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Objectives To investigate whether infants exposed to antimicrobials in hospital during the first 3 months of life had an increased risk of ambulatory antimicrobial use during the following year compared with infants not exposed to antimicrobials during the first 3 months of life. Methods Norwegian cohort study of infants less than 3 months consisting of one group exposed to antimicrobials recruited during hospitalization and one group not exposed to antimicrobials. Ten unexposed infants were matched with one exposed infant according to county of residence, birth year and month, and sex. The Norwegian Prescription Database was applied to register antimicrobial use from the month after discharge and 1 year onward. We defined comorbidity based on antimicrobials prescribed as reimbursable prescriptions due to underlying diseases. Results Of 95 infants exposed to antimicrobials during the first 3 months of life, 23% had recurrent use compared with 14% use in 950 unexposed infants [relative risk (RR) = 1.7 (95% CI = 1.1–2.5) and comorbidity-adjusted RR = 1.4 (95% CI = 0.9–2.2)]. The recurrence use rate in exposed term infants (≥37 weeks, n = 70) was 27% compared with 12% in their unexposed matches [RR 2.3 = (95% CI = 1.4–3.7) and comorbidity-adjusted RR = 1.9 (95% CI = 1.2–3.2). Of 25 exposed preterm infants, 3 (12%) had recurrent use. The total antimicrobial prescription rate was 674/1000 in the exposed group and 244/1000 in the unexposed group [incidence rate ratio = 2.8 (95% CI = 1.6–4.9)]. Conclusions Infants exposed to antimicrobials during the first 3 months of life had an increased risk of recurrent use during the following year. This increased risk also appeared in term infants without infection-related comorbidity.

Objectives Data on cephalosporin consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of cephalosporins. Methods For the period 1997–2017, data on consumption of cephalosporins (i.e. first-, second-, third- and fourth-generation cephalosporins; ATC subgroups J01DB, J01DC, J01DD and J01DE, respectively) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Cephalosporin consumption was analysed based on ATC-4 subgroup, and presented as trends, seasonal variation, presence of change-points and compositional changes. Results In 2017, cephalosporin consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 285 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Cephalosporin consumption did not change significantly between the first quarter of 1997 and the last quarter of 2017. Seasonal variation decreased significantly over time. Proportional consumption of second- and third-generation cephalosporins significantly increased over time compared with that of first-generation cephalosporins, and proportional consumption of fourth-generation cephalosporins significantly decreased compared with that of second- and third-generation cephalosporins. Conclusions Despite considerable variation between countries in the composition of cephalosporin consumption and trends over time, a significant shift towards consumption of more broad-spectrum cephalosporins in the community was observed across the EU/EEA during 1997–2017.

Objectives Data on the consumption of macrolides, lincosamides and streptogramins (MLS) in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in composition of the main subgroups of MLS. Methods For the period 1997–2017, data on consumption of MLS, i.e. ATC group J01F, in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of MLS was analysed and presented as trends, seasonal variation, presence of change-points and compositional changes, using a classification based on mean plasma elimination half-life for macrolides. Results In 2017, consumption of MLS in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 13 between countries with the highest (Greece) and the lowest (Sweden) consumption. Consumption of MLS did not change significantly up to 2003, after which it significantly increased up to 2007. No significant change was observed after 2007. Consumption of MLS showed high seasonal variation. The proportional consumption of long-acting macrolides significantly increased over time compared with that of intermediate-acting macrolides, and proportional consumption of the latter increased compared with that of short-acting macrolides. Conclusions Consumption of MLS did not change significantly over time during 2007–2017, while the proportional consumption of long-acting macrolides increased. Seasonal variation remained high, which suggests that MLS are still prescribed inappropriately in many countries.

Interest has been shown in the use of antibiotics during the COVID-19 pandemic. In this article we present the consumption of systemic antibiotics in Norway during the period of the pandemic.Total sales of systemic antibiotics in defined daily doses (DDD) were retrieved from the wholesaler-based medicinal product statistics for 2019 and 2020, and sales of antibiotics for use outside of healthcare institutions were retrieved from the Norwegian prescription database. Information was retrieved on the proportion of users (prevalence), doses (measured in DDD) and prescriptions.Total sales of systemic antibiotics increased in March 2020, but sales to persons outside of healthcare institutions did not. Compared to previous years, both total consumption and use of antibiotics outside of institutions fell steeply in the months that followed. The reduction was greatest for antibiotics against respiratory infections and in the youngest age groups.The significant reduction in the use of systemic antibiotics during the COVID-19 pandemic is attributed to infection control measures and reduced contact with the health service. In 2016, the Norwegian government set a goal for a 30 % reduction in antibiotic use by the end of 2020. The pandemic has contributed to the achievement of that goal.

Objectives This article introduces a series of articles on antibiotic consumption in the community between 1997 and 2017, which provide an update of previous articles covering the periods 1997–2003 and 1997–2009. Methods In this article, differences in participating countries, the ATC/DDD classification system, and data collection, validation and analysis between the current and previous series are described. Results In the previous series, 33 European countries provided valid data for further analysis, while the current series focused on 30 countries belonging to the EU or the European Economic Area (EEA). For both series, data were collected in accordance with the WHO ATC classification system. While the previous series reported data in accordance with the ATC/DDD index 2011, the current series employed the ATC/DDD index 2019. Both series focused on consumption of antibacterials for systemic use (ATC J01) and collected data expressed in DDD per 1000 inhabitants per day and packages per 1000 inhabitants per day. When studying consumption expressed in packages per 1000 inhabitants per day, countries reporting total care data, i.e. community and hospital sector combined, were included in the previous series but excluded in the current series. While the previous series used non-linear mixed models to evaluate time trends in antibiotic consumption, the current series allowed for inclusion of change-points with a data-driven location. In addition, both series assessed the composition and quality of antibiotic consumption in the EU/EEA. Conclusions The updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description of antibiotic consumption in the community in Europe.

When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)—aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin—and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed., Generics contribute to increased availability of antibiotics, benefiting healthcare systems but potentially leading to increased consumption with implications for antibiotic stewardship and resistance. Here, the authors found no consistent changes in prescribing patterns of the 13 antibiotics that entered the US market as generics from 2000–2012.

Objectives This tutorial describes and illustrates statistical methods to detect time trends possibly including abrupt changes (referred to as change-points) in the consumption of antibiotics in the community. Methods For the period 1997–2017, data on consumption of antibacterials for systemic use (ATC group J01) in the community, aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. Trends over time and presence of common change-points were studied through a set of non-linear mixed models. Results After a thorough description of the set of models used to assess the time trend and presence of common change-points herein, the methodology was applied to the consumption of antibacterials for systemic use (ATC J01) in 25 EU/European Economic Area (EEA) countries. The best fit was obtained for a model including two change-points: one in the first quarter of 2004 and one in the last quarter of 2008. Conclusions Allowing for the inclusion of common change-points improved model fit. Individual countries investigating changes in their antibiotic consumption pattern can use this tutorial to analyse their country data.

Objectives The quality of antibiotic consumption in the community can be assessed using 12 drug-specific quality indicators (DSQIs) developed by the European Surveillance of Antimicrobial Consumption (ESAC) project. We compared quality in 2009 and 2017 in the EU/European Economic Area (EEA) and evaluated the impact of using different DDD values (ATC/DDD indices 2011 and 2019) for the 2009 quality assessment using these DSQIs and a joint scientific opinion (JSO) indicator. Methods We calculated the 12 DSQIs and the JSO indicator for 2017 and for 2009 for EU/EEA countries able to deliver values. For each of the indicators we grouped the 2017 and 2009 indicator values into four quartiles. To evaluate changes in quality between 2009 and 2017, we used the quartile distribution of the 2009 indicator values in 30 EU/EEA countries as benchmarks. In addition, we compared the quality assessment for 2009 using the ATC/DDD indices 2011 and 2019. Results In 2017, a difference in the quality of antibiotic consumption in the community between northern and southern EU/EEA countries remained, but also several eastern EU/EEA countries shifted towards lower quality. Quality of antibiotic consumption decreased between 2009 and 2017 in particular indicator values for penicillin, quinolone, relative β-lactam and broad- versus narrow-spectrum antibiotic consumption, and seasonal variation. Using different ATC/DDD indices did not substantially change countries’ ranking based on their DSQI values. Conclusions The quality of antibiotic consumption in the community as measured by the DSQIs further decreased between 2009 and 2017, especially in Southern and Eastern European countries. A continuous effort to improve antibiotic consumption is essential to reduce antibiotic consumption in general and the use of broad-spectrum antibiotics in particular.

The use of quinolones is subject to strict conditions, in part because of their known tendency to drive antimicrobial resistance. Use of quinolones in Norwegian hospitals increased dramatically from their launch in the 1980s to a peak in 2012. Since then, usage has decreased and had almost halved by 2019. However, little information is available on whether the use of quinolones in hospitals is in accordance with national guidelines.This study included inpatients over 12 years of age who were prescribed quinolones at a local hospital in the Central Norway Regional Health Authority in the period 1 September-31 December 2018. An expert group of infectious disease specialists evaluated the use of quinolones against the national guidelines for the use of antibiotics in hospitals.The use of ciprofloxacin was considered to have been inconsistent with therapeutic recommendations in 45 out of 49 (92 %) inpatient stays in the medical, surgical and orthopaedic departments.In a local hospital, ciprofloxacin was used all too frequently for indications outside those recommended in the Norwegian guidelines.

Background In order to change antibiotic prescribing behaviour, we need to understand the prescribing process. The aim of this study was to identify targets for antibiotic stewardship interventions in hospitals through analysis of the antibiotic prescribing process from admission to discharge across five groups of infectious diseases. Methods We conducted a multi-centre, observational cohort study, including patients with lower respiratory tract infections, exacerbation of chronic obstructive pulmonary disease, skin- and soft tissue infections, urinary tract infections or sepsis, admitted to wards of infectious diseases, pulmonary medicine and gastroenterology at three teaching hospitals in Western Norway. Data was collected over a 5-month period and included antibiotics prescribed and administered during admission, antibiotics prescribed at discharge, length of antibiotic therapy, indication for treatment and discharge diagnoses, estimated glomerular filtration rate (eGFR) on admission, antibiotic allergies, place of initiation of therapy, admittance from an institution, patient demographics and outcome data. Primary outcome measure was antibiotic use throughout the hospital stay, analysed by WHO AWaRe-categories and adherence to guideline. Secondary outcome measures were a) antibiotic prescribing patterns by groups of diagnoses, which were analysed using descriptive statistics and b) non-adherence to the national antibiotic guidelines, analysed using multivariate logistic regression. Results Through analysis of 1235 patient admissions, we identified five key targets for antibiotic stewardship interventions in our population of hospital inpatients; 1) adherence to guideline on initiation of treatment, as this increases the use of WHO Access-group antibiotics, 2) antibiotic prescribing in the emergency room (ER), as 83.6% of antibiotic therapy was initiated there, 3) understanding prescribing for patients admitted from other institutions, as this was significantly associated with non-adherence to guideline (OR = 1.44 95% CI 1.04, 2.00), 4) understanding cultural and contextual drives of antibiotic prescribing, as non-adherent prescribing differed significantly between the sites of initiation of therapy (between hospitals and ER versus ward) and 5) length of therapy, as days of antibiotic therapy was similar across a wide range of diagnoses and with prolonged therapy after discharge. Conclusions Analysing the process of antibiotic prescribing in hospitals with patient-level data identified important targets for antibiotic stewardship interventions in hospitals.

Objective: To describe epidemiology and antimicrobial susceptibility testing (AST) data of bacteria causing invasive infections in Norwegian children (0–18 years). Methods: Population-based observational study using prospectively collected AST data from the Norwegian Surveillance System of Antimicrobial Resistance from 2013 to 2017. We included all clinically relevant bacterial isolates (blood and cerebrospinal fluid), and compared incidence of invasive infections and AST data in isolates from children and adults. Results: We included 1173 isolates from children and 44,561 isolates from adults. Staphylococcus aureus accounted for 220/477 (46.2%, 95% CI: 41.6–50.7) of all isolates in schoolchildren (6–18 years). Compared with Streptococcus pneumonia isolates from adults (N = 2674), we observed higher nonsusceptibility rates to penicillin in isolates from children (N = 151), 11.9% versus 5.8%, P < 0.01; also higher resistance rates to erythromycin (11.3% vs. 4.9%, P < 0.01), clindamycin (9.3% vs. 3.6%, P < 0.001), and trimethoprim/sulfamethoxazole (17.9% vs. 6.4%, P < 0.001). Compared with Escherichia coli isolates in adults (N = 9073), we found lower rates of ESBL in isolates from children (N = 212), 2.4% versus 6.4%, P < 0.05. Conclusion: The study indicates the importance of microbiologic surveillance strategies in children and highlights the need for pediatric AST data. The high rates of nonsusceptibility to commonly used antibiotics among S. pneumoniae in children and the high burden of invasive S. aureus infections in schoolchildren calls for modifications of Norwegian guidelines.

To compare antibiotic treatment failure evaluated as switch from one type of antibiotics to another in ambulatory care.Data on all dispensed doxycycline, amoxicillin, phenoxymethylpenicillin and macrolides in Norway June 2013 - May 2015, was retrieved from the Norwegian Prescription Database. We computed switch rates for the selected antibiotics on day 1-28 after initial dispensing, and the corresponding odds-ratios, adjusted for patients´ age and gender, and prescribers´ specialty.Of 1.860.036 dispensed antibiotics, 103.076 (5.5%) were switched within 28 days. Within 10 days after the index date, the switch rate was highest for phenoxymethylpenicillin (4.1%), followed by amoxicillin (2.5%), macrolides and doxycycline (2.2%).The switch rate after initial dispensing of phenoxymethylpenicillin is higher than that of more broad-spectrum antibiotics. However, it is still low, supporting the recommendation of phenoxymethylpenicillin as first line treatment when an antibiotic is indicated for a respiratory tract infection in primary care.

Here we describe in detail marketing authorization and reimbursement procedures for medicinal products in Norway, with particular reference to nine novel antibiotics that received marketing authorization between 2005 and 2015. The description illustrates that, in places like Norway, with effective antibiotic stewardship policies and an associated low prevalence of antibiotic-resistant bacterial infection, there is little need for newer, more expensive antibiotics whose therapeutic superiority to existing compounds has not been demonstrated. Since resistance begins to emerge as soon as an antibiotic is used, Norway's practice of leaving newer antibiotics on the shelf is consistent with the goal of prolonging the effectiveness of newer antibiotics. An unintended consequence is that the country has signalled to the private sector that there is little commercial value in novel antibiotics, which may nevertheless still be needed to treat rare or emerging infections. Every country aims to improve infection control and to promote responsible antibiotic use. However, as progress is made, antibiotic-resistant bacteria should become less common and, consequently, the need for, and the commercial value of, novel antibiotics will probably be reduced. Nevertheless, antibiotic innovation continues to be essential. This dilemma will have to be resolved through the introduction of alternative reward systems for antibiotic innovation. The DRIVE-AB (Driving re-investment in research and development and responsible antibiotic use) research consortium in Europe has been tasked with identifying ways of meeting this challenge.Nous décrivons ici en détail les procédures d'autorisation de mise sur le marché et de remboursement des médicaments en Norvège, en particulier de neuf nouveaux antibiotiques qui ont reçu une autorisation de mise sur le marché entre 2005 et 2015. Cette description montre que, dans les pays comme la Norvège qui ont adopté des politiques d'utilisation raisonnée des antibiotiques et qui affichent ainsi une faible prévalence d'infections bactériennes résistantes aux antibiotiques, il n'est guère besoin de nouveaux antibiotiques plus coûteux dont la supériorité thérapeutique par rapport aux composés existants n'a pas été démontrée. Étant donné que la résistance apparaît dès que l'on commence à utiliser un nouvel antibiotique, la désaffection de la Norvège pour les nouveaux antibiotiques concorde avec l'objectif d’en prolonger l'efficacité. Conséquence inattendue, le pays a signalé au secteur privé que ces nouveaux antibiotiques ne présentaient qu'un faible intérêt commercial mais qu'ils pourraient cependant être nécessaires pour traiter des maladies infectieuses rares ou nouvelles. Tous les pays souhaitent faire avancer la lutte contre les infections et promouvoir l'utilisation responsable des antibiotiques. Cependant, à mesure qu'ils progresseront, les bactéries résistantes aux antibiotiques devraient devenir moins fréquentes et la nécessité ainsi que l'intérêt commercial de nouveaux antibiotiques devraient par conséquent s'en trouver réduits. L'innovation en matière d'antibiotiques reste toutefois essentielle. Ce dilemme devra être résolu avec l'introduction de systèmes de récompenses alternatifs pour l'innovation dans le domaine des antibiotiques. Le consortium de recherche européen DRIVE-AB (En este documento se detallan los procedimientos de autorización de comercialización y compensación para productos medicinales en Noruega, con especial referencia a nueve antibióticos nuevos que recibieron la autorización de comercialización entre 2005 y 2015. La descripción ilustra que, en lugares como Noruega, que cuentan con políticas eficaces de administración de antibióticos y una prevalencia baja relacionada de infecciones bacterianas resistentes a los antibióticos, hay poca necesidad de antibióticos nuevos más caros cuya superioridad terapéutica respecto a los componentes existentes no ha sido demostrada. Dado que la resistencia comienza a surgir tan pronto como se utiliza un antibiótico, la práctica de Noruega de dejar nuevos antibióticos de lado es coherente con el objetivo de prolongar la eficacia de los nuevos antibióticos. Una consecuencia inesperada es que el país ha explicado al sector privado que los antibióticos nuevos apenas tienen valor comercial, los cuales, sin embargo, pueden ser necesarios para tratar infecciones raras o nuevas. Todos los países tratan de mejorar su control de infecciones y fomentar un uso responsable de los antibióticos. No obstante, conforme se va progresando, las bacterias resistentes a los antibióticos deberían ser cada vez menos comunes y, por tanto, es probable que la necesidad y el valor comercial de los antibióticos nuevos se vean reducidos. Sin embargo, la innovación en el campo de los antibióticos sigue siendo fundamental. Este dilema deberá resolverse mediante la introducción de sistemas de recompensa alternativos por innovar con antibióticos. El consorcio de investigación europeo DRIVE-AB, que fomenta la reinversión en investigación y desarrollo y en el uso responsable de los antibióticos, deberá identificar formas de lograr este objetivo.نتناول بالشرح التفصيلي في هذه الوثيقة إجراءات استرداد التكاليف والحصول على تصريح بتسويق المنتجات الدوائية في النرويج، مع الإشارة على وجه التحديد إلى تسعة أنواع من المضادات الحيوية الجديدة التي تم الحصول على تصريح بتسويقها في الفترة بين عامي 2005 و2015. ويبين هذا الشرح أنه في بعض الأماكن مثل النرويج – حيث تسري سياسات الإشراف على المضادات الحيوية وينخفض ما يرتبط بتلك الأدوية من انتشار للعدوى البكتيرية المقاومة للمضادات الحيوية – تقل الحاجة إلى مضادات حيوية جديدة أغلى سعرًا ولم يظهر دليل على تفوق أثرها عن المركبات الدوائية المتواجدة بالأسواق. ونظرًا لبدء ظهور المقاومة بمجرد استخدام المضاد الحيوي، جاءت الممارسات التي اتبعتها النرويج – والتي تتمثل في التخلي عن المضادات الحيوية الجديدة – متسقةً مع الهدف الرامي إلى إطالة فترة فعالية المضادات الحيوية الجديدة. وأدى ذلك إلى نتيجة غير مقصودة حيث أوضحت النرويج للقطاع الخاص انخفاض القيمة التجارية للمضادات الحيوية الجديدة، والتي قد تظل الحاجة إليها قائمة رغم ذلك لعلاج أنواع العدوى الناشئة أو النادرة. وتسعى كل دولة إلى تحسين مكافحة العدوى وتعزيز الاستخدام المسؤول للمضادات الحيوية، غير أنه، مع المضي قدمًا في سبيل تحقيق ذلك، من المفترض أن يقل شيوع البكتريا المقاومة للمضادات الحيوية، وبالتالي، تظهر احتمالية أن تقل الحاجة إلى المضادات الحيوية الجديدة وأن تنخفض قيمتها التجارية. وبالرغم من ذلك، يظل ابتكار المضادات الحيوية يحتل مكانةً رئيسيةً. ويستلزم الأمر حل هذه المشكلة من خلال توفير نظم بديلة لمنح المكافآت فيما يتعلق بابتكار المضادات الحيوية. وقد تم تكليف اتحاد البحوث في أوروبا DRIVE-AB (القائم على توجيه أنشطة إعادة الاستثمار في مجال البحث والتطوير والاستخدام المسؤول للمضادات الحيوية) بمهمة تحديد سبل مواجهة ذلك التحدي.本文中，我们会特别参考 2005 至 2015 年间获得上市许可的九种新型抗生素，详细地描述挪威医疗产品的上市许可及报销流程。该描述证明，像挪威这样拥有有效抗生素管理政策且耐抗生素细菌感染低相关发病率的地方，几乎不需要对现有化合物治疗优势尚未得到证明的更新、更昂贵的抗生素。 自抗生素使用之初耐药性便开始出现，挪威将新型抗生素束之高阁的做法符合延长新型抗生素效果的目标。 一个意料之外的后果是该国曾向私营部门发出这样的信号：新型抗生素毫无商业价值，但仍可能需要其治疗罕见或新型感染疾病。 每个国家都致力于改善感染控制并促进抗生素的负责任使用。 然而，随着不断进展，耐抗生素细菌感染率应有所减少，并且对新型抗生素的需求及其商业价值也可能会减少。 但是，抗生素的创新仍然至关重要。 这种困境必须通过引进替代性抗生素创新奖励机制进行解决。 位于欧洲的推动对抗生素研发及负责任使用再投资 (DRIVE-AB) 研究联合会已承担起寻找应对该挑战的方法的使命。.Здесь мы подробно описываем процедуры получения регистрационного удостоверения и финансового возмещения для лекарственных средств в Норвегии на примере девяти новых антибиотиков, которые получили регистрационное удостоверение между 2005 и 2015 гг. Описание демонстрирует, что в таких местах, как Норвегия, с эффективной стратегией рационального использования антибактериальных препаратов и со связанной с ней низкой распространенностью устойчивых к антибиотикам бактериальных инфекций практически нет необходимости в новых, более дорогих антибиотиках, терапевтическое превосходство которых не было продемонстрировано. Поскольку устойчивость начинает развиваться сразу при использовании антибиотика, практика Норвегии откладывать применение новых антибиотиков согласуется с целью продления эффективности новых антибиотиков. Непреднамеренным последствием является то, что страна дала понять малому бизнесу, что существует малая коммерческая ценность в новых антибиотиках, которые могут быть по-прежнему необходимы для лечения редких или новых инфекций. Каждая страна стремится усовершенствовать борьбу с инфекциями и стимулировать ответственное применение антибиотиков. Однако при достижении определенного прогресса устойчивые к антибиотикам бактерии должны стать менее распространенными и, как следствие, возможно, снизится потребность в новых антибиотиках и их коммерческая ценность. Тем не менее инновации антибиотиков продолжают оставаться значимыми. Эта дилемма должна быть решена за счет внедрения альтернативных систем вознаграждения за инновации антибиотиков. Исследовательскому консорциуму в Европе DRIVE-AB («Введение реинвестирования в научные исследования и разработки и ответственное использование антибиотиков») была поставлена задача определить пути решения этой проблемы.

The objective of this study was to update a 2011 survey, conducted on behalf of the ESCMID Study Group for Antibiotic Policies (ESGAP), studying the availability of old but clinically useful antibiotics in North America, Europe and Australia. This follow-up survey was performed in 2015 in 40 countries among specialists from the pharmaceutical, infectious diseases and microbiology sectors in North America, Europe and Australia in order to assess the availability through usual marketing processes of 36 systemic antibiotics (addition of 3 antibiotics compared with the 2011 survey) selected for their ability to treat infections caused by resistant bacteria and their unique value for specific criteria. The questionnaire was sent by e-mail to national contacts belonging to ESGAP and ReAct networks. In all, 39 of the 40 countries participated in this survey. The number of available antibiotics differed considerably from one drug to another as well as from one country to another (e.g. 7 antibiotics available in Estonia, 24 in France). Overall, 25/36 selected antibiotics were marketed in 20/39 countries or less. From 2011 to 2015 (data available for both periods in 37 countries for 33 antibiotics), the number of available selected antibiotics increased in 13 countries and decreased in 17. In conclusion, despite the ongoing bacterial resistance crisis, the situation regarding the availability of ‘forgotten antibiotics’ has worsened since 2011. Urgent measures are needed to ensure better availability of these antibiotics on a global scale as a conservation measure to ensure sustainable and responsible use of antibiotics., peer-reviewed

A recent analysis of antibiotics approved between 1999 and 2014, conducted by researchers at the Norwegian Institute of Public Health; the University of Oslo; the Center for Disease Dynamics, Economics & Policy (CDDEP); and Boston University, showed a lack of novelty and diversity regarding target pathogens and indications and a failure to address the most urgent resistance threats, including resistant Gram-negative bacteria. A global research and development strategy should incentivize development of broad-spectrum antibiotics for critically ill patients, as well as therapeutic alternatives to antibiotics, decreasing our dependence on traditional, small-molecule antibiotics.

ObjectivesTo describe and compare antibiotic use in relation to indications, doses, adherence rate to guidelines and rates of broad-spectrum antibiotics (BSA) in two different paediatric departments with different academic cultures, and identify areas with room for improvement.DesignProspective observational survey of antibiotic use.SettingPaediatric departments in a university hospital (UH) and a district hospital (DH) in Norway, 2017. The registration period was 1 year at the DH and 4 months at the UH.Participants201 children at the DH (mean age 3.8: SD 5.1) and 137 children at the UH (mean age 2.0: SD 5.9) were treated with systemic antibiotics by a paediatrician in the study period and included in the study.Outcome measuresMain outcome variables were prescriptions of antibiotics, treatments with antibiotics, rates of BSA, median doses and adherence rate to national guidelines.ResultsIn total, 744 prescriptions of antibiotics were given at the UH and 638 at the DH. Total adherence rate to guidelines was 75% at the UH and 69% at the DH (p=0.244). The rate of treatments involving BSA did not differ significantly between the hospitals (p=0.263). Use of BSA was related to treatment of central nervous system (CNS) infections, patients with underlying medical conditions or targeted microbiological treatment in 92% and 86% of the treatments, at the UH and DH, respectively (p=0.217). A larger proportion of the children at the DH were treated for respiratory tract infections (pConclusionOur results indicate that Norwegian paediatricians have a common understanding of main aspects in rational antibiotic use independently of working in a UH or DH. Variations in treatment of respiratory tract infections and in doses of antibiotics should be further studied.

BACKGROUND: Antimicrobial resistance (AMR) is low in Norway, but to prevent an increase the Norwegian Government has launched a National Strategy including a 30% reduction of broad-spectrum antibiotics (BSA) in hospitals within 2020. BSA are defined as second- and third-generation cephalosporins, carbapenems, piperacillin/tazobactam and quinolones. There are no recent studies of antibiotic use in Norwegian hospitalized children. AIM OF THE STUDY: To describe the use of antibiotics with emphasis on BSA in Norwegian hospitalized children and neonates in order to detect possibilities for optimization. METHODS: Data were extracted from eight national point prevalence surveys of systemic antibiotic prescriptions in Norwegian hospitals between 2015 and 2017. The choices of antibiotics were compared with the empirical recommendations given in available Norwegian guidelines. In total, 1323 prescriptions were issued for 937 patients. RESULTS: Twenty-four percent of pediatric inpatients were given antibiotics. Adherence to guidelines was 48%, and 30% (95% CI 27%-33%) of all patients on antibiotics received BSA. We identified only small variations in use of BSA between hospitals. One third of the patients on antibiotic therapy received prophylaxis whereof 13% where given BSA. In 30% of prescriptions with BSA, no microbiological sample was obtained prior to treatment. CONCLUSION: This study reveals an excess of prescriptions with BSA in relation to the low resistance rate in Norway. Our findings reveal areas for improvement that can be useful in the forthcoming antibiotic stewardship programs in Norwegian pediatric departments

Source at https://doi.org/10.1186/s12889-019-6409-x. Licensed CC BY-NC-ND 4.0. Background: Antibiotic resistance is a global health threat. Public knowledge is considered a prerequisite for appropriate use of antibiotics and limited spread of antibiotic resistance. Our aim was to examine the level of knowledge of antibiotics and antibiotic resistance among Norwegian pharmacy customers, and to assess to which degree beliefs, attitudes and sociodemographic factors are associated with this knowledge. Methods: A questionnaire based, cross-sectional study was conducted among pharmacy customers in three Norwegian cities. The questionnaire covered 1) knowledge of antibiotics (13 statements) and antibiotic resistance (10 statements), 2) the general beliefs about medicines questionnaire (BMQ general) (three subdomains, four statements each), 3) attitudes toward antibiotic use (four statements), and 4) sociodemographic factors, life style and health. High knowledge level was defined as > 66% of maximum score. Factors associated with knowledge of antibiotics and antibiotic resistance were investigated through univariate and multiple linear regression. Hierarchical model regression was used to estimate a population average knowledge score weighted for age, gender and level of education. Results: Among 877 participants, 57% had high knowledge of antibiotics in general and 71% had high knowledge of antibiotic resistance. More than 90% knew that bacteria can become resistant against antibiotics and that unnecessary use of antibiotics can make them less effective. Simultaneously, more than 30% erroneously stated that antibiotics are effective against viruses, colds or influenza. Factors positively associated with antibiotic knowledge were health professional background, high education level, and a positive view on the value of medications in general. Male gender, a less restrictive attitude toward antibiotic use, and young age were negatively associated with antibiotic knowledge. The mean overall antibiotic knowledge score was relatively high (15.6 out of maximum 23 with estimated weighted population score at 14.8). Conclusions: Despite a high level of knowledge of antibiotics and antibiotic resistance among Norwegian pharmacy customers, there are obvious knowledge gaps. We suggest that action is taken to increase the knowledge level, and particularly target people in vocational, male dominated occupations outside the health service, and primary/secondary school curricula.

Background. The study aimed to evaluate inpatient antibiotic use in both the State Second Hospital and State Third Hospital in Mongolia, using the WHO developed and standardized ATC/DDD methodology. Methods. Data were collected from the State Second Hospital and State Third Hospital which are major public hospitals that provide health care for approximately one fifth of the Mongolian population. Antibiotic utilization was monitored retrospectively for five years (2013–2017) using the ATC/DDD methodology and data were presented in DDD/ admission and DDD/100 bed days. Statistical analysis was performed using a Student’s t-test for parametric data. A P value of ≤0.05 was considered to be statistically significant. Results. The annual consumption rates in the State Second Hospital were stable over time while in the State Third Hospital consumption rates varied considerately between years. Overall, the total antibiotic consumption rate was very high, but has decreased in both hospitals. The rate of consumption of all antibiotics was approximately twice that in the State Third Hospital (421.7 DDD/100 bed days) between 2013 and 2017 when compared with the State Second Hospital (199.7 DDD/ 100 bed days), P<0.001). The seven most frequently used antibiotics comprised approximately 75% of all DDDs in both hospitals, in the period 2013–2017; being: amoxicillin, cefazolin, cefotaxime, ceftriaxone, clarithromycin, ciprofloxacin, and nitroxoline. However, this was not consistent when considering the individual years, since in 2015 and 2016, these seven active agents represented approximately 50%. Conclusion. This is the first hospital-based study of antibiotic consumption rates reported in Mongolia. In addition to very high consumption rates, large differences occurred between the hospitals investigated. Inappropriate and high levels of antibiotic use lead to increased costs and also increased nosocomial infection rates with potentially resistant species. The Government and health professionals need to take more active roles in improving and promoting quality antibiotic use among inpatients.

Unnecessary and inappropriate use of antibiotics in human healthcare is a major driver for the development and spread of antimicrobial resistance; many countries are implementing measures to limit the overuse and misuse of antibiotics e.g. through the establishment of antimicrobial use reduction targets. We performed a review of antimicrobial use reduction goals in human medicine in Transatlantic Taskforce on Antimicrobial Resistance partner countries. On 31 March 2017, the European Centre for Disease Prevention and Control sent a questionnaire to National Focal Points for Antimicrobial Consumption and the National Focal Points for Antimicrobial Resistance in 28 European Union countries, Iceland and Norway. The same questionnaire was sent to the TATFAR implementers in Canada and the United States. Thirty of 32 countries replied. Only nine countries indicated that they have established targets to reduce antimicrobial use in humans. Twenty-one countries replied that no target had been established. However, 17 of these 21 countries indicated that work to establish such targets is currently underway, often in the context of developing a national action plan against antimicrobial resistance. The reported targets varied greatly between countries and can be a useful resource for countries willing to engage in the reduction of antibiotic use in humans.

Background Clinical antibiotic prescribing guidelines are essential in defining responsible use in the local context. Our objective was to investigate the association between adherence to national antibiotic prescribing guidelines and patient outcomes across a wide range of infectious diseases in hospital inpatients. Methods Over five months in 2014, inpatients receiving antibiotics under the care of pulmonary medicine, infectious diseases and gastroenterology specialties across three university hospitals in Western Norway were included in this observational cohort study. Patient and antibiotic prescribing data gathered from electronic medical records included indication for antibiotics, microbiology test results, discharge diagnoses, length of stay (LOS), comorbidity, estimated glomerular filtration rate (eGFR) on admission and patient outcomes (primary: 30-day mortality; secondary: in-hospital mortality, 30-day readmission and LOS). Antibiotic prescriptions were classified as adherent or non-adherent to national guidelines according to documented indication for treatment. Patient outcomes were analysed according to status for adherence to guidelines using multivariate logistic, linear and competing risk regression analysis with adjustments made for comorbidity, age, sex, indication for treatment, seasonality and whether the patient was admitted from an institution or not. Results In total, 1756 patients were included in the study. 30-day-mortality and in-hospital mortality were lower (OR = 0.48, p = 0.003 and OR = 0.46, p = 0.001) in the guideline adherent group, compared to the non-adherent group. Adherence to guideline did not affect 30-day readmission. In linear regression analysis there was a trend towards shorter LOS when LOS was analysed for patients discharged alive (predicted mean difference − 0.47, 95% CI (− 1.02, 0.07), p = 0.081). In competing risk analysis of LOS, the adherent group had a subdistribution hazard ratio (SHR) of 1.17 95% CI (1.02, 1.34), p = 0.025 for discharge compared to the non-adherent group. Conclusions Adhering to antibiotic guidelines when treating infections in hospital inpatients was associated with favourable patient outcomes in terms of mortality and LOS. Electronic supplementary material The online version of this article (10.1186/s13756-019-0515-5) contains supplementary material, which is available to authorized users.

Background Despite the urgent need for new, effective antibiotics, few antibiotics of value have entered the market during the past decades. Therefore, incentives have been developed to stimulate antibiotic R&D. For these incentives to be effective, geographic availability for recently approved antibiotics needs to be better understood. In this study, we analyze geographic availability and market introduction of antibiotics approved between 1999 and 2014. Material and method We identified antibiotics, considered new chemical entities (NCEs) for systemic use approved globally between 1999 and 2014, from national medicine agencies’ lists of approved drugs, and data from the WHO Collaborating Center for Drug Statistics. Geographic availability was mapped using sales data from IQVIA, and analyzed with regards to class, indication, safety, and origin. Results Of the 25 identified NCEs, only 12 had registered sales in more than 10 countries. NCEs with the widest geographic availability had registered sales in more than 70 countries within a ten-year timeframe and 30 countries within a three-year timeframe, spreading across five different geographic regions and three country income classes. Half (52%) of the NCEs had an indication for infections caused by antibiotic- resistant bacteria, little diversity was seen regarding target pathogen and indication. Antibiotics originated from and/or marketed by companies from the US or Europe had greater geographic availability compared to Japanese antibiotics, which seldom reached outside of Asia. For 20 NCEs developers chose to fully or partially sublicense marketing rights to a number of companies of different sizes. Conclusion Our findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization. Sublicensing agreements between multiple companies was common practice. Moreover, differences were seen between countries regarding benefit/risk evaluations and company behavior. These findings could be a potential source of uncertainties, and create barriers to assure that working antibiotics are developed and made available according to public health needs.

Background: There is limited evidence from multicenter, randomized controlled studies to inform planning and implementation of antibiotic stewardship interventions in hospitals. Methods: A cluster randomized, controlled, intervention study was performed in selected specialities (infectious diseases, pulmonary medicine and gastroenterology) at three emergency care hospitals in Western Norway. Interventions applied were audit with feedback and academic detailing. Implementation strategies included co-design of interventions with stakeholders in local intervention teams and prescribers setting local targets for change in antibiotic prescribing behaviour. Primary outcome measures were adherence to national guidelines, use of broad-spectrum antibiotics and change in locally defined targets of change in prescribing behaviour. Secondary outcome measures were length of stay, 30-day readmission, in-hospital- and 30-day mortality. Results: One thousand eight hundred two patients receiving antibiotic treatment were included. Adherence to guidelines had an absolute increase from 60 to 66% for all intervention wards (p = 0.04). Effects differed across specialties and pulmonary intervention wards achieved a 14% absolute increase in adherence (p = 0.003), while no change was observed for other specialties. A pulmonary ward targeting increased use of penicillin G 2 mill IU × 4 for pneumonia and COPD exacerbations had an intended increase of 30% for this prescribing behaviour (p

A cross-national comparison was performed on paediatric (0-19 years) antibiotic use in Hungary, Norway and Portugal to explore and compare the scale and pattern of paediatric antibiotic use in these three European countries. Ambulatory care systemic antibiotic use (ATC: J01) was retrieved from national databases for year 2014. The main outcome measure was number of antibacterial packages per child inhabitant per year (packages/child/year) and was further stratified by age groups. Paediatric antibiotic use peaked in Hungary with 1.3 packages/child/year, followed by Portugal (0.8) and Norway (0.3). This ranking was retained and was most prominent in the 5- to 9-year and 10- to 14-year age groups. The pattern of antibiotic use in different paediatric age groups varied also substantially between countries. Narrow-spectrum penicillins were much commonly used in Norway in all paediatric age subgroups in comparison with Hungary and Portugal. Newer, broad-spectrum cephalosporins and macrolides were widely prescribed for Hungarian and Portuguese children in all paediatric subgroups in contrast to Norway, while tetracyclines were commonly prescribed for Norwegian adolescents. The scale and pattern of paediatric antibiotic use in Hungary and Portugal were very different compared with Norway. The high antibiotic exposure and the high consumption of broad-spectrum penicillins begin in childhood in Hungary and Portugal which underpins the responsibility of paediatric GPs.

BackgroundUncomplicated urinary tract infections in women are common, and urine samples from these patients are not routinely cultured. Empirical treatment is based on knowledge of resistance patterns for common uropathogens.AimTo evaluate the bacteriological findings and resistance patterns in urine samples from women with uncomplicated urinary tract infections, and to assess the relationship between antimicrobial use and resistance patterns from 2000–2015 in Norway.MethodBacteriology and resistance patterns were compared in 184 urine cultures from 2001, 406 urine cultures from 2010–2011 and 259 urine cultures from 2013–2015. Antibiotic use data from 2000–2015 were obtained from national databases.ResultsEscherichia coli (E. coli) was the main bacterial agent in 80% of the cultures. Staphylococcus saprophyticus (Staph. saprophyticus) represented 6–17%. For E. coli, resistance to mecillinam showed some variation but remained below 9%. There was negligible resistance to nitrofurantoin. Resistance to trimethoprim seemed to stabilise over the last 5 years at around 20%. Amoxicillin resistance had some variations, but remained stable around 30%. There was a steady rise in total consumption of selected antibiotics commonly used to treat urinary tract infections for the period 2000–2015.ConclusionMecillinam and nitrofurantoin are both excellent first choices for empirical treatment of uncomplicated urinary tract infections. This study suggests that increasing resistance to trimethoprim challenges the rationale for its use as a first-line agent.

Overforbruk av antibiotika øker faren for resistensutvikling, dessuten kan antibiotika ha uheldige konsekvenser for individet både på kort og lang sikt. De tidlige leveår er en spesielt sårbar fase, det er da tarmens mikroflora blir etablert. Vi ønsket å studere antibiotikabruken hos barn i Norge.Vi hentet data fra Reseptregisteret for perioden 2004 – 16 for barn og ungdom18 år og undersøkte endring over tid i antall resepter på antibiotika hentet på apotek, delt i undergrupper av antibiotika, barnets alder, kjønn og bostedsfylke.Den samlede antibiotikabruken endret seg lite fra 2005 til 2012, men falt med 24 % fra 2012 til 2016. Med unntak av en økning i tetrasyklinbruken falt forskrivningen for alle typer og mest uttalt for makrolider. Barn under tre år fikk antibiotika vesentlig oftere enn eldre barn. I fylker med høyt forbruk var det 47 % flere utleveringer per barn enn i fylker med lavt forbruk. Bruken av makrolider og kefalosporiner var høy i enkelte fylker.Variasjonen over tid og mellom fylker tyder på at antibiotikaforskrivningen fortsatt kan reduseres. Informasjon til helsepersonell om rasjonell bruk har trolig begrenset forbruket, og informasjon til befolkningen om antibiotika kan være et viktig virkemiddel.

BACKGROUND One of the objectives in the action plan to reduce antimicrobial resistance in the health services in Norway is to reduce the use of broad-spectrum antibiotics in Norwegian hospitals. This study describes the use of certain broad-spectrum antibiotics mentioned in the action plan in Norwegian hospitals, and assesses prescribing practices in relation to the Norwegian guidelines for antibiotic use in hospitals.MATERIAL AND METHOD Data were analysed from a nationwide non-identifiable point prevalence survey in May 2016 where all systemic use of antibiotics was recorded.RESULTS Broad-spectrum antibiotics accounted for 33 % of all antibiotics prescribed. Altogether 84 % of all broad-spectrum antibiotics were prescribed as treatment, 8 % were for prophylactic use, and 8 % were classified as other/unknown. Lower respiratory tract infections were the most frequent indication for treatment with broad-spectrum antibiotics, involving 30 % of all broad-spectrum treatment.INTERPRETATION This point prevalence survey in Norwegian hospitals in spring 2016 indicates a possibility for reducing the use of broad-spectrum antibiotics in the treatment of lower respiratory tract infections and for prophylactic use. Reduction of healthcare-associated infections may also contribute.

SUMMARYMycoplasma pneumoniaeoutbreaks cause increased use of macrolides and tetracyclines. We aimed to investigate whether drug use data, in addition to laboratory data, could improve understanding of the spread ofM. pneumoniaeepidemics. Number of users ofMycoplasmaantibiotics (erythromycin, doxycycline, clarithromycin) per week and county of residence in an indicator age group (6–12 years) was retrieved from the Norwegian prescription database for the epidemic season 2011–2012 and compared to non-epidemic seasons. In 2011, increased use ofMycoplasmaantibiotics was first observed in September on the west coast of Norway. The Norwegian laboratory-based surveillance system showed the first increase in positive tests in August 2011 and an epidemic was announced on 25 October 2011. At that time the use ofMycoplasmaantibiotics had already exceeded three times the use in non-epidemic periods. Data for three counties from the regional microbiological laboratories showed that the increase in number of positive samples coincided in time with the increase in prescription data. Laboratory data cannot accurately determine the extent of an epidemic, and drug use data cannot identify the cause. Establishing a systematic interaction between the two monitoring systems will enhance surveillance and probably contribute to improved infection control and prudent antibiotic prescribing.

Objectives To investigate the prescribing of systemic drugs for the treatment of acne in adolescents in the period 2005-15. Methods The study population consisted of 14-24-year-old users of tetracyclines, isotretinoin or hormonal therapy retrieved from the Norwegian Prescription Database. The 1 year period prevalence was calculated as the number of patients who had redeemed at least one prescription during the year divided by the mean population. If the user had no prescriptions in the preceding 12 months he/she was defined as a new user. The incidence rate was defined by the number of new users during the year divided by the mean population. Results Increased prescribing rates for systemic tetracyclines and isotretinoin were observed in the period 2005-15, while a decreased prescribing rate for hormonal therapy was observed from 2007. The majority (75%) of the tetracycline prescriptions were prescribed by general practitioner specialists or physicians with no specialty/under training for a specialty. The average durations of treatment in men and women who only used tetracyclines were 3.3 and 2.8 months, respectively. For men and women that switched to isotretinoin, the average durations of treatment were 4.3 and 3.9 months. Conclusions The increased use of systemic tetracyclines in general, and the prolonged use of tetracyclines in patients who later switch to isotretinoin, raise the question of whether isotretinoin treatment should be considered at an earlier stage to reduce the use of systemic tetracyclines.

Objectives To describe the rates of pediatric antibiotic use across 6 countries on 3 continents. Study design Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries. Results A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population. Conclusions We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.

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 firstgeneration 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., peer-reviewed

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 b-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., peer-reviewed

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., peer-reviewed

Background: Data on 13 years (1997–2009) of outpatient penicillin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project and analysed in detail. Methods: For the period 1997–2009, data on outpatient use of systemic penicillins 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 penicillin use in 33 European countries, we distinguished between narrow-spectrum penicillins (NSP), broad-spectrum penicillins (BSP), penicillinaseresistant penicillins (PRP) and combinations with b-lactamase inhibitors (COP). Results: Total outpatient penicillin (ATC group J01C) use in 2009 varied by a factor of 3.8 between the countries with the highest (16.08 DID in France) and lowest (4.23 DID in the Russian Federation) use. COP represented 45.8%, BSP 40.7%, NSP 10.8% and PRP 2.6% of total European outpatient penicillin use. Total outpatient penicillin use significantly increased over time by 1.53 (SD 0.71) DID between 1997 and 2009. COP (mainly co-amoxiclav) increased by 2.17 (SD 0.40) DID, which was the result of its absolute increase as well as the observed shift from NSP and BSP towards COP. This increase exceeded 10% in 20 countries, where it coincided with a similar decrease in either BSP (15 countries) or NSP (5 countries). Conclusions: Penicillins represented the most widely used antibiotic subgroup in all 33 participating countries, albeit with considerable variation in their use patterns. For Europe, a continuous increase in overall penicillin use and of COP use was observed during the period 1997–2009., peer-reviewed

Antibacterial prescribing is driving antibiotic resistance. We aimed to analyse whether smoking habits are associated with susceptibility to be prescribed antibacterials in primary care and to examine whether patients' smoking habits influence physicians' choice of therapy.Information on smoking habits from health surveys in 1985-99 was related to use of antibacterials 5-25 years later by linkage to the Norwegian Prescription Database. The study population included 365 117 men and women, 40-45 years old. Individuals likely to have chronic obstructive airway disease were excluded. Relative risk (RR) of being dispensed antibacterials for systemic use was calculated for five levels of smoking intensity with never smokers as reference. Adjustments were made for age, education, marital status, household size, body mass index and residence (rural/urban).Fifty-six percent of the male and 69% of the female never smokers received at least one antibacterial prescription in the whole period, increasing to 68% and 82%, respectively, in heavy smokers (19 cigarettes/day) (adjusted RR 1.17 and 1.16). The percentage receiving at least one antibacterial prescription every year was 0.5% in male and 1.9% in female never smokers, increasing to 1.1% and 4.0%, respectively, in heavy smokers (adjusted RR 2.07 and 1.89). The proportion of antibacterial users who were prescribed broad-spectrum antibacterials increased with increasing cigarette consumption.Smoking habits influenced the usage of antibacterials years later with a dose-response relationship. Prescribers seem to acknowledge smoking as a risk factor for resistant bacteria since broad-spectrum antibacterials are more frequently prescribed to smokers than never smokers.

A cross-sectional descriptive study among Norwegian nursing homes was conducted in 2003 to examine pharmacoepidemiological characteristics of antibacterials in nursing homes and also to estimate their share of overall antibacterial use in Norway. Antibacterial data were collected for ATC group J01 antibacterials for systemic use, A07AA09 vancomycin and P01AB01 metronidazole in DDDs/y. The amount of drugs principally prescribed for urinary tract infections (UTI) were depicted and used as an indicator for the treatment frequency for UTI in the nursing homes. Prescription of antibacterials in the 133 nursing homes that delivered data varied - from 4 to 44 DDD/100 bed-d. The urinary prophylactic agent, methenamine, represented nearly half of DDDs used, mean 7.3 DDD/100 bed-d. Penicillins with extended spectrum (J01CA) were most frequently used, followed by trimethoprim and sulfonamides (J01E), mean 2.3 and 1.5 DDD/100 bed-d, respectively. On average, 49% of the therapeutic antibacterials were drugs used for UTI, range 12%-88%. In 2003, the nursing home setting purchased an estimated 6% of human antibacterial use in Norway. Nursing homes represent an important share of national human use of antibacterials. The large variation in antibacterial use between facilities underlines the need for increased focus on rational prescribing in nursing homes.

Background. Inappropriate use of drugs in patients with renal impairment (RI) may be harmful and may have deleterious effects. We aimed to investigate the use of renal risk drugs in such patients in general hospitals and to analyse the relationship to demographic factors, risk factors and occurrence of drug-related problems (DRPs). Methods. Patients admitted to departments of internal medicine and rheumatology in five general hospitals were included. We recorded demographic data, drugs used, drugs described to be a risk in RI (renal risk drugs), relevant medical history, laboratory data and clinical/pharmacological risk factors. We used levels of glomerular filtration rates, calculated by the Modification of Diet in Renal Disease formula to classify patients into five stages of renal function. DRPs were recorded and assessed in multidisciplinary hospital team discussions. Results. Of the 808 included patients, 293 (36%) had normal renal function (stage 1), 314 (39%) had mild RI (stage 2), 160 (20%) had moderate RI (stage 3), 35 (4%) had severe RI (stage 4) and six (0.7%) had kidney failure (stage 5). Mean number of drugs used per patient in patients with RI (stages 3, 4 and 5) and patients evaluated to have adequate renal function relative to drug therapy (stages 1 and 2): on admission 6.2 vs 4.1; started in hospital 4.3 vs 3.9 and total number of renal risk drugs 6.1 vs 4.5. All but six patients with RI stages 3, 4 and 5 used two or more renal risk drugs. 124 (62%) of the patients with RI stages 3, 4 and 5 had DRPs linked to the renal risk drugs, and 26% of the renal risk drugs were associated with DRPs. The most common drug classes associated with DRPs were antibacterials, antithrombotic agents, angiotensin-converting enzyme (ACE) inhibitors, opioids and non-steroidal anti-inflammatory drugs (NSAIDs). Conclusions. Among patients admitted to general hospitals, a considerable proportion had renal impairment. In patients with reduced renal function, renal risk drugs were widely used and often in combination. DRPs were frequently associated with the use of renal risk drugs.

Residents in nursing homes have a heightened risk of developing infections that should be treated with antibiotics. Inappropriate use of antibiotics may generate drug-related problems and increase resistance. In this study, we describe the use of antibiotics in nursing homes on the basis of prevalence surveys and drug sales statistics.Five nursing homes in Oslo participated in two one-day surveys in 2009. All use of systemic antibiotics was registered. The data collection was undertaken according to a protocol developed by the European Surveillance of Antimicrobial Consumption (ESAC) Network and was part of a European study. The nursing homes' drug sales statistics for systemic antibiotics during 2009, distributed by the number of bed days for each nursing home, were estimated. Information on indications for each antibiotic from the prevalence surveys was collated with sales data to achieve an estimate of how the purchased antibiotics were used.The prevalence surveys showed that more than 8% of the residents received antibiotics. Prophylactic treatment accounted for 33% of the prescriptions. A prevalence of antibiotic use of 10% was estimated from the drug sales statistics. Urinary tract infection was the most frequently registered indication. Pivmecillinam and methenamine were most frequently prescribed and most frequently purchased. Most courses of treatment were prescribed in accordance with the national guidelines for antibiotic use.The results from the drug sales statistics concurred well with the prevalence surveys, and the methods can thus be relevant for purposes of monitoring the use of antibiotics.

The use of some drugs is significantly higher among 19-year-olds than among young people in adjacent age groups. We aimed to investigate the use of prescribed drugs in young people aged 17, 19 and 21 in order to identify trends in patterns of consumption.Data were collected from the Norwegian Prescription Database 2005-2011. Prevalence (proportion of drug users) by gender, age (17, 19, 21 years), prescription date and county of residence are presented. Only drugs with more than 100 users per year in each age group (17, 19, 21) were included.Use of some antibiotics and drugs for cough and eye infections was higher in 19-year-olds than in 17 and 21-year-olds. Moreover, the seasonal variation in the use of these drugs was different for 19-year-olds, with a marked peak in May and a lower winter peak than in the general population. The day-to-day prevalence showed a peak in the prescription rate just after the Norwegian Independence Day on 17 May. Girls had a higher consumption than boys. Considerable county variation was observed for 19-year-olds in the month of May.The increased incidence of antibiotics, cough medicine and drugs used for eye infections in 19-year-olds compared with other young people can be explained by increased risk behaviour in the weeks before 17 May linked to graduation from Norwegian upper secondary schools. The findings give reason to warn against the present form of graduation celebrations which involve little sleep and all-night partying in close contact with others. They also give urgency to the question of whether to move the final examination period at upper secondary level away from the weeks immediately following 17 May.

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., peer-reviewed

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-, intermediateand 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 longacting 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., peer-reviewed

Background Urinary tract infections (UTIs, including upper and lower symptomatic) are the most common infections in nursing homes and prevention may reduce patient suffering, antibiotic use and resistance. The spectre of agents used in preventing UTIs in nursing homes is scarcely documented and the aim of this study was to explore which agents are prescribed for this purpose. Methods We conducted a one-day, point-prevalence study in 44 Norwegian nursing homes during April-May 2006. Nursing home residents prescribed any agent for UTI prophylaxis were included. Information recorded was type of agent and dose, patient age and gender, together with nursing home characteristics. Appropriateness of prophylactic prescribing was evaluated with references to evidence in the literature and current national guidelines. Results The study included 1473 residents. 18% (n = 269) of the residents had at least one agent recorded as prophylaxis of UTI, varying between 0-50% among the nursing homes. Methenamine was used by 48% of residents prescribed prophylaxis, vitamin C by 32%, and cranberry products by 10%. Estrogens were used by 30% but only one third was for vaginal administration. Trimethoprim and nitrofurantoin were used as prophylaxis by 5% and 4%, respectively. Conclusions The agents frequently prescribed to prevent UTIs in Norwegian nursing homes lack documented efficacy including methenamine and vitamin C. Recommended agents like trimethoprim, nitrofurantoin and vaginal estrogens are infrequently used. We conclude that prescribing of prophylactic agents for UTIs in nursing homes is not evidence-based.

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), thirdgeneration (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., peer-reviewed

To describe the use of antibacterials among nursing home residents in Norway according to diagnosis, therapy choice, doses and expected duration of treatment.A one-day point-prevalence study was carried out in 44 Norwegian nursing homes, spring 2006. Use of systemic antibacterials was recorded by indication, antibiotic name, dose and expected length of treatment.Of the 1473 nursing home residents, 224 (15%) were prescribed antibiotics. 149 (10%) were given antibiotics as prophylaxis, while 85 residents (6%) were treated with an antibiotic for an infection. 10 residents received both prophylaxis and treatment simultaneously. Antibiotics for treatment were in 66% of the cases for urinary tract infections (UTI) and in 20% for respiratory tract infections (RTI) with pivmecillinam and phenoxymethylpenicillin most frequently used, respectively.Antibiotics are often used in nursing homes, both as treatment and prophylaxis. The most common infections treated with antibiotics were UTIs, followed by RTIs. Choice of antibacterial, dosage and duration of treatment were in accordance with recommendations in guidelines.

Antibiotic use is a major cause of development and spread of resistant bacteria. Sensible antibiotic use should aim at decreasing total antibiotic use and replace broad-spectrum antibiotics with narrow-spectrum ones; pharmaceutical drug statistics are vital in this context.Data were collected from the wholesaler-based drug statistics (for the period 1974 - 2007) and from the Norwegian Prescription Database (2006). The ATC/DDD methodology is used in the drug statistics. Data are presented as number of users (prevalence), number of dispensed prescriptions, defined daily doses (DDD per 1 000 inhabitants per day) and in Norwegian kroner.Longitudinal trends show a relatively stable and high use of narrow-spectrum antibiotics, even though broad-spectrum antibiotic use is slightly increasing. Antibiotic use varies largely by age and sex. The highest prevalences are seen among small children (0 - 5 years), women in their twenties and in people over 70 years. Over 30 % of people in these groups receive at least one antibiotic per year. The therapy profile differs between the types of prescription issued. Neither the wholesaler statistics nor the Prescription Database contains information on diagnosis, making it difficult to monitor whether the Norwegian primary health service has a rational antibiotic therapy.

Purpose To investigate the use of antibiotics in hospitals, to explore drug-related problems (DRPs) linked to antibiotics and to introduce a novel way of expressing the risks accompanying use of various antibiotics. Methods Patients from internal medicine departments in four Norwegian hospitals were prospectively included in 2002. Demographics, drugs used, medical history, laboratory data and clinical/pharmacological risk factors were recorded. DRPs were identified by clinical pharmacists and assessed in multidisciplinary hospital teams. A new term, the drug risk ratio, was established and defined as the number of times the antibiotic was associated with DRPs in relation to the number of times it was used. Results Out of the 668 patients included, 283 patients (42%) used antibiotics (AB users). AB users were older (76.2 vs. 73.9), used more drugs on admission (5.1 vs. 4.4) and had more DRPs (3.0 vs. 2.2) than non-users. The DRP categories no further need for drug, non-optimal drug and non-optimal dose were most frequently observed. The drug risk ratio, calculated for 12 antibiotic groups, was highest for aminoglycosides (0.77), β-lactamase-resistant penicillins (0.56), macrolides (0.54) and quinolones (0.48) and lowest for first- and third-generation cephalosporins, 0.17 and 0.13, respectively. Conclusions Nearly half of the hospitalised patients were prescribed antibiotics and antibiotic associated DRPs occurred frequently. The drug risk ratio for the different antibiotic groups varied with a factor of six from the lowest to the highest. A high drug risk ratio would alert of antibiotics which require heightened awareness when going to be used in clinical practice. Copyright © 2008 John Wiley & Sons, Ltd.

Purpose The objective of this study was to evaluate the level of use and therapy profile of antibacterial agents in hospitals. Further to explore whether type, size or geographical situation influenced antibacterial agents used. Methods Antibacterial use during 1998–1999, in 13 hospitals, including emergency, referral and university hospitals from all health regions in Norway, were collected retrospectively. Drugs were classified according to the ATC classification and the ATC/DDD index 2001 and standardised bed-days were used. Results Total annual use varied significantly between hospitals (p

To describe the methodological problems in collecting retrospectively comparable data on drug use and to compare the use of antibacterials in some European countries.A spreadsheet was distributed in 2000 through the European Drug Utilisation Research Group (EuroDURG) network, requesting 1994-1999 data on use of antibacterials for systemic use (ATC group J01), from ambulatory, hospital, or total care, aggregated at ATC 4th level, and presented in defined daily doses per 1000 inhabitants per day (in the 1999 ATC/DDD version or specified other version).The network was able to provide national utilization data for two or more years in the requested period from 16 countries (4 only from primary care, 3 both from primary care and total use, and 9 only total use data). The main methodological problems identified were: use of divergent ATC/DDD versions, divergent assignment of DDDs for combination products and the use of unofficial or national DDDs. It was possible to correct for the different ATC/DDD versions to some extent, except for the cephalosporin group (not included in the analysis), as the collection of data at the ATC 4th level precluded recalculation of DDDs. In the seven countries with primary care data the total J01 antibacterials use varied by a factor of 2.5 (Belgium 23.4 and The Netherlands 9.5 DDDs per 1000inhabitants per day). The use of J01A tetracyclines varied fourfold, and the use of J01C penicillins and J01F macrolides and lincosamides approximately threefold. Significant reduction over time was seen in J01A and an increase in J01F.In the scientific and regulatory community it is still difficult to perform a valid and comprehensive cross-national collection of utilization data on antibacterials. White spots on the European map persist for ambulatory care data, and data are missing for the hospital sector in most countries. For a thorough explanation of the considerable intercountry variability (especially in antibacterial subgroups and time trends analysis) a sustained and concerted effort is necessary to implement a validation process of the ATC/DDD use in the various countries and to adopt a common methodological approach to the collection of utilization data at the substance level (ATC 5th level).