited farms. A systematic literature review was conducted using Embase, Ovid Medline and Agris databases, which were searched on 7^th of July 2019, limited to English language papers but with no time exclusion criteria. A narrative synthesis was undertaken utilizing the Centre for Reviews and Dissemination approach, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Risk of bias within and across the included studies was performed using established checklists. Out of 869 studies retrieved through database searches, 11 studies were selected. In addition, three studies were found through study reference lists. Fourteen studies were therefore included in this review. Biosecurity interventions were grouped into five categories: hand washing, sanitization and hygienic measures (six studies); personal protective equipment (five studies); vaccination (two studies); other interventions (e.g. air ventilation flap) (four studies); and routine farm activities (two studies). Across studies that investigated odds of human colonization or infection (three studies), odds were seen to both be increased and decreased through use of tested biosecurity measures. Large confidence intervals that often crossed the threshold of an odds ratio equal to 1 were found. Most of the studies' overall risk of bias was ‘medium risk’ (11 studies), with selection bias domains generally being scored ‘medium risk.’ Biosecurity interventions are potentially beneficial in reducing bacterial transmission from animals to humans. However, more high‐quality evidence is needed to increase certainty in which interventions, in which contexts, are most effective from the human health perspective.

Introduction: Antibiotic resistance (ABR) may increase hospital costs, utility loss and mortality risk per patient. Understanding these losses at national, regional and global scales is necessary for efficiently tackling ABR. Our aim is to estimate the global economic burden of antibiotic-resistant infections and the potential for bacterial vaccines to mitigate this burden. Methods: We take healthcare system and labour productivity perspectives. Hospital cost-per-case and length-of-stay estimates were calculated through meta-analyses and reviewing published systematic reviews. Unit labour productivity losses were estimated through a human capital approach. Modelled estimates were used where secondary data were missing. Death and incidence data were combined with unit cost data to estimate the economic burden associated with ABR in 2019, and the potential costs averted (in 2019 US$) based on uptake scenarios of vaccines that currently exist or are likely to be developed. Results: Multidrug-resistant tuberculosis had the highest mean hospital cost attributable to ABR per patient, the range was US$3000 in lower-income settings to US$41 000 in high-income settings, with carbapenem-resistant infections associated with a high cost-per-case of US$3000–US$7000 depending on syndrome. ABR was associated with a median value of US$693 billion (IQR: US$627 bn–US$768 bn) in hospital costs globally, with US$207 bn (IQR: US$186 bn–US$229 bn) potentially avertable by vaccines. Productivity losses were quantified at almost US$194 billion, with US$76 bn avertable by vaccines. Conclusions: The economic burden of ABR is associated with high levels of hospital bed-days occupied, hospital spending and labour productivity losses globally and should, therefore, remain high on national and international policy agendas. Vaccines against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae would avert a substantial portion of the economic burden associated with ABR. More robust evidence, particularly in low-income countries, on the hospital costs, associated with and attributable to ABR, is needed.