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Norovirus is a leading cause of epidemic acute gastroenteritis. More than 30 genotypes circulate in humans, some are common, and others are only sporadically detected. Here, we investigated whether serology can be used to determine which genotypes infect children. We established a multiplex protein microarray with structural and non-structural norovirus antigens that allowed simultaneous antibody testing against 30 human GI and GII genotypes. Antibody responses of sera obtained from 287 children aged < 1 month to 5.5 years were profiled. Most specific IgG and IgA responses were directed against the GII.2, GII.3, GII.4, and GII.6 capsid genotypes. While we detected antibody responses against rare genotypes, we found no evidence for wide circulation. We also detected genotype-specific antibodies against the non-structural proteins p48 and p22 in sera of older children. In this study, we show the age-dependent antibody responses to a broad range of norovirus capsid and polymerase genotypes, which will aid in the development of vaccines. [ABSTRACT FROM AUTHOR]

Background: The impact of the COVID-19 pandemic on patients' and clinicians' perceptions of healthcare-seeking behaviour and delivery of care is unclear. The pandemic accelerated the use of remote care, and understanding its benefits and drawbacks may inform its implementation during current and future healthcare emergencies. Aim: To explore patients' and primary care professionals' (PCPs) experiences of primary care delivery in the first wave of the pandemic. Design & setting: Qualitative study using semi-structured interviews in primary care in eight European countries (England, Ireland, Belgium, the Netherlands, Greece, Poland, Sweden, and Germany). Method: A total of 146 interviews were conducted with 80 PCPs and 66 patients consulting for respiratory tract infection (RTI) symptoms, in eight European countries. Data were collected between April and July 2020, and analysed using thematic analysis. Results: It was found that patients accepted telemedicine when PCPs spent time to understand and address their concerns, but a minority preferred in-person consultations. PCPs felt that remote consultations created emotional distance between themselves and patients, and they reported having to manage diverse COVID-19-related medical and social concerns. Conclusion: Remote consultations for RTI symptoms may be acceptable long term if both groups are happy to use this format, but it is important that PCPs take time to address patients' concerns and provide safety-netting advice. [ABSTRACT FROM AUTHOR]

Clinicians have worked feverishly to treat patients with COVID-19 while also carrying out clinical research studies. We discuss how the clinical research community responded to the pandemic in Europe, what lessons were learned, and provide recommendations for future clinical research response during pandemics. We focused on two platform trials: RECOVERY and REMAP-CAP. Both trials were able to enrol patients very rapidly during the beginning of the pandemic because of pre-established structures and procedures, and because they share simple execution and flexibility to adjust when evidence emergences. However, contracting, regulatory hurdles, and competition with (often inadequately designed or underpowered) national trials was a major challenge in several EU countries. We recommend the creation of structures and partnerships that facilitate prioritisation of clinical research, simplification of clinical trial delivery, development of digital models and procedures for data collection and sharing, development of a mechanism to rapidly leverage pandemic funding and to connect EU funding with national funding, and investment in clinical trial networks, platform trials, and master protocols. Finally, the future pandemic clinical research response of the EU should be embedded in the global response. We believe that globally connected clinical trial networks will be essential to respond more effectively to future infectious diseases outbreaks. [ABSTRACT FROM AUTHOR]

Background: Working under pandemic conditions exposes health care workers (HCWs) to infection risk and psychological strain. A better understanding of HCWs' experiences of following local infection prevention and control (IPC) procedures during COVID-19 is urgently needed to inform strategies for protecting the psychical and psychological health of HCWs. The objective of this study was therefore to capture the perceptions of hospital HCWs on local IPC procedures and the impact on their emotional wellbeing during the first wave of the COVID-19 pandemic in Europe. Methods: Participants were recruited in two sampling rounds of an international cross-sectional survey. Sampling took place between 31 March and 17 April 2020 via existing research networks and between 14 May and 31 August 2020 via online convenience sampling. Main outcome measures were behavioural determinants of HCWs' adherence to IPC guidelines and the WHO-5 Well-Being Index, a validated scale of 0–100 reflecting emotional wellbeing. The WHO-5 was interpreted as a score below or above 50 points, a cut-off score used in previous literature to screen for depression. Results: 2289 HCWs from 40 countries in Europe participated. Mean age was 42 (±11) years, 66% were female, 47% and 39% were medical doctors and nurses, respectively. 74% (n = 1699) of HCWs were directly treating patients with COVID-19, of which 32% (n = 527) reported they were fearful of caring for these patients. HCWs reported high levels of concern about COVID-19 infection risk to themselves (71%) and their family (82%) as a result of their job. 40% of HCWs considered that getting infected with COVID-19 was not within their control. This feeling was more common among junior than senior HCWs (46% versus 38%, P value <.01). Sufficient COVID-19-specific IPC training, confidence in PPE use and institutional trust were positively associated with the feeling that becoming infected with COVID-19 was within their control. Female HCWs were more likely than males to report a WHO-5 score below 50 points (aOR 1.5 (95% confidence interval (CI) 1.2–1.8). Conclusions: In Europe, the COVID-19 pandemic has had a differential impact on those providing direct COVID-19 patient care, junior staff and women. Health facilities must be aware of these differential impacts, build trust and provide tailored support for this vital workforce during the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Differences in clinical impact between rhinovirus (RVs) species and types in adults are not well established. The objective of this study was to determine the epidemiology and clinical impact of the different RV species.Methods: We conducted a prospective study of RVs infections in adults with acute cough/lower respiratory tract infection (LRTI) and asymptomatic controls. Subjects were recruited from 16 primary care networks located in 11 European countries between 2007 and 2010. RV detection and genotyping was performed by means of real time and conventional reverse-transcriptase polymerase chain reaction assays, followed by sequence analysis. Clinical data were obtained from medical records and patient symptom diaries.Results: RVs were detected in 566 (19%) of 3016 symptomatic adults, 102 (4%) of their 2539 follow-up samples and 67 (4%) of 1677 asymptomatic controls. Genotyping was successful for 538 (95%) symptomatic subjects, 86 (84%) follow-up infections and 62 (93%) controls. RV-A was the prevailing species, associated with an increased risk of LRTI as compared with RV-B (relative risk (RR), 4.5; 95% CI 2.5 to 7.9; p<0.001) and RV-C (RR 2.2; 95% CI 1.2 to 3.9; p=0.010). In symptomatic subjects, RV-A loads were higher than those of RV-B (p=0.015). Symptom scores and duration were similar across species. More RV-A infected patients felt generally unwell in comparison to RV-C (p=0·023). Of the 140 RV types identified, five were new types; asymptomatic infections were associated with multiple types.Interpretation: In adults, RV-A is significantly more often detected in cases with acute cough/LRTI than RV-C, while RV-B infection is often found in asymptomatic patients. [ABSTRACT FROM AUTHOR]

Background: Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir.Aim: To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic patients who have tested positive for coronavirus (not including SARS-CoV-2).Design and Setting: Exploratory analysis of data from an open-label, pragmatic, randomised controlled trial during three influenza seasons, from 2016 to 2018, in primary care research networks, in 15 European countries.Method: Patients aged ≥1 year presenting to primary care with influenza-like illness (ILI), and who tested positive for coronavirus (not including SARS-CoV-2), were randomised to usual care or usual care plus oseltamivir. The primary outcome was time to recovery defined as a return to usual activities, with minor or absent fever, headache, and muscle ache.Results: Coronaviruses (CoV-229E, CoV-OC43, CoV-KU1 and CoV-NL63) were identified in 308 (9%) out of 3266 randomised participants in the trial; 153 of these were allocated to usual care and 155 to usual care plus oseltamivir; the primary outcome was ascertained in 136 and 147 participants, respectively. The median time to recovery was shorter in patients randomised to oseltamivir: 4 days (interquartile range [IQR] 3-6) versus 5 days (IQR 3-8; hazard ratio 1.31; 95% confidence interval = 1.03 to 1.66; P = 0.026).Conclusion: Primary care patients with ILI testing positive for coronavirus (not including SARS-CoV-2) recovered sooner when oseltamivir was added to usual care compared with usual care alone. This may be of relevance to the primary care management of COVID-19. [ABSTRACT FROM AUTHOR]

Background This study was conducted to assess the variation in prescription practices for systemic antimicrobial agents used for prophylaxis among pediatric patients hospitalized in 41 countries worldwide. Methods Using the standardized Antibiotic Resistance and Prescribing in European Children Point Prevalence Survey protocol, a cross-sectional point-prevalence survey was conducted at 226 pediatric hospitals in 41 countries from October 1 to November 30, 2012. Results Overall, 17693 pediatric patients were surveyed and 36.7% of them received antibiotics (n = 6499). Of 6818 inpatient children, 2242 (32.9%) received at least 1 antimicrobial for prophylactic use. Of 11899 prescriptions for antimicrobials, 3400 (28.6%) were provided for prophylactic use. Prophylaxis for medical diseases was the indication in 73.4% of cases (2495 of 3400), whereas 26.6% of prescriptions were for surgical diseases (905 of 3400). In approximately half the cases (48.7% [1656 of 3400]), a combination of 2 or more antimicrobials was prescribed. The use of broad-spectrum antibiotics (BSAs), which included tetracyclines, macrolides, lincosamides, and sulfonamides/trimethoprim, was high (51.8% [1761 of 3400]). Broad-spectrum antibiotic use for medical prophylaxis was more common in Asia (risk ratio [RR], 1.322; 95% confidence interval [CI], 1.202–1.653) and more restricted in Australia (RR, 0.619; 95% CI, 0.521–0.736). Prescription of BSA for surgical prophylaxis also varied according to United Nations region. Finally, a high percentage of surgical patients (79.7% [721 of 905]) received their prophylaxis for longer than 1 day. Conclusions A high proportion of hospitalized children received prophylactic BSAs. This represents a clear target for quality improvement. Collectively speaking, it is critical to reduce total prophylactic prescribing, BSA use, and prolonged prescription. [ABSTRACT FROM AUTHOR]

Objectives: Overprescribing of antibiotics by general practitioners (GPs) is seen as a major driver of antibiotic resistance. Training in communication skills and C-reactive protein (CRP) testing both appear effective in reducing such prescribing. This study assesses the cost-effectiveness (compared with usual care) of: (i) training GPs in the use of CRP testing; (ii) training GPs in communication skills; and (iii) training GPs in both CRP testing and communication skills.Methods: Economic analyses [cost-utility analysis (CUA) accounting for the cost of antibiotic resistance and cost-effectiveness analysis (CEA)] were both conducted from a healthcare perspective with a time horizon of 28 days alongside a multinational, cluster, randomized, factorial controlled trial in patients with respiratory tract infections in five European countries. The primary outcome measures were QALYs and percentage reduction in antibiotic prescribing. Hierarchical modelling was used to estimate an incremental cost per QALY gained and an incremental cost per percentage reduction in antibiotic prescribing.Results: Overall, the results of both the CUA and CEA showed that training in communication skills is the most cost-effective option. However, excluding the cost of antibiotic resistance in the CUA resulted in usual care being the most cost-effective option. Country-specific results from the CUA showed that training in communication skills was cost-effective in Belgium, UK and Netherlands whilst training in CRP was cost-effective in Poland.Conclusions: Internet-based training in communication skills is a cost-effective intervention to reduce antibiotic prescribing for respiratory tract infections in primary care if the cost of antibiotic resistance is accounted for. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of ICU pneumonia caused by Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) is not fully described, but is urgently needed to support the development of effective interventions. The objective of this study is to estimate the incidence of S. aureus and P. aeruginosa ICU pneumonia and to assess its association with patient-related and contextual risk factors.Methods: ASPIRE-ICU is a prospective, observational, multi-center cohort study nested within routine surveillance among ICU patients in Europe describing the occurrence of S. aureus and P. aeruginosa ICU pneumonia. Two thousand (2000) study cohort subjects will be enrolled (50% S. aureus colonized) in which specimens and data will be collected. Study cohort subjects will be enrolled from a larger surveillance population, in which basic surveillance data is captured. The primary outcomes are the incidence of S. aureus ICU acquired pneumonia and the incidence of P. aeruginosa ICU acquired pneumonia through ICU stay. The analysis will include advanced survival techniques (competing risks and multistate models) for each event separately as well as for the sub-distribution of ICU pneumonia to determine independent association of outcomes with risk factors.. A risk prediction model will be developed to quantify the risk for acquiring S. aureus or P. aeruginosa ICU pneumonia during ICU stay by using a composite score of independent risk factors.Discussion: The diagnosis of pathogen-specific ICU pneumonia is difficult, however, the criteria used in this study are objective and comparable to those in the literature.Trial Registration: This study is registered on clinicaltrials.gov under identifier NCT02413242 . [ABSTRACT FROM AUTHOR]

Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide.Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H).Results: Of 17,693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America).Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children. [ABSTRACT FROM AUTHOR]

Background: Most cases of adult pertussis probably remain undiagnosed.Aim: To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough.Design and Setting: Prospective observational study between 2007 and 2010 in primary care in 12 European countries.Method: Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days.Results: Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation.Conclusion: Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence shows a high rate of unnecessary antibiotic prescriptions in primary care in Europe and the United States. Given the costs of widespread use and associated antibiotic resistance, reducing inappropriate use is a public health priority. OBJECTIVE: We aimed to explore clinicians' experiences of training in communication skills and use of a patient booklet and/or a C-reactive protein (CRP) point-of-care test to reduce antibiotic prescribing for acute respiratory tract infections (RTIs). DESIGN: We used a qualitative research approach, interviewing clinicians who participated in a randomised controlled trial (RCT) testing two contrasting interventions. PARTICIPANTS: General practice clinicians in Belgium, England, The Netherlands, Poland, Spain and Wales participated in the study. APPROACH: Sixty-six semi-structured interviews were transcribed verbatim, translated into English where necessary, and analysed using thematic and framework analysis. KEY RESULTS: Clinicians from all countries attributed benefits for themselves and their patients to using both interventions. Clinicians reported that the communication skills training and use of the patient booklet gave them greater confidence in addressing patient expectations for an antibiotic by providing answers to common questions and supporting the clinician's own explanations. Clinicians felt the booklet could be used for a variety of patients and for different types of infections. The CRP test was viewed as a tool to decrease diagnostic uncertainty, to support non-prescription decisions, and to reassure patients, but was only necessary when clinicians were uncertain about the need for antibiotics. CONCLUSION: Providing clinicians with training and support tools for use in practice was received positively and was valued by clinicians across countries. Interventions seemed to have influenced behaviour by increasing clinician knowledge about illness severity and prescribing, increasing confidence in making non-prescribing decisions when antibiotics were unnecessary, and enabling clinicians to anticipate positive outcomes when making such decisions. Addressing such determinants of behaviour change enabled interventions to be relevant for clinicians working across different contexts. [ABSTRACT FROM AUTHOR]

In this paper, we propose a change-point mixed model to assess the change in the trend of outpatient antibiotic use in a Bayesian framework, where the change-points are unknown parameters of the model. Model selection using DIC indicates that the data supports the model with a country-specific change-point. The location of the change-points may be related to points in time where public health strategies aiming at increasing the awareness of the public to a more rational use of antibiotics or targeting to reduce overconsumption of antibiotics were initiated. [ABSTRACT FROM AUTHOR]

Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection. A study was conducted to assess prospectively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels in different countries. Design Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries. Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001e8 were expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The fit of models and the degree of ecological association between antibiotic use and resistance data were assessed using generalised linear mixed models. Results Of 2204 patients included, H pylori resistance rates for adults were 17.5% for clarithromycin, 14.1% for levofloxacin and 34.9% for metronidazole, and were significantly higher for clarithromycin and levofloxacin in Western/Central and Southern Europe (>20%) than in Northern European countries (<10%). Model fit improved for each additional year of antibiotic use accumulated, but the best fit was obtained for 2005. A significant association was found between outpatient quinolone use and the proportion of levofloxacin resistance (p=0.0013) and between the use of longacting macrolides only and clarithromycin resistance (p=0.036). Conclusion In many countries the high rate of clarithromycin resistance no longer allows its empirical use in standard anti-H pylori regimens. The knowledge of outpatient antibiotic consumption may provide a simple tool to predict the susceptibility of H pylori to quinolones and to macrolides and to adapt the treatment strategies [ABSTRACT FROM AUTHOR]

The article presents a cross-sectional prevalence study that determines the prevalence of airway obstruction and bronchodilator responsiveness in adults with acute cough in Europe. It states that 3,105 adult patients with acute cough were recruited by family physicians and were diagnosed for any complaints of the recurrent wheezing or dyspnea. It further concludes that persistent airway obstruction and bronchodilator responsiveness are both common in adults without established asthma.

Background: Interventions to promote prudent antibiotic prescribing by general practitioners (GPs) have often only been developed for use in one country. We aimed to develop an intervention which would be appropriate to implement in multiple European countries in order to offer greater benefit to practice whilst using fewer resources. The INTRO (INternet TRaining for antibiOtic use) intervention needed to deliver training to GPs in the use of C-Reactive Protein (CRP) near patient tests to help diagnose acute cough and in communication skills to help explain prescribing decisions to patients. We explored GPs' views on the initial version of INTRO to test acceptability and potentially increase applicability for use in multiple countries before the start of a randomised trial. Method: 30 GPs from five countries (Belgium, England, the Netherlands, Poland and Spain), were interviewed using a "think aloud" approach. GPs were asked to work through the intervention and discuss their views on the content and format in relation to following the intervention in their own practice. GPs viewed the same intervention but versions were created in five languages. Data were coded using thematic analysis. Results: GPs in all five countries reported the view that the intervention addressed an important topic, was broadly acceptable and feasible to use, and would be a useful tool to help improve clinical practice. However, GPs in the different countries identified aspects of the intervention that did not reflect their national culture or healthcare system. These included perceived differences in communication style used in the consultation, consultation length and the stage of illness at which patient typically presented. Conclusion: An online intervention to support evidence-based use of antibiotics is acceptable and feasible to implement amongst GPs in multiple countries. However, tailoring of the intervention to suit national contexts was necessary by adding local information and placing more emphasis on the fact that GPs could select the communication skills they wished to use in practice. Using think aloud methods to complement the development of interventions is a powerful method to identify regional contextual barriers to intervention implementation. [ABSTRACT FROM AUTHOR]

Background: Residents in long-term care facilities are predisposed to healthcare- associated infections that are likely caused by antimicrobial-resistant micro- organisms. Long-term care facilities are increasingly able to offer parenteral antimicrobial treatment but there are few data on the use and appropriateness of such treatment in this setting. Information on the use of parenteral anti- microbials and associated factors in long-term care facilities is necessary to assess the risks and benefits of this treatment and to support the development of antimicrobial policies aimed at minimizing the emergence and spread of antimicrobial resistance. Objective: The aim of this study was to describe the extent of parenteral and oral antimicrobial use in participating European nursing homes (NHs) and to analyse the resident characteristics and determinants associated with route of antimicrobial administration. Methods: Data on resident characteristics and antimicrobials were collected by means of a point-prevalence survey. Logistic regression was used to ana- lyse the data. Results: Based on data from 21 European countries for 2046 antimicrobial prescriptions, an average of 9.0% (range by country: 0.0-66.7%) of treatment was administered parenterally. Multivariate analysis showed that residents receiving parenteral antimicrobials had greater morbidity, such as increased risk of having a urinary catheter (p <0.001), a vascular catheter (p <0.001), impaired mobility (p=O.007) and disorientation (p=O.O05). Residents re- ceiving parenteral antimicrobials also had been admitted more recently into the NH (p = 0.007). Empirical treatment of respiratory tract infections (RTIs) accounted for the majority of parenteral antimicrobials, while prophylaxis of urinary tract infection (UTI) was the most common indication for oral anti- microbials. Beta-lactam antibacterials (cephalosporins and aminopenicillins) were the predominant classes used. Conclusions: Our study showed that risk and care-load factors (i.e. the pres- ence of a urinary or vascular catheter, impaired mobility, disorientation and relatively short length of stay) were associated with parenteral administration of antimicrobials in NHs. Furthermore, both the indication and the class of antimicrobial agent used were associated with administration route. For empirical treatment of RTIs, antimicrobials were most often administered parenterally. [ABSTRACT FROM AUTHOR]

Aims: Antibiotic prescriptions for lower respiratory tract infection (LRTI) account for a large proportion of antibiotic consumption. Many of these prescriptions do not benefit patients and contribute to antibiotic resistance. Research to improve evidence-based management requires clear definitions of clinical entities. We aimed to generate definitions for common LRTIs that are applicable to clinical practice and low-intensity investigation research settings in European primary care. Methods: Candidate definitions identified through a systematic review and a nominal group meeting were put to a Delphi panel of selected experts from Europe and the US over three rounds. The definitions achieving high consensus were then tested for face validity by an expert panel. Results: 253 papers met our search criteria. The nominal group meeting generated highly-ranked definitions for two LRTIs. The Delphi panel considered five candidate definitions derived from the systematic review and nominal group meeting, and agreed upon definitions and open comments that the expert panel assessed for face validity. Conclusions: We combined empirical evidence with expert opinion for the development of a set of relevant clinical and research definitions for the four most common LRTIs presenting in general practice. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to investigate antimicrobial prescribing in nursing homes in countries across Europe. Methods Point prevalence studies were completed in April and November 2009 in 85 nursing homes in 15 European countries and two UK administrations. Results A total of 10 388 and 9430 residents participated in April and November 2009, respectively. The mean prevalence of antimicrobial prescribing in the nursing homes was 6.5% in April and 5.0% in November. The most commonly prescribed antimicrobials were methenamine (17.5%), trimethoprim (11.4%) and co-amoxiclav (11.1%) in April and co-amoxiclav (12.2%), nitrofurantoin (12.2%) and methenamine (11.5%) in November. There was large variation in the overall mean antimicrobial prescribing in the selected nursing homes from each of the contributing countries, ranging from 1.4% in Germany and Latvia to 19.4% in Northern Ireland in April and 1.2% in Latvia to 13.4% in Finland in November. Furthermore, differences in prescribing were apparent within countries with the largest variation evident in nursing homes in Northern Ireland (21.5%) in April and Finland in November (30.1%). Conclusions This is the first study to investigate antimicrobial prescribing in nursing homes in a large number of European countries. The findings suggest that there is considerable variation in antimicrobial prescribing in nursing homes across and within European countries. Nursing homes provide a significant service to the European community and must be supported in order to optimize antimicrobial use and limit the development of antimicrobial resistance. [ABSTRACT FROM PUBLISHER]

All 27 EU member states and another seven countries participate in the European Surveillance of Antimicrobial Consumption (ESAC) project. ESAC carried out three hospital point-prevalence surveys on antimicrobial use. Point-prevalence surveys linked antimicrobial use to indication and also assessed dosing using a standardized methodology for data collection and online data submission with feedback capability using a dedicated web-based tool. The objectives of the ESAC hospital point-prevalence surveys were to first determine the feasibility of a pan-European survey and identify targets for quality improvement. Hospitals were voluntarily selected by the lead national or hospital representatives for each country. The WHO Anatomical Therapeutic Chemical Classification of drugs was used for classification of antimicrobials. The three surveys were carried out during a maximum of 2 weeks in the second quarter of 2006, 2008 and 2009. Each department had to be surveyed in 1 day. All systemic antibacterials (J01), rifampicin (J04AB), oral vancomycin (A07AA) and oral/rectal metronidazole (P01AB) were the antimicrobials surveyed, including the prescribed regimen. The number of participating hospitals increased from 20 to 172 from 2006 to 2009. The patient demographics and indications for treatment were similar throughout the three point-prevalence surveys. 'Reason in notes' and 'surgical prophylaxis >24 hours' were also similar. Guideline compliance (51 %) was only introduced in the 2009 point-prevalence survey, replacing 'sample for culture and sensitivity' (<50% in 2006 and 2008) since samples were either not taken or no information was available for the majority (>50%) of patients. The use of combination therapy, although exhibiting a wide range within each category, was related to hospital type, with teaching and tertiary hospitals having a significantly higher use of combination therapy (teaching on- teaching hospitals [p< 0.0001]; and primary: tertiary hospitals [p< 0.0001]). Point-prevalence surveys are useful when time and resources do not allow for continuous surveillance. Repeated point-prevalence surveys within the same institution(s) can be used to monitor trends and effectiveness of antimicrobial-stewardship initiatives. Targets should be set as quality indicators for the individual hospital(s) and effectiveness of any intervention monitored through repeated point-prevalence surveys. Spin-off initiatives, such as the Antibiotic Resistance and Prescribing in European Children, and the European Centre for Disease Prevention and Control point-prevalence survey on healthcare-associated infections and antimicrobial use, will utilize adapted versions of WebPPS. the point-prevalence survey software developed by ESAC. WebPPS will also be made available for non-commercial use to third parties. Interest has been shown from three continents outside Europe, namely North America, Australia and Africa. [ABSTRACT FROM AUTHOR]

Objectives Since electronic prescribing is limited to few hospitals, point prevalence surveys, such as the standardized European Surveillance of Antimicrobial Consumption point prevalence survey (ESAC PPS), are an alternative tool for monitoring prescribing and helping to identify performance indicators and prescribing trends. The main objective of this study was to identify and assess targets for quality improvement. Methods Each hospital had to carry out the survey within 2 weeks. Each department had to be surveyed in 1day. Data collected, for all inpatients, included age and gender. For patients on systemic antimicrobial treatment, the antimicrobial/s, infection/prophylaxis site, reason in medical notes and guideline compliance were also collected. A central database using a web-based tool (WebPPS) developed in-house was used for data entry. Results Combination of two or more antimicrobials accounted for 30% of use. Surgical prophylaxis was prolonged (>1 day) in 53% of cases. ‘Intensive care’ had higher proportions of treated patients (53% versus 29%), combination therapy (49% versus 31%), hospital-acquired infections (49% versus 31%) and parenteral administration (91% versus 61%). ‘Reason in notes’ was documented in 76%, and ‘guideline compliance’ occurred in 62% of patients. Conclusions The ESAC PPS provided useful information on the quality of prescribing, which identified a number of targets for quality improvement. These could apply to specific departments or whole hospitals. Intensive care, which has different characteristics, should not be compared with general wards with respect to combination therapy, hospital-acquired infections or parenteral proportion. The study confirmed that the ESAC PPS methodology can be used on a large number of hospitals at regional, national, continental or global level. [ABSTRACT FROM PUBLISHER]

Background: Antimicrobials are the most common medicines prescribed to children, but very little is known about patterns of hospital paediatric antimicrobial prescribing. This study aimed at describing paediatric antimicrobial prescribing in European hospitals to identify targets for quality improvement. [ABSTRACT FROM PUBLISHER]

Objectives: To assess the total outpatient systemic antimycotic and antifungal use in Europe, and to identify the antimycotic and antifungal substances most commonly used. Methods: Within ESAC (www.esac.ua.ac.be), using the anatomical therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on outpatient use of all 14 antimycotics (12) and antifungals (2) for systemic use (ATC J02 and D01B, respectively), aggregated at the level of the active substance, were collected for 2007. Use was expressed in DDD (WHO ATC/DDD, version 2008) per 1000 inhabitants per day (DID). Only countries for which data on both J02 and D01B use were available were included in the analysis. Results: In 20 European countries (data for Cyprus and Estonia include hospital use), total outpatient systemic antimycotic and antifungal use varied by a factor of 6.7 between the country with the highest (3.03 DID in Belgium) and the country with the lowest (0.45 in Croatia) use. Terbinafine, ketoconazole, itraconazole and fluconazole represented >94% of the total outpatient antimycotic and antifungal use in all countries. Terbinafine use represented >50% of the total systemic antimycotic and antifungal use in 16 out of 20 countries (not in Croatia, Italy, Luxembourg and Bulgaria). Conclusions: We present for the first time a standardized and validated data set of outpatient systemic antimycotic and antifungal use in Europe. Our study demonstrates a variation of antimycotic and antifungal use in Europe, as striking as that of antibiotic use. The ESAC data facilitate the auditing of antimycotic and antifungal prescribing, and the evaluation of the implementation of guidelines and public health policies to promote their judicious use. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Several noncardiovascular drugs with QT liability are currently on the market. • Previous epidemiological studies have shown significant exposure of the general population to drugs with QT liability with similar consumption in many European countries. • Several regulatory measures have concerned medicinal products carrying a pro-arrhythmic risk in humans. WHAT THIS STUDY ADDS • The list of antibacterial agents with documented QT liability has grown over the last few years. • Notwithstanding stringent regulatory measures, population exposure to antibiotics with QT liability is still significant in several countries. • The magnitude of the problem is clearly heterogeneous, with remarkable diversity between Northern and Southern countries (lower and higher exposure, respectively). AIMS (i) To classify antibacterial agents with QT liability on the basis of the available evidence, and (ii) to assess trends in their consumption over an 8-year period (1998–2005) in 14 European countries. METHODS Current published evidence on QT liability of antibiotics was retrieved through MEDLINE search and joined to official warnings from regulatory agencies. Each drug was classified according to an already proposed algorithm based on the strength of evidence: from group A (any evidence) to group E (clinical reports of torsades de pointes and warnings on QT liability). Consumption data were provided by the European Surveillance of Antibacterial Consumption (ESAC) project and were expressed as defined daily doses per 1000 inhabitants per day (DID). RESULTS Among 21 detected compounds, nine [six fluoroquinolones (FQs) and three macrolides (MACs)] belonged to group E. Use of group E drugs ranged from 1.3 (Sweden) to 4.1 DID (Italy) in 1998 and from 1.2 (Sweden) to 6.5 DID (Italy) in 2005. Significant exposure was observed in Italy and Spain (6.5 and 3.8 DID, respectively, in 2005). Only Denmark, Sweden and UK showed a slight decrease in use. Exposure to clarithromycin increased in 10 out of 14 countries, with a marked increment in Italy (3 DID in 2005). CONCLUSIONS Notwithstanding regulatory measures, in 2005 there was still significant exposure to antibacterials with strong evidence of QT liability and, in most countries, it was even increased. This warrants further investigation of appropriateness of use and suggests closer monitoring of group E drugs. Physicians should be aware when prescribing them to susceptible patients. [ABSTRACT FROM AUTHOR]

Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000-2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe. [ABSTRACT FROM AUTHOR]

The European Surveillance of Antimicrobial Consumption (ESAC) project collects data on antibacterial use in Europe, applying the Anatomic Therapeutic Chemical classification system and defined daily dose methodology, as recommended by the World Health Organization. Comparable data for the United States have been collected from IMS Health. The IMS Health sales data, processed according to ESAC methodology, suggest that outpatient antibacterial use in the United States is high (only 3 of 27 European countries used more) and is mainly characterized by a shift towards newer antibiotics. [ABSTRACT FROM AUTHOR]

Background: Surveillance studies are mandatory to carefully monitor changing trends in Europe. Methods: Surveys on antibiotic resistance conducted in European hospitals were reviewed. Data were obtained from own studies, through searches of Medlines, Pubmed, abstracts and posters presented at meetings, from the World Wide Web and from surveillance studies conducted by the pharmaceutical industry. Results: A high prevalence of MRSA was found in most European hospitals, except in northern Europe, and an increasing trend in non-intensive care unit patients was observed. In most European hospitals, the prevalence of infections caused by vancomycin-resistant enterococci remains very low and most outbreaks have occurred in at-risk wards. No major changes of resistance among Enterobacteriaceae were observed. Very few of the major antibiotics are now reliably effective for the treatment of severe nosocomial carbapenem-resistant Acinetobacter infections. Conclusions: Although antimicrobial resistance appears to be increasing all over Europe, it is difficult to accurately estimate the extent of this emerging problem. One of the main reasons for this can be attributed to the fact that the published susceptibility data are difficult to compare due to the different methods used, population bias, and clonal variation. Increasing antimicrobial resistance necessitates a critical appraisal of the remaining antibiotic treatment options. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Recent studies have shown large differences in the use of antibacterial agents among European countries. We found a relationship between community consumption and the number of trade names of oral antibacterial agents. This relationship was observed in countries in which consumption was high, as well as in countries in which it was low, and in markets that were opened or were not opened to the sale of copies of original agents. [ABSTRACT FROM AUTHOR]

The article discusses the factors that influence inappropriate antibiotic prescription in Europe including patient pressure and lack of suitable alternatives, diagnostic uncertainty and the level of communication and co-operation between pharmacists, physicians and microbiologists. It states that the overuse and misuse of antibiotics are the major reasons for the development of antibiotic resistance which vary greatly between and even within different European countries.

Background: The epidemiology of CNS infections in Europe is dynamic, requiring that clinicians have access to up-to-date clinical management guidelines (CMGs) to aid identification of emerging infections and for improving quality and a degree of standardisation in diagnostic and clinical management practices. This paper presents a systematic review of CMGs for community-acquired CNS infections in Europe.Methods: A systematic review. Databases were searched from October 2004 to January 2019, supplemented by an electronic survey distributed to 115 clinicians in 33 European countries through the CLIN-Net clinical network of the COMBACTE-Net Innovative Medicines Initiative. Two reviewers screened records for inclusion, extracted data and assessed the quality using the AGREE II tool.Results: Twenty-six CMGs were identified, 14 addressing bacterial, ten viral and two both bacterial and viral CNS infections. Ten CMGs were rated high quality, 12 medium and four low. Variations were identified in the definition of clinical case definitions, risk groups, recommendations for differential diagnostics and antimicrobial therapy, particularly for paediatric and elderly populations.Conclusion: We identified variations in the quality and recommendations of CMGs for community-acquired CNS infections in use across Europe. A harmonised European "framework-CMG" with adaptation to local epidemiology and risks may improve access to up-to-date CMGs and the early identification and management of (re-)emerging CNS infections with epidemic potential. [ABSTRACT FROM AUTHOR]

The article presents a study to determine whether measurement of C reactive protein (CRP) and procalcitonin help in the analysis of pneumonia in primary care. It states that presence of pneumonia was considered if the local radiologist reported lobar or bronchopneumonia. Results showed that CRP helped to eliminate pneumonia and procalcitonin had no clinically applicable added value. CRP and procalcitonin concentrations were measured with conventional venous blood tests is also mentioned.

Resistance to antibiotics is a major public health problem and antibiotic use is being increasingly recognized as the main selective pressure driving this resistance. Yearly and quarterly data on outpatient antibiotic use were collected by the European Surveillance of Antimicrobial Consumption (ESAC) project for the period 1997–2009 from 33 and 27 European countries, respectively, and expressed in defined daily doses per 1000 inhabitants per day. Since repeated measures were taken for the countries, correlation has to be taken into account when analysing the data. This paper illustrates the application of mixed-effects models to the study of country-specific outpatient antibiotic use in Europe. Mixed models are useful in a wide variety of disciplines in the biomedical, physical and social sciences. In this application for outpatient antibiotic use, the linear mixed model is extended to a non-linear mixed model, allowing analysis of seasonal variation on top of a global trend, with country-specific effects for global mean use and amplitude, and trends over time in use and in amplitude. [ABSTRACT FROM PUBLISHER]

Objectives To assess quality of outpatient antibiotic use in Europe in 2009 based on the 12 European Surveillance of Antimicrobial Consumption (ESAC) drug-specific quality indicators and to evaluate changes in quality between 2004 and 2009. Methods Quality of outpatient antibiotic use in 2009 was compared between 32 countries by calculating the indicator values for 2009 for each of the 12 ESAC drug-specific quality indicators based on outpatient antibiotic use data expressed in defined daily doses per 1000 inhabitants per day (DID). For each of the indicators we grouped the 2009 indicator values into four quartiles. To evaluate changes in quality between 2004 and 2009, based on their respective indicator values, countries were also grouped according to the quartile distribution of the 2004 indicator values. Only countries able to deliver data for both years were included in this analysis. Results In 2009 a difference in the quality of outpatient antibiotic use between Nordic and Southern European countries was observed. Quality of outpatient antibiotic use decreased between 2004 and 2009. In particular, there were increases in the quality indicators [J01F_DID], [J01M_DID], [J01CR_%] and [J01_B/N], i.e. the use of macrolides, lincosamides and streptogramins in DID, the use of quinolones in DID, the proportional use of combinations of penicillins, including β-lactamase inhibitors and the ratio of broad- to narrow-spectrum antibiotics. Conclusions Quality of outpatient antibiotic use in DID decreased between 2004 and 2009. A continuous effort to improve outpatient antibiotic consumption seems to be essential to reduce outpatient antibiotic use in general and the use of broad-spectrum antibiotics in particular. [ABSTRACT FROM PUBLISHER]

Objectives To describe total outpatient systemic antibiotic use in Europe from 1997 to 2009 and to analyse statistically trends of total use and composition of use over time. Methods For the period 1997–2009, data on outpatient use of systemic antibiotics aggregated at the level of the active substance were collected and expressed in defined daily doses (WHO, version 2011) and packages per 1000 inhabitants per day (DID and PID, respectively). Outpatient antibiotic (ATC J01) use in DID in the 33 European countries able to deliver valid data was analysed using longitudinal and compositional data analyses. Results Total outpatient antibiotic use in 2009 varied by a factor of 3.8 between the countries with the highest (38.6 DID in Greece) and lowest (10.2 DID in Romania) use. For Europe, a significant increase was found in total outpatient antibiotic use, as well as a significant seasonal variation, which decreased over time from 1997 to 2009. Relative use of penicillins and quinolones significantly increased over time with respect to sulphonamides and trimethoprim, and relative use of quinolones increased with respect to macrolide/lincosamide/streptogramin as well. More detailed analyses of these major antibiotic subgroups will be described in separate papers. Conclusions Outpatient antibiotic use in Europe measured as DID has increased since 1997, whereas seasonal variation has decreased over time. European Surveillance of Antimicrobial Consumption (ESAC) data on outpatient antibiotic use in Europe enable countries to audit their antibiotic use. Complemented by longitudinal and compositional data analyses, these data provide a tool for assessing public health strategies aimed at reducing antibiotic resistance and optimizing antibiotic prescribing. [ABSTRACT FROM PUBLISHER]

Background Data on more than a decade of outpatient quinolone use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). Methods For the period 1997–2009, data on outpatient use of systemic quinolones aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011), and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Using a classification based on pharmacokinetic and in vitro potency profiles, quinolone use was analysed with regard to trends over time, seasonal variation and composition. Results Total outpatient quinolone use in 2009 varied by a factor of 7.5 between the country with the highest (Italy, 3.61 DID) and the country with the lowest (the UK, 0.48 DID) quinolone use. The second-generation quinolones accounted for >50% of quinolone use (mainly ciprofloxacin), except for Croatia, where first-generation quinolones (mainly norfloxacin) were mostly used. A significant increase in outpatient quinolone use was found for Europe, as well as a large seasonal variation, which increased significantly over time from 1997 to 2009. Relative use of third-generation quinolones significantly increased over time with respect to the use of second-generation quinolones, while the relative use of both significantly increased with respect to the first-generation quinolones. Levofloxacin and moxifloxacin (respiratory quinolones) represented >10% of quinolone outpatient use in 17 countries, with extreme seasonal variation in all countries. Conclusions There was a substantial increase and change in the pattern of quinolone use between 1997 and 2009, a period during which quinolones that are effective for the treatment of respiratory tract infections were introduced. These quinolones are not the first-line antibiotics for this indication and their use should generally be limited, and quinolones should ideally show no substantial seasonal variation in terms of their use. [ABSTRACT FROM PUBLISHER]

In this tutorial, statistical methods for studying outpatient use of antibiotics in Europe are described, using data provided by IMS Health. The methods are applied to two related research questions, namely the assessment of changes in the relative volume of use of different antibiotic subclasses over time and changes in the absolute volume of antibiotic use. [ABSTRACT FROM PUBLISHER]

Background Data on more than a decade of outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe were collected from 33 countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), using the WHO Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) methodology. Methods For the period 1997–2009, data on outpatient use of systemic MLS aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2011) per 1000 inhabitants per day (DID). Using a classification based on mean plasma elimination half-life, macrolide use was analysed for trends over time, seasonal variation and composition. Results Total outpatient MLS use in 2009 varied by a factor of 18 between the countries with highest (11.5 DID in Greece) and lowest (0.6 DID in Sweden) use. MLS use showed high seasonal variation. Short-, intermediate- and long-acting macrolides were the most commonly used agents in 2, 25 and 5 countries, respectively (mainly erythromycin, clarithromycin and azithromycin, respectively). In Sweden, mainly lincosamides (clindamycin) were used. Lincosamide use was observed in all countries, while substantial use of a streptogramin was only seen in France (pristinamycin). For Europe, a significant increase in outpatient MLS use was found, as well as a significant seasonal variation, which increased over time from 1997 to 2009. Relative use of long-acting macrolides and lincosamides significantly increased over time with respect to intermediate-acting macrolides, and relative use of the latter increased with respect to short-acting macrolides. Conclusions The observed differences between European countries in the levels of MLS use and the extreme seasonal variations in their use suggest that this subgroup of antibiotics is still prescribed inappropriately in many countries. [ABSTRACT FROM PUBLISHER]

Background Data on more than a decade of outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe were collected from 33 countries as part of the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). Methods For the period 1997–2009, data on outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials aggregated at the level of the active substance were collected and expressed in defined daily doses (DDD; WHO, version 2011) per 1000 inhabitants per day (DID). Using the Anatomical Therapeutic Chemical (ATC) classification, trends in the use of tetracyclines (J01A), sulphonamides and trimethoprim (J01E) and other antibacterials (J01X) over time, seasonal variation and composition of use were analysed. Results In 2009, the variations in outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials between countries, and also in the composition of use over time, were huge. For tetracyclines a significant and for sulphonamides and trimethoprim a non-significant decrease in use was observed between 1997 and 2009 in Europe. The seasonal variation in their use significantly decreased over time. For the other antibacterials, no significant changes in the volume of use or its seasonal variation were seen. Conclusions As for all other major antibiotic subgroups, a striking variation in use and composition of use between countries in Europe was observed for outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials. In combination with the decreasing use, especially of recommended substances, this represents an opportunity not only to reduce antibiotic use but also to improve its quality. [ABSTRACT FROM PUBLISHER]

Background Data on 13 years of outpatient cephalosporin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), and analysed in detail. Methods For the period 1997–2009, data on outpatient use of systemic cephalosporins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient cephalosporin use in 33 European countries, we distinguished between first-generation (J01DB), second-generation (J01DC), third-generation (J01DD) and fourth-generation (J01DE) cephalosporins. Results Total outpatient cephalosporin use in 2009 varied from 8.7 DID in Greece to 0.03 DID in Denmark. In general, use was higher in Southern and Eastern European countries than in Northern European countries. Total outpatient cephalosporin use increased over time by 0.364 (SD 0.473) DID between 1997 and 2009. Cephalosporin use increased for half of the countries. Low-consuming Northern European countries and the UK further decreased their use. Second-generation cephalosporins increased by >20% in seven countries (mainly cefuroxime), coinciding with a decrease in first-generation cephalosporins. Substantial parenteral use of third-generation substances (mainly ceftriaxone) was observed in France, Italy and the Russian Federation. Conclusions Since 1997, the use of the older (narrow-spectrum) cephalosporins decreased in favour of the newer (i.e. broad-spectrum) cephalosporins in most countries. Extreme variations between European countries in cephalosporin use over time suggest that they are to a large extent inappropriately used. [ABSTRACT FROM PUBLISHER]

Objectives To assess the proportion of parenteral treatment of the total outpatient antibiotic use in Europe, and to identify the antibiotic groups and individual antibiotics most commonly administered in this way. Methods Within the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be), using the anatomic therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on outpatient use of antibacterials for systemic use (ATC J01), aggregated at the level of the active substance and expressed in DDD per 1000 inhabitants per day (DID; WHO version 2007), were extracted for 2006 by route of administration and by country. Parenteral use was expressed as a percentage of the total outpatient use in DID. Results In 20 European countries, the total outpatient antibiotic use ranged from 27.91 DID in France to 9.58 DID in Russia. The proportion of outpatient parenteral antibiotic treatment ranged from 6.75% in Russia to 0.001% in Iceland. The three most commonly used antibiotic groups for parenteral treatment in Europe were the cephalosporins (J01D; 44.58%), the aminoglycosides (J01G; 25.27%) and the penicillins (J01C; 17.78%). Four antibiotics [gentamicin (J01GB03) 18.53%; ceftriaxone (J01DD04) 17.85%; cefazolin (J01DB04) 13.16%; and lincomycin (J01FF02) 5.47%] represented more than half of the use. Conclusions In all 20 European countries studied together, 2.04% of outpatient antibiotics were used for parenteral treatment. However, as for the total outpatient antibiotic use and the use of different antibiotic groups and antibiotics, there is a striking variation in the proportions of parenteral antibiotic use in Europe. More in-depth data on outpatient antibiotic use are needed to explain this variation. [ABSTRACT FROM AUTHOR]

The in vitro antimicrobial susceptibility of organisms isolated from bacteraemic versus non-bacteraemic patients was evaluated using data (1997–2001) from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme. Minimum inhibitory concentration values and susceptibility breakpoints of meropenem and other broad-spectrum antimicrobials were determined using standard methodology. Three thousand one hundred and thirty-six blood culture (BC) isolates and 17,261 non-BC isolates were obtained from 51 European MYSTIC centres. Gram-positive bacteria appeared to be more prevalent in BC isolates compared with other sources. Escherichia coli, methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa were isolated most frequently. Antimicrobial susceptibility of isolates from bacteraemic versus non-bacteraemic patients was similar. Meropenem and imipenem were the most active agents against the majority of the Gram-positive and Gram-negative organisms. Ceftazidime, gentamicin and ciprofloxacin generally exhibited the lowest activities against the most commonly isolated organisms. Meropenem was most active against P. aeruginosa and showed the highest potency and activity against all extended-spectrum and AmpC β-lactamase producers. These results are relevant to the choice of initial, empirical therapy for patients with suspected bacteraemia. [Copyright &y& Elsevier]

Background: Antibacterial resistant infections are rising continuously, resulting in increased morbidity and mortality worldwide. With no new antibiotic classes entering the market and the possibility of returning to the pre-antibiotic era, the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) was established to address this problem. We aimed to quantify the scale and scope of publicly funded antibacterial resistance research across JPIAMR countries and at the European Union (EU) level to identify gaps and future opportunities.Methods: We did a systematic observational analysis examining antibacterial resistance research funding. Databases of funding organisations across 19 countries and at EU level were systematically searched for publicly funded antibacterial resistance research from Jan 1, 2007, to Dec 31, 2013. We categorised studies on the basis of the JPIAMR strategic research agenda's six priority topics (therapeutics, diagnostics, surveillance, transmission, environment, and interventions) and did an observational analysis. Only research funded by public funding bodies was collected and no private organisations were contacted for their investments. Projects in basic, applied, and clinical research, including epidemiological, public health, and veterinary research and trials were identified using keyword searches by organisations, and inclusion criteria were based on the JPIAMR strategic research agenda's six priority topics, using project titles and abstracts as filters.Findings: We identified 1243 antibacterial resistance research projects, with a total public investment of €1·3 billion across 19 countries and at EU level, including public investment in the Innovative Medicines Initiative. Of the total amount invested in antibacterial resistance research across the time period, €646·6 million (49·5%) was invested at the national level and €659·2 million (50·5%) at the EU level. When projects were classified under the six priority topics we found that 763 (63%) of 1208 projects funded at national level were within the area of therapeutics, versus 185 (15%) in transmission, 131 (11%) in diagnostics, 53 (4%) in interventions, and only 37 (3%) in environment and 39 (3%) in surveillance.Interpretation: This was the first systematic analysis of research funding of antibacterial resistance of this scale and scope, which relied on the availability and accuracy of data from organisations included. Large variation was seen between countries both in terms of number of projects and associated investment and across the six priority topics. To determine the future direction of JPIAMR countries a clear picture of the funding landscape across Europe and Canada is needed. Countries should work together to increase the effect of research funding by strengthening national and international coordination and collaborations, harmonising research activities, and collectively pooling resources to fund multidisciplinary projects. The JPIAMR have developed a publicly available database to document the antibacterial resistance research collected and can be used as a baseline to analyse funding from 2014 onwards.Funding: JPIAMR and the European Commission. [ABSTRACT FROM AUTHOR]

Abstract: To broaden our understanding of outpatient systemic antimycotic and antifungal use in Europe, use data in defined daily doses (DDD) were complemented with data in packages and the results were compared. Within the European Surveillance of Antimicrobial Consumption project and using the Anatomical Therapeutic Chemical (ATC) classification, data on outpatient use of all 14 antimycotics (12) and antifungals (2) for systemic use (ATC J02 and D01B), aggregated at the level of the active substance, were collected for 2009. Their use was expressed in DDD per 1000 inhabitants per day (DID) and in packages per 1000 inhabitants per day (PID) (WHO Collaborating Centre for Drug Statistics Methodology ATC/DDD version 2011). In total, 24 countries delivered data in DID; 13 countries also delivered data in PID. In DID, Belgium had the highest (3.24 DID) and Romania the lowest (0.38 DID) total outpatient antimycotic and antifungal use. In PID, Greece had the highest (0.44 PID) and Sweden the lowest (0.08 PID) use. In DID, terbinafine was the most used substance in 19/24 countries (10/13 countries providing DID and PID data). In PID, fluconazole was the most used substance in all 13 countries. Combining DID and PID data substantially improved the interpretation of total outpatient antimycotic and antifungal use in Europe, and both outcome measures should be used for surveillance of these compounds. High use of fluconazole in PID might be more relevant for surveillance of antimicrobial consumption in relation to resistance than high use of terbinafine in DID. [Copyright &y& Elsevier]

Abstract: This paper presents a screening tool for the location-specific prioritization of human pharmaceutical emissions in Europe, based on risk quotients for the aquatic environment and human health. The tool provides direction towards either monitoring activities or additional research. Its application is illustrated for a set of 11 human antibiotics and 7 antineoplastics. Risk quotients for the aquatic environment were highest for levofloxacin, doxycycline and ciprofloxacin, located in Northern Italy (Milan region; particularly levofloxacin) and other densely populated areas in Europe (e.g. London, Krakow and the Ruhr area). Risk quotients for human health not only depend on pharmaceutical and location, but also on behavioral characteristics, such as consumption patterns. Infants in eastern Spain that consume locally produced food and conventionally treated drinking water were predicted to run the highest risks. A limited comparison with measured concentrations in surface water showed that predicted and measured concentrations are approximately within one order of magnitude. [Copyright &y& Elsevier]

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients)., Methods: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied., Results: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment., Conclusions: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Despite considerable research into COVID-19 sequelae, little is known about differences in illness duration and complications in patients presenting in primary care with symptoms of acute respiratory tract infections (RTI) that are and are not attributed to SARS-CoV-2 infection., Objective: To explore whether aetiology impacted course of illness and prediction of complications in patients presenting in primary care with symptoms of RTI early in the COVID-19 pandemic., Methods: Between April 2020-March 2021 general practitioners from nine European countries recruited consecutively contacting patients with RTI symptoms. At baseline, an oropharyngeal-nasal swab was obtained for aetiology determination using PCR after follow-up of 28 days. Time to self-reported recovery was analysed with Kaplan-Meier curves. Predictors (baseline variables of demographics, patient and disease characteristics) of a complicated course (composite of hospital admission and persisting signs/symptoms at 28 days follow-up) were explored with logistic regression modelling., Results: Of 855 patients with RTI symptoms, 237 (27.7%) tested SARS-CoV-2 positive. The proportion not feeling fully recovered (15.6% vs 18.1%, p  = 0.39), reporting being extremely tired (9.7% vs 12.8%, p  = 0.21), and not having returned to usual daily activities (18.1% vs 14.4%, p  = 0.18) at day 28 were comparable between SARS-CoV-2 positive ( n  = 237) and negative ( n  = 618) groups. However, among those feeling fully recovered (SARS-CoV-2 positive: 200 patients, SARS-CoV-2 negative: 506 patients), time to full recovery was significantly longer in SARS-CoV-2 patients (10.6 vs 7.7 days, p  < 0.001). We found no evidence that predictors of a complicated course differed between groups ( p  = 0.07)., Conclusion: Early in the pandemic, the proportion of patients not feeling fully recovered by 28 days was similar between SARS-CoV-2 positive and negative patients presenting in primary care with RTI symptoms, but it took somewhat longer for SARS-CoV-2 patients to feel fully recovered. More research is needed on predictors of a complicated course in RTI.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are of particular concern due to the spread of antibiotic resistance genes associated with mobile genetic elements. In this study, we collected 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018). We identified 11 major clonal lineages, with most isolates belonging to the high-risk clones ST258/512, ST101, ST11, and ST307. bla KPC-like was the most prevalent carbapenemase-encoding gene (46%), with bla OXA-48 present in 39% of isolates. Through the combination and comparison of this EURECA collection with the previous EuSCAPE collection (2013-2014), we investigated the spread of high-risk clones circulating in Europe exhibiting regional differences. We particularly found bla KPC-like ST258/512 in Greece, Italy, and Spain, bla OXA-48 ST101 in Serbia and Romania, bla NDM ST11 in Greece, and bla OXA-48-like ST14 in Türkiye. Genomic surveillance across Europe thus provides crucial insights for local risk mapping and informs necessary adaptions for implementation of control strategies., (© 2024. The Author(s).)

Objectives: Point prevalence surveys (PPS) provide valuable data on patterns of hospital antimicrobial administration. To identify quality improvement indicators, we evaluated antimicrobial prescribing patterns in children and neonates admitted to three referral centres in Sanandaj, Western Iran, and compared these with Southeast Asian and European paediatric benchmark data., Methods: The standardised Global-PPS was performed to assess antimicrobial use in Southeast Asia, including Sanandaj and European hospitals, in 2019., Results: Of the 4118, 2915, and 443 paediatric patients enrolled in Southeast Asian, European and Sanandaj hospitals, 2342 (56.9%), 833 (28.6%) and 332 (74.9%), respectively, received at least one antimicrobial in 2019. The most administered antibiotics in neonates were ampicillin in Southeast Asia (30.3%) and Sanandaj (41.5%, often in combination with cefotaxime (29.0%)), compared with amoxicillin in Europe (20.0%). In children, ceftriaxone was most prescribed in Sanandaj (62.4%) and Southeast Asia (20.5%) as opposed to amoxicillin (11.8%) in Europe. Twice as many Watch antibiotics (83.0%) were prescribed on paediatric wards in Sanandaj compared with European paediatric wards (41.1%). All antimicrobials in Sanandaj hospitals were prescribed empirically, and prolonged surgical prophylaxis was common (75.5%)., Conclusion: The high prevalence of antibiotic prescribing, high empirical therapies, and poor outcomes for antibiotic quality indicators strongly suggest the urgent need for an antibiotic stewardship program in Sanandaj hospitals, where improved diagnostic laboratory capacity and reconsideration of training may be good targets for intervention in their hospitals., (Copyright © 2024 University of Antwerp, Faculty of Medicine and Health Science, Antwerp, Belgium. Published by Elsevier Ltd.. All rights reserved.)