Rebound in community antibiotic consumption after the observed decrease during the COVID-19 pandemic, EU/EEA, 2022.

We observed a rebound in consumption of antibacterials for systemic use (ATC J01) in the community sector in the European Union/European Economic Area during 2021 and 2022, after an observed decrease between 2019 and 2020. The rates in 2022 returned to pre-COVID-19-pandemic levels and were exceeded in 13 countries. Although these patterns could partly be a result of changes in disease transmission during the study period, it could also reflect a lost opportunity to strengthen and reinforce prudent antibiotic use.

Antimicrobial Prescribing Preparedness of Croatian Medical Students-Did It Change between 2015 and 2019?

BACKGROUND: Antimicrobials are some of the most prescribed drugs by junior doctors, but studies suggest most medical graduates feel unprepared for their future prescribing tasks. The aim of the present study was to compare the self-reported preparedness to prudently prescribe antimicrobials of final-year medical students in Croatia in 2015 and 2019. METHODS: The same self-reported web-based survey on the preparedness to prescribe antibiotics was used in both 2015 and 2019. All final-year students at all four medical schools in Croatia (Osijek, Rijeka, Split, and Zagreb) were invited to participate in both 2015 and 2019. Preparedness scores were divided into "topic preparedness scores" and "global preparedness scores". Topic preparedness scores represented the percentage of students at a medical school who felt sufficiently prepared for each topic. They were first established at a medical school level and then at the national level. Global preparedness scores were determined for each student separately and then calculated at the medical school and national levels. RESULTS: The country's global preparedness score, representing the average proportion of topics in which students felt sufficiently prepared, was slightly higher in 2015 compared with the 2019 results (62.7% vs. 56.5%; p = 0.191). Croatian students reported higher preparedness in 2015 than in 2019 for 25 out of 27 topics included in the survey. The majority of students reported a need for more education on antibiotic use both in 2015 and 2019 (78.0% vs. 83.0%; p = 0.199). CONCLUSIONS: Despite increasing antimicrobial stewardship activities in various healthcare settings, medical students who are about to start prescribing antibiotics on their own do not feel sufficiently prepared to do so. Antimicrobial stewardship programs should be designed to incorporate undergraduate medical student education, for instance, as a specific, mandatory course or integrated into other courses, such as clinical pharmacology.

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy.

Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.

An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.

Trends in the hospital-sector consumption of the WHO AWaRe Reserve group antibiotics in EU/EEA countries and the United Kingdom, 2010 to 2018.

BackgroundIn 2019, the World Health Organization published the 21st Model list of Essential Medicines and updated the Access, Watch Reserve (AWaRe) antibiotics classification to improve metrics and indicators for antibiotic stewardship activities. Reserve antibiotics are regarded as last-resort treatment options.AimWe investigated hospital-sector consumption quantities and trends of Reserve group antibiotics in European Union/European Economic Area countries and the United Kingdom (EU/EEA/UK).MethodsHospital-sector antimicrobial consumption data for 2010-2018 were obtained from the European Centre for Disease Prevention and Control. Antibacterials' consumption for systemic use (Anatomical Therapeutic Chemical classification (ATC) group J01) were included in the analysis and expressed as defined daily doses (DDD) per 1,000 inhabitants per day. We defined reserve antibiotics as per AWaRe classification and applied linear regression to analyse trends in consumption of reserve antibiotics throughout the study period.ResultsEU/EEA/UK average hospital-sector reserve-antibiotic consumption increased from 0.017 to 0.050 DDD per 1,000 inhabitants per day over the study period (p = 0.002). This significant increase concerned 15 countries. In 2018, four antibiotics (tigecycline, colistin, linezolid and daptomycin) constituted 91% of the consumption. Both absolute and relative (% of total hospital sector) consumption of reserve antibiotics varied considerably (up to 42-fold) between countries (from 0.004 to 0.155 DDD per 1,000 inhabitants per day and from 0.2% to 9.3%, respectively).ConclusionAn increasing trend in reserve antibiotic consumption was found in Europe. The substantial variation between countries may reflect the burden of infection with multidrug-resistant bacteria. Our results could guide national actions or optimisation of reserve antibiotic use.

Impact of the COVID-19 pandemic on hospital antimicrobial consumption in Croatia.

OBJECTIVES: The aim of the study was to assess the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in the hospital sector in Croatia by analysing data reported to the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) between 2016 and 2020. METHODS: AMC was measured as the number of DDDs/1000 inhabitants/day and as the number of DDDs/100 bed days. To assess trends, linear regression was performed. To assess the impact of the pandemic on AMC, the compound annual growth rate was calculated for the years preceding the pandemic based on which AMC for 2020 was forecasted and compared with the actual consumption. RESULTS: While hospital AMC expressed as DDDs/1000 inhabitants/day between 2019 and 2020 decreased by 17%, when expressed as DDDs/100 bed days, an 8% increase was observed. Hospital consumption of antibacterials for systemic use in the 5 year period did not significantly change when expressed as DDDs/1000 inhabitants/day, while it statistically significantly increased when expressed as DDDs/100 bed days. An increasing trend in consumption of broad-spectrum antimicrobials was found. CONCLUSIONS: During the pandemic there was an increase in hospital AMC with a shift towards broad-spectrum antimicrobials requiring further in-depth qualitative analysis based on patient-level data. Contrasting results obtained using different denominators indicate that the metric DDDs/1000 inhabitants/day is not sensitive enough to evaluate hospital AMC. When assessing hospital AMC, the population under surveillance should be relevant for healthcare context. Antimicrobial stewardship remains one of the most important strategies to tackle antimicrobial resistance and antimicrobial surveillance methods must be as sensitive as possible.

Importance of antimicrobial stewardship in solid organ transplant recipients: An ESCMID perspective.

BACKGROUND: In the last decades, solid organ transplantation (SOT) has emerged as an important method in the management of chronic kidney, liver, heart, and lung failure. Antimicrobial use has led to a significant reduction of morbidity and mortality due to infectious complications among patients with SOT; however, it can lead to adverse events and drive the development of antimicrobial resistance; thus, antimicrobial stewardship is of extreme importance. Even though there are ongoing efforts of transplant societies to implement principles of antimicrobial stewardship in everyday practice in SOT, there is still a lack of guidelines in this patient population. AIM: The aim of this study was to review the status of antimicrobial stewardship in patients with SOT, highlight its importance from the perspective of an ongoing vivid dialogue among ESCMID experts in the field of antimicrobial stewardship, and depict opportunities for future study in the field. REVIEW: Antimicrobial stewardship programs are important in order to allow appropriate initiation and termination of antimicrobials in SOT recipients, and also aid in the most appropriate dosing and choosing of the route of administration of antimicrobials. Application of already known antimicrobial stewardship principles and application of currently used biomarkers and newly developed molecular rapid diagnostic testing tools can aid to the rationalization of antimicrobial prescribing and to a more targeted treatment of infections. Finally, physicians caring for SOT recipients should be actively involved in antimicrobial stewardship in order to assure optimization of antimicrobial prescribing and become familiar with the principles of antimicrobial stewardship.

Antimicrobial Use in Hospitalised Patients with COVID-19: An International Multicentre Point-Prevalence Study.

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9-85.6%) on the day of the study. Differences between hospitals were statistically significant (χ2 (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4-100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the "Watch" group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.

Indications for medical antibiotic prophylaxis and potential targets for antimicrobial stewardship intervention: a narrative review.

BACKGROUND: Most of the antimicrobial stewardship (AMS) literature has focused on antimicrobial consumption for the treatment of infections, for the prophylaxis of surgical site infection and for the prevention of endocarditis. The role of AMS for medical antibiotic prophylaxis (AP) has not been adequately addressed. AIMS: To identify targets for AMS interventions for medical AP in adult patients. SOURCES: Targeted searches were conducted in PubMed. CONTENT: The various indications for medical AP and relevant evidence from practice guidelines are outlined. The following were identified as potential targets for AMS interventions: (a) addressing under-utilization of antibiotic-sparing strategies (e.g. for recurrent urinary tract infections, recurrent soft-tissue infections, recurrent exacerbations associated with bronchiectasis or chronic obstructive pulmonary disease), (b) reducing unnecessary AP beyond recommended indications (e.g. for acute pancreatitis, bite wounds, or urinary catheter manipulations), (c) reducing the use of AP with a broader spectrum than necessary, (d) reducing the use of AP for longer than the recommended duration (e.g. AP for prevention of osteomyelitis in open fractures or AP in high-risk neutropenia), (e) evaluating the role of antibiotic cycling to prevent the emergence of resistance during prolonged AP (e.g. in recurrent urinary tract infections or prophylaxis for spontaneous bacterial peritonitis), and (f) addressing research gaps regarding appropriate indications or antibiotic regimens for medical prophylaxis. IMPLICATIONS: This review summarizes current trends in AP and proposes targets for AMS interventions.

Decrease in community antibiotic consumption during the COVID-19 pandemic, EU/EEA, 2020.

We present a European Union/European Economic Area-wide overview of the changes in consumption of antibacterials for systemic use (ATC J01) in the community between 2019 and 2020 as reported to the European Surveillance of Antimicrobial Consumption Network. Overall antibiotic consumption decreased by 18.3% between 2019 and 2020, the largest annual decrease in the network's two-decade history. We observed a strong association between the level of community antibiotic consumption in 2019 and the size of the decrease between 2019 and 2020.

Corrigendum: Variations in the Consumption of Antimicrobial Medicines in the European Region, 2014-2018: Findings and Implications From ESAC-Net and WHO Europe.

[This corrects the article DOI: 10.3389/fphar.2021.639207.].

Variations in the Consumption of Antimicrobial Medicines in the European Region, 2014-2018: Findings and Implications from ESAC-Net and WHO Europe.

Background: Surveillance of antimicrobial consumption (AMC) is important to address inappropriate use. AMC data for countries in the European Union (EU) and European Economic Area (EEA) and Eastern European and Central Asian countries were compared to provide future guidance. Methods: Analyses of 2014-2018 data from 30 EU/EEA countries of the European Surveillance of Antibiotic Consumption network (ESAC-Net) and 15 countries of the WHO Regional Office for Europe (WHO Europe) AMC Network were conducted using the Anatomical Therapeutic Chemical (ATC) classification and Defined Daily Dose (DDD) methodology. Total consumption (DDD per 1000 inhabitants per day) of antibacterials for systemic use (ATC group J01), relative use (percentages), trends over time, alignment with the WHO Access, Watch, Reserve (AWaRe) classification, concordance with the WHO global indicator (60% of total consumption should be Access agents), and composition of the drug utilization 75% (DU75%) were calculated. Findings: In 2018, total consumption of antibacterials for systemic use (ATC J01) ranged from 8.9 to 34.1 DDD per 1000 inhabitants per day (population-weighted mean for ESAC-Net 20.0, WHO Europe AMC Network 19.6, ESAC-Net Study Group, and WHO Europe AMC Network Study Group). ESAC-Net countries consumed more penicillins (J01C; 8.7 versus 6.3 DDD per 1000 inhabitants per day), more tetracyclines (J01A; 2.2 versus 1.2), less cephalosporins (J01D; 2.3 versus 3.8) and less quinolones (J01M; 1.7 versus 3.4) than WHO Europe AMC Network countries. Between 2014 and 2018, there were statistically significant reductions in total consumption in eight ESAC-Net countries. In 2018, the relative population-weighted mean consumption of Access agents was 57.9% for ESAC-Net and 47.4% for the WHO Europe AMC Network. For each year during 2014-2018, 14 ESAC-Net and one WHO Europe AMC Network countries met the WHO global monitoring target of 60% of total consumption being Access agents. DU75% analyses showed differences in the choices of agents in the two networks. Interpretation: Although total consumption of antibacterials for systemic use was similar in the two networks, the composition of agents varied substantially. The greater consumption of Watch group agents in WHO Europe AMC Network countries suggests opportunities for improved prescribing. Significant decreases in consumption in several ESAC-Net countries illustrate the value of sustained actions to address antimicrobial resistance.

Repeated point prevalence survey on antimicrobial use in a university hospital: what have we learned?

OBJECTIVES: To evaluate the quality of antimicrobial prescribing, at the Department of Internal Medicine University Hospital Centre Rijeka, by assessing the necessity for antimicrobial treatment and adherence to the local Guidelines for hospital antimicrobial drug use and to compare results with previously conducted point prevalence surveys (PPSs). METHODS: A PPS was conducted on 7th May 2019. Demographic and relevant clinical data of each patient receiving systemic antimicrobials were recorded anonymously in a patient-specific form. The appropriateness of antibiotic prescribing was assessed as adherence to the fourth edition of the Guidelines for hospital antimicrobial drug use. KEY FINDINGS: One hundred and seventy-one patients were hospitalized at the Department of Internal Medicine; 37.4% (n = 64) of patients received 102 prescriptions for an antimicrobial drug [62.8% (n = 64) of prescriptions were for intravenous and 37.2% (n = 38) for oral administration]. Of these, 52 were treated for an identified existing infection, 5 were treated for an unknown indication and 7 received antibiotics as prophylaxis. The necessity for antimicrobial treatment was unclear in 19.3% (n = 11) of cases. The antimicrobials were prescribed according to the Guidelines in 65.4% (n = 34) of cases. Adherence to the Guidelines when treating lower respiratory tract infections, urinary tract infections and gastrointestinal tract infections was 47.8%, 55.6% and 92.9%, respectively. CONCLUSIONS: Our study revealed antibiotic prescription frequency similar to EU/EEA average and high percentage of unjustified antimicrobial treatment introduction. The rate of adherence to the Guidelines was lower than those observed in western countries. The results lay a basis for tailoring antimicrobial stewardship programs/activities.

Does Fluoroquinolones and Third-Generation Cephalosporins Restriction Reverse Extended-Spectrum ß-Lactamases Klebsiella pneumoniae Resistance Rates?

Aim: To decrease the incidence and resistance rates of extended-spectrum ß-lactamases (ESBL) Klebsiella pneumoniae (KP) by restriction of the use of third-generation cephalosporins (3GCs) and fluoroquinolones. Methods: Consumption of 3GCs, fluoroquinolones, and carbapenems in association with ertapenem and fluoroquinolone-resistant KP isolates, were analyzed in 21 months by autoregressive integrated moving average models. A follow-up analysis was performed 5 years later. Results: Consumption of 3GCs decreased significantly during the postintervention period. Their restriction was associated with a decrease in ertapenem-resistant KP isolates by 17.5%. Fluoroquinolone, 3GCs, and carbapenem use did not significantly predict the percentage of ertapenem-resistant KP isolates. Fluoroquinolone, but not cephalosporin use, significantly predicted the percentage of fluoroquinolone-resistant isolates, with an increase of 1 defined daily dose (DDD) of fluoroquinolone/100 occupied bed-days (OBDs) corresponding to a 0.32% increase of fluoroquinolone-resistant isolates (p = 0.008). A decrease of 1 DDD of carbapenem/100 OBD was associated with a 16.94% increase of fluoroquinolone-resistant isolates (p = 0.007). Five years later, the consumption of all three antimicrobial classes increased significantly compared with the 2011-2013 period, whereas ertapenem-resistant KP rates significantly decreased. Conclusion: This study may bring a valuable contribution to the understanding of the intricate association between antibiotic consumption and bacterial resistance. Reporting a spectrum of different results could present a useful basis for more profound research of various interventions' effects.

An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams.

BACKGROUND: Healthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training. OBJECTIVES: Little is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians' awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation. METHODS: AMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September-October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme. RESULTS: A total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes. CONCLUSIONS: The development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.

HALF A CENTURY OF DEBT: SIME VLAHOVIC (1932­1977) AND IMMUNOLOGICAL PREPARATION OF THE FIRST KIDNEY TRANSPLANTATION IN CROATIA / POLUSTOLJETNI DUG: SIME VLAHOVIC (1932. ­ 1977.) I IMUNOLOSKA PRIPREMA PRVE TRANSPLANTACIJE BUBREGA U HRVATSKOJ

Despite some earlier significant discoveries and widespread vaccination successful practices, the history of understanding immunological mechanisms is actually relatively short and associated only with the second half of the 20th century when, among other things, the laws of activation of these mechanisms are crucial for transplantation medicine. Among the first experts in Croatia who turned to these topics was Sime Vlahovic. Born in Split, he graduated and received his PhD in Zagreb. He worked on the problems of transplant immunology from 1963 to 1965 at the eminent centers in the United States. He was the head of the Rijeka Department of Physiology at the Faculty of Medicine from 1965 to 1977, since 1976 as a full professor. He was the winner of the Ruder Boskovic award and many others, but his crucial contribution to the medical heritage of Rijeka and Croatia is certainly less known. Based on family archives and memories, this work will attempt to at least partially correct that gap. Thanks to the immunological preparation of Sime Vlahovic, as well as, of course, a large team led by surgeon Vinko Franciskovic, in January 1971, the first kidney transplant was performed in Croatia from a living relative (mother to son), a year later from a cadaver, and in the decades following that, an experimental liver and pancreas transplant program has been developed in Rijeka. Today, we can only speculate about the intriguing directions of the development of the Rijeka Transplant and Immunology School, which would have been led by Sime Vlahovic, had he not passed away at the age of less than 45.

Impact of guidelines on antibiotic prescribing approach in primary care-a 10-year study.

BACKGROUND: Publication and implementation of clinical guidelines is an important educational measure that considerably helps physicians in choosing appropriate antimicrobial drug. OBJECTIVES: To evaluate long-term changes in antimicrobial prescribing habits before and after publishing the guidelines and to determine the factors that influence physician's decision to prescribe an antimicrobial drug. METHODS: The study among general practitioners in Primorsko-Goranska County was conducted in three periods (January 2009, January 2011 and April 2019) by using a structured questionnaire that included general data about the physician, questions about their habits in antibiotic prescribing, criteria that influenced decision to prescribe antibiotics and antimicrobial agent(s) preferred in treating common infections. RESULTS: Concomitant chronic (non-pulmonary) disease was the most important factor influencing decision to prescribe an antimicrobial drug. Over 88% of physicians that completed the survey declared themselves as rational prescribers of antimicrobials but more than half of them (53.3%) sometimes prescribed an antibiotic even though it was not indicated compared to 75% of self-reported non-rational prescribers (P ˂ 0.05). Self-reported adherence to the guidelines increased from 34.6% in 2011 to 51.8% in 2019. CONCLUSION: The research showed improvement in physicians' knowledge in choosing the right antibiotic based on the analysis of answers but indicated the necessity for improving communication skills and empowering physicians not to prescribe antibiotics 'just in case' because of diagnostic uncertainty or patient demand. Further qualitative research is needed to understand physicians' prescribing behaviour and decision-making processes in order to develop interventions that will effectively improve the use of antibiotics.

What is the most appropriate metric for the assessment of volume of antibiotic use?

One of the core elements of antibiotic stewardship is surveillance and monitoring of quantity of antibiotic use. This requires tools for measuring the quantity of antibiotic use. However, these metrics have not been standardized, and different metrics are used across different countries, regions and individual healthcare settings. In the literature, there is much controversy on the most appropriate metric for monitoring antibiotic use. Several authors have questioned the relevance of DDDs, which are recommended by the WHO, while others still prefer using DDDs as the best available metric. The results of the recent DRIVE-AB project suggest that a combination of metrics may be the best approach, since all metrics have limitations and provide different perspectives.

Decreasing and stabilising trends of antimicrobial consumption and resistance in Escherichia coli and Klebsiella pneumoniae in segmented regression analysis, European Union/European Economic Area, 2001 to 2018.

Investments to reduce the spread of antimicrobial resistance (AMR) in the European Union have been made, including efforts to strengthen prudent antimicrobial use. Using segmented regression, we report decreasing and stabilising trends in data reported to the European Surveillance of Antimicrobial Consumption Network and stabilising trends in data reported to the European Antimicrobial Resistance Surveillance Network. Our results could be an early indication of the effect of prioritising AMR on the public health agenda.

Quality indicators assessing antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

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.