SOCIOCULTURAL PERSPECTIVE ON OUTPATIENT ANTIBIOTIC USE AND PREVALENCE OF ANTIBIOTIC-RESISTANT PNEUMOCOCCI: A COMPARISON BETWEEN TWO LARGE EUROPEAN COUNTRIES Harbarth S, Albrich W, Brun-Buisson C Univ. of Geneva Hospitals, Geneva, Switzerland; Emory Univ., Atlanta, USA; Univ. Hospital Henri Mondor, Créteil, France

BACKGROUND The epidemiology of antibiotic- resistant Streptococcus pneumoniae (ARSP) varies tremendously between different countries. In Europe, high rates of ARSP have been recorded in France and Spain, while countries like Germany and Switzerland are only marginally affected. The reasons for the uneven geographic distribution of ARSP are not fully understood.

STUDY QUESTIONS For the purpose of this report, we reviewed recent surveillance data about ARSP prevalence in France and Germany and explored different hypotheses to explain the observed differences. The main questions addressed are: (1) Are there important differences in antibiotic prescribing practices in the outpatient setting? (2) Are there differences in factors influencing decisions on antibiotic use? (3) Are these differences related to sociocultural and other macro-level determinants?

METHODS A computer-based literature review was undertaken using the MEDLINE database from 1980 to the present. This extended search included articles about differences in economic and sociocultural determinants (e.g., perception of illness, societal background of pharmaceutical consumption). Papers in English, German and French were reviewed.

RESULTS (1) PROPORTION OF RESISTANT ISOLATES

RESULTS (2) Analyses of national sales data from Germany and France are summarized in the Figure below. It shows that between 1985 and 1997, retail sales of oral antibiotics in France were almost 3x higher than in Germany. In addition, Germany had a higher relative use of narrow-spectrum penicillins, cotrimoxazole and tetracyclines and a much lower use of broad-spectrum penicillins, cephalosporins, and fluoroquinolones, compared to France (Cars et al, Lancet 2001).

RESULTS (3) Antibiotic prescribing practices for respiratory tract infections vary tremendously between France and Germany. As shown in the Table, antibiotic prescription rates in France and Germany for common cold and tonsillopharyngitis were 48.7 and 94.6 vs. 7.7 and 69.6 per 100 outpatient consultations, respectively. FranceGermany Average number of office visits for acute tonsillopharyngitis per 1,000 population Average number of antibiotic prescriptions per 100 office visits for acute tonsillopharyngitis Average number of office visits for common cold per 1,000 population Average number of antibiotic prescriptions per 100 office visits for common cold No antibiotic prescription at 1 st office visit for (%): Suspected community-acquired pneumonia823 Acute bronchitis731 Exacerbation of chronic bronchitis526 Viral lower respiratory tract infection2041 Proportion of cases of suspected lower respiratory tract infection with diagnostic tests performed (%): Chest radiograph1827 Peripheral blood leucocyte count1427 Microbiological sputum examination312

The Cultural Perspective A survey commissioned by the EU among 1,577 opinion leaders in the health care sector showed that alternative medicines such as homeopathy were supported by 42% of the questioned persons in Germany vs. 23% in France. Moreover, a recently published survey among 2,111 Germans older than 16 years revealed that 83% had some sympathy for complementary medicine, whereas 40% disliked antibiotics, because they could “undermine natural immunity”. In a Pan-European survey, the demand index for antibiotics among patients in France was 2.2, only surpassed by Turkey (2.4). In that survey, France was the only country were over 50% of the interviewees definitely expected an antibiotic for the treatment of a "flu".

Social factors also influence antibiotic use and resistance rates in both countries. This can be best illustrated by the example of otitis media, which is the leading reason for excessive antimicrobial use in French children. Attendance at a childcare center outside the home correlates strongly with an increased risk of otitis media and acquisition of drug-resistant pneumococci. Therefore, it is not surprising to see great differences in the availability and use of non-parental daycare facilities between France and Germany. In France, there is a long tradition of early childhood education in the public sector. Known as "écoles maternelles", nearly 100% of 3 to 5 year olds in France attend these publicly funded pre-schools. About 35% of two-year-olds also attend. In contrast, less than 10% of German infants in this age group were in the care of an external childcare provider. The Social Perspective

DIFFERENCES IN REGULATORY PRACTICES Antibiotic prescriptions are affected through reimbursement policies and the structure of the pharmaceutical market. The average level of retail prices for pharmaceutical products is very low in France: if France is 100, the level would be 162 in the U.K. and 175 in Germany. Due to this low level of pharmaceutical pricing, France is not only ranked first in the consumption per capita of outpatient antibiotics, but also had the 3rd highest consumption of pharmaceutical products per capita among all OECD-countries. Until recently, generic medicines have played only a minor role (< 5%) in the French pharmaceutical market. By contrast, generics accounted for 39% of all prescribed medicines in Germany. This feature contributes to the observed trend in France of using newer antibiotics compared to Germany, where narrow-spectrum, generic agents are more commonly used. Until recently, French pharmacies were better remunerated if they dispensed large volumes of expensive drugs such as oral cephalosporins. By contrast, pharmacy remuneration in Germany is calculated applying regressive percentages to different price bands: the lower the price, the higher the pharmacist's share.

CONCLUSIONS The published literature regarding the prevalence of antibiotic-resistant pneumococci provides convincing evidence that there is a sharp divide between France and Germany. The reasons for the observed resistance gap are multifactorial and include substantial differences in physicians' and patients' attitudes towards antibiotics; sociocultural and economic factors; and disparities in regulatory practices. Most importantly, the literature is remarkably consistent in documenting the high frequency with which antibiotics are utilized in France for upper respiratory tract infections without appropriate microbiologic rationale. Unfortunately, despite the widespread publication of recommendations over the last decade and some modest modifications in the pattern of antibiotic utilization, the willingness of French general practitioners to change their antibiotic prescribing habits has been at best grudging and at worst nonexistent.

POLICY IMPLICATIONS We argue that effects exerted at the macro-level by the cultural and socioeconomic environment contribute substantially to the observed differences in prescribing practices and related antibiotic resistance rates (Figure). Consequently, failure to understand the sociocultural and economic perspectives of antibiotic consumption and resistance will lead to inadequate conclusions about the chances of success for possible interventions. More research to inform decision-makers on the determinants of the variation in antibiotic use and resistance patterns is urgently needed. Antibiotic- resistant pneumococci Patient factors Cultural influences Social determinants Regulatory practices Antibiotic overuse and misuse Prescriber factors

Harbarth et al, Emerg Infect Dis 2002; 8: online available at: