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To reduce antimicrobial resistance (AMR), pathogen-specific AMR burden data are crucial to guide target selection for research and development of vaccines and monoclonal antibodies (mAbs). We identified knowledge gaps through previously conducted systematic reviews, which informed a Delphi expert consultation on future AMR research priorities and harmonisation strategies to support data-driven decision-making. Consensus (≥80% agreement) on importance and feasibility of research topics was achieved in two rounds, involving 24 of 39 and 19 of 24 invited experts, respectively. Priority pathogens and resistance profiles for future research were identified: third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli, for bloodstream and urinary tract infections, respectively, and meticillin-resistant Staphylococcus aureus for surgical-site infections. Prioritised high-risk populations included surgical, haemato-oncological and transplant patients. Mortality and resource use were prioritised as health-economic outcomes. The importance of age-stratified data and inclusion of a non-infected comparator group were highlighted. This agenda provides guidance for future research to fill knowledge gaps and support data-driven selection of target pathogens and populations for new preventive and treatment strategies, specifically vaccines and mAbs, to effectively address the AMR burden in Europe. These research priorities are also relevant to improve the evidence base for future AMR burden estimates.

Background: The WHO fungal priority list classifies Candida species as critical and high-priority pathogens, and the WHO GLASS fungi initiative seeks to establish a standardised global framework for antifungal resistance monitoring. We aimed to review resistance rates and antifungal resistance patterns across European surveillance systems and studies in response to these recent calls for action., Methods: A systematic review of national and international surveillance systems and peer-reviewed surveillance studies available up to June 2024 was conducted. Descriptive and trend analyses were performed on surveillance data reporting resistance to different antifungals in Candida spp., Results: In total, 6 national surveillance systems and 28 studies from 13 countries provided candidemia resistance data, mostly about the C. albicans , C. glabrata and C. parapsilosis complex. Azole resistance was most frequently reported (6/6 surveillance systems and 27/28 studies) with the highest resistance rate, especially for C. glabrata , in Croatia (100%, 28/28 isolates) and Slovenia (85.7%, 82/96) and C. parapsilosis in Croatia (80.6%, 54/67) and Italy (72.6%, 106/146). Echinocandin and polyene resistance rates were nearly zero. The number of isolates included in the surveillance systems increased over the years, particularly for C. albicans (+40-60 isolates/year), C. glabrata , and C. parapsilosis (+15-30 isolates/year). No surveillance system or study reported resistance data for C. auris . Pooled data from national surveillance revealed a decreasing trend in azole resistance in C. albicans and C. glabrata . The increasing azole-resistance trend in C. parapsilosis disappeared after adjusting for between-country heterogeneity. Overall, echinocandin and polyene resistance trends appeared relatively stable., Conclusions: Awareness of antifungal resistance is growing, but further actions are needed to strengthen surveillance capacity and knowledge-sharing networks across Europe.

Background: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined., Objectives: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe., Methods: A systematic review and meta-analysis., Data Sources: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022., Study Eligibility Criteria: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries., Participants: Paediatric and adult patients diagnosed with drug-resistant BSI., Interventions: Not applicable., Assessment of Risk of Bias: An adapted version of the Joanna-Briggs Institute assessment tool., Methods of Data Synthesis: Random-effect models were used to pool pathogen-specific burden estimates., Results: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively)., Conclusions: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To prioritize healthcare investments, ranking of infections caused by antibiotic-resistant bacteria should be based on accurate incidence data., Objectives: We performed a systematic review to estimate frequency measures of antimicrobial resistance for six key bacteria causing bloodstream infections (BSI) in European countries., Data Sources: We searched PubMed, Web of Science, Embase databases, and the ECRAID-Base Epidemiological-Network platform., Study Eligibility Criteria: We included studies and surveillance systems assessing resistance-percentage, prevalence, or incidence-density of BSI because of carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli, third-generation cephalosporins-resistant E. coli and K. pneumoniae, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus., Methods: Reviewers independently assessed published data and evaluated study quality with the modified Joanna Briggs Institute critical appraisal tool. Pooled estimates were determined using random effects meta-analysis. Consistency of data was assessed using random effects meta-regression (Wald test, p > 0.05)., Results: We identified 271 studies and 52 surveillance systems from 32 European countries. Forty-five studies (16%) reported on BSI, including 180 frequency measures most commonly as resistance-percentage (88, 48.9%). Among 309 frequency measures extracted from 24 (46%) surveillance systems, 278 (89%) were resistance-percentages. Frequency measures of methicillin-resistant S. aureus and vancomycin-resistant E. faecium BSI were more frequently reported from Southern Europe and Western Europe (80%), whereas carbapenem-resistant P. aeruginosa BSI from Northern Europe and Western Europe (88%). Highest resistance-percentages were detected for carbapenem-resistant A. baumannii (66% in Central Eastern Europe) and carbapenem-resistant K. pneumoniae (62.8% in Southern Europe). Pooled estimates showed lower resistance-percentages in community versus healthcare-associated infections and in children versus adults. Estimates from studies and surveillance systems were mostly consistent among European regions. The included data was of medium quality., Discussion: Pathogen-specific frequency measures of antimicrobial resistance in BSI are insufficient to inform antibiotic stewardship and research and development strategies. Improving data collection and standardization of frequency measures is urgently needed., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Infection control programs and antimicrobial stewardship have been proven effective in reducing the burden of diseases due to multidrug-resistant organisms, but quantifying the effect of each intervention is an open issue. For this aim, we propose a model to characterize the effect of interventions at single ward level. We adapted the Ross-Macdonald model to describe hospital cross-transmission dynamics of carbapenem resistant Klebsiella pneumoniae (CRKP), considering healthcare workers as the vectors transmitting susceptible and resistant pathogens among admitted patients. The model parameters were estimated from a literature review, further adjusted to reproduce observed clinical outcomes, and validated using real life data from a 2-year study in a university hospital. The model has been further explored through extensive sensitivity analysis, in order to assess the relevance of single interventions as well as their synergistic effects. Our model has been shown to be an effective tool to describe and predict the impact of interventions in reducing the prevalence of CRKP colonisation and infection, and can be extended to other specific hospital and pathological scenarios to produce tailored estimates of the most effective strategies., (© 2023. Springer Nature Limited.)

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries-52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach., Competing Interests: JA received grants/contracts from the Spanish Ministry of Agriculture, Food and Fisheries and EU Horizon 2020. Work of BPG was funded by the German Center for Infection research Clinical Research Unit (DZIF-CRU) at Tübingen. RD participated on Data Safety Monitoring Board of the ASTARTÉ study (for which no payments were received). WG received grants/contracts from the Horizon Europe grant (supported by UKRI) on AMR and pathogen evolution in costal environments and the UK Natural Environment Research Council grants on AMR Knowledge Exchange NE/V019279/1 and AMR evolution NE/W006251/1; WG received consultation fee for EU DG Sante AMR policy evaluation and recommendations. Work of AK was funded in the context of the project One Health EJP, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 773830. EP received grants/contracts from the Austrian Ministry of Health for the National Surveillance Network of healthcare-associated infections (ANISS); EP received honorarium for participation as a chair of the Advisory board on AMR and MDRO Pfizer Austria (27.09.22). MB received grants/contracts from Janssen Vaccines, Novartis, CureVac, and Merck; MB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Takeda (November 2019); MB participated on Data Safety Monitoring Board or Advisory Board of Sanofi, Spherecydes, Pfizer, Merck, Novartis, and Astra-Zeneca. MM received support for attending meetings and/or travel from the Global Antibiotic Research and Development Partnership (12.10.22–13.10.2022). LS received grants or contracts from the JPIAMR network grant 2020; LS received support for attending meetings and/or travel from ESCMID for the attendance of ECCMID 2022. DT is an employee of GlaxoSmithKline and holds shares in GlaxoSmithKline. TVB received consultation fees from Stonehaven Consulting; TVB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Swedish Veterinary Council. Work of AV was supported by the COMBACTE-MAGNET consortium; AV serves as the ISAC president (International Society of Antimicrobial Chemotherapy) and board member of NVMM (Dutch Microbiology Society). All other authors declare no competing interests., (© 2022 The Authors.)

Introduction: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for distinguishing infected subjects after vaccination. This study thus evaluates the performance of the anti-S IgG assay in identifying subjects with breakthrough infections (BIs) and its potential usefulness for screening healthcare workers (HCWs). Methods: Out of 6400 HCWs of the University Hospital of Verona vaccinated with two doses of BNT162b2, 4462 never infected before subjects who had completed primary vaccination were tested for IgG anti-S 6 to 9 months after the second dose. Of these, 59 (1.3%) had a BI. The discriminant power of IgG anti-S in detecting previous breakthrough infection was tested by constructing receiver operating characteristic (ROC) curves. Results: The discriminant power for BI was rather good (area under the curve (AUC), 0.78) and increased with decreasing time elapsed between antibody titer assessment and previous SARS-CoV-2 infection. Accuracy (AUC) sensitivity increased from 0.78 (95% CI 0.70−0.85) for BI in the previous six months to 0.83 (95% CI 0.67−0.99) for those in the previous two months, and from 0.68 to 0.80, respectively. The specificity (0.86) and optimal cut-off (935 BAU/mL) remained unchanged. However, BI were rather rare (1.3%), so the positive predictive value (PPV) was low. Only 40 of the 664 HCWs with antibody titer > 935 BAU/mL had previously confirmed BI, yielding a PPV of only 6.0%. When adopting as cut-off the 90th percentile (1180 BAU/mL), PPV increased to 7.9% (35/441). Conclusions: The anti-S IgG assay displayed good sensitivity and specificity in discriminating subjects with BI, especially in recent periods. However, BIs were rare among HCWs, so that the anti-S IgG assay may have low PPV in this setting, thus limiting the usefulness of this test as a screening tool for HCWs. Further studies are needed to identify more effective markers of a previous infection in vaccinated subjects.

Background: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers., Methods: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion)., Results: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection ( p = 0.008 and p = 0.007, respectively)., Conclusion: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

Background: International travel has been recognized as a risk factor contributing to the spread of antimicrobial resistance (AMR). However, tools focused on AMR in the context of international travel and designed to guide decision-making are limited. We aimed at developing an evidence-based educational tool targeting both healthcare professionals (HCPs) and international travellers to help prevent the spread of AMR., Methods: A literature review on 12 antimicrobial-resistant bacteria (ARB) listed as critical and high tiers in the WHO Pathogen Priority List covering four key areas was carried out: AMR surveillance data; epidemiological studies reporting ARB prevalence data on carriage in returning travellers; guidance documents reporting indications on screening for ARB in returning travellers and recommendations for ARB prevention for the public. The evidence, catalogued at country-level, provided the content for a series of visualizations that allow assessment of the risk of AMR acquisition through travel., Results: Up to January 2021, the database includes data on: (i) AMR surveillance for 2.018.241 isolates from 86 countries; (ii) ARB prevalence of carriage from 11.679 international travellers and (iii) 15 guidance documents published by major public health agencies. The evidence allowed the development of a consultation scheme for the evaluation of risk factors, prevalence of carriage, proportion and recommendations for screening of AMR. For the public, pre-travel practical measures to minimize the risk of transmission were framed., Conclusions: This easy-to-use, annually updated, freely accessible AMR travel tool (https://epi-net.eu/travel-tool/overview/), is the first of its kind to be developed. For HCPs, it can provide a valuable resource for teaching and a repository that facilitates a stepwise assessment of the risk of AMR spread and strengthen implementation of optimized infection control measures. Similarly, for travellers, the tool has the potential to raise awareness of AMR and outlines preventive measures that reduce the risk of AMR acquisition and spread., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine.)

Background: The increasing burden of candidemia and the emergence of resistance, especially among non- Candida albicans strains, represent a new threat for public health. We aimed to assess the status of surveillance and to identify publicly accessible resistance data in Candida spp. blood isolates from surveillance systems and epidemiological studies in 28 European and 4 European Free Trade Association member states., Methods: A systematic review of national and international surveillance networks, from 2015 to 2020, and peer-reviewed epidemiological surveillance studies, from 2005 to 2020, lasting for at least 12 consecutive months and with at least two centers involved, was completed to assess reporting of resistance to amphotericin B, azoles, and echinocandins in C. albicans , C. glabrata , C. parapsilosis , C. tropicalis , C. krusei , and C. auris ., Results: Only 5 (Austria, Italy, Norway, Spain, and United Kingdom) of 32 countries provided resistance data for Candida spp blood isolates. Among 322 surveillance studies identified, 19 were included from Belgium, Denmark, Iceland, Italy, Portugal, Spain, Sweden, Switzerland, and United Kingdom. C. albicans and C. glabrata were the most monitored species, followed by C. parapsilosis and C. tropicalis . C. krusei was not included in any national surveillance system; 13 studies assessed resistance. No surveillance system or study reported resistance for C. auris . Fluconazole, voriconazole, caspofungin, and amphotericin B resistance in C. albicans , C. glabrata , and C. parapsilosis were the most common drug-species combination monitored. Quality of surveillance data was poor, with only two surveillance systems reporting microbiological methods and clinical data. High heterogeneity was observed in modalities of reporting, data collection, and definitions., Conclusion: Surveillance of antifungal resistance in Candida spp blood-isolates is fragmented and heterogeneous, delaying the application of a translational approach to the threat of antifungal resistance and the identification of proper targets for antifungal stewardship activities. International efforts are needed to implement antifungal resistance surveillance programs in order to adequately monitor antifungal resistance.

Introduction: Intensive Care Units (ICU) are among the hospital wards exhibiting the highest prevalence of antimicrobial resistance (AMR), and resulting impact on patient outcomes. Antimicrobial resistance surveillance and antimicrobial stewardship (AMS) programs play a pivotal role in promoting interventions tailored to optimize infection diagnosis and treatment in the final attempt to limit unnecessary antimicrobial use and development of resistance., Areas Covered: A narrative review of the literature was carried out to summarize the available evidence and develop a set of actions that should be considered for integration into the ICU stewardship framework. Four questions were addressed: how AMR surveillance can inform antibiotic policy in ICU; whether pharmacokinetic and pharmacodynamic (PK/PD) principles and the use of procalcitonin should be incorporated as a standard practice in ICU AMS programs to optimize antibiotic treatment and to drive antibiotic discontinuation; which criteria should drive treatment duration of ICU-associated infections., Expert Opinion: In this review we aim to highlight that the ICU must be considered in its own right. Each ICU has its own characteristics depending on the country, on the local antibiotic resistance profile, on the patients feature and the severity of infection.

Background: The health impact of antimicrobial resistance (AMR) has not been included in the Global Burden of Disease (GBD) report, as reliable data have been lacking. AMR burden estimates have been derived from models combining incidence and/or prevalence data from national and/or international surveillance systems and mortality estimates from clinical studies. Depending on utilized empirical data, statistical methodology and applied endpoints, the validity and reliability of results can differ substantially., Objectives: We assessed comprehensiveness, and internal and external validity of studies estimating the clinical impact of infections caused by the priority antibiotic resistant pathogens monitored by the WHO Global Antimicrobial Resistance Surveillance System., Data Sources: Ovid MEDLINE, January 1950 to March 2019, In-Process and other non-indexed citations were searched., Study Eligibility Criteria: Studies reporting mortality, length of hospital stay, duration of the disease until remission and/or death, complications, hospital re-admissions, and follow-up beyond hospital discharge were eligible., Methods: The literature was searched according to the Cochrane recommendations and reported according to Preferred Reporting Items for Systematic Reviews., Results: Two-hundred and eighty-six studies out of 3529 were eligible. Studies derived mainly from high-income countries (215, 75%) and relied on data from retrospective (226, 79%), single-centre (201, 70%), cohort studies (243, 85%). The health impact was mostly limited to all-cause mortality (128, 45%) with heterogeneity in timing of assessment; attributable length of hospital stay was seldom adjusted for pre-infection admission time and a few studies had enough follow-up for assessing long-term sequelae. Overall, adjustment for confounding has shown a substantial improvement. Data on health state definitions and duration of diseases are generally lacking, precluding calculation of disability-adjusted life years, critical for application of the GBD study methodology., Conclusion: Efforts to improve harmonization, representativeness, quality of AMR surveillance data and cohort studies to determine AMR attributable mortality and morbidity are urgently required. Policy makers need accurate and detailed burden estimates to inform prioritization of resource allocation, and to select the most effective intervention strategies to halt the AMR crisis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings., Methods: The research group identified 10 key questions about the link between AMR surveillance and AMS using a checklist of 9 elements for good practice in health research priority settings and a modified 3D combined approach matrix, and conducted a systematic review of published original studies and guidelines on the link between AMR surveillance and AMS., Results: The questions identified focused on AMS team composition; minimum infrastructure requirements for AMR surveillance; organisms, samples and susceptibility patterns to report; data stratification strategies; reporting frequency; resistance thresholds to drive empirical therapy; surveillance in high-risk hospital units, long-term care, outpatient and veterinary settings; and surveillance data from other countries. Twenty guidelines and seven original studies on the implementation of AMR surveillance as part of an AMS programme were included in the literature review., Conclusions: The evidence summarized in this review provides a useful basis for a more integrated process of developing procedures to report AMR surveillance data to drive AMS interventions. These procedures should be extended to settings outside the acute-care institutions, such as long-term care, outpatient and veterinary. Without proper AMR surveillance, implementation of AMS policies cannot contribute effectively to the fight against MDR pathogens and may even worsen the burden of adverse events from such interventions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: In long-term care facilities (LTCFs) residents often receive inappropriate antibiotic treatment and infection prevention and control practices are frequently inadequate, thus favouring acquisition of MDR organisms. There is increasing evidence in the literature describing antimicrobial stewardship (AMS) activities in LTCFs, but practical guidance on how surveillance data should be linked with AMS activities in this setting is lacking. To bridge this gap, the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks joined their efforts to provide practical guidance for linking surveillance data with AMS activities., Materials and Methods: Considering the three main topics [AMS leadership and accountability, antimicrobial usage (AMU) and AMS, and antimicrobial resistance (AMR) and AMS], a literature review was performed and a list of target actions was developed. Consensus on target actions was reached through a RAND-modified Delphi process involving 40 experts from 18 countries and different professional backgrounds adopting a One Health approach., Results: From the 25 documents identified, 25 target actions were retrieved and proposed for expert evaluation. The consensus process produced a practical checklist including 23 target actions, differentiating between essential and desirable targets according to clinical relevance and feasibility. Flexible proposals for AMS team composition and leadership were provided, with a strong emphasis on the need for well-defined and adequately supported roles and responsibilities. Specific antimicrobial classes, AMU metrics, pathogens and resistance patterns to be monitored are addressed. Effective reporting strategies are described., Conclusions: The proposed checklist represents a practical tool to support local AMS teams across a wide range of care delivery organization and availability of resources., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: The outpatient setting is a key scenario for the implementation of antimicrobial stewardship (AMS) activities, considering that overconsumption of antibiotics occurs mainly outside hospitals. This publication is the result of a joint initiative by the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks, which is aimed at formulating a set of target actions for linking surveillance data with AMS activities in the outpatient setting., Methods: A scoping review of the literature was carried out in three research areas: AMS leadership and accountability; antimicrobial usage and AMS; antimicrobial resistance and AMS. Consensus on the actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine or public health, from 18 low-, middle- and high-income countries., Results: Evidence was retrieved from 38 documents, and an initial 25 target actions were proposed, differentiating between essential or desirable targets according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for all targets. Further to a second review, 6 statements were re-considered and 3 were deleted, leading to a final list of 22 target actions in the form of a practical checklist., Conclusions: This White Paper is a pragmatic and flexible tool to guide the development of calibrated surveillance-based AMS interventions specific to the outpatient setting, which is characterized by substantial inter- and intra-country variability in the organization of healthcare structures, maintaining a global perspective and taking into account the feasibility of the target actions in low-resource settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: Antimicrobial surveillance and antimicrobial stewardship (AMS) are essential pillars in the fight against antimicrobial resistance (AMR), but practical guidance on how surveillance data should be linked to AMS activities is lacking. This issue is particularly complex in the hospital setting due to structural heterogeneity of hospital facilities and services. The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions for linking surveillance data with AMS activities., Methods: A scoping review of the literature was carried out addressing research questions on three areas: (i) AMS leadership and accountability; (ii) antimicrobial usage and AMS; (iii) AMR and AMS. Consensus on the target actions was reached through a RAND-modified Delphi process involving over 40 experts in different fields from 18 countries., Results: Evidence was retrieved from 51 documents. Initially 38 targets were proposed, differentiated as essential or desirable according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for 32 targets. Following a second consultation, 27 targets were approved, 11 were deleted and 4 were suggested for rephrasing, leading to a final approved list of 34 target actions in the form of a practical checklist., Conclusions: This White Paper provides a pragmatic and flexible tool to guide the development of calibrated hospital-surveillance-based AMS interventions. The strength of this tool is that it is a comprehensive perspective that takes into account the hospital patient case-mix and the related epidemiology, which ultimately drives antimicrobial usage, and the feasibility in low-resource settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Introduction: Despite the increasing importance of infections due to multidrug-resistant organisms (MDROs), there is a lack of comprehensive information about the burden of disease and outcomes of key infections caused by these pathogens. The aim of the ABOUT-MDRO (A systematic review on the burden and outcomes of infections due to multidrug resitant organisms) project is to provide estimations of the burden of some key infections and their outcomes caused by the target MDROs., Methods and Analysis: A systematic literature search will be performed using MEDLINE/PubMed, Elsevier's SCOPUS, Cochrane library, Clinical trials and Web of Science, as well as the Surveillance Systems from Public Health Institutions and Scientific Societies for Antimicrobial Resistance and Healthcare-Associated Infections in Europe database of European surveillance systems, for data on prevalence/incidence, mortality and length of stay of target infections in hospitalised patients (including ventilator-associated pneumonia, hospital-acquired pneumonia, complicated intra-abdominal infections, complicated urinary tract infections, skin and soft tissue infections and bloodstream infections) and in specific populations (children, hospital wards, neutropenic patients) caused by cephalosporin-resistant or carbapenem-resistant Enterobacteriaceae , carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp., methicillin-resistant Staphylococcus aureus , and vancomycin-resistant Enterococcus spp. The information retrieved will be tabulated and pooled estimates and 95% CIs calculated of rates and outcomes, using random effects models. Relationships between rates and outcomes in randomised control trials and epidemiological studies, and data of proportions and incidence/prevalence rates will also be analysed. The information collected in this study will be useful for identifying gaps in our knowledge in terms of incidence/prevalence and clinical outcomes of infections caused by MDROs, and for informing priorities in infection control and the research and design of appropriate studies., Ethics and Dissemination: This study will be based on published data so we did not require ethical approval. Formal consent is not required. The results of this review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Data will be presented at international conferences and published in peer-reviewed journals., Registration Details: PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42019124185)., Competing Interests: Competing interests: ZRP-B received honoraria for educational talks by Gilead. JR-B received honoraria for accredited educational activities funded by Merck through unrestricted grants. All other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gastrointestinal basidiobolomycosis (GIB) is a rare mycosis affecting almost exclusively immunocompetent subjects., Methods: We describe a case of GIB caused by Basidiobolus ranarum in a 25-year-old Italian immunocompetent man resident in Ireland who presented a 2-month history of epigastric pain. Suspecting colon cancer he underwent a right hemicolectomy subsequently leading to a diagnosis of GIB by means of molecular biology. After surgery a 9-month therapy with itraconazole was employed with a good outcome. A review of medical literature regarding GIB cases published in the period 1964-2017 is presented., Results: One-hundred and two cases of GIB were included in this analysis. The disease was observed predominantly in male gender (74.5%) and children (41.2%). Abdominal pain was the single most common complaint (86.3%) followed by fever (40.2%) and evidence of an abdominal mass (30.4%). Peripheral blood eosinophilia was detected in 85.7% of cases. Most of the patients were diagnosed in Saudi Arabia (37.2%) followed by USA (21.6%) and Iran (20.6%). Surgery plus antifungal therapy was employed in the majority of patients (77.5%). An unfavourable outcome was documented globally in 18.6% of patients., Conclusions: GIB seems to be an emerging intestinal mycosis among immunocompetent patients living in the Middle East and Arizona., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of β-lactam/β-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.25) and Turkey (aOR 2.09, 95% CI 1.14-3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89, 95% CI 1.05-3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Antibiotic resistance in Gram-negative uropathogens is a major global concern. Worldwide, the prevalence of Enterobacteriaceae that produce extended-spectrum β-lactamase or carbapenemase enzymes continues to increase at alarming rates. Likewise, resistance to other antimicrobial agents including aminoglycosides, sulphonamides and fluoroquinolones is also escalating rapidly. Bacterial resistance has major implications for urological practice, particularly in relation to catheter-associated urinary tract infections (UTIs) and infectious complications following transrectal-ultrasonography-guided biopsy of the prostate or urological surgery. Although some new drugs with activity against Gram-negative bacteria with highly resistant phenotypes will become available in the near future, the existence of a single agent with activity against the great diversity of resistance is unlikely. Responding to the challenges of Gram-negative resistance will require a multifaceted approach including considered use of current antimicrobial agents, improved diagnostics (including the rapid detection of resistance) and surveillance, better adherence to basic measures of infection prevention, development of new antibiotics and research into non-antibiotic treatment and preventive strategies.