A step forward in antibiotic use and resistance monitoring: a quarterly surveillance system pilot in 11 European Union/European Economic Area countries, September 2017 to May 2020.

BackgroundSurveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) in Europe is currently annual.AimTo study the feasibility and scalability of a quarterly AMR/AMU surveillance system in the European Union/European Economic Area (EU/EEA).MethodsWe conducted a longitudinal study within the scope of the EU-JAMRAI project. Seventeen partners from 11 EU/EEA countries prospectively collected 41 AMU and AMR indicators quarterly from September 2017 to May 2020 for the hospital sector (HS) and primary care (PC). Descriptive statistics and coefficients of variation (CV) analysis were performed.ResultsData from 8 million hospital stays and 45 million inhabitants per quarter were collected at national (n = 4), regional (n = 6) and local (n = 7) levels. Of all partners, five were able to provide data within 3 months after each preceding quarter, and eight within 3-6 months. A high variability in AMU was found between partners. Colistin was the antibiotic that showed the highest CV in HS (1.40; p < 0.0001). Extended-spectrum beta-lactamase-producing Escherichia coli presented the highest incidence in HS (0.568 ± 0.045 cases/1,000 bed-days per quarter), whereas ciprofloxacin-resistant E. coli showed the highest incidence in PC (0.448 ± 0.027 cases/1,000 inhabitants per quarter). Barriers and needs for implementation were identified.ConclusionThis pilot study could be a first step towards the development of a quarterly surveillance system for AMU and AMR in both HS and PC in the EU/EEA. However, committed institutional support, dedicated human resources, coordination of data sources, homogeneous indicators and modern integrated IT systems are needed first to implement a sustainable quarterly surveillance system.

[Procedure for the marketing authorization of an antibacterial agent]. / Procedimiento de registro de un antibacteriano.

The marketing authorization of a new medicinal product is the first step before being placed on the market, and includes the full investigation programme. In order to ensure their quality, safety and efficacy, medicinal products are closely regulated from their initial phases of investigation to their use in clinical practice. For registration purposes, the results of all the clinical and preclinical studies, along with quality data and the description of the manufacturing process should be submitted. All information collected is presented for review by the competent authority. The European Medicines Agency regulates the registration of medicines in Europe, and national agencies in each EU member state are responsible for the assessment of the marketing authorisation application. To facilitate the development of clinical programmes, there is a common framework for the evaluation of an antibacterial, which includes guidelines and an addendum, detailing the specific requirements that must be carried out in clinical trials to assess the efficacy and safety for most of the infections.

Recommendations of the Spanish Antibiogram Committee (COESANT) for in vitro susceptibility testing of antimicrobial agents by disk diffusion.

Disk diffusion is a well standardized method that provides reliable categorical results to guide antimicrobial therapy in numerous types of infections. Based on the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which are widely implemented in Spain, the Spanish Antibiogram Committee (COESANT) has drawn up recommendations for antimicrobial selection by the disk diffusion technique, including selective reporting and its use for the detection of resistance mechanisms. Factors affecting disk diffusion results, along with advantages and shortcomings of the method, are also discussed.

Spanish Antibiogram Committee (COESANT) recommendations for cumulative antibiogram reports.

The Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) presents in this document a series of recommendations intending to unify how cumulative antibiogram reports must be made in Clinical Microbiology Spanish laboratories. This article is based on the information included in the Clinical Microbiology Procedure No. 51, «Preparation of cumulative reports on antimicrobial susceptibility¼ of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), published in 2014. The recommendations also include the modifications in the definition of clinical interpretive categories recently published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2019. Its final objective is to establish a homogeneous way of preparing these summaries to compare results from different centers or aggregate the information from these in order to carry out an adequate local or even national surveillance regarding the evolution of antimicrobial susceptibility.

[Use of antibiotics in Spain and regulatory framework for clinical development in the European Union]. / Uso de antibióticos en España y marco regulador para su desarrollo clínico en la Unión Europea.

The high use of antibiotics in the community is closely related to the increase in resistance to antibiotics. Monitoring antibiotic use is a key step to understanding whether trends are changing, and in this way efforts towards more prudent use can be implemented. Over the last 9 years, available active ingredients have decreased in Spain while at the same time the number of antibiotic offerings has increased. Presentations of generic pharmaceutical specialties account for almost 50% of the most frequently used subgroups. The use of antibiotics remains stable or shows a slight decrease depending on the unit of measure (DID or PIM) used. These differences are explained mainly by amoxicillin-clavulanate, since in recent years packages with greater concentrations and greater number of pharmaceutical formulations per package have been used. Ten active ingredients constitute 80% of antibiotic use. Throughout the study period, more than 50% of total antibiotic use was due to amoxicillin-clavulanate and amoxicillin. There is significant seasonal variation in the use of antibiotics. Peaks in influenza incidence are correlated with the maximum consumption of antibiotics. The criteria on which the marketing authorization for medication, including antibiotics, is based are quality, safety and effectiveness, regardless of the registration procedure used. The criteria that dictate the use of these antibiotics in clinical practice go beyond the purely regulatory framework. For this reason, it would be useful to have clinical practice guidelines based on broad consensus that incorporate criteria for a more rational use of antibiotics, such as the local prevalence of resistance.

From CLSI to EUCAST, a necessary step in Spanish laboratories. / Del CLSI al EUCAST, una transición necesaria en los laboratorios españoles.

The Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) presents in this document a simple "roadmap" or decalogue of recommendations, with a view to facilitating the transition from the Clinical and Laboratory Standards Institute (CLSI) to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) antimicrobial susceptibility testing regulations to the Clinical Microbiology Spanish laboratories that still use the CLSI guidelines. The objectives are to adapt the closer European regulations to the Spanish clinical and epidemiological reality and to fully implement the EUCAST recommendations in all microbiology laboratories in Spain.

Recommendations of the Spanish Antibiogram Committee (COESANT) for selecting antimicrobial agents and concentrations for in vitro susceptibility studies using automated systems.

Automated antimicrobial susceptibility testing devices are widely implemented in clinical microbiology laboratories in Spain, mainly using EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints. In 2007, a group of experts published recommendations for including antimicrobial agents and selecting concentrations in these systems. Under the patronage of the Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) and the Study Group on Mechanisms of Action and Resistance to Antimicrobial Agents (GEMARA) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and aligned with the Spanish National Plan against Antimicrobial Resistance (PRAN), a group of experts have updated this document. The main modifications from the previous version comprise the inclusion of new antimicrobial agents, adaptation of the ranges of concentrations to cover the EUCAST breakpoints and epidemiological cut-off values (ECOFFs), and the inference of new resistance mechanisms. This proposal should be considered by different manufacturers and users when designing new panels or cards. In addition, recommendations for selective reporting are also included. With this approach, the implementation of EUCAST breakpoints will be easier, increasing the quality of antimicrobial susceptibility testing data and their microbiological interpretation. It will also benefit epidemiological surveillance studies as well as the clinical use of antimicrobials aligned with antimicrobial stewardship programs.

Successful improvement of antibiotic prescribing at Primary Care in Andalusia following the implementation of an antimicrobial guide through multifaceted interventions: An interrupted time-series analysis.

BACKGROUND: Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care. METHODS: A quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018. Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018. RESULTS: Overall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use (33% in Aljarafe, 25% in Andalusia), and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018. CONCLUSIONS: Multifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care.

Use of colistin-containing products within the European Union and European Economic Area (EU/EEA): development of resistance in animals and possible impact on human and animal health.

Since its introduction in the 1950s, colistin has been used mainly as a topical treatment in human medicine owing to its toxicity when given systemically. Sixty years later, colistin is being used as a last-resort drug to treat infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumoniae), for which mortality can be high. In veterinary medicine, colistin has been used for decades for the treatment and prevention of infectious diseases. Colistin has been administered frequently as a group treatment for animal gastrointestinal infections caused by Gram-negative bacteria within intensive husbandry systems. Given the ever-growing need to retain the efficacy of antimicrobials used to treat MDR infections in humans, the use of colistin in veterinary medicine is being re-evaluated. Despite extensive use in veterinary medicine, there is limited evidence for the development of resistance to colistin and no evidence has been found for the transmission of resistance in bacteria that have been spread from animals to humans. Since surveillance for colistin resistance in animals is limited and the potential for such transmission exists, there is a clear need to reinforce systematic monitoring of bacteria from food-producing animals for resistance to colistin (polymyxins). Furthermore, colistin should only be used for treatment of clinically affected animals and no longer for prophylaxis of diseases, in line with current principles of responsible use of antibiotics.