Northern Europe

3.2. Northern Europe

In Ireland the National Disease Surveillance Centre was asked by the gov- ernment to make recommendations about combating antimicrobial resistance. The committee prepared a report known as SARI (Strategy for the Control of Antimicrobial Resistance in Ireland) (National Disease Surveillance Centre, 2001). There are five major constituents of this strategy:

1. The surveillance of antimicrobial resistance both in the community and the hospitals.

2. The monitoring of the supply and use of antimicrobials. Especially in this field it is recommended that: (a) The tight legislative controls that exist in the area of antibiotic prescrib-

ing should be maintained and enforced. (b) A system for the collection and analysis of antimicrobial use and pre-

scribing in hospitals and the community should be established.

National Policies and Antibiotic Prescribing 551 (c) A basic set of data agreed by the committee should be collected, that is,

the origin of the prescription (hospital or community), the agent and dose prescribed, the indication and the length of treatment.

3. The development of guidance in relation to the appropriate use of antimicrobials: (a) Expert opinion on infectious diseases should be available 365 days a year

to all medical practitioners both in the community and the hospitals. (b) National guidelines for appropriate use of antibiotics should be drawn up and introduced in practice both in the community and the hospitals. (c) A process for reduction of the inappropriate use of antibiotics should be defined, different for the community and the hospitals. (d) Interventions aimed at changing clinical practice should be supported, encouraged, and reinforced by a process of regular audit. (e) A priority should be given to improvement of vaccine uptake, espe- cially for influenza and pneumococcus.

4. Education: (a) Education should commence at undergraduate level. (b) Education should be directed at, all clinical professional groups provid-

ing patient care, the pharmaceutical industry, and the general public.

5. The development of principles in relation to infection control in the hospital and community setting.

Furthermore the committee recommended the prioritization of funding the campaign against resistance and defined the areas of future research in the area of antimicrobial prescribing and the development of new treatment modalities and new antimicrobial agents.

In the UK almost a decade ago, a survey was performed among consultant microbiologists and pharmacists nationwide on methods used to control antibi- otic usage (Working Party Report, 1994). A written policy for surgical prophylaxis was available in 51% of hospitals, 62% had a written policy for therapy, and 79% an antibiotic formulary. Compliance was monitored in approximately 40% and steps were taken in half to control non-compliance. A restricted list was operated in 77% of hospitals and 90% of respondents believed formularies to be beneficial.

After that, the British Society for Antimicrobial Chemotherapy (BSAC), who commissioned the survey, recommended that the following minimum control measures should be implemented in all UK hospitals (Working Party Report, 1994).

1. Formulary and policies should be updated frequently with appropriate funding for both staff and printing costs.

2. There should be widespread consultation before inception and effective enforcement thereafter via good educational programs.

552 Moyssis Lelekis and Panos Gargalianos

3. A broadly representative committee should be set up to consider timely introduction of new antibiotics with the authority to ensure their availability or non availability. Quality of care should take preference over financial considerations such as antibiotic cost.

4. Agents not included in the formulary should be only available for formal clinical trials or after discussion with the requesting consultant.

5. Microbiology and pharmacy departments should have adequate facilities to ensure that educational programs can be carried out.

6. Programs for assessment and appropriate adoption of automatic stop dates, antibiotic prescription forms, and utilization coordinators should be introduced.

7. There should be compulsory notification of pharmaceutical promotional activities to the formulary committee in order that permission for these activities be granted and that a member of the committee may be present if appropriate.

8. Laboratories should regularly make local sensitivity patterns widely known and routinely should only report on those agents, which appear on their for- mulary and policy.

Despite apparent use of control measures like these, there were reports of increasing antibiotic prescribing both in the hospitals and the community (Gould, 1996). The experience of Grampian is very characteristic. In the northeastern part of Scotland despite the implementation of a very strict antibiotic policy, a significant increase in antibiotic consumption was recorded between 1992–3 and 1996–7 (Gould and Jappy, 2000). The results from this experience highlight the current difficulty in controlling prescribing budgets, the increasing use of antibiotics and the consequent increase of antimicrobial- resistant organisms.

In 1998 the Government’s response to the House of Lords Select Committee on Science and Technology’s report “Resistance to antibiotics and other antimicrobial agents,” indicated its intention to implement a comprehensive strategy to tackle the problem of resistance. Key elements of this strategy are (Standing Medical Advisory Committee, 1998):

1. Surveillance to provide the data on resistant organisms, illness due to them, and antimicrobial usage necessary to inform action.

2. Prudent antimicrobial use to reduce the pressure for resistance by reducing unnecessary and inappropriate exposure of microorganisms to antimicro- bial agents in clinical practice, veterinary practice, animal husbandry, agri- culture and horticulture. Prudent antimicrobial use in humans in particular should be promoted through (a) Professional education in all levels of seniority

National Policies and Antibiotic Prescribing 553 (b) Prescribing support (national, local guidelines etc)

(c) Organizational support.

3. Infection control to reduce the spread of infection in general and of resis- tant microorganisms in particular.

All these need to be supported by the provision of tailored information, education, communication, research, the necessary infrastructure, organization support, and where necessary, legislation or regulation.

The first result of this strategy was a public education campaign advising patients not to pressure their doctors to give them antibiotics for colds and flu and recommended 3 days treatment for simple urinary tract infections (Gould, 2001). With the evidence of reduced expectations by patients, there has been downturn in community prescribing but this had already started before 1998.

Lastly, a favourable impact on antibiotic prescribing is expected after the last reforms of the National Health Service, with its drive to improve quality and ensure better education of and performance by doctors. This includes the introduction of Clinical Governance, which intends to make doctors responsi- ble for the quality of their antibiotic prescribing and empower their employers to ensure that this quality is achieved (Gould, 2001).

Even though significant differences exist between various regions, antibi- otic use in the Netherlands is the lowest in Europe (Bruinsma et al., 2002; Cars et al., 2001). Antibiotic use in this country was always restrictive. Earlier stud- ies revealed that most Dutch hospitals had formularies, which contained recom- mendations for antibiotic prescribing (Stobberingh et al., 1993). Furthermore, most hospitals have, in general, adopted a conservative approach when devising antibiotic policies and there has been a tendency to limit the use of newer, more broad-spectrum agents (Janknegt et al., 1994). It is worth noting that until 1996, Dutch governmental legislation obliged hospitals to have a drugs and therapeu- tics committee. The development and implementation of formulary agreements was an objective explicitly stated. After 1996 the law changed and policies and methods for rational pharmacotherapy can now be designed and implemented on the institution’s own view (Fijn et al., 1999). In a survey performed among all Dutch hospitals in 1998 the participation was 99%. From this survey it was apparent that the presence of a drugs and therapeutics committee and antibiotic policies in general hospitals appears independent of hospital characteristics. However, formulary agreements and treatment guidelines were less likely to be present in hospitals with only one pharmacist employed. More than half of the hospitals claimed to have restrictive formulary agreements. This was more likely the case for large hospitals and hospitals in the eastern and southern provinces (Fijn et al., 1999).

In order to further promote the responsible use of existing antibiotics, a foun- dation was established in the Netherlands. The SWAB (Stichting Werkgroep

554 Moyssis Lelekis and Panos Gargalianos Antibioticabeleid—Foundation Antibiotics Policy Work Group) has, as a primary

goal, to optimize the use of antibiotics in the Netherlands, in order to diminish the development of resistance (van Kasteren et al., 1998a). One of the SWAB pro- jects was to develop national guidelines for the use of antibiotics in hospitals. The guidelines are prepared by a committee of experts and reviewed by external con- sultants: infectious diseases specialists, medical microbiologists, and pharma- cists. The revised version was then submitted for publication. The aim of SWAB is to make prevention of antibiotic resistance a major factor in the choice of the antibiotic. Up to now SWAB guidelines have been published for pneumonia (van Kasteren et al., 1998b), for antimicrobial therapy in adults hospitalized with bronchitis (van Kasteren et al., 1998c), for antimicrobial therapy of adults with sepsis in hospitals (van Kasteren et al., 1999), perioperative prophylaxis (van Kasteren et al., 2000), and selective decontamination of intensive care patients on mechanical ventilation (Bonten et al., 2001). Interesting is the fact that

a multicenter audit in Dutch hospitals of adherence to guidelines for surgical chemoprophylaxis, revealed that there was a willingness to adhere to guidelines (van Kasteren et al., 2003).

In Belgium, a country with significantly higher antibiotic usage, the noso- comial usage of antimicrobial agents increased by 7% in volume and 21% in value between 1991 and 1993. Moreover there was a trend toward an increased usage of broad-spectrum and newer drugs (Struelens and Peetermans, 1999). The introduction of a normative reimbursement system for antimicrobial prophylaxis of surgical procedures in Belgian hospitals in 1997, has had a dramatic impact on antibiotic consumption (Struelens and Peetermans, 1999). Following the recommendations of the European Conference “The Microbial Threat,” a Committee for the Coordination of Antibiotic Policy (BCCAP [Com- mission de Coordination de la Politique Antibiotique/Commissie voor Coordinatie van de Antibiotica Beleid ]) was created in 1999, jointly by the Ministry of Social Affairs, Public Health and Environment and the Ministry of Agriculture (Nagler et al., 1999). All interested parties are represented in the Committee. Its main tasks are:

● collection and organization of all available information on antibiotic use and resistance

● publication of reports on antibiotic use and resistance ● information and increase of public awareness on antibiotic resistance and

the risks associated with the irrational use of antibiotics ● making recommendations on relevant points, such as detection of resistance,

cross-resistance mechanisms, use and consumption of antibiotics in both man and animal, etc.

● making recommendations for research on antibiotic resistance and on the transfer of resistance among bacteria and among ecosystems.

National Policies and Antibiotic Prescribing 555 Given the volume of antibiotic use in ambulatory care, a campaign was

launched by the committee (Bauraind et al., 2001a). The aims of the campaign were:

● to inform the public about antibiotic resistance and to warn it about the med- ical and general health issues related to the inappropriate use of antibiotics

● to foster the patient–physician and patient–pharmacist dialog about the appropriate use of antibiotics.

The materials used for this campaign were, booklets, folders and posters targeting patients, TV-spots and radio-spots targeting the public, direct press and media communications targeting general public and MDs, Pharm and Web sites for general public and MDs. The campaign was launched in November 2000 and it lasted until March 2001. Its evaluation (Bauraind et al., 2001b) revealed that:

● it improved the awareness of the public and reduced requests for antibiotics ● it reduced antibiotic prescriptions only transiently ● media and especially TV are the most powerful tools for such a campaign for

both the public and GPs. After these, the final conclusion was that this campaign should be repeated

and further improved (Bauraind et al., 2001b). In France, in an effort to control ambulatory care costs, regulatory practice guidelines, known as “références médicales opposables” (RMOs) or regulatory medical references, were introduced by law in 1993 (Durieux et al., 2000). According to the law, physicians who do not comply with RMOs can be fined. In terms of antibiotic prescribing, the aim of this strategy was not to decrease the number of prescriptions, but to reduce the total cost of antibiotics and reduce especially the prescription of broad-spectrum, expensive agents (Chahwakilian, 2000). Moreover they were not planned to promote good antibiotic prescribing practice. The RMO policy was questioned in 1997, when the reform of the French Health System changed the rules (Colin et al., 1997). According to the reform, French physicians having private practice could be collectively fined at the end of each year if they overspent the budget prescribed by the French parliament. On the contrary they could receive a bonus if they stayed within this budget. This regulation resulted in protest on the part of physicians as being unethical and it created an intense conflict. In a survey done in 1998 among French family physicians, it was quite obvious that despite financial penalties French physicians’ knowledge of RMOs was poor (Durieux et al., 2000).

The introduction of RMOs did not decrease the overall volume of outpatient antibiotic use and had only a modest economic impact. However, the prescription

556 Moyssis Lelekis and Panos Gargalianos patterns changed with this policy, leading to a decrease in the use of fluoro-

quinolones and oral cephalosporins and to a substantial increase in macrolide use (Choutet, 2001).

Thus, in 1999 a national plan of actions for the control of antimicrobial resistance was initiated in France and represents the most complete effort in this direction. It includes (Chahwakilian, 2000):

1. Surveillance of resistance and antibiotic consumption for both the commu- nity and the hospital and also evaluation of the practices.

2. Infection control programs in the hospitals and the day care facilities.

3. Actions for the promotion of good antibiotic prescribing with the applica- tion of the existing recommendations, with the use of rapid diagnostic tests, and with the development of visits free of charge.

4. Reinforcement of the control of the advertisement of antibiotics.

5. Promotion of research, especially in the field of optimization of antibiotic prescribing and intervention studies on this subject.

In a comparison of France and Germany in terms of outpatient antibiotic use, many interesting points were made, some of which refer to antibiotic poli- cies implemented in these two countries (Harbarth et al., 2002).

Analyses of national sales data show that the use of oral antibiotics in France is almost three times higher than in Germany. This can be attributed to several reasons:

First, antibiotic practices vary tremendously between France and Germany.

A pan-European survey revealed that in Germany many more patients do not get a prescription for an antibiotic at the first consultation visit for respiratory tract infections, even in cases of suspected pneumonia (Harbarth et al., 2002). This lower rate of prescriptions can be explained at least partly by a higher recourse to diagnostic investigations and a watchful waiting approach very common in Germany (Woodhead et al., 1996).

Second, there are differences in terms of cultural factors. Expectancy of French people for an antibiotic prescription for respiratory tract symptoms is much higher than that of Germans (Bouvenot, 1999; Pradier et al., 1999). This allows German doctors to follow a much more conservative and watchful-waiting approach in cases of non-life threatening situations. It is worth noting that in a pan-European survey the demand index for an antibiotic prescription was 2.2 for French people surpassed only by Turkish patients (index 2.4 —Branthwaite and Pechere, 1996).

Third, there are differences in regulatory practices. Antibiotic prescriptions are affected by reimbursement policies and the structure of the pharmaceutical

National Policies and Antibiotic Prescribing 557 market. Historically the French drug economy has been regulated by product

price control and has been considered as a low price, high quantity system, whereas the German one was a high price, low quantity system. As a result (a) Generics have played a minimal role in French pharmaceutical market in con-

trast to Germany (⬍5% vs 39%). This feature contributes to the trend in France for using newer antibiotics (Garratini and Tediosi, 2000).

(b) Until recently, French pharmacies were better remunerated if they dis- pensed large volumes of expensive drugs such as oral broad-spectrum cephalosporins (Garratini and Tediosi, 2000). In Germany, on the contrary, pharmacy remuneration is calculated by applying regressive percentages to different price bands; the lower the price, the higher the pharmacy’s share (Huttin, 1996).

(c) The French pricing system forces pharmaceutical companies to imple- ment aggressive promotional efforts and marketing campaigns to com- pensate for low prices. Thus German and French physicians are exposed to different marketing information and pressure for prescribing antibiotics (Le Pen, 1997).

A very important difference is that health authorities in Germany have more regulatory power and thus a broader impact on drug use. In 1993 the introduc- tion of capped physician budgets and a system of reference pricing in Germany, led to a switch in prescribing preferences and an incentive for German physi- cians to avoid expensive drugs priced above the reference price (Danzon and Chao, 2000). As a result, from 1994 to 1997 the volume of antibiotics pre- scribed decreased from 334 to 305 million DDDs (Giulani et al., 1998).

The consumption of antibacterials has remained relatively stable in Scandinavia and is low compared with most other countries (Bergan, 2001). However, among these countries there are differences concerning the volume and the distribution of different classes of antimicrobials (Bergan, 2001). The con- sumption is highest in Iceland and Finland and lowest in Denmark and Norway.

In Denmark there has been a long standing tradition for maintaining registries for monitoring of a variety of healthcare parameters. The Danish Medicines Agency is legally obliged to monitor the consumption of all medicinal products in Denmark. This is done by regular reporting from all pharmacies, including pharmacies located in hospitals to the agency (Sørensen and Monnet, 2000). For every antimicrobial dispensed, the patient’s central personal registration (CPR) number, the date, the place (pharmacy, hospital pharmacy, institute, etc.) the reimbursement (if any) and the license number of the prescribing doctor are auto- matically recorded and the data are transferred to the Danish Medicines Agency.

In Denmark there is no over the counter sale of antimicrobials. The emergence of resistant Staphylococcus aureus in the mid-1960s had many favourable results

558 Moyssis Lelekis and Panos Gargalianos due to the actions taken (Sørensen and Monnet, 2000). At that time the post nurs-

ing school education as a “hygiene nurse” was established. Furthermore, a formal collaboration started in every county between hygiene nurses, clinical microbiol- ogists, hospital pharmacists, hospital doctors, and general practitioners in close collaboration with the national center for hospital hygiene, in order to focus on reduction of the number of nosocomial infections, reduce resistance, and optimize the use of antimicrobials. Subsequently a number of interventions were taken at all levels of the Danish healthcare system ranging from medical audit projects in small groups of general practitioners to national legislation.

The low level of resistance of the major pathogens allows for conservative recommendations for the treatment of infectious diseases both in the hospital and the community. These recommendations are printed and sent free of charge to every doctor in Denmark (Sørensen and Monnet, 2000). Another way to reduce the use of antibiotics at the general practitioner level is by encouraging the use of rapid diagnostic tests. Fast negative results prevent inappropriate prescriptions of antibiotics. Doctors are reimbursed for the test itself and are paid for performing it (Sørensen and Monnet, 2000). At a national level a powerful tool for controlling antibiotic use in Denmark is the reimbursement policy. Changes in reimbursement policy resulted in a decrease in antibiotic use (Sørensen and Monnet, 2000). In Danish Hospitals antimicro- bials are not subsidized. Hospital pharmacies buy antimicrobials from phar- maceutical companies after negotiation about the price through a union of hospital pharmacies and sell them to the medical wards. Aside this economic incentive, most hospitals have implemented local policies for the promotion of prudent use of antibiotics (Monnet and Sørensen, 1999).

In Sweden in response to the increasing sales of antibiotics and the spread of penicillin non-susceptible pneumococcus, a national project named STRAMA (Swedish Strategic Program for The Rational Use of Antimicrobial Agents and Surveillance of Resistance) was initiated in 1994 (Mölstad and Cars, 1999). Since the immediate threat was the emergence of resistant pneu- mococcus, the project focused initially on treatment of RTIs, antibiotic usage in pre-school children and surveillance of resistance in pneumococci.

At the national level, STRAMA was formed by clinical specialists from the Swedish Reference Group for Antibiotics (SRGA) representing infectious diseases, microbiology, general practice, ENT and pediatricians, as well as representatives from scientific and administrative authorities. The primary objective was to stimulate the formation of local STRAMA groups in each county. National STRAMA coordinates surveillance programmes and follows antibiotic consumption and the incidence of resistance nationwide. It also makes recommendations on identified problems. The main goal was to contain inappropriate use of antibiotics and antimicrobial resistance both in the community and the hospital (Mölstad and Cars, 1999).

National Policies and Antibiotic Prescribing 559 The regional STRAMA groups that were formed in the counties of Sweden

had, as a main objective to evaluate antibiotic utilisation and patterns of resis- tance in their geographical area. They influence healthcare workers to improve diagnostic procedures and change the prescribing patterns of antibiotics. They also decide whether proposed recommendations should be implemented in their county.

In 1995 the national STRAMA group prepared antibiotic treatment poli- cies for respiratory tract infections caused by resistant pneumococci and in the following years on the treatment of urinary tract infections, chronic bronchitis, and skin and wound infections. Guidelines were also issued for the use of macrolides, vancomycin, and fluoroquinolones. Furthermore, STRAMA pro- duced a brochure with patient information on respiratory tract infections, antibiotics and resistance, which was distributed to all Swedish medical health centres and surgeries. The folder gave the physician a possibility to offer writ- ten, non-commercial information to patients with respiratory tract infections.

Another activity was the production of guidelines for the management of resistant pneumococci in day care centres and family day care. A return visit free of charge was proposed to encourage expectancy, instead of an antibiotic prescription to patients with respiratory tract infections, who had no obvious signs and symptoms of bacterial infection.

During the period that the STRAMA project has been running, antibiotic consumption has decreased continuously. Between 1993 and 1997 it was reduced by 22% and the reduction was most pronounced for children 0–6 years old. Since large differences were recorded between counties, a further decrease may be possible. The national frequency of resistant pneumococci did not increase during the 1990s, while the increasing incidence in southern counties seems to have been curtailed (Mölstad and Cars, 1999).

The Finnish experience is a paradigm of successful intervention for lower- ing antimicrobial resistance in the community (Seppälä et al., 1997). In 1991,

a recommendation was made to decrease the use of macrolides in infections caused typically by Group A streptococcus. As a result, the usage of macrolides was nearly halved in all parts of the country and the resistance rate of strepto- coccus to macrolides decreased significantly (from 19% to 9%).

Compared to other Nordic countries Finland has noticeably higher antibi- otic consumption. Only Iceland has the same high level of use as Finland. This high level of antibiotic usage in Finland could at least partly be attributed to the prescription of antibiotic courses of long duration (Rautakorpi et al., 1997). In late 1990s a countrywide programme called MIKSTRA was launched, having as its main goal to develop an optimal antibiotic policy for outpatient infec- tions (Rautakorpi et al., 2001). This joint research and development program was planned for a 5-year duration and included new evidence-based recommendations for diagnosis and treatment of the most common outpatient

560 Moyssis Lelekis and Panos Gargalianos infections with a careful follow up, cost–benefit analysis of the new recom-

mendations, educational initiatives for both health professionals and the public, as well as measurement of the changes in the attitudes of the health professionals and the public. In particular the infection-specific, evidence- based guidelines were issued by the Finnish Medical Society Duodecim with the support of the Finnish Ministry of Social Affairs and Health. Six such guidelines were published in 1999–2000 in a medical journal and on the Internet (Rautakorpi et al., 2001). The targeted infections were otitis media, throat infection, acute sinusitis, acute bronchitis, skin infections, and urinary tract infections. Changes in bacterial resistance of the most common com- munity pathogens were to be surveyed by the Finnish Study Group for Antimicrobial Resistance.

The Icelandic experience is an example of a successful nationwide policy, which was carried out without being overseen by an official body (Kristinsson, 1999). In fact, the intervention was carried out by key opinion leaders in clinical microbiology, infectious diseases, general practice, and pediatrics. It included use of television, radio, and newspaper for conveying the message. Furthermore, articles in the Icelandic Medical Journal, medical meetings, and conferences were used for the same purpose. The intervention focused on the overuse of antibiotics in children. Physicians were urged to avoid prescribing antibiotics for viral illnesses and to give antibiotics less frequently for otitis media, sinusitis, and bronchitis in children. Moreover, new prescribing guide- lines were prepared for general practitioners and the issue of prudent use of antibiotics was a frequent topic for discussions both in the journal of the Icelandic Medical Association and at numerous meetings.

The general feeling of Icelandic physicians is that the campaign changed the parents’ attitude towards antibiotics. From 1991 until 1997 that this cam- paign lasted, a decrease in antibiotic use was recorded. The overall decrease was only 10%, but it was 35% for the use in children (Kristinsson et al., 1998). Interestingly and most importantly, the incidence of penicillin–non susceptible pneumococci showed a significant decline during the same period (Kristinsson et al., 1998).