Carl Suetens

Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study

BACKGROUNDnPatients admitted to intensive-care units are at high risk of health-care-associated infections, and many are caused by antimicrobial-resistant pathogens. We aimed to assess excess mortality and length of stay in intensive-care units from bloodstream infections and pneumonia.nnnMETHODSnWe analysed data collected prospectively from intensive-care units that reported according to the European standard protocol for surveillance of health-care-associated infections. We focused on the most frequent causative microorganisms. Resistance was defined as resistance to ceftazidime (Acinetobacter baumannii or Pseudomonas aeruginosa), third-generation cephalosporins (Escherichia coli), and oxacillin (Staphylococcus aureus). We defined 20 different exposures according to infection site, microorganism, and resistance status. For every exposure, we compared outcomes between patients exposed and unexposed by use of time-dependent regression modelling. We adjusted results for patients characteristics and time-dependency of the exposure.nnnFINDINGSnWe obtained data for 119u2008699 patients who were admitted for more than 2 days to 537 intensive-care units in ten countries between Jan 1, 2005, and Dec 31, 2008. Excess risk of death (hazard ratio) for pneumonia in the fully adjusted model ranged from 1·7 (95% CI 1·4-1·9) for drug-sensitive S aureus to 3·5 (2·9-4·2) for drug-resistant P aeruginosa. For bloodstream infections, the excess risk ranged from 2·1 (1·6-2·6) for drug-sensitive S aureus to 4·0 (2·7-5·8) for drug-resistant P aeruginosa. Risk of death associated with antimicrobial resistance (ie, additional risk of death to that of the infection) was 1·2 (1·1-1·4) for pneumonia and 1·2 (0·9-1·5) for bloodstream infections for a combination of all four microorganisms, and was highest for S aureus (pneumonia 1·3 [1·0-1·6], bloodstream infections 1·6 [1·1-2·3]). Antimicrobial resistance did not significantly increase length of stay; the hazard ratio for discharge, dead or alive, for sensitive microorganisms compared with resistant microorganisms (all four combined) was 1·05 (0·97-1·13) for pneumonia and 1·02 (0·98-1·17) for bloodstream infections. P aeruginosa had the highest burden of health-care-acquired infections because of its high prevalence and pathogenicity of both its drug-sensitive and drug-resistant strains.nnnINTERPRETATIONnHealth-care-associated bloodstream infections and pneumonia greatly increase mortality and pneumonia increase length of stay in intensive-care units; the additional effect of the most common antimicrobial resistance patterns is comparatively low.nnnFUNDINGnEuropean Commission (DG Sanco).

Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study

Background Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011–2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. Methods and Findings The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009–2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models’ case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data. Conclusions We estimated the EU/EEA burden of HAIs in DALYs in 2011–2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.

Mortality associated with in-hospital bacteraemia caused by Staphylococcus aureus: a multistate analysis with follow-up beyond hospital discharge

OBJECTIVESnThe main objective was to study the impact of in-hospital bacteraemia caused by Staphylococcus aureus on mortality within 90 days after admission. We compared methicillin-resistant S. aureus (MRSA) with methicillin-susceptible S. aureus (MSSA).nnnPATIENTS AND METHODSnThe study population consisted of adult residents of Tayside, Scotland, UK, from 1 January 2005 to 30 September 2006 who had a new admission to Ninewells Hospital between 1 July 2005 and 30 June 2006. All patients (n = 3132) in the same wards as the patients infected with S. aureus were included. We addressed key weaknesses in previous studies by using a cohort design and applying a multistate model, which addressed the temporal dynamics. Critically, the model recognized that death and discharge from the hospital are competing events and that delay in discharge independently increases the risk of death.nnnRESULTSnThe cohort included 3132 patients, of whom 494 died within 90 days after admission, 34 developed MRSA bacteraemia and 26 MSSA bacteraemia in the hospital. In comparison with patients without S. aureus bacteraemia, the death hazard was 5.6 times greater with MRSA [95% confidence interval (CI) 3.36-9.41] and 2.7 times greater with MSSA bacteraemia (95% CI 1.33-5.39). After adjustment for co-morbidity, hospitalization, age and sex, the death hazard was 2.9 times greater with MRSA (95% CI 1.70-4.88) and 1.7 times greater with MSSA bacteraemia (95% CI 0.84-3.47).nnnCONCLUSIONSnTime-dependent models such as the proposed multistate model are necessary to address the temporal dynamics of admission, infection, discharge and death. The impact of S. aureus bacteraemia on mortality should be considered on two levels: the burden of disease, i.e. nosocomial infection with S. aureus bacteraemia, and the burden of resistance to methicillin.

The rise of carbapenem resistance in Europe: just the tip of the iceberg?

The European Antimicrobial Resistance Surveillance Network (EARS-Net) collects data on carbapenem resistance from invasive bacterial infections. Increasing percentages of carbapenem resistance in K. pneumoniae isolates were reported from progressively more countries in Europe between 2005 and 2010. A trend analysis showed increasing trends for Greece, Cyprus, Hungary and Italy (pu2009<u20090.01). EARS-Net collects data on invasive bacterial isolates, which likely correspond to a fraction of the total number of infections. Increasing reports of community cases suggest that dissemination of carbapenem-resistant K. pneumoniae has penetrated into the community. Good surveillance and infection control measures are urgently needed to contain this spread.

Health-care-associated infections in neonates, children, and adolescents: an analysis of paediatric data from the European Centre for Disease Prevention and Control point-prevalence survey.

BACKGROUNDnIn 2011-12, the European Centre for Disease Prevention and Control (ECDC) held the first Europe-wide point-prevalence survey of health-care-associated infections in acute care hospitals. We analysed paediatric data from this survey, aiming to calculate the prevalence and type of health-care-associated infections in children and adolescents in Europe and to determine risk factors for infection in this population.nnnMETHODSnPoint-prevalence surveys took place from May, 2011, to November, 2012, in 1149 hospitals in EU Member States, Iceland, Norway, and Croatia. Patients present on the ward at 0800 h on the day of the survey and who were not discharged at the time of the survey were included. Data were collected by locally trained health-care workers according to patient-based or unit-based protocols. We extracted data from the ECDC database for all paediatric patients (age 0-18 years). We report adjusted prevalence for health-care-associated infections by clustering at the hospital and country level. We also calculated risk factors for development of health-care-associated infections with use of a generalised linear mixed-effects model.nnnFINDINGSnWe analysed data for 17u2008273 children and adolescents from 29 countries. 770 health-care-associated infections were reported in 726 children and adolescents, corresponding to a prevalence of 4·2% (95% CI 3·7-4·8). Bloodstream infections were the most common type of infection (343 [45%] infections), followed by lower respiratory tract infections (171 [22%]), gastrointestinal infections (64 [8%]), eye, ear, nose, and throat infections (55 [7%]), urinary tract infections (37 [5%]), and surgical-site infections (34 [4%]). The prevalence of infections was highest in paediatric intensive care units (15·5%, 95% CI 11·6-20·3) and neonatal intensive care units (10·7%, 9·0-12·7). Independent risk factors for infection were age younger than 12 months, fatal disease (via ultimately and rapidly fatal McCabe scores), prolonged length of stay, and the use of invasive medical devices. 392 microorganisms were reported for 342 health-care-associated infections, with Enterobacteriaceae being the most frequently found (113 [15%]).nnnINTERPRETATIONnInfection prevention and control strategies in children should focus on prevention of bloodstream infections, particularly among neonates and infants.nnnFUNDINGnNone.

Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a minimal option (aggregated hospital data), a light option (including patient data for CDI cases) and an enhanced option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe.

Concordance between European and US case definitions of healthcare-associated infections

BackgroundSurveillance of healthcare-associated infections (HAI) is a valuable measure to decrease infection rates. Across Europe, inter-country comparisons of HAI rates seem limited because some countries use US definitions from the US Centers for Disease Control and Prevention (CDC/NHSN) while other countries use European definitions from the Hospitals in Europe Link for Infection Control through Surveillance (HELICS/IPSE) project. In this study, we analyzed the concordance between US and European definitions of HAI.MethodsAn international working group of experts from seven European countries was set up to identify differences between US and European definitions and then conduct surveillance using both sets of definitions during a three-month period (March 1st -May 31st, 2010). Concordance between case definitions was estimated with Cohen’s kappa statistic (κ).ResultsDifferences in HAI definitions were found for bloodstream infection (BSI), pneumonia (PN), urinary tract infection (UTI) and the two key terms “intensive care unit (ICU)-acquired infection” and “mechanical ventilation”. Concordance was analyzed for these definitions and key terms with the exception of UTI. Surveillance was performed in 47 ICUs and 6,506 patients were assessed. One hundred and eighty PN and 123 BSI cases were identified. When all PN cases were considered, concordance for PN was κu2009=u20090.99 [CI 95%: 0.98-1.00]. When PN cases were divided into subgroups, concordance was κu2009=u20090.90 (CI 95%: 0.86-0.94) for clinically defined PN and κu2009=u20090.72 (CI 95%: 0.63-0.82) for microbiologically defined PN. Concordance for BSI was κu2009=u20090.73 [CI 95%: 0.66-0.80]. However, BSI cases secondary to another infection site (42% of all BSI cases) are excluded when using US definitions and concordance for BSI was κu2009=u20091.00 when only primary BSI cases, i.e. Europe-defined BSI with ”catheter” or “unknown” origin and US-defined laboratory-confirmed BSI (LCBI), were considered.ConclusionsOur study showed an excellent concordance between US and European definitions of PN and primary BSI. PN and primary BSI rates of countries using either US or European definitions can be compared if the points highlighted in this study are taken into account.

Health and Economic Impacts of Antibiotic Resistance in European Hospitals – Outlook on the BURDEN Project

Infections by resistant pathogens cause a financial burden to European hospitals and societies through the exacerbation or prolongation of illness and subsequent in-hospital treatment, with potentially serious health consequences for the infected individual [1, 2]. Increased morbidity and mortality with a long-term impact on working ability, productivity, and family life lead to scarce health care resources being diverted to increased infection control efforts and may result in a loss of confidence in the medical profession and the public health care delivery system [3]. Economists consider the existence of an expected net benefit at the level of the individual as one pre-requisite for collective action [4]. This incentive is often overlooked. Measuring the financial burden of antimicrobial resistance (AMR) also means estimating the possible benefit of avoiding the emergence and spread of resistant bacteria. From this point of view, an estimate of the economic consequences of AMR for hospitals, health care systems, and societies may be looked upon as a first step toward cross-national collective action in addressing the problem of AMR. Most of the existing cost-of-illness studies on AMRrelated infections are limited to a narrow perspective from which an analysis is conducted. This is mainly due to methodological problems associated with the inclusion of cost data, such as the determination of intangible costs or the identification of costs associated with organizational changes [5]. The few exceptions that have attempted to estimate the financial burden of resistance from a countywide perspective refer to the situation in USA [6–9]. In one of these studies – a 1987 review of more than 100 articles on infections with resistant bacteria – the authors concluded that the incidence of death, the likelihood for hospitalization, and the average length of the hospital stay were at least twofold higher for infections with drug-resistant bacteria as for those with drug-susceptible bacteria [6]. Phelps published a study in 1989 in which he described an economic model with the objective of determining the financial impact posed by drug-resistant bacteria. Estimates ranging from US

Marginal structural models for partial exposure regimes

350 million to US

Neurological sequelae of healthcare-associated sepsis in very-low-birthweight infants: Umbrella review and evidence-based outcome tree

35 billion were reported. The 100-fold range resulted from the varying estimates given by the authors, such as (1) the dose–response rate of resistance due to a change in antibiotic prescription, (2) the probability that a patient would die following an infection with drug-resistant bacteria, and (3) the value of human life [7]. A 1995 study by the US Office of Technology Assessment estimated the annual hospital cost for five major groups of hospital-acquired infections by resistant bacteria to be at least US