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.

Large increase in bloodstream infections with carbapenem-resistant Acinetobacter species during the first 2 years of the COVID-19 pandemic, EU/EEA, 2020 and 2021.

Recent data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) show a large increase of +57% in Acinetobacter species bloodstream infections in the European Union and European Economic Area in the first years of the COVID-19 pandemic (2020-2021) compared with 2018-2019. Most were resistant to carbapenems, from intensive care units, and in countries with ≥ 50% carbapenem resistance in Acinetobacter spp. in 2018-2019. This highlights the requirement for reinforced Acinetobacter preparedness and infection prevention and control in Europe.

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.

Staphylococcus aureus bloodstream infections: diverging trends of meticillin-resistant and meticillin-susceptible isolates, EU/EEA, 2005 to 2018.

BackgroundInvasive infections caused by Staphylococcus aureus have high clinical and epidemiological relevance. It is therefore important to monitor the S. aureus trends using suitable methods.AimThe study aimed to describe the trends of bloodstream infections (BSI) caused by meticillin-resistant S. aureus (MRSA) and meticillin-susceptible S. aureus (MSSA) in the European Union (EU) and the European Economic Area (EEA).MethodsAnnual data on S. aureus BSI from 2005 to 2018 were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net). Trends of BSI were assessed at the EU/EEA level by adjusting for blood culture set rate (number of blood culture sets per 1,000 days of hospitalisation) and stratification by patient characteristics.ResultsConsidering a fixed cohort of laboratories consistently reporting data over the entire study period, MRSA percentages among S. aureus BSI decreased from 30.2% in 2005 to 16.3% in 2018. Concurrently, the total number of BSI caused by S. aureus increased by 57%, MSSA BSI increased by 84% and MRSA BSI decreased by 31%. All these trends were statistically significant (p < 0.001).ConclusionsThe results indicate an increasing health burden of MSSA BSI in the EU/EEA despite a significant decrease in the MRSA percentage. These findings highlight the importance of monitoring antimicrobial resistance trends by assessing not only resistance percentages but also the incidence of infections. Further research is needed on the factors associated with the observed trends and on their attributable risk.

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.

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.

Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in Gram-negative species causing bacteraemia, EU/EEA, 2016.

BackgroundAntibiotic resistance, either intrinsic or acquired, is a major obstacle for treating bacterial infections.AimOur objective was to compare the country-specific species distribution of the four Gram-negative species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter species and the proportions of selected acquired resistance traits within these species.MethodWe used data reported for 2016 to the European Antimicrobial Resistance Surveillance Network (EARS-Net) by 30 countries in the European Union and European Economic Area.ResultsThe country-specific species distribution varied considerably. While E. coli accounted for 31.9% to 81.0% (median: 69.0%) of all reported isolates, the two most common intrinsically resistant species P. aeruginosa and Acinetobacter spp. combined (PSEACI) accounted for 5.5% to 39.2% of isolates (median: 10.1%). Similarly, large national differences were noted for the percentages of acquired non-susceptibility to third-generation cephalosporins, carbapenems and fluoroquinolones. There was a strong positive rank correlation between the country-specific percentages of PSEACI and the percentages of non-susceptibility to the above antibiotics in all four species (rho > 0.75 for 10 of the 11 pairs of variables tested).ConclusionCountries with the highest proportion of P. aeruginosa and Acinetobacter spp. were also those where the rates of acquired non-susceptibility in all four studied species were highest. The differences are probably related to national differences in antibiotic consumption and infection prevention and control routines.

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis.

BACKGROUND: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). METHODS: We estimated the incidence of infections with 16 antibiotic resistance-bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011-12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. FINDINGS: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148-763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480-38 430) attributable deaths and 874 541 (768 837-989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. INTERPRETATION: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. FUNDING: European Centre for Disease Prevention and Control.

The global need for effective antibiotics: challenges and recent advances.

The emerging problem of antibiotic resistance is a serious threat to global public health. The situation is aggravated by a substantial decline in the research and development of antibacterial agents. Hence, very few new antibacterial classes are brought to market when older classes lose their efficacy. There has been renewed and growing attention within policy groups to: (i) address the problem; (ii) discuss incentives for the development of urgently needed new treatments; (iii) preserve the efficacy of existing therapeutic options. We briefly review the basic principles of antibiotic resistance, and contrast the increasing resistance to the dwindling antibacterial 'pipeline'. We also highlight some recent policy initiatives aiming to secure the future need of effective antibiotics.

Cost-effectiveness analysis of a universal vaccination programme with the 7-valent pneumococcal conjugate vaccine (PCV-7) in Sweden.

The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly effective against invasive pneumococcal disease and has also provided some protection against all-cause pneumonia and acute otitis media. The objective of this study was to evaluate the projected health benefits, costs and cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show that vaccination of 1 cohort could potentially prevent 9 cases of pneumococcal meningitis, 22 cases of pneumococcal septicaemia, 509 cases of hospitalized pneumonia, 7812 cases of acute otitis media, and 2.7 fatalities, among children 0-4 y of age and 6 episodes of pneumococcal meningitis and 167 cases of pneumococcal septicaemia among adults. The incremental cost per QALY and LY gained was estimated to Euro 29,200 and Euro 51,400, respectively. When herd immunity was accounted for, the cost per QALYand LY gained was estimated to Euro 5500 and Euro 6600, respectively. Thus, the health benefits of a national vaccination programmeme can be achieved within a 'moderate' or 'low' cost per QALY gained.

Age- and serogroup-related differences in observed durations of nasopharyngeal carriage of penicillin-resistant pneumococci.

Using data from an ongoing Swedish intervention project, the observed durations of nasopharyngeal carriage of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) (MIC of penicillin G of >or=0.5 microg/ml) stratified by both pneumococcal serogroup and age of the carrier were compared. The means and 95% confidence intervals (CIs) were estimated by fitting a gamma distribution to the observed duration of carriage for each age and serogroup stratum. The mean observed duration of carriage for all cases was 37 days (95% CI, 35 to 38 days). Children below the age of 5 years carried PNSP for significantly longer periods (43 days; 95% CI, 41 to 45 days) compared with older individuals (25 days; 95% CI, 24 to 27 days). There were also differences within the group of cases below the age of 5 years, as the duration of carriage became significantly shorter for each increasing age step: <1, 1 to 2, and 3 to 4 years. In addition, patients <5 years of age carried serogroups 9 and 14 for significantly shorter periods than groups 6 and 23. Serogroup 9 was also carried for significantly shorter periods than group 19. For patients aged 5 years or older, no significant difference in carriage duration for different ages or serogroups could be noted. As young children have the longest duration of PNSP carriage, interventions aiming to reduce the prevalence in this group are of great importance. The results highlight the importance of taking both serogroup and age of the carriers into account when studying the dynamics of pneumococcal transmission in young children.

Penicillin-resistant pneumococci in Sweden 1997-2003: increased multiresistance despite stable prevalence and decreased antibiotic use.

Antimicrobial resistance patterns and capsular groups of penicillin-resistant Streptococcus pneumoniae (PRP; MIC penicillin G > or = 0.5 mg/ml) in Sweden between 1997 and 2003 were described, and trends in resistance and antibiotic sales during the same period were compared. The most common serogroups were in descending order 9, 19, 14, 23, and 6. Despite a low and stable annual PRP rate (proportion of PRP out of all pneumococci) of around 2% during the study period, the proportion of PRP resistant to other antibiotics increased. Of all tested PRP isolates, 82% were also resistant to trimethoprim/sulfamethoxazole, 32% had additional resistance to tetracycline, and 26% to erythromycin. Antibiotic sales figures for all studied antibiotic subgroups decreased during the same period. Little correlation was found between antibiotic sales and PRP resistance rates, indicating that there are still other poorly defined factors contributing to the reported resistance levels in the population. However, although PRP strains in Sweden are becoming more commonly resistant to antibiotics other than beta-lactams, the low and further reduced antibiotic sales still might have delayed the development and rapid spread of PRP in the population.

Occurrence of invasive pneumococcal disease and number of excess cases due to influenza.

BACKGROUND: Influenza is characterized by seasonal outbreaks, often with a high rate of morbidity and mortality. It is also known to be a cause of significant amount secondary bacterial infections. Streptococcus pneumoniae is the main pathogen causing secondary bacterial pneumonia after influenza and subsequently, influenza could participate in acquiring Invasive Pneumococcal Disease (IPD). METHODS: In this study, we aim to investigate the relation between influenza and IPD by estimating the yearly excess of IPD cases due to influenza. For this purpose, we use influenza periods as an indicator for influenza activity as a risk factor in subsequent analysis. The statistical modeling has been made in two modes. First, we constructed two negative binomial regression models. For each model, we estimated the contribution of influenza in the models, and calculated number of excess number of IPD cases. Also, for each model, we investigated several lag time periods between influenza and IPD. Secondly, we constructed an "influenza free" baseline, and calculated differences in IPD data (observed cases) and baseline (expected cases), in order to estimate a yearly additional number of IPD cases due to influenza. Both modes were calculated using zero to four weeks lag time. RESULTS: The analysis shows a yearly increase of 72-118 IPD cases due to influenza, which corresponds to 6-10% per year or 12-20% per influenza season. Also, a lag time of one to three weeks appears to be of significant importance in the relation between IPD and influenza. CONCLUSION: This epidemiological study confirms the association between influenza and IPD. Furthermore, negative binomial regression models can be used to calculate number of excess cases of IPD, related to influenza.

Reduction in outpatient antibiotic sales for pre-school children: interrupted time series analysis of weekly antibiotic sales data in Sweden 1992-2002.

OBJECTIVES: The aim of this study was to use detailed weekly data on outpatient antibiotic sales for pre-school children in Sweden to test for the significance of trends during 1992-2002. We also report on the special features found in weekly antibiotic data, and how the interrupted time series (ITS) design can adjust for this. METHODS: Weekly data on the total number of dispensed outpatient antibiotic prescriptions to pre-school children were studied, as well as the individual subgroups commonly used to treat respiratory tract infections in children: narrow-spectrum penicillins, broad-spectrum penicillins and macrolides. In parallel, monthly data of paracetamol sales of paediatric dosages were analysed to reflect trends in symptomatic treatment. An ITS model controlling for seasonality and autocorrelation was used to examine the datasets for significant level and trend shifts. RESULTS: A significant increase in mean and change in level could be found in the total antibiotic data in 1997, also reflected in broad-spectrum penicillin data where a similar trend break occurred in 1996. For macrolides, a trend break with a decrease in mean was noted in 1996, but no trend breaks were found in narrow-spectrum penicillin data. In contrast to the general decreasing trends in antibiotic sales, the yearly over-the-counter sales of paracetamol in paediatric preparations increased during the same period, with no identified trend breaks. CONCLUSIONS: The overall decrease in antibiotic sales and increase in paediatric paracetamol sales might suggest that symptomatic treatment in the home has increased, as antibiotics are less commonly prescribed.

The impact of active intervention on the spread of penicillin-resistant Streptococcus pneumoniae in Swedish day-care centres.

Policies for handling cases of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) in day-care groups vary between different counties in Sweden. The aim of this study was to evaluate the epidemiological effect of excluding PNSP-carriers from children's day-care centres (DCC). We followed the incidence in 14 DCC groups with ongoing PNSP-spread, by repeated group screens until no further cases could be identified. All identified carriers were excluded from DCC attendance in study area A (Skåne region) while they remained in the group in study area B (Göteborg and örebro), according to local policies. The intervention effect was evaluated by comparing the number of additional cases after the baseline screen (start of the intervention period) between the 2 study areas. All PNSP-isolates were characterized by resistance pattern, serotype and pulse-field gel electrophoresis. The relative risk for children in DCCs without active intervention was 6.4 (95% CI: 2.0-20.7). Each prevented case in area A can be estimated to have demanded the exclusion of 2 other children from day care for approximately 4 weeks each. The total cost-benefit outcome of this action has to be seen in the light of the local situation with regard to the population prevalence and the distribution of other risk factors.