High incidence of multisystem inflammatory syndrome and other autoimmune diseases after SARS-CoV-2 infection compared to COVID-19 vaccination in children and adolescents in south central Europe.

OBJECTIVES: To estimate the incidence and describe the spectrum of inflammatory and autoimmune diseases linked to SARS-CoV-2 infection and COVID-19 vaccination in children from two neighbouring south central European countries. METHODS: We performed a multi-centre prospective cohort study of children under 18 years diagnosed with inflammatory/autoimmune diseases linked to SARS-CoV-2 infection or COVID-19 vaccination, who were admitted to the paediatric tertiary care hospitals in Slovenia and Friuli Venezia Giulia, Italy, from January 1, 2020, to December 31, 2021. Disease incidence was calculated based on laboratory-confirmed cases only. RESULTS: Inflammatory and autoimmune diseases linked to SARS-CoV-2 were diagnosed in 192 children (127 laboratory-confirmed), of whom 112 had multisystem inflammatory syndrome (MIS-C), followed by vasculitis, neurological and cardiac diseases. Calculated risk of MIS-C was 1 in 860 children after SARS-CoV-2 infection and cumulative incidence of MIS-C was 18.3/100,000 of all children. Fifteen children had severe COVID-19. Two patients with MIS-C and a patient with myositis presented after COVID-19 vaccination. All 3 had at presentation also a serologically proven recent SARS-CoV-2 infection. After MIS-C, nine patients were vaccinated against COVID-19 and 25 patients had a SARS-CoV-2 reinfection, without recurrence of MIS-C. CONCLUSIONS: Autoimmune diseases following SARS-CoV-2 infection in children were 8.5 times as common as severe COVID-19. MIS-C was the most common manifestation and its incidence in this predominantly white population was higher than previously reported. MIS-C does not seem to recur after SARS-CoV-2 reinfection or COVID-19 vaccination. Autoimmune diseases were much more common after SARS-CoV-2 infection than after COVID-19 vaccination.

European Antibiotic Awareness Day (EAAD): any impact on antibiotic consumption and public awareness in Slovenia?

Objectives: To evaluate the impact of European Antibiotic Awareness Day (EAAD) on antibiotic consumption, improvements in general public awareness and antibiotic resistance in Slovenia. Methods: Outpatient data for the period from 2002 to 2016 and hospital antibiotic consumption data for 2004-16 were collected using the Anatomical Therapeutic Chemical (ATC) classification/DDDs. Outpatient antibiotic consumption data were expressed in DDDs/1000 inhabitants/day (DIDs), number of packages/1000 inhabitant-days and number of prescriptions/1000 inhabitants/year. Hospital consumption data were expressed in DIDs, number of DDDs/100 bed-days and number of DDDs/100 admissions. Segmented regression analysis of interrupted time series was used to estimate the effects of these interventions on antibiotic consumption. Results: During the 8 year period since establishing EAAD, a 9%-17% decrease in outpatient antibiotic consumption has been observed, depending on the measurement unit, which was a little more than in the 6 years prior to EAAD (7%-12%). The trend change in hospital consumption after EAAD was established remained small, with a highly non-significant P value. Eurobarometer data did not show an increase in knowledge on antibiotic use. Resistance of Streptococcus pneumoniae to penicillin and macrolides decreased during EAAD activities. Conclusions: EAAD activities were associated with a decreasing trend in community consumption. Owing to many other national activities on the prudent use of antimicrobials in outpatients and inpatients it is difficult to analyse the direct effect of EAAD.

Antibiotic consumption and resistance of gram-negative pathogens (collateral damage).

Antibiotics are commonly prescribed in community and hospital care. Overuse and misuse favors emergence and spread of resistant bacteria. The ATC/DDD methodology is commonly used for presenting the drug utilization data. In primary care, the consumption is usually expressed in DDD per 1,000 inhabitants per day, in hospital, preferably in DDD per 100 bed days and DDD per 100 admissions. The alternative metric is days of therapy (DOT), which needs IT support. Antibiotics have ecological adverse effects at individual and population level. Antibiotics select resistant bacteria among pathogens and normal flora. Broad-spectrum antibiotics, low dosage and prolonged antibiotic therapy favor the development of resistance. Although total use of antibiotics in hospital is much less than in the community, the intensity of use magnified by cross infection ensures a multitude of resistant bacteria in today's hospitals. Reversal of resistance is complex and might persist for many years despite the introduction of antimicrobial containment and stewardship programs.

The long-term effects of restrictive interventions on consumption and costs of antibiotics.

In the last decade, Slovenia introduced restrictive measures for some antibiotic classes in ambulatory care as well as regulatory interventions to reduce costs. The aim of this study was to analyse the effects of these interventions on consumption and costs of antibiotics in ambulatory care. Consumption data were expressed in defined daily doses/1000 inhabitants per day (DID), number of packages/1000 inhabitants per day and number of prescriptions/1000 inhabitants per year. In 2000, Slovenia introduced restrictive measures for prescription of amoxicillin/clavulanic acid (AMC) and fluoroquinolones, in 2005 for oral third-generation cephalosporins and in 2009 for macrolides. Segmented regression analysis of interrupted time series was used to estimate the effects of restrictive interventions on antibiotic consumption. Total outpatient consumption of antibacterial drugs decreased by 29.65% from 20.27 DID in 1999 to 14.26 DID in 2012. Three years after the introduction of restrictions, consumption of AMC, fluoroquinolones and macrolides decreased by 29.3%, 23.8% and 28.8%, respectively, compared with the year before the intervention, and of non-restricted antibiotics by 3.3% (in 2003). Twelve years after the introduction of restrictive interventions, use of AMC and fluoroquinolones decreased by 28.1% and 28.5%, respectively, and use of non-restricted antibiotics by 18.8% (in 2012). In the same time period, the costs of AMC and fluoroquinolones were reduced by 63.3% and 52.4%, respectively, and of non-restricted antibiotics by 46.9%. Restrictive interventions in ambulatory care are effective in reducing antibiotic consumption and costs. Restrictive interventions had a significantly greater impact on consumption 3 years post-intervention than after 12 years.