Trends in urine sampling rates of general practice patients with suspected lower urinary tract infections in England, 2015-2022: a population-based study.

OBJECTIVES: Inappropriate prescribing of antibiotics is a key driver of antimicrobial resistance. This study aimed to describe urine sampling rates and antibiotic prescribing for patients with lower urinary tract infections (UTIs) in English general practice. DESIGN: A retrospective population-based study using administrative data. SETTING: IQVIA Medical Research Database (IMRD) data from general practices in England, 2015-2022. PARTICIPANTS: Patients who have consulted with an uncomplicated UTI in England general practices captured in the IMRD. OUTCOME MEASURES: Trends in UTI episodes (episodes were defined as UTI diagnosis codes occurring within 14 days of each other), testing and antibiotic prescribing on the same day as initial UTI consultation were assessed from January 2015 to December 2022. Associations, using univariate and multivariate logistic regressions, were examined between consultation and demographic factors on the odds of a urine test. RESULTS: There were 743 350 UTI episodes; 50.8% had a urine test. Testing rates fluctuated with an upward trend and large decline in 2020. Same-day UTI antibiotic prescribing occurred in 78.2% of episodes. In multivariate modelling, factors found to decrease odds of a urine test included age ≥85 years (0.83, 95% CI 0.82 to 0.84), consultation type (remote vs face to face, 0.45, 95% CI 0.45 to 0.46), episodes in London compared with the South (0.74, 95% CI 0.72 to 0.75) and increasing practice size (0.77, 95% CI 0.76 to 0.78). Odds of urine tests increased in males (OR 1.11, 95% CI 1.10 to 1.13), for those episodes without a same-day UTI antibiotic (1.10, 95% CI 1.04 to 1.16) for episodes for those with higher deprivation status (Indices of Multiple Deprivation 8 vs 1, 1.51, 95% CI 1.48 to 1.54). Compared with 2015, 2016-2019 saw increased odds of testing while 2020 and 2021 saw decreases, with 2022 showing increased odds. CONCLUSION: Urine testing for UTI in general practice in England showed an upward trend, with same-day antibiotic prescribing remaining consistent, suggesting greater alignment to national guidelines. The COVID-19 pandemic impacted testing rates, though as of 2022, they began to recover.

Reporting England's progress towards the ambitions in the UK action plan for antimicrobial resistance: the English surveillance programme for antimicrobial utilisation and resistance (ESPAUR).

The plans for a new antimicrobial utilization and resistance national surveillance programme, alongside the development of quality measures and methods to monitor unintended outcomes of antimicrobial stewardship and both public and professional behaviour interventions were published in 2013. Since then, England has published an annual surveillance report including outlining progress against the ambitions of the UK national action plans on antimicrobial resistance (2013 to 2018 and 2019 to 2024). A decade later we provide a brief update on progress so far, with a focus on key highlights from the latest report published in November 2022. We also provide our recommendations for areas of focus as we move into the next decade. From an initial focus on antibiotic consumption and resistance, the report now includes surveillance data for antifungals, antivirals (including novel agents, such as those targeting SARS-CoV-2) and antimalarials. Evaluation of key stewardship interventions including professional and public engagement initiatives are also reported, as well as progress against NHS England's (NHSE's) improvement measures.

National point-prevalence survey of healthcare-associated infections and antimicrobial use: UK-PAS/UKHSA joint call to action for all paediatric services.

The negative impact of high antimicrobial use (AMU), antimicrobial resistance and healthcare-associated infections (HCAIs) on children is concerning. However, a lack of available paediatric data makes it challenging to design and implement interventions that would improve health outcomes in this population, and impedes efforts to secure additional resources. The upcoming 2023 national point-prevalence survey of HCAIs and AMU in hospitals, led by the UK Health Security Agency, is an opportunity to collect valuable information, which will enable healthcare providers and policy makers to optimize antimicrobial stewardship and infection prevention practices in all populations, including children. These data will facilitate benchmarking and sharing of best practice, internally, nationally and internationally. This is a joint call to action asking all healthcare professionals-particularly in paediatrics-to nominate a lead for their institution and participate in this survey, to ensure appropriate paediatric representation, and help protect children from these growing threats.

Quantifying the primary and secondary effects of antimicrobial resistance on surgery patients: Methods and data sources for empirical estimation in England.

Antimicrobial resistance (AMR) may negatively impact surgery patients through reducing the efficacy of treatment of surgical site infections, also known as the "primary effects" of AMR. Previous estimates of the burden of AMR have largely ignored the potential "secondary effects," such as changes in surgical care pathways due to AMR, such as different infection prevention procedures or reduced access to surgical procedures altogether, with literature providing limited quantifications of this potential burden. Former conceptual models and approaches for quantifying such impacts are available, though they are often high-level and difficult to utilize in practice. We therefore expand on this earlier work to incorporate heterogeneity in antimicrobial usage, AMR, and causative organisms, providing a detailed decision-tree-Markov-hybrid conceptual model to estimate the burden of AMR on surgery patients. We collate available data sources in England and describe how routinely collected data could be used to parameterise such a model, providing a useful repository of data systems for future health economic evaluations. The wealth of national-level data available for England provides a case study in describing how current surveillance and administrative data capture systems could be used in the estimation of transition probability and cost parameters. However, it is recommended that such data are utilized in combination with expert opinion (for scope and scenario definitions) to robustly estimate both the primary and secondary effects of AMR over time. Though we focus on England, this discussion is useful in other settings with established and/or developing infectious diseases surveillance systems that feed into AMR National Action Plans.

Exploring temporal trends and risk factors for resistance in Escherichia coli-causing bacteraemia in England between 2013 and 2018: an ecological study.

BACKGROUND: Escherichia coli are Gram-negative bacteria associated with an increasing burden of antimicrobial resistance (AMR) in England. OBJECTIVES: To create a comprehensive epidemiological picture of E. coli bacteraemia resistance trends and risk factors in England by linking national microbiology data sources and performing a longitudinal analysis of rates. METHODS: A retrospective observational study was conducted on all national records for antimicrobial susceptibility testing on E. coli bacteraemia in England from 1 January 2013 to 31 December 2018 from the UK Health Security Agency (UKHSA) and the BSAC Resistance Surveillance Programme (BSAC-RSP). Trends in AMR and MDR were estimated using iterative sequential regression. Logistic regression analyses were performed on UKHSA data to estimate the relationship between risk factors and AMR or MDR in E. coli bacteraemia isolates. RESULTS: An increase in resistance rates was observed in community- and hospital-onset bacteraemia for third-generation cephalosporins, co-amoxiclav, gentamicin and ciprofloxacin. Among community-acquired cases, and after adjustment for other factors, patients aged >65 years were more likely to be infected by E. coli isolates resistant to at least one of 11 antibiotics than those aged 18-64 years (OR: 1.21, 95% CI: 1.18-1.25; P < 0.05). In hospital-onset cases, E. coli isolates from those aged 1-17 years were more likely to be resistant than those aged 18-64 years (OR: 1.33, 95% CI: 1.02-1.73; P < 0.05). CONCLUSIONS: Antibiotic resistance rates in E. coli-causing bacteraemia increased between 2013 and 2018 in England for key antimicrobial agents. Findings of this study have implications for guiding future policies on a prescribing of antimicrobial agents, for specific patient populations in particular.

Epidemiology of Mycobacterium abscessus in England: an observational study.

BACKGROUND: Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England. METHODS: In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]). FINDINGS: 2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis. INTERPRETATION: Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche. FUNDING: The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.

Impact of the childhood influenza vaccine programme on antibiotic prescribing rates in primary care in England.

Vaccines are a key part of the global strategy to tackle antimicrobial resistance (AMR) since prevention of infection should reduce antibiotic use. England commenced national rollout of a live attenuated influenza vaccine (LAIV) programme for children aged 2-3 years together with a series of geographically discrete pilot areas for primary school age children in 2013 extending to older children in subsequent seasons. We investigated vaccine programme impact on community antibiotic prescribing rates. Antibiotic prescribing incidence rates for respiratory (RTI) and urinary tract infections (UTI; controls) were calculated at general practice (GP) level by age category (children<=10 years/adults) and season for LAIV pilot and non-pilot areas between 2013/14 and 2015/16. To estimate the LAIV (primary school age children only) intervention effect, a random effects model was fitted. A multivariable random-effects Poisson regression investigated the association of antibiotic prescribing rates in children with LAIV uptake (2-3-year-olds only) at GP practice level. RTI antibiotic prescribing rates for children <=10 years and adults showed clear seasonal trends and were lower in LAIV-pilot and non-pilot areas after the introduction of the LAIV programme in 2013. The reductions for RTI prescriptions (children) were similar (within 3%) in all areas, which coincided with the start the UK AMR strategy. Antibiotic prescribing was significantly (p < 0.0001) related to LAIV uptake in 2-3-year-olds with antibiotic prescribing reduced by 2.7% (95% CI: 2.1% to 3.4%) for every 10% increase in uptake. We found no evidence the LAIV programme for primary school age children resulted in reductions in RTI antibiotic prescribing, however we detected a significant inverse association between increased vaccine uptake in pre-school age children and antibiotic prescribing at GP level. The temporal association of reduced RTI and UTI antibiotic prescribing with the launch of the UK's AMR Strategy in 2013 highlights the importance of a multifaceted approach to tackle AMR.

National surveillance of bacterial and fungal coinfection and secondary infection in COVID-19 patients in England: lessons from the first wave.

OBJECTIVES: The impact of bacterial/fungal infections on the morbidity and mortality of persons with coronavirus disease 2019 (COVID-19) remains unclear. We have investigated the incidence and impact of key bacterial/fungal infections in persons with COVID-19 in England. METHODS: We extracted laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1st January 2020 to 2nd June 2020) and blood and lower-respiratory specimens positive for 24 genera/species of clinical relevance (1st January 2020 to 30th June 2020) from Public Health England's national laboratory surveillance system. We defined coinfection and secondary infection as a culture-positive key organism isolated within 1 day or 2-27 days, respectively, of the SARS-CoV-2-positive date. We described the incidence and timing of bacterial/fungal infections and compared characteristics of COVID-19 patients with and without bacterial/fungal infection. RESULTS: 1% of persons with COVID-19 (2279/223413) in England had coinfection/secondary infection, of which >65% were bloodstream infections. The most common causative organisms were Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Cases with coinfection/secondary infections were older than those without (median 70 years (IQR 58-81) versus 55 years (IQR 38-77)), and a higher percentage of cases with secondary infection were of Black or Asian ethnicity than cases without (6.7% versus 4.1%, and 9.9% versus 8.2%, respectively, p < 0.001). Age-sex-adjusted case fatality rates were higher in COVID-19 cases with a coinfection (23.0% (95%CI 18.8-27.6%)) or secondary infection (26.5% (95%CI 14.5-39.4%)) than in those without (7.6% (95%CI 7.5-7.7%)) (p < 0.005). CONCLUSIONS: Coinfection/secondary bacterial/fungal infections were rare in non-hospitalized and hospitalized persons with COVID-19, varied by ethnicity and age, and were associated with higher mortality. However, the inclusion of non-hospitalized persons with asymptomatic/mild COVID-19 likely underestimated the rate of secondary bacterial/fungal infections. This should inform diagnostic testing and antibiotic prescribing strategy.

Surveillance of Antibacterial Usage during the COVID-19 Pandemic in England, 2020.

Changes in antibacterial prescribing during the COVID-19 pandemic were anticipated given that the clinical features of severe respiratory infection syndrome caused by SARS-CoV-2 mirror bacterial respiratory tract infections. Antibacterial consumption was measured in items/1000 population for primary care and in Defined Daily Doses (DDDs)/1000 admissions for secondary care in England from 2015 to October 2020. Interrupted time-series analyses were conducted to evaluate the effects of the pandemic on antibacterial consumption. In the community, the rate of antibacterial items prescribed decreased further in 2020 (by an extra 1.4% per month, 95% CI: -2.3 to -0.5) compared to before COVID-19. In hospitals, the volume of antibacterial use decreased during COVID-19 overall (-12.1% compared to pre-COVID, 95% CI: -19.1 to -4.4), although the rate of usage in hospitals increased steeply in April 2020. Use of antibacterials prescribed for respiratory infections and broad-spectrum antibacterials (predominately 'Watch' antibacterials in hospitals) increased in both settings. Overall volumes of antibacterial use at the beginning of the COVID-19 pandemic decreased in both primary and secondary settings, although there were increases in the rate of usage in hospitals in April 2020 and in specific antibacterials. This highlights the importance of antimicrobial stewardship during pandemics to ensure appropriate prescribing and avoid negative consequences on patient outcomes and antimicrobial resistance.

Effect of antibiotic stewardship interventions in primary care on antimicrobial resistance of Escherichia coli bacteraemia in England (2013-18): a quasi-experimental, ecological, data linkage study.

BACKGROUND: Antimicrobial resistance is a major global health concern, driven by overuse of antibiotics. We aimed to assess the effectiveness of a national antimicrobial stewardship intervention, the National Health Service (NHS) England Quality Premium implemented in 2015-16, on broad-spectrum antibiotic prescribing and Escherichia coli bacteraemia resistance to broad-spectrum antibiotics in England. METHODS: In this quasi-experimental, ecological, data linkage study, we used longitudinal data on bacteraemia for patients registered with a general practitioner in the English National Health Service and patients with E coli bacteraemia notified to the national mandatory surveillance programme between Jan 1, 2013, and Dec 31, 2018. We linked these data to data on antimicrobial susceptibility testing of E coli from Public Health England's Second-Generation Surveillance System. We did an ecological analysis using interrupted time-series analyses and generalised estimating equations to estimate the change in broad-spectrum antibiotics prescribing over time and the change in the proportion of E coli bacteraemia cases for which the causative bacteria were resistant to each antibiotic individually or to at least one of five broad-spectrum antibiotics (co-amoxiclav, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin), after implementation of the NHS England Quality Premium intervention in April, 2015. FINDINGS: Before implementation of the Quality Premium, the rate of antibiotic prescribing for all five broad-spectrum antibiotics was increasing at rate of 0·2% per month (incidence rate ratio [IRR] 1·002 [95% CI 1·000-1·004], p=0·046). After implementation of the Quality Premium, an immediate reduction in total broad-spectrum antibiotic prescribing rate was observed (IRR 0·867 [95% CI 0·837-0·898], p<0·0001). This effect was sustained until the end of the study period; a 57% reduction in rate of antibiotic prescribing was observed compared with the counterfactual situation (ie, had the Quality Premium not been implemented). In the same period, the rate of resistance to at least one broad-spectrum antibiotic increased at rate of 0·1% per month (IRR 1·001 [95% CI 0·999-1·003], p=0·346). On implementation of the Quality Premium, an immediate reduction in resistance rate to at least one broad-spectrum antibiotic was observed (IRR 0·947 [95% CI 0·918-0·977], p=0·0007). Although this effect was also sustained until the end of the study period, with a 12·03% reduction in resistance rate compared with the counterfactual situation, the overall trend remained on an upward trajectory. On examination of the long-term effect following implementation of the Quality Premium, there was an increase in the number of isolates resistant to at least one of the five broad-spectrum antibiotics tested (IRR 1·002 [1·000-1·003]; p=0·047). INTERPRETATION: Although interventions targeting antibiotic use can result in changes in resistance over a short period, they might be insufficient alone to curtail antimicrobial resistance. FUNDING: National Institute for Health Research, Economic and Social Research Council, Rosetrees Trust, and The Stoneygate Trust.

Interactions between SARS-CoV-2 and influenza, and the impact of coinfection on disease severity: a test-negative design.

BACKGROUND: The impact of SARS-CoV-2 alongside influenza is a major concern in the northern hemisphere as winter approaches. METHODS: Test data for influenza and SARS-CoV-2 from national surveillance systems between 20 January 2020 and 25 April 2020 were used to estimate influenza infection on the risk of SARS-CoV-2 infection. A test-negative design was used to assess the odds of SARS-CoV-2 in those who tested positive for influenza compared with those who tested negative. The severity of SARS-CoV-2 was also assessed using univariable and multivariable analyses. RESULTS: The risk of testing positive for SARS-CoV-2 was 58% lower among influenza-positive cases and patients with a coinfection had a risk of death of 5.92 (95% confidence interval: 3.21-10.91) times greater than among those with neither influenza nor SARS-CoV-2. The odds of ventilator use or death and intensive care unit admission or death were greatest among coinfected patients. CONCLUSIONS: Coinfection of these viruses could have a significant impact on morbidity, mortality and health-service demand.

Screening for Candida auris in patients admitted to eight intensive care units in England, 2017 to 2018.

BackgroundCandida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.MethodsBetween May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017.ResultsAll C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities.ConclusionThese findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment.

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.

BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.

Babies who are born too early or who are very sick require intensive care after birth and during early life. Most will have a long, narrow, plastic tube, called a catheter, inserted into a vein. The catheter is used to give babies fluids containing medicines and nutrition to keep them well and help them grow. The catheter can remain in place for several days or weeks. But the presence of plastic tubing in the vein increases the risk of infection. This study aimed to find out whether or not catheters coated with antimicrobial medicines, called rifampicin and miconazole, could reduce the risk of infection. These medicines act by stopping germs from growing on the catheter, but do not harm the baby or interfere with other treatments. A randomised controlled trial was carried out in 18 neonatal units in England. Whenever a baby needed a catheter, their parents were asked for consent to participate in the trial. The baby was then randomised, similar to tossing a coin, to receive either the antimicrobial catheter or a standard one. A total of 861 babies participated. We followed up all babies in the same way until after the catheter was removed to compare how often babies in each group had an infection. It was found that antimicrobial catheters were no better or worse at preventing infection than standard catheters. Antimicrobial catheters cost more and we found no evidence of benefit; these results suggest that their use in neonatal intensive care is not justified. It was calculated that further research on ways to reduce infection may be good value for money, depending on the costs of this research. The babies who took part in this study were typical of babies in England receiving catheters, meaning that the results can be applied across the NHS. Future research should focus on catheters that contain other types of antimicrobials and alternative ways of preventing infection.

Monitoring Antimicrobial Resistance and Drug Usage in the Human and Livestock Sector and Foodborne Antimicrobial Resistance in Six European Countries.

INTRODUCTION: Antimicrobial resistance (AMR), associated with antimicrobial use (AMU), is a major public concern. Surveillance and monitoring systems are essential to assess and control the trends in AMU and AMR. However, differences in the surveillance and monitoring systems between countries and sectors make comparisons challenging. The purpose of this article is to describe all surveillance and monitoring systems for AMU and AMR in the human and livestock sectors, as well as national surveillance and monitoring systems for AMR in food, in six European countries (Spain, Germany, France, the Netherlands, the United Kingdom and Norway) as a baseline for developing suggestions to overcome current limitations in comparing AMU and AMR data. METHODS: A literature search in 2018 was performed to identify relevant peer-reviewed articles and national and European grey reports as well as AMU/AMR databases. RESULTS: Comparison of AMU and AMR systems across the six countries showed a lack of standardization and harmonization with different AMU data sources (prescription vs sales data) and units of AMU and AMR being used. The AMR data varied by sample type (clinical/non-clinical), laboratory method (disk diffusion, microdilution, and VITEK, among others), data type, ie quantitative (minimum inhibition concentration (MIC) in mg/L/inhibition zone (IZ) in mm) vs qualitative data (susceptible-intermediate-resistant (SIR)), the standards used (EUCAST/CLSI among others), and/or the evaluation criteria adopted (epidemiological or clinical). DISCUSSION: A One Health approach for AMU and AMR requires harmonization in various aspects between human, animal and food systems at national and international levels. Additionally, some overlap between systems of AMU and AMR has been encountered. Efforts should be made to improve standardization and harmonization and allow more meaningful analyses of AMR and AMU surveillance data under a One Health approach.

Investigation of the impact of the NICE guidelines regarding antibiotic prophylaxis during invasive dental procedures on the incidence of infective endocarditis in England: an electronic health records study.

BACKGROUND: Infective endocarditis is an uncommon but serious infection, where evidence for giving antibiotic prophylaxis before invasive dental procedures is inconclusive. In England, antibiotic prophylaxis was offered routinely to patients at risk of infective endocarditis until March 2008, when new guidelines aimed at reducing unnecessary antibiotic use were issued. We investigated whether changes in infective endocarditis incidence could be detected using electronic health records, assessing the impact of inclusion criteria/statistical model choice on inferences about the timing/type of any change. METHODS: Using national data from Hospital Episode Statistics covering 1998-2017, we modelled trends in infective endocarditis incidence using three different sets of inclusion criteria plus a range of regression models, identifying the most likely date for a change in trends if evidence for one existed. We also modelled trends in the proportions of different organism groups identified during infection episodes, using secondary diagnosis codes and data from national laboratory records. Lastly, we applied non-parametric local smoothing to visually inspect any changes in trend around the guideline change date. RESULTS: Infective endocarditis incidence increased markedly over the study (22.2-41.3 per million population in 1998 to 42.0-67.7 in 2017 depending on inclusion criteria). The most likely dates for a change in incidence trends ranged from September 2001 (uncertainty interval August 2000-May 2003) to May 2015 (March 1999-January 2016), depending on inclusion criteria and statistical model used. For the proportion of infective endocarditis cases associated with streptococci, the most likely change points ranged from October 2008 (March 2006-April 2010) to August 2015 (September 2013-November 2015), with those associated with oral streptococci decreasing in proportion after the change point. Smoothed trends showed no notable changes in trend around the guideline date. CONCLUSIONS: Infective endocarditis incidence has increased rapidly in England, though we did not detect any change in trends directly following the updated guidelines for antibiotic prophylaxis, either overall or in cases associated with oral streptococci. Estimates of when changes occurred were sensitive to inclusion criteria and statistical model choice, demonstrating the need for caution in interpreting single models when using large datasets. More research is needed to explore the factors behind this increase.

Epidemiology of carbapenemase-producing Enterobacterales in England, May 2015-March 2019: national enhanced surveillance findings and approach.

BACKGROUND: In response to increasing numbers of carbapenemase-producing Enterobacterales (CPE) in England, Public Health England (PHE) launched an electronic reporting system (ERS) for the enhanced surveillance of carbapenemase-producing Gram-negative bacteria. Our study aimed to describe system engagement and the epidemiology of CPE in England. METHODS: Engagement with the ERS was assessed by calculating the proportion of referrals submitted this system. ERS data were extracted and cases defined as patients with CPE isolated from a screening or clinical specimen in England between 1st May 2015 to 31st March 2019. Descriptive summary statistics for each variable were prepared. RESULTS: The ERS processed 12,656 suspected CPE reports. Uptake of the ERS by local microbiology laboratories varied, with approximately 70% of referrals made via the ERS by April 2016; this steadily decreased after March 2018. Six-thousand eight-hundred and fifty-seven cases were included in the analysis. Most cases were from colonised patients (80.6%) rather than infected, and the majority were inpatients in acute hospital settings (87.3%). Carbapenemases were most frequently detected in Klebsiella pneumoniae (39.1%) and Escherichia coli (30.3%). The most frequently identified carbapenemase families were OXA-48-like (45.1%) and KPC (26.4%). Enhanced data variables were poorly completed. CONCLUSIONS: The ERS has provided some insight into the epidemiology of CPE in England. An increasing number of routine diagnostic laboratories have introduced methods to routinely identify acquired carbapenemases and PHE has modified its approach to ensure robust surveillance, which is an essential aspect of an effective response to prevent and control the spread of CPE.

Linking surveillance and clinical data for evaluating trends in bloodstream infection rates in neonatal units in England.

OBJECTIVE: To evaluate variation in trends in bloodstream infection (BSI) rates in neonatal units (NNUs) in England according to the data sources and linkage methods used. METHODS: We used deterministic and probabilistic methods to link clinical records from 112 NNUs in the National Neonatal Research Database (NNRD) to national laboratory infection surveillance data from Public Health England. We calculated the proportion of babies in NNRD (aged <1 year and admitted between 2010-2017) with a BSI caused by clearly pathogenic organisms between two days after admission and two days after discharge. We used Poisson regression to determine trends in the proportion of babies with BSI based on i) deterministic and probabilistic linkage of NNRD and surveillance data (primary measure), ii) deterministic linkage of NNRD-surveillance data, iii) NNRD records alone, and iv) linked NNRD-surveillance data augmented with clinical records of laboratory-confirmed BSI in NNRD. RESULTS: Using deterministic and probabilistic linkage, 5,629 of 349,740 babies admitted to a NNU in NNRD linked with 6,660 BSI episodes accounting for 38% of 17,388 BSI records aged <1 year in surveillance data. The proportion of babies with BSI due to clearly pathogenic organisms during their NNU admission was 1.0% using deterministic plus probabilistic linkage (primary measure), compared to 1.0% using deterministic linkage alone, 0.6% using NNRD records alone, and 1.2% using linkage augmented with clinical records of BSI in NNRD. Equivalent proportions for babies born before 32 weeks of gestation were 5.0%, 4.8%, 2.9% and 5.9%. The proportion of babies who linked to a BSI decreased by 7.5% each year (95% confidence interval [CI]: -14.3%, -0.1%) using deterministic and probabilistic linkage but was stable using clinical records of BSI or deterministic linkage alone. CONCLUSION: Linkage that combines BSI records from national laboratory surveillance and clinical NNU data sources, and use of probabilistic methods, substantially improved ascertainment of BSI and estimates of BSI trends over time, compared with single data sources.

'Caveat emptor': the cautionary tale of endocarditis and the potential pitfalls of clinical coding data-an electronic health records study.

BACKGROUND: Diagnostic codes from electronic health records are widely used to assess patterns of disease. Infective endocarditis is an uncommon but serious infection, with objective diagnostic criteria. Electronic health records have been used to explore the impact of changing guidance on antibiotic prophylaxis for dental procedures on incidence, but limited data on the accuracy of the diagnostic codes exists. Endocarditis was used as a clinically relevant case study to investigate the relationship between clinical cases and diagnostic codes, to understand discrepancies and to improve design of future studies. METHODS: Electronic health record data from two UK tertiary care centres were linked with data from a prospectively collected clinical endocarditis service database (Leeds Teaching Hospital) or retrospective clinical audit and microbiology laboratory blood culture results (Oxford University Hospitals Trust). The relationship between diagnostic codes for endocarditis and confirmed clinical cases according to the objective Duke criteria was assessed, and impact on estimations of disease incidence and trends. RESULTS: In Leeds 2006-2016, 738/1681(44%) admissions containing any endocarditis code represented a definite/possible case, whilst 263/1001(24%) definite/possible endocarditis cases had no endocarditis code assigned. In Oxford 2010-2016, 307/552(56%) reviewed endocarditis-coded admissions represented a clinical case. Diagnostic codes used by most endocarditis studies had good positive predictive value (PPV) but low sensitivity (e.g. I33-primary 82% and 43% respectively); one (I38-secondary) had PPV under 6%. Estimating endocarditis incidence using raw admission data overestimated incidence trends twofold. Removing records with non-specific codes, very short stays and readmissions improved predictive ability. Estimating incidence of streptococcal endocarditis using secondary codes also overestimated increases in incidence over time. Reasons for discrepancies included changes in coding behaviour over time, and coding guidance allowing assignment of a code mentioning 'endocarditis' where endocarditis was never mentioned in the clinical notes. CONCLUSIONS: Commonly used diagnostic codes in studies of endocarditis had good predictive ability. Other apparently plausible codes were poorly predictive. Use of diagnostic codes without examining sensitivity and predictive ability can give inaccurate estimations of incidence and trends. Similar considerations may apply to other diseases. Health record studies require validation of diagnostic codes and careful data curation to minimise risk of serious errors.

Adaptation of the WHO Essential Medicines List for national antibiotic stewardship policy in England: being AWaRe.

OBJECTIVES: Appropriate use of and access to antimicrobials are key priorities of global strategies to combat antimicrobial resistance (AMR). The WHO recently classified key antibiotics into three categories (AWaRe) to improve access (Access), monitor important antibiotics (Watch) and preserve effectiveness of 'last resort' antibiotics (Reserve). This classification was assessed for antibiotic stewardship and quality improvement in English hospitals. METHODS: Using an expert elicitation exercise, antibiotics used in England but not included in the WHO AWaRe index were added to an appropriate category following a workshop consensus exercise with national experts. The methodology was tested using national antibiotic prescribing data and presented by primary and secondary care. RESULTS: In 2016, 46/108 antibiotics included within the WHO AWaRe index were routinely used in England and an additional 25 antibiotics also commonly used in England were not included in the WHO AWaRe index. WHO AWaRe-excluded and -included antibiotics were reviewed and reclassified according to the England-adapted AWaRE index with the justification by experts for each addition or alteration. Applying the England-adapted AWaRe index, Access antibiotics accounted for the majority (60.9%) of prescribing, followed by Watch (37.9%) and Reserve (0.8%); 0.4% of antibiotics remained unclassified. There was unexplained 2-fold variation in prescribing between hospitals within each AWaRe category, highlighting the potential for quality improvement. CONCLUSIONS: We have adapted the WHO AWaRe index to create a specific index for England. The AWaRe index provides high-level understanding of antibiotic prescribing. Subsequent to this process the England AWaRe index is now embedded into national antibiotic stewardship policy and incentivized quality improvement schemes.

Selection and co-selection of antibiotic resistances among Escherichia coli by antibiotic use in primary care: An ecological analysis.

BACKGROUND: The majority of studies that link antibiotic usage and resistance focus on simple associations between the resistance against a specific antibiotic and the use of that specific antibiotic. However, the relationship between antibiotic use and resistance is more complex. Here we evaluate selection and co-selection by assessing which antibiotics, including those mainly prescribed for respiratory tract infections, are associated with increased resistance to various antibiotics among Escherichia coli isolated from urinary samples. METHODS: Monthly primary care prescribing data were obtained from National Health Service (NHS) Digital. Positive E. coli records from urine samples in English primary care (n = 888,207) between April 2014 and January 2016 were obtained from the Second Generation Surveillance System. Elastic net regularization was used to evaluate associations between prescribing of different antibiotic groups and resistance against amoxicillin, cephalexin, ciprofloxacin, co-amoxiclav and nitrofurantoin at the clinical commissioning group (CCG) level. England is divided into 209 CCGs, with each NHS practice prolonging to one CCG. RESULTS: Amoxicillin prescribing (measured in DDD/ 1000 inhabitants / day) was positively associated with amoxicillin (RR 1.03, 95% CI 1.01-1.04) and ciprofloxacin (RR 1.09, 95% CI 1.04-1.17) resistance. In contrast, nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin (RR 0.92, 95% CI 0.84-0.97). CCGs with higher levels of trimethoprim prescribing also had higher levels of ciprofloxacin resistance (RR 1.34, 95% CI 1.10-1.59). CONCLUSION: Amoxicillin, which is mainly (and often unnecessarily) prescribed for respiratory tract infections is associated with increased resistance against various antibiotics among E. coli causing urinary tract infections. Our findings suggest that when predicting the potential impact of interventions on antibiotic resistances it is important to account for use of other antibiotics, including those typically used for other indications.