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Antimicrobial resistance must be recognised as a global societal priority - even in the face of the worldwide challenge of the COVID-19 pandemic. COVID-19 has illustrated the vulnerability of our healthcare systems in co-managing multiple infectious disease threats as resources for monitoring and detecting, and conducting research on antimicrobial resistance have been compromised during the pandemic. The increased awareness of the importance of infectious diseases, clinical microbiology and infection control and lessons learnt during the COVID-19 pandemic should be exploited to ensure that emergence of future infectious disease threats, including those related to AMR, are minimised. Harnessing the public understanding of the relevance of infectious diseases towards the long-term pandemic of AMR could have major implications for promoting good practices about the control of AMR transmission.

Background Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. Methods An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. Results We propose a theoretical framework in which consideration of the intervention ration

[Background] Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations., [Methods] An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members., [Results] We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design., [Conclusions] Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.

Appropriate antibiotic use for urinary tract infections (UTIs) is important in order to provide effective and safe treatment while minimising the risk of antimicrobial resistance development. This survey was carried out to compare existing national guidelines for UTIs in Europe. Experts in 37 European countries were asked to participate. An electronic questionnaire was used to obtain information on treatment recommendations, factors considered important when setting guidelines, acceptable resistance rates for empirical therapy, evidence grading, and existing resistance surveillance for uropathogens. Treatment guidelines and antimicrobial susceptibility data were collected. In total, 22 experts (59%) responded to the survey. National guidelines were missing in four countries and data were incomplete in three cases. Fifteen national guidelines published between 2004 and 2017 were included in the analysis. Great variability was found between guidelines in the selection of antibiotics, dosing regimens and treatment duration. For example, 10 different antibiotics were recommended as first-line therapy for uncomplicated cystitis. National surveillance data on antimicrobial susceptibility of uropathogens were available in 13 of 15 countries. Resistance epidemiology could not explain the observed differences between guidelines, and comparison of resistance rates was hampered by variations in methods. This study revealed major differences in treatment guidelines for UTIs within Europe, indicating that there are opportunities for improvement. More clinical research and a more systematic and stratified approach to resistance surveillance, including also antibiotics that are currently not available in all countries, is needed.

Contains fulltext : 193452.pdf (Publisher’s version ) (Open Access), Background: This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods: A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results: The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions: This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use.

Contains fulltext : 193591.pdf (Publisher’s version ) (Open Access), Background: Quantifying antibiotic use is an essential element of antibiotic stewardship since it allows comparison between different settings and time windows, and measurement of the impact of interventions. However, quantity metrics (QMs) and methods have not been standardized. Objectives: To propose a set of QMs for antibiotic use in inpatients (IQMs) that are accepted globally by professionals in a range of disciplines. The study was conducted within the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project. Methods: A systematic literature review using MEDLINE identified articles on measuring inpatient antibiotic use, published up to 29 January 2015. A consensually selected list of national and international web sites was screened for additional IQMs. IQMs were classified according to the type of numerator used and presented to a multidisciplinary panel of stakeholders. A RAND-modified Delphi consensus procedure, which consisted of two online questionnaires and a face-to-face meeting, was performed. Results: The systematic literature review and web site search identified 168 eligible articles from which an initial list of 20 IQMs, composed of 20 different numerators and associated denominators was developed. The consensus procedure resulted in a final set of 12 IQMs. Among this final set, DDDs per 100(0) patient-days and days of therapy per patient-days were most frequently found in the review. The panel recommended that antibiotic use should be expressed in at least two metrics simultaneously. Conclusions: Our consensus procedure identified a set of IQMs that we propose as an evidence-based global standard.

Contains fulltext : 193497.pdf (Publisher’s version ) (Open Access), Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximum and minimum values of a given measure [maximum:minimum ratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low- to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). The most frequent measure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variation was also identified in other measures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low- and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization.

Item does not contain fulltext, Objectives: Quality indicators (QIs) assessing the appropriateness of antibiotic use are essential to identify targets for improvement and guide antibiotic stewardship interventions. The aim of this study was to develop a set of QIs for the outpatient setting from a global perspective. Methods: A systematic literature review was performed by searching MEDLINE and relevant web sites in order to retrieve a list of QIs. These indicators were extracted from published trials, guidelines, literature reviews or consensus procedures. This evidence-based set of QIs was evaluated by a multidisciplinary, international group of stakeholders using a RAND-modified Delphi procedure, using two online questionnaires and a face-to-face meeting between them. Stakeholders appraised the QIs' relevance using a nine-point Likert scale. This work is part of the DRIVE-AB project. Results: The systematic literature review identified 43 unique QIs, from 54 studies and seven web sites. Twenty-five stakeholders from 14 countries participated in the consensus procedure. Ultimately, 32 QIs were retained, with a high level of agreement. The set of QIs included structure, process and outcome indicators, targeting both high- and middle- to low-income settings. Most indicators focused on general practice, addressing the common indications for antibiotic use in the community (particularly urinary and respiratory tract infections), and the organization of healthcare facilities. Twelve indicators specifically addressed outpatient parenteral antimicrobial therapy (OPAT). Conclusions: We identified a set of 32 outpatient QIs to measure the appropriateness of antibiotic use. These QIs can be used to identify targets for improvement and to evaluate the effects of antibiotic stewardship interventions.

Contains fulltext : 193592.pdf (Publisher’s version ) (Open Access), Background: The international Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving Reinvestment in Research and Development and Responsible Antibiotic Use) aims to develop a global definition of 'responsible' antibiotic use. Objectives: To identify consensually validated quantity metrics for antibiotic use in the outpatient setting. Methods: First, outpatient quantity metrics (OQMs) were identified by a systematic search of literature and web sites published until 12 December 2014. Identified OQMs were evaluated by a multidisciplinary, international stakeholder panel using a RAND-modified Delphi procedure. Two online questionnaires and a face-to-face meeting between them were conducted to assess OQM relevance for measuring the quantity of antibiotic use on a nine-point Likert scale, to add comments or to propose new metrics. Results: A total of 597 articles were screened, 177 studies met criteria for full-text screening and 138 were finally included. Twenty different OQMs were identified and appraised by 23 stakeholders. During the first survey, 14 OQMs were excluded and 6 qualified for discussion. During the face-to-face meeting, 10 stakeholders retained five OQMs and suggestions were made considering context and combination of metrics. The final set of metrics included defined daily doses, treatments/courses and prescriptions per defined population, treatments/courses and prescriptions per defined number of physician contacts and seasonal variation of total antibiotic use. Conclusions: A small set of consensually validated metrics to assess the quantity of antibiotic use in the outpatient setting was obtained, enabling (inter)national comparisons. The OQMs will help build a global conceptual framework for responsible antibiotic use.

Zusammenfasung: Bei der infektiösen Spondylitis handelt es sich in der Regel um eine Osteomyelitis von 2benachbarten Wirbelkörpern unter Beteiligung der Zwischenwirbelscheibe (Spondylodiszitis). Am häufigsten ist die Lendenwirbelsäule betroffen, gefolgt von der Brustwirbelsäule. Die Symptome der infektiösen Spondylitis sind unspezifisch, was nicht selten zu einer Verzögerung von einigen Wochen bis zur Diagnosestellung führt. Die infektiöse Spondylitis kann durch eine Vielzahl von Erregern bedingt sein, die überwiegend auf hämatogenem Weg die Wirbelsäule erreichen. Der häufigste Erreger ist Staphyloccocus aureus. Die Spondylitis ist zudem die häufigste skelettale Manifestation der Tuberkulose. Wie bei anderen Formen der Osteomyelitis ist die Kenntnis des Erregers für die Wahl einer adäquaten Therapie entscheidend, weshalb eine mikrobiologische Diagnose auf jeden Fall angestrebt werden sollte. Die Mehrheit der Fälle kann konservativ mit antibiotischer Therapie geheilt werden