Risk of bloodstream infection in children admitted to paediatric intensive care units in England and Wales following emergency inter-hospital transfer.

PURPOSE: Adherence to full sterile procedures may be compromised when central venous catheters are inserted as part of emergency resuscitation and stabilisation, particularly outside the intensive care unit. Half of emergency admissions to paediatric intensive care units (PICU) in the UK occur after stabilisation at other hospitals. We determined whether bloodstream infection (BSI) occurred more frequently in children admitted to PICU after inter-hospital transfer compared to within-hospital admissions. METHODS: Data on emergency admissions to 20 PICUs in England and Wales for children <16 years between 2003-2012 were linked from the national PICU audit database (PICANet) and national infection surveillance (LabBase2). PICU-acquired BSI was defined as any positive blood culture sampled between 2 days after admission and 2 days following discharge from PICU. RESULTS: A total of 32,861/62,515 (53%) admissions were inter-hospital transfers. Multivariable regression showed no significant difference in rates of PICU-acquired BSI by source of admission (incidence-rate ratio for inter-hospital transfer versus within-hospital admission = 0.97; 95% CI 0.87-1.07) after adjusting for other risk-factors. Rates decreased more rapidly between 2003 and 2012 for inter-hospital transfers: 17.0% (95% CI 14.9-19.0% per year) compared with 12.4% (95% CI 9.9-14.9% per year) for within-hospital admissions. The median time to first PICU-acquired BSI did not differ significantly between inter-hospital transfers (7 days; IQR 4-13) and within-hospital admissions (8 days; IQR 4-15). CONCLUSIONS: Nationally, inter-hospital transfer is no longer a significant risk factor for PICU-acquired BSI. Given the large proportion of infection occurring in the second week of admission, initiatives to further reduce PICU-acquired BSI should focus on maintaining sterile procedures after admission

Challenges in linking administrative data for monitoring bloodstream infection in neonatal units in England and Wales

Monitoring risk-adjusted trends of neonatal bloodstream infection is vital and linkage of neonatal electronic health records to national infection surveillance enables this. We demonstrate why changes in data quality over time must be accounted for to minimise spurious findings. First, we evaluated the impact of changes in identifier completeness over time in each database, and determined variation in infection rates according to linkage method (deterministic linkage on NHS number or probabilistic linkage). Second, we will use multiple imputation when link status cannot be determined due to missing identifiers. Completeness of NHS number in infection surveillance increased from 69% (3,296/4,792) in 2010 to 92% (3,037/3,307) in 2017. We linked 12,003 neonatal admissions to 15,571 infection episodes (2% of 497,936 admissions and 41% of 37,660 infections). The proportion of links that were deterministic changed from 83% (1,089/1,307) in 2010 to 96% (968/1,008) in 2017. Link status could not be determined for 12,094 infections due to missing identifiers; multiple imputation will be used to determine if any are links. Spurious infection incidence rates can arise from changes in data quality, impacting the quality of linkage to clinical data. Linkage and imputation of missing data minimises spurious findings due to data quality

Challenges in linking administrative data for monitoring bloodstream infection in neonatal units in England and Wales

Introduction Monitoring risk-adjusted trends of neonatal bloodstream infection (BSI) is vital and linkage of neonatal electronic health records to national infection surveillance enables this. We demonstrate why changes in data quality and collection methods over time must be accounted for to minimise spurious findings. Objectives and Approach First, we determined the effect of a system change in 2014 (changed from only clinically relevant BSI to automated reporting of all BSI), by investigating changes in number of all BSI and BSI excluding the contaminants coagulase-negative staphylococci for infants aged <1 year reported to infection surveillance, using interrupted-time-series Poisson regression. Second, we evaluated the impact of changes in identifier completeness over time in each database, and determined variation in infection rates according to linkage method (deterministic linkage on NHS number or probabilistic linkage). Third, we will use multiple imputation when link status cannot be determined due to missing identifiers. Results The number of BSI reported to infection surveillance system following the change in data collection increased by 34% (incidence rate ratio (IRR) of 1.34, 95% confidence interval 1.28-1.40) for all BSI compared to 19% (IRR 1.19, 1.12-1.27) excluding coagulase-negative staphylococci. Completeness of NHS number in infection surveillance increased from 69% (3,296/4,792) in 2010 to 92% (3,037/3,307) in 2017. We linked 12,003 neonatal admissions to 15,571 BSI episodes (2% of 497,936 admissions and 41% of 37,660 BSI). The proportion of links that were deterministic changed from 83% (1,089/1,307) in 2010 to 96% (968/1,008) in 2017. There were 12,094 BSI for which the link status could not be determined due to missing identifiers; multiple imputation will be used to determine if any are links. Conclusion/Implications Spurious trends in infection incidence can arise from changes in data collection and quality, impacting the quality of linkage to clinical data. Data quality and system changes must be explored in each source dataset before analysis. Probabilistic linkage and imputation of missing data minimises spurious findings due to data quality

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.Peer Reviewe

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

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

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

Generalisability and Cost-Impact of Antibiotic-Impregnated Central Venous Catheters for Reducing Risk of Bloodstream Infection in Paediatric Intensive Care Units in England

Background: We determined the generalisability and cost-impact of adopting antibiotic-impregnated CVCs in all paediatric intensive care units (PICUs) in England, based on results from a large randomised controlled trial (the CATCH trial; ISRCTN34884569). Methods: BSI rates using standard CVCs were estimated through linkage of national PICU audit data (PICANet) with laboratory surveillance data. We estimated the number of BSI averted if PICUs switched from standard to antibiotic-impregnated CVCs by applying the CATCH trial rate-ratio (0.40; 95% CI 0.17,0.97) to the BSI rate using standard CVCs. The value of healthcare resources made available by averting one BSI as estimated from the trial economic analysis was £10,975; 95% CI -£2,801,£24,751. Results: The BSI rate using standard CVCs was 4.58 (95% CI 4.42,4.74) per 1000 CVC-days in 2012. Applying the rate-ratio gave 232 BSI averted using antibiotic CVCs. The additional cost of purchasing antibiotic-impregnated compared with standard CVCs was £36 for each child, corresponding to additional costs of £317,916 for an estimated 8831 CVCs required in PICUs in 2012. Based on 2012 BSI rates, management of BSI in PICUs cost £2.5 million annually (95% uncertainty interval: -£160,986, £5,603,005). The additional cost of antibiotic CVCs would be less than the value of resources associated with managing BSI in PICUs with standard BSI rates >1.2 per 1000 CVC-days. Conclusions: The cost of introducing antibiotic-impregnated CVCs is less than the cost associated with managing BSIs occurring with standard CVCs. The long-term benefits of preventing BSI could mean that antibiotic CVCs are cost-effective even in PICUs with extremely low BSI rates

Monitoring Quality of Care Through Linkage of Administrative Data: National Trends in Bloodstream Infection in U.K. PICUs 2003-2012.

OBJECTIVES Interventions to reduce hospital-acquired bloodstream infection have succeeded in reducing rates in U.S. PICUs, but there is a lack of evidence for the impact of similar interventions in the United Kingdom. We assessed variation in bloodstream infection rates within and between PICUs over a 10-year period, during which time infection control strategies (care bundles) were implemented. DESIGN Observational study linking laboratory data to national audit data of pediatric intensive care admissions (Paediatric Intensive Care Audit Network). SETTING Twenty PICUs in England and Wales, 2003-2012. PATIENTS One hundred and two thousand nine hundred ninety-nine children less than 16 years. INTERVENTIONS Implementation of infection control strategies in PICU captured through a survey of clinicians. MEASUREMENTS AND MAIN RESULTS Rates of bloodstream infection per 1,000 bed-days were estimated from samples taken between 2 days after admission and up to 2 days following discharge from PICU. Two percent of children experienced at least one bloodstream infection, corresponding to 5.11 (95% CI, 4.90-5.31) per 1,000 bed-days. There was a significant difference in trends preimplementation of infection control strategies (annual decrease of 8.0%; 95% CI, 6.3-9.7%) versus postimplementation (annual decrease of 13.4%; 95% CI, 10.3-16.4%). By 24 months postimplementation, the rate of bloodstream infection had fallen 25.5% and was 15.1% lower than would have been expected if preimplementation trends had continued. CONCLUSIONS Our population-based study of PICUs in England and Wales demonstrates a steady decline in bloodstream infection rates over time. In addition, there was a significant and incremental further decrease in rates associated with timing of implementation of infection control strategies. Assessment of bloodstream infection trends before as well as after implementation of infection control strategies can be facilitated using data linkage and is important to avoid overestimating the impact of unit-level interventions to improve infection control. Advances in collection and linkage of real-time data could further support quality improvement efforts