The Impact of National Activities on Antibiotic Consumption in Hospitals and Different Departments over a 14-Year Period.

The aim of this study was to assess the use of antibiotics in hospitals and different departments over 14 years (2006-2019) and the impact of various national activities related to this, including national audits of the use of antibiotics for systemic use. The consumption of antibiotics for systemic use (J01) from all Slovenian hospitals (n = 29) and five departments (internal medicine, surgery, ICU (medicine, surgery), paediatrics and gynaecology/obstetrics) was collected. Total hospital consumption was expressed as the number of defined daily doses (DDDs) per 1000 inhabitants per day (DID), the number of DDDs/100 bed days and the number of DDDs/100 admissions. Over 14 years, J01 hospital consumption increased by 13.8%, expressed in DDDs/100 bed days (p = 0.002). In 2019, compared to 2006, the consumption of J01, expressed in DDD/100 bed days, increased from 19.9% to 33.1% in all departments, except intensive care units. J01 consumption expressed in DDD/100 admissions increased by 7.0% to 39.4% in all but paediatric wards (where it decreased by 12.7%). In all years, we observed large variations in the consumption of antibiotics in departments of the same type. The effectiveness of audit interventions aimed at optimizing antibiotic consumption exhibited notable variation across hospitals, with specialized facilities generally demonstrating superior outcomes compared to general hospitals.

Impact of the COVID-19 Pandemic on Community Consumption of Antibiotics for Systemic Use and Resistance of Invasive Streptococcus pneumoniae in Slovenia.

The present study aims to investigate the impact of the COVID-19 pandemic on community antibiotic consumption and the resistance of invasive Streptococcus pneumoniae (2015-2022) to penicillin in Slovenia. During the pandemic in 2020 and 2021, the total use of antibiotics for systemic use decreased by 23.5% and 24.3%, expressed in defined daily doses per 1000 inhabitants per day (DID), while the use of penicillins, macrolides and broad-spectrum penicillins decreased by 30%, 20% and by 17.5%, respectively, and that of broad-spectrum macrolides fell by 17.1%. The incidence of invasive pneumococcal diseases (IPD) in Slovenia had a large decline during the pandemic. Decreased resistance to macrolides was significantly associated with decreased use of macrolides, while for penicillins the correlation could not be statistically confirmed. The proportion of PCV13 serotypes in IPD in Slovenia decreased after the introduction of the vaccine in the national programme, falling from 81.6% in 2015 to 45.5% in 2022. We noticed a decrease in the serotypes 1, 14, 9V, 7F, 4, 6A and an increase in the serotypes 3, 8, 22F, 11A, 23A and 15A. National interventions during the COVID-19 pandemic substantially decreased outpatients' antibiotic consumption, as well as incidence and resistance of invasive S. pneumoniae.

Correlation between Antibiotic Consumption and Resistance of Invasive Streptococcus pneumoniae.

There is a lack of long-term studies that correlate different metrics of antibiotic consumption and resistance of invasive S. pneumoniae. The present study aims to investigate the correlation between national outpatients total antibiotic, penicillin and broad spectrum penicillins consumption expressed in daily doses per 1000 inhabitants per day (DID) with the ATC/DDDs, WHO version of 2019 (new version) and 2018 (old version), number of prescriptions per 1000 inhabitants per year (RxIDs) and number of packages per 1000 inhabitant per day (PIDs) with the resistance of invasive S. pneumoniae in Slovenia in the period from 2000 to 2018. The prevalence of penicillin resistance of invasive S. pneumoniae decreased by 47.13%, from 19.1% to 10.1%. Decline of resistance showed the highest correlation (R = 0.86) between RxIDs followed by PID (R = 0.85) and resistance of S. pneumoniae. Higher correlation between total use of antibiotics expressed in DID WHO version 2019 (R = 0.80) than for WHO version 2018 (R = 0.78) was found. Very high (R = 0.84) correlation between use of ß-lactams expressed in PID, and RxIDs (R = 0.82) and reasonable (R = 0.59) correlation expressed in DIDs version 2019 was shown as well. The consumption of broad -spectrum penicillins (J01CA and J01CR02) expressed in PID (R = 0.72) and RxIDs (0.57) correlated significantly with the resistance of S. pneumoniae as well. A new finding of this study is that RxIDs correlated better with the resistance of S. pneumoniae than total consumption of antibiotics expressed in DID and significant correlations exist between use of broad-spectrum penicillins expressed in PID and RxIDs.

Lack of correlation between reduced outpatient consumption of macrolides and macrolide resistance of invasive Streptococcus pneumoniae isolates in Slovenia during 1997-2017.

OBJECTIVES: The objective of this study was to investigate the correlation between decreased national consumption of macrolides and resistance of invasive Streptococcus pneumoniae isolates in Slovenia during 1997-2017. METHODS: A total of 4241 invasive S. pneumoniae isolates were collected in Slovenia from 1997 to 2017. The presence of erm(B), mef(E), mef(A) and erm(TR) genes was determined by PCR in 612 erythromycin-resistant isolates. Selected isolates carrying the mef(A) gene were further examined by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) was performed for 161 erythromycin-resistant isolates from 2004 to 2009. RESULTS: Consumption of macrolides decreased by 42.5% between 1997 and 2017, and by 57.0% from the highest consumption during 1999 to 2017. Resistance of S. pneumoniae increased by 120.7% in the same period, from 5.8% in 1997 to 12.8% in 2017. The most prevalent serotypes among macrolide-resistant isolates were 14 (54.9%), 19A (9.0%), 19F (8.3%), 6B (7.2%), 6A (5.2%) and 9V (19; 3.0%). The most prevalent determinant of macrolide resistance in the observed period was erm(B) (43.0%; 263/612), followed by mef(A) (36.3%; 222/612) and mef(E) (14.9%; 91/612). During the study period, an increasing trend in serotype 14, mef(A)-carrying isolates was observed, with a peak in 2011 (P<0.001); 63/71 isolates (88.7%) with the mef(A) gene were clonally related and were related to the international England14-9 clonal cluster. CONCLUSIONS: The reason for the observed increase in macrolide resistance among invasive S. pneumoniae in Slovenia despite decreased macrolide consumption was spread of the England14-9 clonal cluster.

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.

Legal framework of antimicrobial stewardship in hospitals (LEASH): a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) cross-sectional international survey.

Antimicrobial stewardship (AMS) is the cornerstone activity in the combat against antimicrobial resistance. In order to ensure sustainable deployment and development of AMS, a strategic and regulatory framework needs to be provided by national healthcare authorities. Experts from 32 European countries, Israel and Turkey were invited to participate in a cross-sectional internet-based survey from October 2016 to May 2017 on the legal framework and mandatory components (structures, activities) of AMS in hospitals, i.e. components required by legislation or regulations. We collected data from 25 countries and two regions (in countries with federal health administration). Laws regulating AMS existed in seven countries and one region. Other health ministry regulations were applicable in 13 countries and one region. National strategies and/or action plans approved by ministries of health were in place in 13 countries and one region. Conversely, five countries and one region had no regulation of AMS in hospitals. Funding for AMS in hospitals was provided in five countries and one region. Eight countries and one region reported mandatory AMS structures and activities complying with the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) structure, policy and practice indicators. In 10/27 cases, however, the mandatory AMS activities were not being fully carried out. The survey showed heterogeneous legal frameworks for AMS in hospitals, and in many countries it was even lacking. The situation may be critical in countries with poor control of antimicrobial use and resistance. Recent international initiatives calling on policy-makers to address the threat of antimicrobial resistance could yield improvement.

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.

Antibiotic prescribing in long-term care facilities for the elderly: EVIPNet evidence brief for policy, number 3

The Ministry of Health of Slovenia commissioned this evidence brief for policy, to be published under the aegis of the WHO European Evidence-informed Policy Network, to develop evidence-informed options for the country to consider in tackling the problem of prescribing broad-spectrum antibiotics to elderly people in long-term care facilities. Such treatment is taking place without proper diagnosis of infection and microbiological testing, and without indication, choice, dose or duration of therapy, thus representing the key driving factor for antimicrobial resistance. The work was carried out within the framework of the Biennial Collaborative Agreement between the Ministry of Health and WHO, involving high-level national policy institutions and national experts, and supported by the technical experts of WHO Regional Office for Europe. The Slovene National Institute for Public Health convened a working group comprising representatives from the clinical field, pharmacology, public health and health care management. The group identified, selected, appraised and synthesized relevant research evidence on the problem, three options for tackling it and considerations in implementing them. The three options are: surveillance, monitoring and audit/feedback on antibiotic consumption and antimicrobial resistance in long-term care facilities; development and implementation of guidelines and clinical pathways for diagnosing and treating infections; and continuous medical education for health care professionals and provision of health information to residents of long-term care facilities and their relatives/visitors.

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.

The influence of a sustained multifaceted approach to improve antibiotic prescribing in Slovenia during the past decade: findings and implications.

INTRODUCTION: Rising antibiotic resistance has become an increasing public health problem. There is a well-established correlation between antibiotic consumption and antimicrobial resistance. Consequently, measures to rationalize the prescribing of antibiotics should reduce the resistant strains. Following a 24% increase in antibiotic consumption at the end of the 1990s, multiple activities were designed and introduced by the Health Insurance Institute of Slovenia (ZZZS) and other organizations in Slovenia at the end of 1999. These activities reduced the antibiotic consumption by 18.7% by 2002. These measures have continued. OBJECTIVE: To study changes in antibiotic utilization from 1995 to 2012 alongside the multiple interventions and their consequences, including changes in resistance patterns. METHODS: This was a retrospective observational study involving all patients dispensed at least one ZZZS prescription for an antibiotic in Slovenia. Utilization was expressed in defined daily doses per thousand inhabitants per day. Multifaceted interventions were conducted over time involving all key stakeholder groups, that is, the Ministry of Health, ZZZS, physician groups and patients. These included comprehensive communication programs as well as prescribing restrictions for a number of antibiotics and classes. RESULTS: From 1999 to 2012, antibiotic consumption decreased by 2-9% per year, with an overall decrease of 31%. There were also appreciable structural changes. Overall antibiotic utilization and the utilization of 7 out of 10 antibiotics significantly decreased after multiple interventions. The resistance of Streptococcus pneumoniae to penicillin decreased in line with decreased utilization. However, its resistance to macrolides increased from 5.4 to 21% despite halving of its utilization. The resistance of Escherichia coli to fluoroquinolones doubled from 10 to 21% despite utilization decreasing by a third. Expenditures on antibiotics decreased by 53%. CONCLUSION: Multiple demand-side measures introduced following increased utilization significantly decreased subsequent antibiotic utilization and associated costs. However, there was variable impact on antibiotic resistance. Additional targeted activities are planned to further reduce antibiotic prescribing and resistance.

Immunization of high-risk paediatric populations: Central European Vaccination Awareness Group recommendations.

Over the last decade, childhood immunization has substantially reduced morbidity and mortality from vaccine-preventable diseases. However, particular paediatric risk groups, such as those with comorbidities, may not be adequately vaccinated despite being more susceptible to complications and death from certain infectious diseases. This may be due to lack of immunization recommendations, lack of awareness, or incomplete adherence to existing guidelines. Furthermore, recommendations for immunization can be inconsistent across Europe. An expanded initiative from the Central European Vaccination Awareness Group aims to raise awareness of the different high-risk paediatric groups, differentiate them according to their specific risk, and formalise a guidance statement for the immunization of each population.

Risk factors for colonization with ampicillin and high-level aminoglycoside-resistant enterococci during hospitalization in the ICU and the impact of prior antimicrobial exposure definition: a prospective cohort study.

The aim of our prospective cohort study was to determine the incidence, genetic relatedness and risk factors for colonization with ampicillin and high-level aminoglycoside-resistant enterococci (ARHLARE) among patients hospitalized in the intensive care unit. During 15-month period, we included 105 patients. The only independent risk factor for ARHLARE colonization was days of cefotaxime/ceftriaxone therapy [odds ratio (OR): 1.13; 95% confidence interval (CI) 1.10-1.27; P  =  0.045]. Patients with higher total use of antibiotics, patients on prolonged mechanical ventilation, and patients with urinary tract infection (UTI), were also found to be at increased risk to become colonized with ARHLARE. Pulsed-field gel electrophoresis suggested multifocal origin of the majority of the colonizing strains. Our results show that an increase in total antibiotic consumption for 10 defined daily doses (DDD)/patient increased the odds of colonization with ARHLARE for 36%. Further efforts to optimize antimicrobial use in high risk patients are proposed.

Rotavirus vaccination in central Europe.

Each year, rotavirus (RV) infection is the leading cause of acute gastroenteritis requiring hospitalisation and of nosocomially transmitted diseases in children younger than 5 years across Central European Vaccination Awareness Group (CEVAG) countries; however, inadequate surveillance systems and lack of routine RV testing still exist in most CEVAG countries, making it difficult to accurately assess the present burden of acute RV gastroenteritis in the younger population. Furthermore, routine immunisation of infants with RV vaccines has not been implemented, and no official and uniform recommendations exist in most of the countries in these territories. The present study provides CEVAG country-specific estimates of the disease burden of RV gastroenteritis among the youngest population and presents evidence-based advice on the use of RV vaccines in the region, while providing a framework for vaccination at the national level.

Recommendations for tick-borne encephalitis vaccination from the Central European Vaccination Awareness Group (CEVAG).

Tick-borne encephalitis (TBE) is a viral neurological zoonotic disease transmitted to humans by ticks or by consumption of unpasteurized dairy products from infected cows, goats, or sheep. TBE is highly endemic in areas of Central and Eastern Europe and Russia where it is a major public health concern. However, it is difficult to diagnose TBE as clinical manifestations tend to be relatively nonspecific and a standardized case definition does not exist across the region. TBE is becoming more important in Europe due to the appearance of new endemic areas. Few Central European Vaccination Awareness Group (CEVAG) member countries have implemented universal vaccination programmes against TBE and vaccination coverage is not considered sufficient to control the disease. When implemented, immunization strategies only apply to risk groups under certain conditions, with no harmonized recommendations available to date across the region. Effective vaccination programmes are essential in preventing the burden of TBE. This review examines the current situation of TBE in CEVAG countries and contains recommendations for the vaccination of children and high-risk groups. For countries at very high risk of TBE infections, CEVAG strongly recommends the introduction of universal TBE vaccination in children > 1 y of age onwards. For countries with a very low risk of TBE, recommendations should only apply to those traveling to endemic areas. Overall, it is generally accepted that each country should be free to make its own decision based on regional epidemiological data and the vaccination calendar, although recommendations should be made, especially for those living in endemic areas.

Adult vaccination in 11 Central European countries - calendars are not just for children.

As Europe's population ages, disease morbidity and treatment costs in the adult population are likely to rise substantially, making this a pertinent time to review and revise preventive strategies such as vaccination. Vaccine uptake remains a problem for adults and there is a lack of coordinated programmes for vaccination of adults. Countries in Western Europe have begun to identify the need to increase adult vaccination, but the situation in Central European countries remains poorly identified and inadequately described. This paper summarises the evidence to support the development of an adult vaccination calendar in the Central European Vaccination Awareness Group (CEVAG) member countries (Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Romania, Slovakia, Slovenia and Turkey). CEVAG recommends the introduction of an adult vaccination calendar, which should include vaccination against diseases that represent a large burden in adults in terms of mortality and morbidity. This calendar could be modified to meet the priorities of individual countries.

Rubella revisited: where are we on the road to disease elimination in Central Europe?

Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing. Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015. This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory-confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened.

Severe Clostridium difficile-associated disease in children.

Three cases of Clostridium difficile-associated disease in children were detected within a short time interval. Intensive therapy was required in 2 cases with colectomy in one of them. One of the severe cases was community-acquired. Two patients had underlying diseases (Hirschprung disease, Down syndrome) and also tested positive for enteric viruses (rotavirus, calicivirus).

Hospital antibiotic management in Slovenia--results of the ABS maturity survey of the ABS International group.

BACKGROUND: The ever-increasing resistance to antibiotics is a serious worldwide problem. Antibiotic strategies for appropriate use of antimicrobials in hospitals are not well defined. METHODS: A questionnaire on "ABS maturity of hospitals" was the basis of an analysis as a part of an EU project. This questionnaire was sent to 12 hospitals in Slovenia including 11 general hospitals and one university hospital. MAIN FINDINGS: All 12 hospitals returned the questionnaires. Maturity of antibiotic strategies were considered moderate (3.74). Antibiotic consumption had the highest maturity ratio (4.44), followed by diagnostics (3.96), antibiotic-related relationships (3.58), antibiotic-related personnel development (3.44) and antibiotic-related organization (3.36). The availability of data on antibiotic consumption had the highest ranking; designation of and time resources for antibiotic officers were ranked lowest. CONCLUSION: In Slovenia the maturity of antibiotic strategies in general hospitals and in one university hospital is moderate. The data provide a basis for further development of antibiotic-related issues in hospitals.