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Recently, the topic of assessing clinical relevance on top of statistical significance in the analysis of randomized control trials (RCTs) has got increasing attention, in particular as part of benefit assessments. Several formal criteria to serve this purpose have been published. In this paper, we present a framework to assess the value of the application of such criteria. We propose to quantify the need for the assessment of clinical relevance by the actual risk of having accepted a benefit for a treatment with an irrelevant effect in a successful RCT. We then study how this risk can be controlled by two popular criteria based on comparing the effect estimate or the lower bound of the confidence interval with a given threshold. We further propose to quantify the impact of using formal criteria by considering the expected costs when specifying error-specific costs for each of the three possible types of errors: A benefit may be accepted for a treatment, which is actually inferior, or which is not inferior, but only implies an irrelevant improvement, or a benefit may be rejected for a treatment implying a relevant improvement. This way we can demonstrate that the impact depends on parameters which are typically not explicitly defined in the frame of benefit assessments. Depending on the values of these parameters, formal checks of clinical relevance may imply better decisions on average, but they may also imply more harm than good on average. [ABSTRACT FROM AUTHOR]

Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action. Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe. A systematic review and Bayesian meta-analysis. MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022. Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii , CR or third-generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae , methicillin-resistant Staphylococcus aureus , and vancomycin-resistant Enterococcus faecium , and patients with drug-susceptible or no infection. All patients diagnosed with drug-resistant bloodstream infections (BSIs). NA. An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks. Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates. Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], −0.72 to 4.17) and 1.78 (95% CrI, −0.02 to 3.38) days, respectively. Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed. [ABSTRACT FROM AUTHOR]

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.

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: Improving our understanding of outbreaks due to antibiotic-resistant bacteria (ARB) and their control is critical in the current public health scenario. The threat of outbreaks due to ARB requires multifaceted efforts. However, a global overview of epidemiological characteristics of outbreaks due to ARB and effective infection control measures is missing. In this paper, we describe the protocol of a systematic review aimed at mapping and characterising the epidemiological aspects of outbreaks due to ARB and infection control measures in European countries., Methods and Analysis: The databases MEDLINE, Web of Knowledge and Cochrane library will be searched using a 3-step search strategy. Selection of articles for inclusion will be performed by 2 reviewers using predefined eligibility criteria. All study designs will be included if they report an outbreak and define the microbiological methods used for microorganism identification. The target bacteria will be methicillin-resistant and vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, ceftazidime-resistant and carbapenem-resistant Acinetobacter baumannii, ceftazidime-resistant and carbapenem-resistant Pseudomonas aeruginosa, ciprofloxacin-resistant Escherichia coli, extended-spectrum β-lactamase-producing E. coli and Klebsiella pneumoniae, carbapenem-resistant and carbapenamase-producing Enterobacteriaceae. Data will be extracted using a tailored pilot tested form and the quality of reporting will be assessed using the ORION (Outbreak Reports and Intervention Studies Of Nosocomial infections) tool. Data will be synthesised and reported by the type of ARB, setting and country. Infection control measures and bundles of measures will be described. The effectiveness will be reported as defined by the authors. Regression analysis will be used to define independent factors associated with outbreaks' control. Heterogeneity between studies will be assessed by forest plots and I² statistics., Ethics and Dissemination: Ethical approval is not applicable for this study. Findings will be disseminated through journal publication and conference presentations and talks., Competing Interests: FS is an employee of AstraZeneca, an EFPIA (European Federation of Pharmaceutical Industries and Association) member company in the IMI JU and costs related to his research contributions were covered by AstraZeneca as in-kind contribution under the IMI JU agreement., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Rotavirus infections by G12 strains in several countries have recently been described. In this study, we report the emergence of G12 strains in south India. Fourteen cases of G12 infection were identified between June and September 2005. G12 was seen in combination with P[6], P[8], or nontypeable P type. Nine cases, including five symptomatic infections and four asymptomatic infections, were identified as part of routine surveillance for rotavirus infections in a birth cohort in the community between June and July 2005. Significant temporal and time-space clustering of eight of these cases represents a possible recent introduction of a new rotavirus VP7 genotype. Previous rotavirus infections had been documented for six of the nine children in the community. In the following 2 months, five cases of G12 infection were identified among children presenting to a referral hospital with diarrhea. This is the first description of symptomatic and asymptomatic G12 infections in children in the community. The detection of G12 strains from different parts of the world in recent years suggests the possibility of its emergence as an important global genotype. Monitoring of cocirculating rotavirus strains and detection of emerging strains is important in the context of the availability of rotavirus vaccines.