Recommendations for detection and rapid management of carbapenemase-producing Enterobacterales outbreaks.

There is large heterogeneity in approaches to tackling nosocomial outbreaks caused by carbapenemase-producing Enterobacterales (CPE), however there is limited guidance on how to approach their management. Rapid and robust infection prevention and control interventions can be effective in preventing and reducing the impact of outbreaks in healthcare environments. We present a stepwise approach to aspects of CPE outbreak management, including the development of an action plan, engagement and communication with key stakeholders, developing a dynamic risk assessment, and staff education. These can provide a blueprint for organisations to create templates and checklists to inform their own outbreak response.

Epidemiology and health-economic burden of urinary-catheter-associated infection in English NHS hospitals: a probabilistic modelling study.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) and bloodstream infection (CABSI) are leading causes of healthcare-associated infection in England's National Health Service (NHS), but health-economic evidence to inform investment in prevention is lacking. AIMS: To quantify the health-economic burden and value of prevention of urinary-catheter-associated infection among adult inpatients admitted to NHS trusts in 2016/17. METHODS: A decision-analytic model was developed to estimate the annual prevalence of CAUTI and CABSI, and their associated excess health burdens [quality-adjusted life-years (QALYs)] and economic costs (£ 2017). Patient-level datasets and literature were synthesized to estimate population structure, model parameters and associated uncertainty. Health and economic benefits of catheter prevention were estimated. Scenario and probabilistic sensitivity analyses were conducted. FINDINGS: The model estimated 52,085 [95% uncertainty interval (UI) 42,967-61,360] CAUTIs and 7529 (UI 6857-8622) CABSIs, of which 38,084 (UI 30,236-46,541) and 2524 (UI 2319-2956) were hospital-onset infections, respectively. Catheter-associated infections incurred 45,717 (UI 18,115-74,662) excess bed-days, 1467 (UI 1337-1707) deaths and 10,471 (UI 4783-13,499) lost QALYs. Total direct hospital costs were estimated at £54.4M (UI £37.3-77.8M), with an additional £209.4M (UI £95.7-270.0M) in economic value of QALYs lost assuming a willingness-to-pay threshold of £20,000/QALY. Respectively, CABSI accounted for 47% (UI 32-67%) and 97% (UI 93-98%) of direct costs and QALYs lost. Every catheter prevented could save £30 (UI £20-44) in direct hospital costs and £112 (UI £52-146) in QALY value. CONCLUSIONS: Hospital catheter prevention is poised to reap substantial health-economic gains, but community-oriented interventions are needed to target the large burden imposed by community-onset infection.

Intensive care unit (ICU)-acquired bacteraemia and ICU mortality and discharge: addressing time-varying confounding using appropriate methodology.

BACKGROUND: Studies often ignore time-varying confounding or may use inappropriate methodology to adjust for time-varying confounding. AIM: To estimate the effect of intensive care unit (ICU)-acquired bacteraemia on ICU mortality and discharge using appropriate methodology. METHODS: Marginal structural models with inverse probability weighting were used to estimate the ICU mortality and discharge associated with ICU-acquired bacteraemia among patients who stayed more than two days at the general ICU of a London teaching hospital and remained bacteraemia-free during those first two days. For comparison, the same associations were evaluated with (i) a conventional Cox model, adjusting only for baseline confounders and (ii) a Cox model adjusting for baseline and time-varying confounders. FINDINGS: Using the marginal structural model with inverse probability weighting, bacteraemia was associated with an increase in ICU mortality (cause-specific hazard ratio (CSHR): 1.29; 95% confidence interval (CI): 1.02-1.63) and a decrease in discharge (CSHR: 0.52; 95% CI: 0.45-0.60). By 60 days, among patients still in the ICU after two days and without prior bacteraemia, 8.0% of ICU deaths could be prevented by preventing all ICU-acquired bacteraemia cases. The conventional Cox model adjusting for time-varying confounders gave substantially different results [for ICU mortality, CSHR: 1.08 (95% CI: 0.88-1.32); for discharge, CSHR: 0.68 (95% CI: 0.60-0.77)]. CONCLUSION: In this study, even after adjusting for the timing of acquiring bacteraemia and time-varying confounding using inverse probability weighting for marginal structural models, ICU-acquired bacteraemia was associated with a decreased daily ICU discharge risk and an increased risk of ICU mortality.

Seasonality of urinary tract infections in the United Kingdom in different age groups: longitudinal analysis of The Health Improvement Network (THIN).

Evidence regarding the seasonality of urinary tract infection (UTI) consultations in primary care is conflicting and methodologically poor. To our knowledge, this is the first study to determine whether this seasonality exists in the UK, identify the peak months and describe seasonality by age. The monthly number of UTI consultations (N = 992 803) and nitrofurantoin and trimethoprim prescriptions (N = 1 719 416) during 2008-2015 was extracted from The Health Improvement Network (THIN), a large nationally representative UK dataset of electronic patient records. Negative binomial regression models were fitted to these data to investigate seasonal fluctuations by age group (14-17, 18-24, 25-45, 46-69, 70-84, 85+) and by sex, accounting for a change in the rate of UTI over the study period. A September to November peak in UTI consultation incidence was observed for ages 14-69. This seasonality progressively faded in older age groups and no seasonality was found in individuals aged 85+, in whom UTIs were most common. UTIs were rare in males but followed a similar seasonal pattern than in females. We show strong evidence of an autumnal seasonality for UTIs in individuals under 70 years of age and a lack of seasonality in the very old. These findings should provide helpful information when interpreting surveillance reports and the results of interventions against UTI.

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

AIMS: This narrative review aimed to collate recent evidence on the cost-effectiveness and cost-benefit of antimicrobial stewardship (AMS) programmes, to address the question 'is AMS cost-effective?', while providing resources and guidance for future research in this area. SOURCES: PubMed was searched for studies assessing the cost-effectiveness, cost-utility or cost-benefit of AMS interventions in humans, published from January 2000 to March 2017, with no setting inclusion/exclusion criteria specified. Reference lists of retrieved reviews were searched for additional articles. CONTENT: Recent evidence on the cost-effectiveness and cost-benefit of AMS is described, studies suggest persuasive and structural AMS interventions may provide health economic benefits to the hospital setting. However, overall, cost-effectiveness evidence for AMS is severely limited, especially for the community setting. Recommendations for future research in this area are therefore provided, including discussion of appropriate health economic methodological choice. IMPLICATIONS: Health systems have a finite and decreasing resource, decision makers currently do not have necessary evidence to assess whether AMS programmes provide sufficient benefits. Although the evidence-base of the cost-effectiveness of AMS is increasing, it remains inadequate for investment decision-making. Robust health economics research needs to be completed to enhance the generalizability and usability of cost-effectiveness results.

Burden, duration and costs of hospital bed closures due to acute gastroenteritis in England per winter, 2010/11-2015/16.

BACKGROUND: Bed closures due to acute gastroenteritis put hospitals under pressure each winter. In England, the National Health Service (NHS) has monitored the winter situation for all acute trusts since 2010/11. AIM: To estimate the burden, duration and costs of hospital bed closures due to acute gastroenteritis in winter. METHODS: A retrospective analysis of routinely collected time-series data of bed closures due to diarrhoea and vomiting was conducted for the winters 2010/11 to 2015/16. Two key issues were addressed by imputing non-randomly missing values at provider level, and filtering observations to a range of dates recorded in all six winters. The lowest and highest values imputed were taken to represent the best- and worst-case scenarios. Bed-days were costed using NHS reference costs, and potential staff absence costs were based on previous studies. FINDINGS: In the best-to-worst case, a median of 88,000-113,000 beds were closed due to gastroenteritis each winter. Of these, 19.6-20.4% were unoccupied. On average, 80% of providers were affected, and had closed beds for a median of 15-21 days each winter. Hospital costs of closed beds were £5.7-£7.5 million, which increased to £6.9-£10.0 million when including staff absence costs due to illness. CONCLUSIONS: The median number of hospital beds closed due to acute gastroenteritis per winter was equivalent to all general and acute hospital beds in England being unavailable for a median of 0.88-1.12 days. Costs for hospitals are high but vary with closures each winter.

Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

BACKGROUND: Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. AIM: To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature. METHODS: Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes. FINDINGS: Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). CONCLUSION: ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge.

Isolation demand from carbapenemase-producing Enterobacteriaceae screening strategies based on a West London hospital network.

OBJECTIVE: To estimate the isolation demands arising from high-risk specialty-based screening for carbapenemase-producing Enterobacteriaceae (CPE), and the potential fraction of CPE burden detected. METHODS: Clinical specialty groups from three London hospitals were ranked by incidence of carbapenem resistance among Escherichia coli and Klebsiella spp. Contact precaution bed-days were estimated for three screening strategies: Strategy 1, 'circulation science and renal medicine'; Strategy 2, Strategy 1 plus 'specialist services'; and Strategy 3, Strategy 2 plus 'private patients'. Isolation bed occupancy rates and potential CPE detection rates were estimated. RESULTS: Of 99,105 admissions to the three hospitals in Financial Year 2014/15, Strategies 1, 2 and 3 would have screened 4371 (4.4%), 7482 (7.6%), and 13,542 (13.7%) patients, respectively. The specialties' isolation bed occupancy rates varied between 3% and 696% depending on strategy, number of consecutive tests, and whether or not pre-emptive isolation had been applied. Expected detection rates of the potential CPE burden in the hospital network would have varied between 17.1% and 47.5%. CONCLUSIONS: High-risk specialty-based screening has the potential to detect nearly half of the potential CPE burden, and would be more pragmatic than patient-level risk-factor-based screening. Pre-emptive isolation increases isolation requirements substantially. CPE screening strategies need to balance risk and resources.

Quantifying the Burden of Hospital-Acquired Bloodstream Infection in Children in England by Estimating Excess Length of Hospital Stay and Mortality Using a Multistate Analysis of Linked, Routinely Collected Data.

BACKGROUND: Hospital-acquired bloodstream infection (HA-BSI) is associated with substantial morbidity, mortality, and healthcare costs in all patient populations. Young children have been shown to have a high rate of healthcare-associated infections compared with the adult population. We aimed to quantify the excess mortality and length of stay in pediatric patients from HA-BSI. METHODS: We analyzed data collected retrospectively from a probabilistically linked national database of pediatric (aged 1 month-18 years) in-patients with a microbiologically confirmed HA-BSI in England between January and March 2009. A time-dependent Cox regression model was fit to determine the presence of any effect. Furthermore, a multistate model, adjusted for the time to onset of HA-BSI, was used to compare outcomes in patients with HA-BSI to those without HA-BSI. We further adjusted for patients' characteristics as recorded in hospital admission data. RESULTS: The dataset comprised 333 605 patients, with 214 cases of HA-BSI. After adjustment for time to HA-BSI and comorbidities, the hazard for discharge (dead or alive) from hospital for patients with HA-BSI was 0.9 times (95% confidence interval [CI], .8-1.1) that of noninfected patients. Excess length of stay associated with all-cause HA-BSI was 1.6 days (95% CI, .2-3.0), although this duration varied by pathogen. Patients with HA-BSI had a 3.6 (95% CI, 1.3-10.4) times higher hazard for in-hospital death than noninfected patients. CONCLUSIONS: Hospital-acquired bloodstream infection increased the length of stay and mortality of pediatric inpatients. The results of this study provide an evidence base to judge the health and economic impact of programs to prevent and control HA-BSI in children.

Seasonal changes in the incidence of Escherichia coli bloodstream infection: variation with region and place of onset.

Previous research has shown that Escherichia coli infection rates peak in the summer; however, to date there has been no investigation as to whether this is seen in both hospital and community-onset cases, and how this differs across regions. We investigated and quantified E. coli bloodstream infection (BSI) seasonality. A generalized additive Poisson model was fitted to mandatory E. coli BSI surveillance data reported in England. There was no impact of seasonality in hospital-onset cases; however, for the community-onset cases, there was statistically significant seasonal variation over time nationally. When examined regionally, seasonality was significant in the North of England only. This variation resulted in an absolute increase of 0.06 (95% CI 0.02-0.1) cases above the mean (3.25) in each hospital trust for each week of the peak summer season, and a decrease of (-) 0.07 (95% CI -0.1 to -0.03) in the autumn. We estimate that fewer than one hospital bed-day per week per hospital is lost because of seasonal increases during the summer. Our findings highlight the need to understand the distinct community and hospital dynamics of E. coli BSI, and to explore the regional differences driving the variation in incidence, in order to design and implement effective control measures.

Excess length of stay and mortality due to Clostridium difficile infection: a multi-state modelling approach.

BACKGROUND: The burden of healthcare-associated infections, such as healthcare-acquired Clostridium difficile (HA-CDI), can be expressed in terms of additional length of stay (LOS) and mortality. However, previous estimates have varied widely. Although some have considered time of infection onset (time-dependent bias), none considered the impact of severity of HA-CDI; this was the primary aim of this study. METHODS: The daily risk of in-hospital death or discharge was modelled using a Cox proportional hazards model, fitted to data on patients discharged in 2012 from a large English teaching hospital. We treated HA-CDI status as a time-dependent variable and adjusted for confounders. In addition, a multi-state model was developed to provide a clinically intuitive metric of delayed discharge associated with non-severe and severe HA-CDI respectively. FINDINGS: Data comprised 157 (including 48 severe) HA-CDI cases among 42,618 patients. HA-CDI reduced the daily discharge rate by nearly one-quarter [hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.61-0.84] and increased the in-hospital death rate by 75% compared with non-HA-CDI patients (HR: 1.75; 95% CI: 1.16-2.62). Whereas overall HA-CDI resulted in a mean excess LOS of about seven days (95% CI: 3.5-10.9), severe cases had an average excess LOS which was twice (∼11.6 days; 95% CI: 3.6-19.6) that of the non-severe cases (about five days; 95% CI: 1.1-9.5). CONCLUSION: HA-CDI contributes to patients' expected LOS and risk of mortality. However, when quantifying the health and economic burden of hospital-onset of HA-CDI, the heterogeneity in the impact of HA-CDI should be accounted for.

Targeted versus universal screening and decolonization to reduce healthcare-associated meticillin-resistant Staphylococcus aureus infection.

BACKGROUND: The benefits of universal meticillin-resistant Staphylococcus aureus (MRSA) admission screening, compared with screening targeted patient groups and the additional impact of discharge screening, are uncertain. AIMS: To quantify the impact of MRSA screening plus decolonization treatment on MRSA infection rates. To compare universal with targeted screening policies, and to evaluate the additional impact of screening and decolonization on discharge. METHODS: A stochastic, individual-based model of MRSA transmission was developed that included patient movements between general medical and intensive care unit (ICU) wards, and between the hospital and community, informed by 18 months of individual patient data from a 900-bed tertiary care hospital. We simulated the impact of universal and targeted [for ICU, acute care of the elderly (ACE) or readmitted patients] MRSA screening and decolonization policies, both on admission and discharge. FINDINGS: Universal admission screening plus decolonization resulted in 77% (95% confidence interval: 76-78) reduction in MRSA infections over 10 years. Screening only ACE specialty or ICU patients yielded 62% (61-63) and 66% (65-67) reductions, respectively. Targeted policies reduced the number of screens by up to 95% and courses of decolonization by 96%. In addition to screening on admission, screening on discharge had little impact, with a maximum 7% additional reduction in infection. CONCLUSIONS: Compared with universal screening, targeted screening substantially reduced the amount of screening and decolonization required to achieve only 12% lower reduction in infection. Targeted screening and decolonization could lower the risk of resistance emerging as well as offer a more efficient use of resources.

Meticillin-resistant Staphylococcus aureus (MRSA) in hospitals and the community: model predictions based on the UK situation.

Theoretical modelling has shown that patient movements in and out of hospitals are likely to affect nosocomial transmission dynamics considerably. The community acts as a "reservoir" and readmission of individuals colonised during previous admissions can result in sporadic transmission episodes within hospitals. We investigated patient movement patterns and frequency of readmissions using seven years of complete data from the University Hospitals of Leicester NHS Trust. Sufficient information is held on individual patients to study the heterogeneity in readmission. Overall, we found that an infected person has a 44.2% chance of being readmitted to the Trust while still infected. This value is far higher than previous estimates (3.7% [Cooper et al., Health Technol Assess 2003;7(39)]), highlighting the potential importance of transmission driven by hospital admissions. For this reason we believe consideration of readmissions from the community population to be critical to the success of hospital acquired infection control.

Screening strategies in surveillance and control of methicillin-resistant Staphylococcus aureus (MRSA).

With reports of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) continuing to increase and therapeutic options decrease, infection control methods are of increasing importance. Here we investigate the relationship between surveillance and infection control. Surveillance plays two roles with respect to control: it allows detection of infected/colonized individuals necessary for their removal from the general population, and it allows quantification of control success. We develop a stochastic model of MRSA transmission dynamics exploring the effects of two screening strategies in an epidemic setting: random and on admission. We consider both hospital and community populations and include control and surveillance in a single framework. Random screening was more efficient at hospital surveillance and allowed nosocomial control, which also prevented epidemic behaviour in the community. Therefore, random screening was the more effective control strategy for both the hospital and community populations in this setting. Surveillance strategies have significant impact on both ascertainment of infection prevalence and its control.