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Clin Microbiol Infect Abstract We investigated bacteraemia trends for five major bacterial pathogens, Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium, and determined how expanding antimicrobial resistance influenced the total burden of bacteraemias in Europe. Aetiological fractions of species and antibiotic phenotypes were extracted from the European Antimicrobial Resistance Surveillance System (EARSS) database for laboratories, which consistently reported between 2002 and 2008. Trend analyses used generalized linear models. Robustness of results was assessed by iterative analysis for different geographic regions. From 2002 to 2008, the overall number of reports increased annually by 6.4% (95% confidence interval (CI) 6.2-6.5%), from 46 095 to 67 876. In the subset of laboratories providing denominator information, the overall incidence increased from 0.58/1000 patient-days to 0.90/1000 patient-days (7.2% per year; 95% CI 6.9-7.5%). The frequency of reported bacteraemia isolates of S. aureus and Streptococcus pneumoniae increased moderately, while increase in E. coli and Enterococcus faecium was more pronounced. Bacteraemias caused by methicillin-resistant S. aureus increased until 2005 (7.6% per year; 95% CI 6.1-9.1%), and then decreased (−4.8% per year; 95% CI −6.1 to −3.5%), whereas the number attributable to methicillin-sensitive S. aureus increased continuously (3.4% per year; 95% CI 3.0-3.7). Increasing rates of E. coli were mainly caused by antibiotic-resistant phenotypes. Our data suggest that the burden of bacterial bloodstream infection has been increasing for all species during EARSS surveillance. Trends were mainly driven by resistant strains and clearly dissociated between resistant and susceptible isolates. It appears that infections with resistant clones add to rather than replace infections caused by susceptible bacteria. As a consequence, expansion of antibiotic resistance creates an additional strain on healthcare systems. [ABSTRACT FROM AUTHOR]

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.

Objectives: Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship., Methods: For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups., Results: For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013., Conclusions: Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

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.

Currently, surveillance of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in humans in Europe is not systematic but mainly event-based. In September 2014, the European Centre for Disease Prevention and Control (ECDC) initiated a questionnaire to collect data on the number of LA-MRSA from human samples (one isolate per patient) from national/regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. Identification of LA-MRSA as clonal complex (CC) 398 by multilocus sequence typing (MLST) was preferred, although surrogate methods such as spa -typing were also accepted. The questionnaire was returned by 28 laboratories in 27 EU/EEA countries. Overall, LA-MRSA represented 3.9% of 13,756 typed MRSA human isolates, but it represented ≥ 10% in five countries (Belgium, Denmark, Spain, the Netherlands and Slovenia). Seven of the reference laboratories did not type MRSA isolates in 2013. To monitor the dispersion of LA-MRSA and facilitate targeted control measures, we advocate periodic systematic surveys or integrated multi-sectorial surveillance.

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

For more than a decade human campylobacteriosis has been the leading zoonosis in many developed countries. Consumption of poultry or poultry products has been identified as the primary source of infection in humans. This study was conducted to identify risk factors for the occurrence of Campylobacter in Danish broiler flocks. The study was based on a large data set consisting of Campylobacter positive status for nearly 6000 broiler flocks and 43 explanatory variables. Data were obtained from the Danish Campylobacter surveillance programme in poultry and from the responses to a standardized questionnaire answered via interviews with broiler farm owners. Two hundred and forty broiler farms, comprising 539 broiler houses, were included in the study and their Campylobacter status was followed over a 2-year period (1999-2000). The large number of observations made it possible to carry out a multivariate analysis including all 43 variables. A multivariate analysis was conducted using a generalized linear model, and the correlations between the houses from the same farms were accounted for by adding a variance structure to the model. The procedures for analyses included backward elimination, forward selection and expanding of the number of observations used in the variance analysis along with the reduction of the number of parameters in the model. The unit of analysis was 'broiler house', meaning that all results from a broiler house were aggregated into one prevalence figure (number of positive flocks/total number of flocks delivered over the 2-year period). The following factors were found to be significantly associated with the occurrence of Campylobacter in the broiler flocks: old broiler houses, late introduction of whole wheat in the feed, relatively high broiler age at slaughter, improper rodent control, large number of chimneys on the broiler house, farm located in an area with a high density of cattle farms, having more than one broiler house on the farm, and improper storage of wheat. This large-scale study confirms several risk factors identified in previous studies. The results concerning chimneys may be explained by the easier access that flies have to the broiler houses, which seems in agreement with recent Danish studies on the significance of fly-screens to reduce Campylobacter in broiler flocks. The results of this study may be used in identification of effective interventions aimed at controlling Campylobacter in Danish broiler flocks., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The glycopeptide growth promoter avoparcin was banned from animal production in the EU in 1997 due to concern for the spread of vancomycin-resistant enterococci (VRE) from food animals to humans. In recent Norwegian and Danish studies, extensive occurrence of VRE on broiler farms and in broiler flocks after the avoparcin ban has been reported. The present study was undertaken to investigate the epidemiology of VRE on broiler farms in the absence of the selective pressure exerted by avoparcin. Environmental samples were obtained from five broiler houses after depopulation, cleaning, and disinfection of the houses between rotations, and two consecutive broiler flocks from each house were sampled by taking cloacal swabs from the broilers at the time of slaughter. A total of 69 vancomycin-resistant Enterococcus faecium isolates obtained from broiler flocks and broiler houses were subjected to molecular typing by pulsed-field gel electrophoresis (PFGE). Forty-one PFGE-profiles were observed. VRE with indistinguishable or highly similar PFGE profiles were isolated from consecutive broiler flocks and from environmental samples from the houses in which the flocks were reared, whereas VRE-isolates from different broiler houses and from flocks reared in different houses appeared to be genetically unrelated. These findings indicated that VRE was transmitted between consecutive broiler flocks by clones of resistant bacteria surviving in the broiler houses despite cleaning and disinfection between rotations. Thus, the extensive occurrence of VRE in broiler flocks after the avoparcin ban may be explained by persistence of VRE in the broiler house environment.

Objectives: To evaluate the effects of the nitric oxide (NO)-donating drugs sodium nitroprusside, S-nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteineetylester (SNACET), and linsidomine (SIN-1), as well as the adenylyl cyclase-stimulating agent forskolin, on electrically induced contractions and on tissue levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) of isolated human seminal vesicle strip preparations. The significance of the L-arginine-NO-cGMP pathway in the regulation of smooth muscle tone in the human genitourinary tract has been well established; however, information on the relevance of NO-mediated signal transduction in the functional control of mammalian seminal vesicles is still sparse., Methods: Seminal vesicle strip preparations were applied to an organ bath system under standard conditions. Phasic contractions were induced by electrical field stimulation (frequency 80 Hz, amplitude 10 V, single pulse 1 ms, total pulse duration 1 second, pause 90 seconds). After stable contraction amplitudes had been reached, the drugs were added in a cumulative manner (0.001 to 10 microM), and the isometric responses were registered. After drug exposure, freezing, tissue homogenization, and extraction of cyclic nucleotides, cAMP and cGMP were measured by means of enzyme-linked immunosorbent assays., Results: Electrical field stimulation-induced amplitudes were attenuated by the drugs in a dose-dependent manner. The rank order of potency was GSNO > sodium nitroprusside > forskolin > SNACET > or = SIN-1. The relaxing effect of GSNO was antagonized in the presence of 10 microM of guanylyl cyclase inhibitor methylene blue. The inhibitory effects of GSNO, sodium nitroprusside, and forskolin on the contractile activity were paralleled by an increase in tissue cGMP (2 to 100-fold) and cAMP (7 to 9-fold)., Conclusions: Our results strongly support the hypothesis that the contractility of human seminal vesicles is in part regulated by the NO-cGMP-cascade. This may give a rationale for the use of S-nitrosothiols, such as GSNO, in the pharmacotherapy of hyperexcitatory disturbances of ejaculation.

The glycopeptide growth promoter avoparcin was banned from animal production in Denmark in 1995. In this study, we investigated the occurrence of vancomycin-resistant enterococci (VRE) in broiler flocks in the absence of the selective pressure exerted by the use of avoparcin. One hundred sixty-two broiler flocks from rearing systems with different histories of avoparcin exposure were investigated for the presence of VRE. Using a direct selective plating procedure, VRE were isolated from 104 of 140 (74.3%) broiler flocks reared in broiler houses previously exposed to avoparcin on conventional and extensive indoor broiler farms. In contrast, only 2 of 22 (9.1%) organic broiler flocks reared on free-range farms with no history of previous exposure to avoparcin were VRE-positive. Furthermore, the occurrence of VRE over time in flocks reared in broiler houses previously exposed to avoparcin was investigated. Results obtained by direct selective plating showed no significant decrease in the proportion of VRE-positive flocks during the study period (1998-2001). This study demonstrated the extensive occurrence of VRE in broiler flocks more than 5 years after the avoparcin ban in Denmark, and indicates that VRE may persist in the absence of the selective pressure exerted by avoparcin. The results differ markedly from previously published Danish surveillance data on VRE in broilers. This may reflect differences in isolation procedures.

Aims: To determine the flock prevalence and to estimate the within flock prevalence of Campylobacter in broiler flocks from different rearing systems, and to determine the antimicrobial susceptibility of Campylobacter isolates to selected antimicrobial substances., Methods and Results: One hundred and sixty broiler flocks originating from organic, conventional and extensive indoor production farms were investigated for the presence of Campylobacter at the time of slaughter. Campylobacter isolates from a subsample of positive flocks were subjected to susceptibility testing. Campylobacter spp. were isolated from 100% of organic broiler flocks, from 36.7% of conventional broiler flocks and from 49.2% of extensive indoor broiler flocks. Six of 62 Campylobacter isolates were resistant to one or more of the antimicrobials tested., Conclusion: These results indicate that the special characteristics of organic broiler production provide a high prevalence of Campylobacter-positive flocks. Antimicrobial resistance was scarce among Campylobacter isolates from all rearing systems., Significance and Impact of the Study: Organic broiler flocks constitute a strong potential for introduction of Campylobacter to the processing line upon arrival at slaughter.

In order to analyse the occurrence of viral haemorrhagic septicaemia virus (VHSV) in the marine environment surrounding Denmark, fish tissue samples were collected on four cruises with the research vessel H/S Dana in 1996 and 1997. The sampling comprised 923 samples totalling 7344 fish representing 29 different species. VHSV was isolated from 24 fish samples from the Baltic Sea, four samples from Skagerrak and three samples from the North Sea. The virus-positive host species included herring Clupea harengus (11 isolates), sprat Sprattus sprattus (eight isolates), cod Gadus morhua (six isolates), rockling Rhinonemus cimbrius (one isolate), Norway pout Trisopterus esmarkii (one isolate), blue whiting Micromesistius poutassou (one isolate), whiting Merlangius merlangus (two isolates) and lesser argentine Argentina sphyraena (one isolate). VHSV has previously been reported from cod and herring, but not from the other five species. A virus belonging to serogroup II of the aquatic birnaviruses was isolated from three samples of flounder Platichthys flesus and three samples of dab Limanda limanda and a virus preliminary identified as iridovirus (lymphocystis virus) was isolated from seven samples of long rough dab Hippoglossoides platessoides.