Improving Antibiotic use through a Nationwide Decentralized Project – A Nine-Year Experience Cars O, Stålsby Lundborg C, Mölstad S Swedish Strategic Programme for the Rational use of Antimicrobial Agents and Surveillance of Resistance (STRAMA), Sweden Problem Statement: In the early 1990s, an increase in penicillin-resistant pneumococci (PRP) in children in southern Sweden led to the creation of a multiprofessional national network of experts from all main stakeholders in the antibiotic field to address the problem. Objectives: To describe antibiotic use and resistance patterns in different regions, age groups, and patient populations; and to reduce inappropriate antibiotic use, especially in primary care, in order to hold antimicrobial resistance (AMR) at the lowest possible level. Design: Randomized controlled trials, different types of quasi-experimental designs, time- series analysis, and cross-sectional studies, depending on possibilities in each situation. Setting and Population: All Swedish counties, mainly in the area of public primary care, with data collection through pharmacies and primary care services. Intervention: National media and information campaigns, aimed at influencing consumers and prescribers, were developed and implemented with the collaboration of various stakeholders such as Drug and Therapeutic Committees (DTCs) and pharmacies. In addition, multifaceted interventions, mainly targeting general practicioners and focusing on specific subject areas appropriate to local needs, were developed and carried out. Interventions included development of local treatment guidelines and implementation of the guidelines through educational outreach that utilized discussion as well as group and/or individual feedback on prescriptions and written simulated cases. Outcome Measures: National and local dispensing data in general, and divided by age and sex, expressed as defined daily dose/1,000 inhabitants per day (DDD/TID) or number of prescriptions per ATC code; resistance frequencies in key pathogens. Results: National antibiotic sales decreased by 22% from 1993 to 2002 (17.7 to 13.9 DDD/TID). National dispensing of macrolides decreased among children 0–6 years from 3.7 DDD/TID in 1993 to 1 DDD/TID in Use of quinolones for uncomplicated urinary tract infection decreased from 21% to 12% (p<0.05) between 2000 and 2002, in accordance with guidelines, in five counties that conducted a diagnosis-prescribing study. Unexplained wide variations in antibiotic sales data between counties and communities is seen; antibiotic prescriptions per 1,000 children 0–6 years varied from 400 to 1,400 per year in 1998, and between 250 and 1,000 in For the age group above 80, variation was between 600 and 1,700. Antibiotic resistance in general is stable. For PRP, a decrease in incidence from 100 to 53 per 100,000 inhabitants was seen for children 0–6 years from 1997 to Conclusions: There were significant changes in total antibiotic use in targeted groups and antibiotic classes. Marginal or no increase in national resistance rates has been seen, in contrast to the situation in many other countries. PRP incidence has decreased among children 0–6 years.

Sweden  Population – million  Total expenditure on health as % of GDP – 8.7  Life expectancy – 80.4 years  Under five mortality rate per 1000 – 3.5  Mainly publicly funded healthcare  Drug sales are exclusively through the National Corporation of Swedish Pharmacies (Apoteket AB), owned by the state and non profit-orientated

Background In the early 1990s, an increase in penicillin-resistant pneumococci (PRP) in children in southern Sweden led to the creation of a multiprofessional national network of experts from all main stakeholders in the antibiotic field to address the problem. It’s main objectives are to describe antibiotic use and resistance patterns in different regions, age groups, and patient populations; and to reduce inappropriate antibiotic use, especially in primary care, in order to hold antimicrobial resistance (AMR) at the lowest possible level. STRAMA The Swedish Strategic programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance; STRAMA was established in 1995 following discussions between several national authorities and organisations. The main aim was to create a decentralised organisation to establish a broad base throughout the country. Through the County Medical Officers at least one regional STRAMA-group was established in each county. The national management board of STRAMA is made up of the following Swedish public bodies and organisations: The Institute for Infectious Disease Control, The Association of County Medical Officers, The National Board of Health and Welfare, The Medical Products Agency, The Society of Medicine's Reference Group on Antibiotics, The Infection Control Association, The Federation of County Councils, The Association of Local Authorities, Apoteket AB, The National Veterinary Institute and The Board of Agriculture. Since 2000 STRAMA has financial support from the Swedish the government.

Local STRAMA groups In each county at least one STRAMA-group has been formed. The County Medical Officers for Communicable Diseases are acting as chairmen of these regional groups which include specialists from different medical fields e.g. general practice, infectious diseases, ENT, paediatrics, clinical microbiology, as well as pharmacists. The group's main objective is to evaluate the local utilisation of antibiotics and the local pattern of bacterial resistance as well as to implement guidelines for treatment of common infectious diseases.

Drug consumption data Since 1975, the national Corporation of Swedish Pharmacies produces sales statistics on medicines. Data can be presented as out patient care divided in sex and age or hospital care data. To facilitate studies from a medical point of view, defined daily doses (DDD) as well as number of prescriptions are used as a unit of comparison. The DDD for a drug is established on the basis of the assumed average dose per day for the drug given to adults for its main indication. This classification together with the Anatomical Therapeutic chemical (ATC) classification system is recommended and continuously updated by WHO. Resistance data In Sweden surveillance of certain resistant pathogens are regulated in the Communicable Disease Act. Reports of isolated penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Notification shall be done to The Swedish Institute for Infectious Disease Control. In addition to this a combined surveillance and quality control programme has been in place since 1994 where 30 microbiological laboratories, using standardized methods, collect quantitative data for defined antibiotics in consecutive clinical isolates of a number of bacterial species.

Intervention National media and information campaigns, aimed at influencing consumers and prescribers, were developed and implemented with the collaboration of various stakeholders such as Drug and Therapeutic Committees (DTCs) and pharmacies. In addition, multifaceted interventions, mainly targeting general practitioners and focussing on specific subject areas appropriate to local needs, were developed and carried out. Interventions included development of local treatment guidelines and implementation of the guidelines through educational outreach that utilized discussions as well as group and/or individual feedback on prescriptions and written simulated cases. Examples of local projects  Parent education in day care centres  Educational material about infections and antibiotics for 10 year old school children  Written simulated cases as educational tools in infectious diseases  Evaluation of antibiotic treatment for acute otitis media among children  Nosocomial infections within community nursing homes  Infections in primary care – antibiotic use in relation to diagnosis

Results  National antibiotic sales decreased by 22% from 1993 to 2002 (17.7 to 13.9 DDD/TID), even more prominent in children 0-6 years (Figure 1).  National dispensing of macrolides decreased among children 0–6 years from 3.7 DDD/TID in 1993 to 1 DDD/TID in 2002 (Figure 2).  Use of quinolones for uncomplicated urinary tract infection decreased from 21% to 12% (p<0.05) between 2000 and 2002 in accordance with guidelines, in five counties that conducted a diagnosis-prescribing study (Figure 3).  However the same study showed an continued high consumption for acute bronchitis (Figure 4).  Unexplained wide variations in antibiotic sales data between counties and communities was seen; antibiotic prescriptions per 1,000 children 0–6 years varied from 400 to 1,400 per year in 1998, and between 250 and 1,000 in For the age group above 80, variation was between 600 and 1,700. Antibiotic resistance in general is stable. For PRP, a decrease in incidence from 100 to 53 per 100,000 inhabitants was seen for children 0–6 years from 1997 to 2002.

Conclusions  A nationwide decentralised system for rational antibiotic use has been effective in Sweden for 10 years.  There were significant changes in total antibiotic use especially for children.  Resistance levels for upper respiratory tract pathogens has been stable.  PRP incidence has decreased among children 0-6 years.

Examples of references  Mölstad S, Cars O. Major Change in the Use of Antibiotics following a National Programme: Swedish Strategic Programme for the Rational use of Antimicrobial Agents and Surveillance of Resistance (STRAMA). Scand J Infect Dis 1999;31:  Ekdahl K, Cars O. Role of communicable disease control measures in affecting the spread of resistant pneumococci: the Swedish model. Clin Microbiol Infect 1999;5:4S48-4S54.  Stålsby Lundborg C, Olsson E, Mölstad S, and the Swedish Study Group on Antibiotic Use. Antibiotic prescribing in outpatients – a one- week diagnosis–prescribing study in five counties in Sweden. Scand J Infect Dis 2002;34:442,48.  Andre M, Odenholt I, Schwan A, Axelsson I, Eriksson M, Hoffman M, Molstad S, Runehagen A, Stålsby Lundborg C, Wahlstrom R; Swedish Study Group on Antibiotic Use. Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests. Scand J Infect Dis. 2002;34:  Andre M, Mölstad S, Stålsby Lundborg C, Odenholt I, Axelsson I, Eriksson M, Runehagen A, Schwan Å. Management of urinary tract infections in primary care: a repeated 1-week diagnosis-prescribing study in 5 counties in 2000 and Accepted in Scand J Infect Dis. 