university of groningen self-medication with antibiotics

University of Groningen

Self-medication with antibiotics in Europe and its determinantsGrigoryan, Larissa

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SelfSelfSelfSelf----Medication with Antibiotics in Europe and Medication with Antibiotics in Europe and Medication with Antibiotics in Europe and Medication with Antibiotics in Europe and

its Determinants its Determinants its Determinants its Determinants

Larissa Grigoryan

Paranimfen:Paranimfen:Paranimfen:Paranimfen:

Liana Martirosyan

Jasperien van Doormaal

The studies in this thesis were funded by the European Commission Public Health

Directorate DG SANCO and Ubbo Emmius scholarship at the University of Groningen.

In addition, funding was also provided from funds of the participating institutions.

Publication of this thesis was supported by generous contributions from the Northern

Center for Healthcare Research (NCH), Faculty of Medical Sciences, University of

Groningen (RUG), department of Clinical Pharmacology and department of Medical

Microbiology, University Medical Center Groningen (UMCG) , Pfizer BV and Wyeth

Pharmaceuticals BV.

Grigoryan, Larissa

SelfSelfSelfSelf----Medication with Antibiotics in Europe and its Determinants Medication with Antibiotics in Europe and its Determinants Medication with Antibiotics in Europe and its Determinants Medication with Antibiotics in Europe and its Determinants

Dissertation University of Groningen, The Netherlands – with a summary in Dutch

ISBN: 978 90 77113 63 9

© Copyright Larissa Grigoryan, 2007

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system,

or transmitted, in any form or by any means, electronically, mechanically, by photocopying,

recording, or otherwise, without the prior written permission of the author.

Cover Design: Maya Saribashyan, “Antares” Media Holding, (www.antares.am), Yerevan,

Armenia

Printed by: Gildeprint BV, Enschede, The Netherlands

RIJKSUNIVERSITEIT GRONINGEN

SelfSelfSelfSelf----Medication with Antibiotics in Europe and its Determinants Medication with Antibiotics in Europe and its Determinants Medication with Antibiotics in Europe and its Determinants Medication with Antibiotics in Europe and its Determinants

Proefschrift

ter verkrijging van het doctoraat in de

Medische Wetenschappen

aan de Rijksuniversiteit Groningen

op gezag van de

Rector Magnificus, dr. F. Zwarts,

in het openbaar te verdedigen op

woensdag 26 september 2007

om 14.45 uur

door

Larissa Grigoryan

geboren op 2 november 1976

te Yerevan, Armenië

PromotoresPromotoresPromotoresPromotores::::

Prof. dr. F.M. Haaijer-Ruskamp

Prof. dr. J.E. Degener

BeoordelingscommissieBeoordelingscommissieBeoordelingscommissieBeoordelingscommissie::::

Prof. dr. T.J.M. Verheij

Prof. dr. H. Grundmann

Prof. dr. M.J.M. Bonten

ISBN: 978 90 77113 63 9

1

ContentsContentsContentsContents

Chapter Chapter Chapter Chapter PagePagePagePage

IIII General introduction 3

IIIIIIII Self-medication with antimicrobial drugs in Europe 13

Emerging Infectious Diseases 2006; 12(3): 452-9

IIIIIIIIIIII Is self-medication with antibiotics in Europe driven by 33

prescribed use?

Journal of Antimicrobial Chemotherapy, 2007;59(1): 152-156

IVIVIVIV Determinants of self-medication with antibiotics in Europe: 45

the impact of beliefs, country wealth and health care system

Submitted

VVVV Attitudes, beliefs and knowledge concerning antibiotic use and 61

self-medication: a comparative European study

Submitted

VIVIVIVI Are cultural dimensions relevant for explaining cross-national 79

differences in antibiotic use in Europe?

Submitted

VIIVIIVIIVII General Discussion 93

English summary 101

Nederlandse Samenvatting 107

Acknowledgements 115

About the author 119

List of publications 121

Northern Center for Healthcare Research and previous dissertations 123

General introduction

Chapter 1

4

General introductionGeneral introductionGeneral introductionGeneral introduction

Introduction

The discovery of penicillin by Alexander Fleming in 1928 triggered enormous progress

in medicine (1). Since the first generation of antibiotics became clinically available in the 1940s,

they have been the cornerstone of infectious disease therapy and have saved millions of lives.

However, after Abraham and Chain described a substance (penicillinase) that could inactivate

penicillin (2), Fleming warned that the misuse of antibiotics can lead to loss of their

effectiveness in the treatment of life-threatening infections. At the beginning of the 21st

century antimicrobial resistance has developed against every class of antimicrobial drug (3) and

has become a rapidly increasing global problem (3,4), with widely varying prevalence among

countries (5). Resistant bacteria can be rapidly transferred across international borders (6). An

important international issue is to avoid further increase in resistance by reducing unnecessary

and inappropriate use of antibiotics. The World Health Organization (WHO) and the European

Commission (EC) have recognized the importance of studying the emergence and

determinants of resistance and the need for strategies for its control (7,8). The European

Antimicrobial Resistance Surveillance System (EARSS) and the European Surveillance of

Antimicrobial Consumption (ESAC) both funded by the EC were set up (9,10). The purpose of

EARSS is to document variations in antimicrobial resistance over time and place and to provide

the basis for and assess the effectiveness of prevention programs and policy decisions. The

ESAC project aimed to obtain comparable and reliable data about antibiotic use in Europe. Data

for antibiotic use were reimbursement, distribution or sales data and did not include

information about the prevalence of self-medication by the general population. Information on

the prevalence of self-medication with antibiotics would be extremely valuable, in particular

when implementing programs aiming to prevent inappropriate use of antibiotics in Europe.

Relevance of self-medication with antibiotics in Europe

Prevalence of resistance is positively correlated with prescribed outpatient antibiotic

use on a national level (11-13). Southern and Eastern European countries, in particular, report

high levels of both antibiotic use and resistance (12). However, actual consumption of

antibiotics may also include self-medication, i.e. using antibiotics obtained without

prescription. Other sources of self-medication may include “left-over” antibiotics from

treatment courses prescribed earlier, antibiotics obtained from relatives, friends or other

sources. Self-medication with antibiotics may lead to a wrong choice of antibiotics, use of


5

insufficient dosages or unnecessary treatment. This inappropriate use increases the risk of

selection of resistant bacteria (14) and may contribute to antibiotic resistance (15). Other

problems related to self-medication with antibiotics include adverse effects, drug interactions,

masked diagnoses and superinfection.

Self-medication is an important driver of antimicrobial overuse in low-income

countries (3). However, the information on self-medication with antibiotics in the high income

world is limited. In the US, several studies indicate considerable use of antibiotics obtained

from “leftovers”(16-18), a family member, directly from a pharmacy, or from a source outside

the US (19,20). For example, in the Hispanic neighborhood of New York city, antibiotics have

been found to be available without a prescription (21). In Europe, studies describing self-

medication and storage of antibiotics in Spain (22,23), Greece (24,25), Russia (26), and Malta (27)

and the UK (28) also suggest a considerable use of antibiotics without consulting a physician.

However, these studies were small or used selected samples and were not carried out in

Northern and Western Europe. Moreover, due to the different research methods used, no

meaningful comparison between countries was possible. In addition, there is little information

on “at risk” self-medication i.e. willingness to self-medicate (intended self-medication) and

opportunity for self-medication (storage of antibiotics).

Addressing the determinants of self-medication

Self-medication patterns may parallel prescribing habits of physicians (29). Several

studies have suggested that patient expectations regarding antibiotic use for self-limiting

diseases, such as upper respiratory tract infections (URTIs) may be generated by previous

inappropriate prescribing by the physician (16,30,31). A Spanish study found that self-

medication use was triggered by prescribed use of the same medication (32). This was likely to

be true for antibiotics as they were one of the commonly used medications in the study (32).

Previous prescribed use of antibiotics may be a potential determinant of self-medication.

Besides previous prescribed use other factors may influence use of self-medication with

antibiotics. Studies conducted in low-income countries found that over-the-counter sale of

antibiotics (33), misconceptions regarding the efficacy of antibiotics (34), the cost of medical

consultation and low satisfaction with medical practitioners (35) were among the factors

related to use of self-medication with antibiotics. A study in the US showed that cultural

beliefs and lack of health insurance encouraged residents from Latin-American descent to self-

medicate with antibiotics (36). In Europe, differences in attitudes to antibiotic use have been

described (37), but little is known about their effect on self-medication. Understanding the

relative importance of various determinants for self-medication in Europe is a pre-requisite to

develop effective interventions. Most health behaviors are determined by multiple factors.

According to the PRECEDE model, health behavior is influenced by predisposing factors

Chapter 1

6

(characteristics that lead to or motivated behavior such as knowledge and beliefs), enabling

factors (characteristics that facilitate or are needed to perform the particular behavior, such as

the recourses in the environment) and reinforcing factors (rewards and punishments received

from others). The PRECEDE model of behavior change (38) is a standardized theoretical

framework that has been used to design successful, large-scale health interventions (39,40).

Cultural differences between countries influencing antibiotic use in Europe

Cultural factors may play an important role in the consumption of antibiotics (41;42).

Cultural views of infectious conditions that require antimicrobial treatment differ between

countries (41). For example, many French people seeking medical care because of cough and

sputum production request to be treated by antibiotics; by contrast most Germans consider

such treatment as unnecessary overmedication (42). In another study, the Dutch respondents

were more confident that mild ailments will heal spontaneously and more skeptical about the

efficacy and side effects of medicines while the Flemish were mainly concerned with the risk of

doing nothing and “nursing one’s illness”(43). A first Pan-European study in five EC countries

and Turkey conducted in 1993(37) and extended to other continents(44) suggested that

patients’ attitudes to antibiotic use varied according to their country of residence. In particular,

the proportion of patients definitely expecting to receive antibiotics for respiratory tract

infections was the highest in Turkey, France and Spain among European countries. However,

that survey did not test whether differences were statistically significant between countries.

Moreover, no attention was given to attitudes towards self-medication with antibiotics,

awareness about antibiotic resistance and knowledge about effectiveness of antibiotics on

bacteria and viruses.

Besides cultural views on antibiotic use, the concept of culture includes broader and

general characteristics of a country such as cultural dimensions developed by Hofstede (45).

These dimensions represent culture-specific values with regard to general problems faced in all

countries and include power distance index (PDI), individualism (IDV), masculinity (MAS) and

uncertainty avoidance index (UAI). PDI is a measure for the extent a society is organized

hierarchically. It s defined as the extent to which the less powerful members of institutions and

organizations within a society expect and accept that power is distributed unequally. If a

society scores high on IDV the ties in this society between individuals are loose: a person is

expected to look after himself or herself and his or her immediate family only. By contrast, a

low IDV score points to a society that is more collectivist in nature. A high MAS-score stands for

a society in which emotional gender roles are clearly distinct: men are supposed to be assertive,

tough, and focused on material success; women are supposed to be more modest, tender, and

concerned with the quality of life. A low MAS-score means a society has a lower level of


7

differentiation and inequity between genders. UAI is defined as the extent to which the

members of institutions and organizations within a society feel threatened by uncertain,

unknown, ambiguous, or unstructured situations. Uncertainty avoiding cultures try to

minimize the possibility of such situations by strict laws and rules, safety and security

measures and people within these cultures are more emotional. The opposite type, uncertainty

accepting cultures, are more tolerant of opinions different from what they are used to; they try

to have as few rules as possible and people within these cultures are more phlegmatic. It is

plausible that cultural dimensions also have an influence on culturally sensitive domains such

as illness behavior and use of medicines (46,47). However, very few studies have linked the

scores on cultural dimensions with diseases and illness behaviour (48). No study, to our

knowledge, investigated correlations between these cultural dimensions and use of medicines.

Objectives and structure of this thesis

This thesis aims to study the prevalence of self-medication with antibiotics in

European countries and explore its determinants with a focus on 1) prescribed use of

antibiotics, 2) predisposing and enabling factors. In addition, differences in attitudes, beliefs

and knowledge concerning antibiotic use and self-medication between countries and the

influence of cultural dimensions on antibiotic use in Europe were studied. The study was

funded by the European Commission Public Health Directorate DG SANCO.

Chapter 2Chapter 2Chapter 2Chapter 2 presents the results of the survey estimating the prevalence of self-medication with

antibiotics and prescribed use in the previous 12 months among the general population of 19

European countries (Austria, The Netherlands, Sweden, United Kingdom, Ireland, Denmark,

Italy, Malta, Luxembourg, Belgium, Spain, Israel, Romania, Czech Republic, Slovakia, Lithuania,

Slovenia, Croatia and Poland). We also studied “at risk” self-medication, including intended

self-medication and storage of antibiotics at home. The demographic characteristics associated

with such use, the types of drugs used, the sources of self-medication, the symptoms for which

antibiotics were reportedly used, and duration of use were also examined.

In Chapter 3Chapter 3Chapter 3Chapter 3 we investigate whether self-medication in Europe was triggered by prescribed use.

We studied the relationship between prescribed use and self-medication in general (for all

symptoms/diseases). We also studied the relationship between prescribed use and self-

medication for URTIs.

In Chapter 4Chapter 4Chapter 4Chapter 4, we studied the determinants of self-medication by investigating the relevance of

predisposing (attitudes, beliefs and knowledge concerning antibiotic use and self-medication)

Chapter 1

8

and enabling factors (country wealth and health care system factors) for use of self-medication

with antibiotics.

Moving beyond use of self-medication, in Chapter 5Chapter 5Chapter 5Chapter 5 we examined attitudes, beliefs and

knowledge concerning antibiotic use in general and self-medication between countries.

In Chapter 6Chapter 6Chapter 6Chapter 6, we investigate the relevance of cultural dimensions as described by Hofstede for

cross-national differences in antibiotic use.

Finally in Chapter 7Chapter 7Chapter 7Chapter 7, we discuss general findings of the studies, implications for the strategies

to prevent unnecessary and inappropriate use of antibiotics and provide recommendations for

future research.


9

ReferencesReferencesReferencesReferences

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infections in a diverse community. J Fam Pract 1999 December;48(12):993-6.

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Urban Health 2004 September;81(3):498-504.

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medicine cabinets. Clin Infect Dis 2003 August 15;37(4):498-505.

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population. Int J of Antimicrob Agents 2002 October;20(4):253-7.


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28. McNulty CA, Boyle P, Nichols T et al. Antimicrobial drugs in the home, United Kingdom. Emerg

Infect Dis 2006 October;12(10):1523-6.

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1987;25(3):307-18.

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patients. BMJ 1998 September 5;317(7159):668-71.

31. Hong JS, Philbrick JT, Schorling JB. Treatment of upper respiratory infections: do patients really

want antibiotics? Am J Med 1999 November;107(5):511-5.

32. Moral Serrano S, Aguaron Joven E, Adan Gil FM et al. Do the patients medicate themselves

correctly? Aten Primaria 1994 March 31;13(5):242-6.

33. Lansang MA, Lucas-Aquino R, Tupasi TE et al. Purchase of antibiotics without prescription in

Manila, the Philippines. Inappropriate choices and doses. J Clin Epidemiol 1990;43(1):61-7.

34. Radyowijati A, Haak H. Improving antibiotic use in low-income countries: an overview of

evidence on determinants. Soc Sci Med 2003 August;57(4):733-44.

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antibiotics without prescription in Kerala State, south India. Soc Sci Med 2000 March;50(6):891-

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community, South Carolina. Emerg Infect Dis 2005 June;11(6):883-8.

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Approach. 2nd ed. Mountain View, Calif: Mayfield Publishing Co. 1991.

39. Gans KM, Jack B, Lasater TM et al. Changing physicians' attitudes, knowledge, and self-efficacy

regarding cholesterol screening and management. Am J Prev Med 1993 March;9(2):101-6.

40. Murray DM, Kurth CL, Finnegan JR, Jr. et al. Direct mail as a prompt for follow-up care among

persons at risk for hypertension. Am J Prev Med 1988 November;4(6):331-5.

41. Harbarth S, Albrich W, Goldmann DA, Huebner J. Control of multiply resistant cocci: do

international comparisons help? Lancet Infect Dis 2001 November;1(4):251-61.

42. Harbarth S, Albrich W, Brun-Buisson C. Outpatient antibiotic use and prevalence of antibiotic-

resistant pneumococci in France and Germany: a sociocultural perspective. Emerg Infect Dis

2002 December;8(12):1460-7.

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43. Deschepper R, Vander Stichele RH, Haaijer-Ruskamp FM. Cross-cultural differences in lay

attitudes and utilisation of antibiotics in a Belgian and a Dutch city. Patient Education and

Counseling 2002;48(2):161-9.

44. Pechere JC. Patients' interviews and misuse of antibiotics. Clin Infect Dis 2001 September 15;33

Suppl 3:S170-S173.

45. Hofstede G.VSM 94 Values survey module 1994. Available from

http://feweb.uvt.nl/center/hofstede/manual.html, last accessed February 11, 2007.

46. Payer L. Medicine and culture: varietes of treatment in the United States, England, West

Germany and France. London, Victor Gollancz. 1990.

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relevance of social science for medicine. Dordrecht: Reidel. 1981.

48. Draguns JG, Tanaka-Matsumi J. Assessment of psychopathology across and within cultures:

issues and findings. Behav Res Ther 2003 July;41(7):755-76.

Self-medication with antimicrobial drugs in Europe

Larissa Grigoryan, Flora M Haaijer-Ruskamp,

Johannes G M Burgerhof, Reli Mechtler, Reginald Deschepper,

Arjana Tambic-Andrasevic, Retnosari Andrajati, Dominique L Monnet,

Robert Cunney, Antonella Di Matteo, Hana Edelstein, Rolanda Valinteliene,

Alaa Alkerwi, Elizabeth A Scicluna, Pawel Grzesiowski, Ana- Claudia Bara,

Thomas Tesar, Milan Cizman, Jose Campos, Cecilia Stålsby Lundborg and Joan Birkin

Emerging Infectious Diseases 2006; 12(3): 452-9

Chapter 2

14

AbsAbsAbsAbstracttracttracttract

We surveyed the populations of 19 European countries to compare the prevalence of

antimicrobial drug self-medication in the previous 12 months and intended self-medication and

storage and to identify the associated demographic characteristics. By using a multistage

sampling design, 1,000–3,000 adults in each country were randomly selected. The prevalence

of actual self-medication varied from 1 to 210 per 1,000 and intended self-medication from 73

to 449 per 1,000; both rates were high in eastern and southern Europe and low in northern and

western Europe. The most common reasons for self-medication were throat symptoms (e.g.,

dry, inflamed, red, or sore throat, inflamed tonsils, tonsil pain). The main medication sources

were pharmacies and medication leftover from previous prescriptions. Younger age, higher

education, and presence of a chronic disease were associated with higher rates of self-

medication. Attempts to reduce inappropriate self-medication should target prescribers,

pharmacists, and the general public.


15

IntroductionIntroductionIntroductionIntroduction

Antimicrobial drug resistance is a rapidly increasing global problem (1,2), and

prevalence varying widely among countries (3). Prevalence of resistance is positively correlated

with prescribed outpatient drug use on a national level (4,5). However, actual consumption of

drugs may also include self-medication, i.e., using drugs obtained without prescription. Other

sources of self-medication may include leftover drugs from treatment courses prescribed

earlier or drugs obtained from relatives or friends. Use without medical guidance is

inappropriate because using insufficient dosages or incorrect or unnecessary drugs increases

the risk of the selection of resistant bacteria (6) and the spread of antimicrobial drug resistance

(7).

To date, the information on self-medication with antimicrobial drugs in the

industrialized world is limited. In the United States, several studies indicate considerable use of

leftovers (8–10), drugs obtained from a family member, a pharmacy, or a source outside the

country (11,12). For example, in an Hispanic neighborhood of New York City, antimicrobial drugs

are available without a prescription (13). In Europe, studies describing self-medication and

storage of antimicrobial drugs in Spain (14,15), Greece (16,17), Russia (18), and Malta (19) also

suggest considerable use of the drugs without consulting a physician. However, these studies

were small or used selected samples and were not carried out in northern and western Europe.

Moreover, because of the different research methods used, no meaningful comparison

between countries was possible. In addition, little information exists on factors that puts

person at-risk for self-medication. This survey was designed to fill that gap for 19 European

countries: Austria, the Netherlands, Sweden, United Kingdom, Ireland, Denmark, Italy, Malta,

Luxembourg, Belgium, Spain, Israel, Romania, Czech Republic, Slovakia, Lithuania, Slovenia,

Croatia, and Poland. The aim of this study was to estimate and compare the prevalence of

actual self-medication and at-risk for self-medication with antimicrobial drugs in participating

countries. The demographic characteristics associated with such use, the types of drugs used,

the sources of self-medication, the symptoms for which the drugs were reportedly used, and

duration of use were also examined.

MethodsMethodsMethodsMethods

Countries participating in the study were recruited from 2 networks of surveillance

systems: European Surveillance of Antimicrobial Consumption (20) and European Antimicrobial

Resistance Surveillance System (21). A multistage sampling design was used for sample

selection in each participating country. Within each country, a region with average prescribed

antimicrobial drug consumption was chosen. In those countries where this information was

Chapter 2

16

not available (Poland, Czech Republic, Lithuania, Croatia, and Romania), a region was selected

that was representative of the country’s population in terms of age and sex. In each region, a

city (75,000−750,000 inhabitants) and a rural area (5,000−10,000) were selected. By using

population registries, including lists of persons in the identified cities and rural areas, persons

>18 years of age were selected by simple random sampling (computer-generated random

numbers). To calculate the sample size, we needed the standard deviation of the unknown

prevalence. As the standard deviation was a function of this unknown prevalence, we took the

maximal possible value of the standard deviation (22). To obtain a precision of 0.05, the sample

size needed was 400 persons per country. To adjust for possible non-response, we selected

larger samples; sample sizes in the countries were 1,000–3,000 persons, equally distributed in

urban and rural areas. Self-administered questionnaires were mailed between March and July

2003, and reminders with a new questionnaire attached were sent 2−4 weeks later.

We developed an English questionnaire specifically for this survey, translated it into

national languages, and back translated it to ensure consistency.1 The questionnaire was pilot-

tested in each country. It could be completed either anonymously or with identifiable details to

allow a follow-up study. Questions asked about the respondent’s use of antimicrobial drugs

during the past 12 months, how they were obtained, how they were stored at home, and

whether the respondent would consider using drugs without consulting a physician. Details of

the drugs used (name of the medicine, symptom or disease coded with International

Classification of Primary Care codes [23], and duration of use) and demographic characteristics

of the respondents were included. Antibacterial drugs for systemic use (Anatomical

Therapeutic Chemical class J01) (24) were included in the analyses. Medicines erroneously

reported as antimicrobial drugs were excluded from the analyses.

Ethics or data committee approval for the survey was required in Sweden, Denmark,

Belgium, United Kingdom, Ireland, Malta, Czech Republic, Slovenia, Croatia, Romania, and

Lithuania and was obtained from the local ethics or data committees of these countries.

Respondents were classified as self-medicating if they reported that they had taken any

antimicrobial drugs in the previous 12 months without a prescription from a physician, dentist,

or nurse and as prescribed users if antimicrobial drugs had been prescribed. (Physician

respondents who reported using non-prescribed drugs were not classified as self-medicating.)

Those classified as at-risk for self-medication included those who indicated the intention to

self-medicate or store drugs at home. Intended self-medication was defined as answering

“yes” or “maybe” to the question, “In general, would you use antimicrobial drugs for yourself

without contacting a doctor/nurse/hospital?” Two estimates were used to assess storage of

drugs: a maximum estimate, including all respondents who stored antimicrobial drugs, and a

conservative estimate that excluded those respondents who stored antimicrobial drugs and

had taken the same drugs for a prescribed course in the previous 12 months.

1 A copy of the questionnaire is available from the corresponding author upon request.


17

Statistical AnalysesStatistical AnalysesStatistical AnalysesStatistical Analyses

Descriptive statistics were used to estimate the prevalence rates per 1,000 respondents

and 95% confidence intervals (CI) for actual self-medication and prescribed use in the previous

12 months and for at-risk self-medication in each country. To assess possible bias from low

response rates, we also estimated adjusted prevalence rates. We applied the continuum of the

resistance model (25), based on the assumption that late respondents most resemble non-

respondents. Late respondents in our study were those who replied after the reminder. The

adjusted prevalence is considered similar to the observed prevalence when it falls in the 95% CI

of the observed prevalence.

The effects of individual characteristics and country on antimicrobial drug self-

medication were studied with logistic regression analyses by using 3 outcome variables: actual

self-medication in the previous 12 months, storage of antimicrobial drugs, and intended self-

medication. Countries were grouped together in 3 European regions: northern and western

(Sweden, Denmark, the Netherlands, Austria, Belgium, Luxemburg, United Kingdom, and

Ireland), southern (Malta, Italy, Israel, and Spain), and eastern (Czech Republic, Slovenia,

Croatia, Poland, Slovakia, Romania, and Lithuania). This grouping was based on patterns of

prescribed use of antimicrobial drugs (4), geographic location (26), similarities in healthcare

systems, and socioeconomic development. The former socialist countries are referred to as

eastern countries. We tested possible interactions between the factors found to be significant

and set the significance at p<0.01 for interaction terms due to multiple testing. Multivariate

logistic regression was also used to study the relationship between intended self-medication,

storage, and actual self-medication in the previous 12 months. Data were analyzed by using

SPSS (version 11) for Windows (SPSS Inc, Chicago, IL, USA).

ResultsResultsResultsResults

A total of 15,548 respondents completed the questionnaires. The mean response rate of

the countries was 40% (Table 1).

Prevalence of self-medication and prescribed use

The prevalence rates of antimicrobial drug self-medication (actual and at-risk) and

prescribed use are presented separately for countries with response rates >40% and <40%

(Table 2). In both of these groups, prevalence rates for actual self-medication were highest in

eastern (in particular, Romania and Lithuania), followed by rates in southern (Malta, Spain, and

Italy) Europe.

Chapter 2

18

Table 1. G

eneral chara

Table 1. G

eneral chara

Table 1. G

eneral chara

Table 1. G

eneral characteristics of respondents in each country

cteristics of respondents in each country



* Low education was defined as incomplete primary education, completed primary education, and lower vocational or general education

† Including any of the following diseases: asthma, chronic bronchitis, emphysem

a, H

IV, cystic fibrosis, diabetes, endocarditis, tuberculosis, prostatitis, chronic

urinary tract infection, chronic osteomyeltis, peptic ulcer disease, chronic pyelonephritis or cancer

§ Rem

inders were not sent to non-respondents

Note: N

L (The Netherlands); SE (Sweden); DK (Denmark); AT (Austria); BE (Belgium); LU (Luxembourg); UK (United Kingdom); IE (Ireland); IL (Israel); M

T (M

alta);

IT (Italy); ES (Spain); CZ (Czech Republic); SI (Slovenia); HR (Croatia); PL (Poland); SK (Slovakia); RO (Romania) and LT (Lithuania)

N

ort

h a

nd W

est

South

E

ast

N

L

S

E

DK

AT

BE

LU

UK

§

IE

IL

M

T

IT

E

S

C

Z

S

I H

R

P

L

S

K

R

O

LT

Respon

se

rate

(%

) 55

69

6

3

28

54

50

23

26

18

54

21

20

59

38

31

3

2

55

4

3

25

Num

ber

of

resp

ond

ents

1,6

34

70

4

1,8

81

44

2

1,7

34

6

75

675

793

46

7

541

21

3

204

1,1

69

1,1

43

6

15

935

5

46

430

7

47

Mea

n a

ge

(yrs

) ±

SD

48

±17

54

±1

9

48

±17

49

±1

6

45

±16

46

±

18

50

±

10

48

±16

50

±1

7

46

±

16

45

±1

8

47

±

14

54

±1

5

48

±17

53

±

16

45

±18

41

±

16

50

±18

59

±

18

Fe

ma

le (

%)

58

53

56

50

55

51

58

59

61

55

61

47

36

58

55

6

0

54

4

9

35

Low

ed

ucatio

n*

(%)

30

53

60

64

32

49

40

53

19

60

37

31

45

70

10

4

2

27

4

3

32

Pre

sen

ce o

f a

ch

ron

ic

dis

ea

se

(%)†

15

14

14

15

13

15

15

17

22

21

27

18

27

20

26

2

3

23

2

7

39

Urb

an lo

cation

(%

) 48

49

49

53

50

45

58

47

36

47

51

57

48

47

58

5

2

54

4

3

54

Self-m

edication with antimicrobial drugs in Europe

19

Table 2. Actual use of system

ic antibiotics in


ic antibiotics in


ic antibiotics in


ic antibiotics in the

the

the

the last 12 months and “at risk” self

last 12 months and “at risk” self

last 12 months and “at risk” self

last 12 months and “at risk” self- ---m

edication in 19 European countries

medication in 19 European countries



Rate

per

1,0

00 r

esp

ond

ents

(95%

CI)

Co

untr

y (

regio

n in c

ountr

y)

Actu

al self-m

edic

atio

n

Pre

scri

bed u

se

Inte

nded s

elf-

medic

ation

Sto

rag

e†

(conserv

ative e

stim

ate

) S

tora

ge‡

(maxim

um

estim

ate

) C

ou

ntr

ies w

ith

resp

on

se r

ate

>40

%

N

ort

h a

nd W

est

T

he N

eth

erl

an

ds (

Tw

ente

) 1 (

0.2

-4)

15

2 (

13

4-1

70)

85 (

71-1

01)

10 (

6-1

7)

36 (

28-4

6)

Sw

ede

n (

Vastm

anla

nd)

4 (

0.9

-12)

13

5 (

10

9-1

61)

11

8 (

94-1

43)

14 (

7-2

6)

43 (

29-6

0)

Denm

ark

(F

une

n, A

arh

us,

Copen

hag

en

* )

7 (

4-1

2)

17

2 (

15

4-1

89)

13

2 (

11

6-1

47)

42 (

33-5

2)

84 (

72-9

7)

Lu

xem

burg

(w

hole

co

untr

y)

9 (

3-1

9)

28

8 (

25

2-3

24)

83 (

62-1

07)

90 (

69-1

14)

13

2 (

10

6-1

58)

Belg

ium

(E

ast F

landers

, F

lem

ish B

rab

ant)

9 (

5-1

5)

22

2 (

20

1-2

42)

80 (

67-9

5)

71 (

59-8

4)

12

3 (

10

7-1

38)

South

Malta (

whole

co

untr

y)

56 (

38-7

9)

42

2 (

38

0-4

65)

22

8 (

19

2-2

64)

156 (

125-1

86)

26

9 (

23

2-3

06)

East

C

zech R

ep

ublic

(H

radec K

rlov)

7 (

3-1

3)

25

3 (

22

8-2

79)

17

9 (

15

6-2

01)

45 (

33-5

8)

64 (

51-8

0)

Slo

vakia

(M

iddle

Slo

vakia

regio

n)

42 (

27-6

3)

56

9 (

52

7-6

12)

32

4 (

28

4-3

65)

192 (

159-2

25)

30

2 (

26

3-3

40)

Rom

ania

(D

olj)

198 (

160-2

35)

30

7 (

26

3-3

51)

43

1 (

38

3-4

78)

200 (

162-2

38)

32

1 (

27

7-3

65)

Co

un

trie

s w

ith

resp

on

se r

ate

<40

%§

N

ort

h a

nd W

est

52 (

33-7

7)

Austr

ia (

Up

per

Austr

ia)

9 (

2-2

3)

15

9 (

12

4-1

95)

73 (

49-1

03)

34 (

19-5

5)

52 (

33-7

7)

UK

(N

ott

ingha

mshire)

12 (

5-2

3)

22

1 (

18

9-2

54)

16

6 (

13

7-1

95)

33 (

21-4

9)

74 (

56-9

7)

Irela

nd (

Cork

) 14 (

7-2

5)

35

3 (

32

0-3

86)

15

0 (

12

5-1

76)

29 (

19-4

3)

10

0 (

80-1

23)

South

Isra

el (N

ort

hern

Isra

el)

15 (

6-3

1)

33

0 (

28

7-3

74)

18

7 (

15

0-2

23)

12

0 (

91-1

49)

23

6 (

19

7-2

74)

Italy

(A

bru

zzo

) 62 (

33-1

03)

51

2 (

44

4-5

80)

24

3 (

18

5-3

01)

379 (

314-4

45)

56

9 (

50

2-6

36)

Spain

(A

uto

nom

ous C

om

munity o

f M

adrid)

152 (

103-2

01)

31

5 (

25

1-3

79)

31

4 (

24

9-3

80)

260 (

200-3

20)

50

0 (

43

1-5

69)

East

S

lovenia

(Lju

blja

na r

egio

n)

17 (

10-2

6)

29

3 (

26

6-3

20)

28

0 (

25

3-3

07)

119 (

100-1

37)

18

3 (

16

0-2

05)

Cro

atia (

Za

gre

b c

ou

nty

) 31 (

19-4

8)

43

9 (

39

9-4

78)

20

5 (

17

2-2

37)

130 (

103-1

56)

21

2 (

17

9-2

44)

Pola

nd (

Pom

ors

kie

) 33 (

23-4

7)

19

9 (

17

2-2

25)

11

5 (

94-1

36)

69 (

53-8

7)

13

7 (

11

5-1

60)

Lith

ua

nia

(K

laip

ed

a,

Rie

tavas)

210 (

181-2

39)

27

5 (

24

3-3

08)

44

9 (

41

2-4

86)

177 (

149-2

04)

33

3 (

29

9-3

67)

* Although Copenhagen has population >750,000, both self-medication and prescribed use of antibiotics were not significantly different between the sample

of Copenhagen and sample of the other two Danish counties (chi square tests)

†Included only those respondents who stored antibiotics and had not taken the same antibiotics for a prescribed course in the previous 12 m

onths

‡Including all respondents who stored antibiotics

§The rates for these countries should be interpreted as first rough estim

ates

Chapter 2

20

The lowest rates were in northern and western (the Netherlands and Sweden) Europe.

The rates of at-risk self-medication also tended to be higher in southern and eastern Europe

than in northern and western Europe. The adjusted estimates of prevalence rates of

self-medication were similar to the observed rates for many of the countries.2 In Luxembourg,

Austria, Israel, Spain, and Lithuania, the adjusted rates of self-medication were consistently

higher than the observed rates, indicating that the observed rates may underestimate the

prevalence in these countries. By contrast, in Romania, Croatia, and Slovenia, the adjusted rates

were lower than the observed rates, indicating that the prevalence rates might be

overestimated in our study. We compared our estimates of antimicrobial drug self-medication

with data available from the European Union’s Eurobarometer survey in October 2002 (27). We

calculated the prevalence of drug use from “leftovers” and drugs “directly from the pharmacy”

by using the Eurobarometer data and compared these figures with the same estimates in our

study. The estimates were similar with overlapping 95% CIs (data not shown) for countries

with both high and low response rates.

Our figures differed regarding Spain, for which we found a higher prevalence of self-

medication than did the Eurobarometer. Three other studies (4,15,28) indicated an even higher

prevalence of self-medication in Spain than in our estimate.

Types of antimicrobial drugs used for self-medication and duration of use

Antimicrobial drugs from all classes were used for self-medication in countries with

response rates both >40% and <40% (Figure 1) Penicillins were the most commonly used,

representing 54% of total courses in all countries. Among the countries with response rate

>40%, southern and eastern countries used significantly more broad-spectrum penicillin for

self-medication than northern and western countries (χ2, p<0.05). This difference was

significant when the analysis was repeated and included all countries (χ2, p<0.01).

Seventeen courses of self-medication with chloramphenicol in Lithuania and 1 course in

the Czech Republic were found (data not shown). Ten courses of self-medication with

parenteral (injectable) antimicrobial drugs, namely streptomycin or gentamicin, were found in

Lithuania (data not shown). The median duration of actual self-medication was 5 days (1 to 100

days) and was significantly longer among the respondents who had chronic diseases (Mann-

Whitney U test, p<0.01).

2 The “adjusted” estimates for each country are available from the corresponding author upon request.


21

Figure 1. Use of major groups of antibiotics for actual selfFigure 1. Use of major groups of antibiotics for actual selfFigure 1. Use of major groups of antibiotics for actual selfFigure 1. Use of major groups of antibiotics for actual self----medication in 17 countries* medication in 17 countries* medication in 17 countries* medication in 17 countries*

*Excluding countries that reported less than 5 self-medication courses

†includes systemic amphenicols (J01B), aminoglycosides (J01G), combinations of systemic antibiotics

(J01R) and other systemic antibiotics (J01X)

**number of courses (taken in the previous 12 months) per 1,000 respondents per country

Note: DK (Denmark); CZ (Czech Republic); LU (Luxembourg); BE (Belgium); SK (Slovakia); MT (Malta); RO

(Romania); AT (Austria); UK (United Kingdom); IL (Israel); IE (Ireland); SI (Slovenia); PL (Poland); HR

(Croatia); IT (Italy); ES (Spain); and LT (Lithuania)

Reasons for self-medication and sources

A throat symptom (including red or sore throat), teeth or gum symptoms, and

bronchitis were the most common reasons for self-medicating (Figure 2). Eye infection, pain,

prostatitis, urogenital infection, headache, and “bad health” were among the other reasons for

self-medication (data not shown). In countries with response rates >40%, a throat symptom

was also the most common, followed by symptoms of the teeth or gums (Figure 2). Symptoms

such as inflammation, skin infection, or diarrhea were reported only in countries with lower

response rates. Self-medication for pyelonephritis or pyelitis was reported only in Lithuania;

diarrhea was reported in Lithuania (10 patients; 9 used chloramphenicol), Austria (1 patient),

and United Kingdom (1 patient).

Countries with response rate >40% Countries with response rate <40%

0%

20%

40%

60%

80%

100%

DK CZ LU BE SK MT RO AT UK IL IE SI PL HR IT ES LT

rela

tive f

req

uen

cy

broad-spectrum penicillins (J01CA) narrow-spectrum penicillins (J01CE)

other penicillins (J01CF and J01CR) macrolides and lincosamides (J01F)

tetracyclines (J01A) sulphonamides and trimethoprim (J01E)

systemic cephalosoprins (J01DA) systemic quinolones (J01M)

other†

7** 9 10 1214 17 19 23 3642 65 66 162258 31211 37

Chapter 2

22

Figure 2. Prevalence of actual selfFigure 2. Prevalence of actual selfFigure 2. Prevalence of actual selfFigure 2. Prevalence of actual self----medication by symptoms or diseases classified by ICPC codes (rates per medication by symptoms or diseases classified by ICPC codes (rates per medication by symptoms or diseases classified by ICPC codes (rates per medication by symptoms or diseases classified by ICPC codes (rates per

1,000 1,000 1,000 1,000 respondents and 95%CI)respondents and 95%CI)respondents and 95%CI)respondents and 95%CI)

* * * * Symptoms or diseases with rates less than 1 per 1000 respondents, including eye infection,

pain, prostatitis, urogenital infection, headache and “bad health”

For intended self-medication as with actual self-medication, a sore throat was the most

common symptom, followed by urinary tract infection and toothache (Figure 3). When

including only those countries that had response rates >40%, sore throat and urinary tract

infection were also the most common symptoms (Figure 3).

rates per 1,000 respondents

0 2 4 6 8 10

Other*

Cough(R05)

Sinus symptom complaint, other(R09)

Tonsillitis acute(R76)

Laryngitis, tracheitis, acute(R77)

Pneumonia(R81)

Pyelonephritis/pyeltis(U70)

Fever(A03)

Diarrhoea(D11)

Respiratory infection, other(R83)

Skin infection, other(S76)

Ear infections(H70)

Inflammation/infection, not specified

Cystitis/urinary infection(U71)

Influenza(R80)

Upper resp.infection(R74), sneezing/nasal congestion(R07)

Acute bronchitis/bronchiolitis(R78)

Teeth/gum symptom/complaint(D19)

Throat symptom/complaint(R21)

All countries

Countries with response rate >40%


23

Figure3. The prevalence of intended selfFigure3. The prevalence of intended selfFigure3. The prevalence of intended selfFigure3. The prevalence of intended self----medication per prmedication per prmedication per prmedication per predefined symptom (rates per 1,000 edefined symptom (rates per 1,000 edefined symptom (rates per 1,000 edefined symptom (rates per 1,000

respondents and 95% CI) respondents and 95% CI) respondents and 95% CI) respondents and 95% CI)

In eastern countries, the major source of self-medication was the pharmacy without

prescription (309 courses, 68%), followed by leftover medications (120 courses, 26%). By

contrast, in southern, northern, and western countries use of leftover medication was more

prevalent (46 courses [51%] in southern countries and 35 courses [44%] in northern and western

countries), followed by medications obtained directly from the pharmacy (41 courses [46%] in

southern countries and 15 courses [19%] in northern and western countries). Among other

sources of self-medication were drugs obtained from relatives or friends (52 courses, 8%, in all

countries), drugs that were stored after being obtained abroad (10 courses, 2%, in all countries),

and drugs obtained over the Internet (3 courses, all in Lithuania).

0 20 40 60 80

Other infections/diseases

Diarrhoea

Sinusitis

Ear infections

Runny nose/cold

Bronchitis

Cough

Fever

Influenza

Toothache

Urinary tract infections

Sore throat

All countries Countries with response rate >40%

rates per 1,000 respondents

Chapter 2

24

Effects of Individual Characteristics

The effects of demographic characteristics and chronic disease on actual self-

medication, intended self-medication, and storage of antimicrobial drugs are shown in Table 3.

Sex and location (urban or rural) had no significant relevance in any of the 3 models.

Respondents from southern and eastern countries were more likely to self-medicate (adjusted

odds ratio [OR] 6.8, 95% CI 4.8−9.7, and 7.5, 5.7−10.0, respectively) than respondents from

northern and western countries. Younger age, higher educational level, and presence of a

chronic disease were all significantly associated with self-medication. Similar results were

obtained for the relationship between demographic characteristics and storage of

antimicrobial drugs, by using the conservative estimate of storage. Younger age, higher

educational level, and presence of a chronic disease were also significant predictors of intended

self-medication. Presence of a chronic disease increased the risk of intended self-medication,

but this effect diminished with increasing age. We repeated all analyses including only those

countries that had response rates >40% and obtained similar results. We also repeated these

analyses separately for early and late respondents and obtained similar results. iii

Relation between intended self-medication, storage, and actual self-medication

Intended self-medication and storage are both predictors of actual self-medication. A

significant relationship was found between intended self-medication and storage. Intended

self-medication was a strong predictor for actual self-medication for both respondents who

stored drugs (OR 20.9, 95% CI 15.5−28.2) and those who did not (OR 17.8, 95% CI 14.0−22.7).

However, for those who did not intend to self-medicate, storage also predicted higher actual

self-medication (OR 3.5, 95% CI 2.2−5.6). When the analyses were repeated, including only those

countries that had response rates >40%, similar results were obtained.

iii Results are available on request from the corresponding author.

Self-m

edication with antimicrobial drugs in Europe

25

Table 3. Effects of dem

ographic characteristics on actual and “at risk” self






ographic characteristics on actual and “at risk” self- ---m

edication with systemic antibiotics

medication with systemic antibiotics



* North and W

est includes Sweden, D

enmark, The Netherlands, Austria, Belgium, Luxemburg, U

nited Kingdom, Ireland; South includes Israel, M

alta, Italy, and

Spain; East includes Czech Republic, Slovenia, Croatia, Poland, Slovakia, Romania and Lithuania

† Low education was defined as incomplete primary education, completed primary education, and lower vocational or general education

‡including any of the following diseases: asthma, chronic bronchitis, emphysem

a, H

IV, cystic fibrosis, diabetes, endocarditis, tuberculosis, prostatitis, chronic


Adju

ste

d O

dd

s R

atio

(95

% C

I)

Dete

rmin

ants

Actu

al self-m

ed

ication

Sto

rage

(co

nserv

ative

estim

ate

) In

ten

de

d s

elf-m

ed

icatio

n

Ag

e

0.9

85

(0.9

79

-0.9

92)

0.9

77 (

0.9

73-0

.982)

0.9

84

(0.9

80

-0.9

87)

R

eg

ion in E

uro

pe*

No

rth a

nd

We

st

South

E

ast

1 (

refe

ren

ce

) 6.7

76

(4.7

52

-9.6

62)

7.5

29

(5.6

76

-9.9

85)

1

5.1

01 (

4.2

40-6

.137)

3.3

11 (

2.8

68-3

.822)

1

2.2

33

(1.9

09

-2.6

13)

2.8

51

(2.5

77

-3.1

54)

E

du

catio

n

low

edu

ca

tio

n†

hig

h e

ducatio

n

1 (

refe

ren

ce

) 1.3

57

(1.0

95

-1.6

80)

1

1.6

90 (

1.4

70-1

.943)

1

1.2

33

(1.1

16

-1.3

61)

C

hro

nic

dis

ease

‡ no c

hro

nic

dis

ea

se

an

y ch

ron

ic d

ise

ase

1 (

refe

ren

ce

) 1.8

88

(1.4

97

-2.3

83)

1

1.2

25 (

1.0

38-1

.446)

1

2.3

20

(1.5

94-3

.378)

Ag

e×

an

y ch

ron

ic d

ise

ase

0.9

89

(0.9

82

-0.9

96)

Expon

entia

l (c

onsta

nt)

0.0

12

0

.08

3

0.2

19

Chapter 2

26

DiscussionDiscussionDiscussionDiscussion

Self-medication with antimicrobial drugs occurred in all countries that participated in

this survey. We included the data from both countries that had high and low response rates. In

most of the countries with low response rates (except Spain), no other information is available

about self-medication, an often overlooked issue. The second reason for including these

countries was that low response was not a problem of this study only, but a general problem of

surveys in these countries (29,30). This finding implies that if we want to include information

about these countries, the results may be biased. In addition, debate is growing that low

response is less problematic in affecting survey estimates than previously assumed (31).

Nevertheless, the prevalence rates of self-medication in countries with low response rates

should be considered as a rough estimate and interpreted as an indication that the problem

exists.

Antimicrobial drug self-medication prevalence varies widely among different European

regions, with the highest rates in eastern and southern countries, and the lowest in northern

and western. Besides actual self-medication, intended self-medication is clearly relevant: it is a

strong predictor of actual self-medication. Intended self-medication has a much higher

prevalence than actual self-medication, indicating that the population at-risk is much larger

than those who have actually self-medicated in the previous 12 months. Another risk factor for

actual self-medication is the availability of drugs at home; opportunity encourages use. Our

findings contribute to the growing evidence that estimates of antimicrobial drug use that are

based on prescription data only are likely to underestimate actual consumption in both Europe

and the United States (11,32). Our European estimates are low in comparison with those from a

recent study in the US Hispanic community that showed that ≈20% of the respondents

acknowledged getting drugs without a prescription in the United States (32). The only

comparable high rates were found in Spain, Romania, and Lithuania, where they ranged from

9% to 18%. However, these figures should be compared with caution because our estimates

refer to acquiring drugs without prescription in the last 12 months and the United States study

refers to ever acquiring them.

We found that many persons used antimicrobial drug leftovers from previous

prescriptions, as was the case in reports from the United States (8−10,12). Drugs could be left

over because extra tablets were dispensed (in many countries pharmacies dispense drugs per

package, not exact number of tablets) or because of patient noncompliance. Noncompliance

may result in 2 inappropriate courses if the patient does not take the amount of medication

prescribed and self-medicates later. Earlier findings indicated lower compliance in Italy and

Spain than in Belgium, France, and the United Kingdom (33). In Italy, 41% of the interviewees

who had taken drugs in the previous 12 months saved part of the course for future use,

whereas only 4% of British interviewees reported this behavior (33).


27

In general, respondents’ self-diagnosed disorders were self-limiting and antimicrobial

drugs would not have been indicated. In contrast to studies in developing countries, this study

identified few cases of self-medication for sexually transmitted diseases (34,35). Only 2

respondents in Lithuania reported self-medication for “gynaecological infection” that might

have been a sexually transmitted infection.

In this survey, persons who were more prone to self-medicate with antimicrobial drugs

were younger persons, more educated, and had chronic diseases. This finding corresponds to

those of studies conducted in the United States and Greece, which also found that higher

educational status is associated with misuse of drugs (8,17). This relationship cannot be directly

attributed to educational status. The interpretation of symptoms is also relevant. Previously, a

study in the United States showed that persons with a higher education level tended to believe

that antimicrobial drugs were less effective for upper respiratory infections with clear

discharge but more effective with discoloured discharge (36).

Antimicrobial drug self-medication is a cause for concern because it may contribute to

the spread of antimicrobial drug resistance. Self-treatment with a drug that is ineffective

against the causative organism or with an inappropriate dosage may increase the risk of

selection of resistant organisms that are difficult to eradicate. These resistant organisms may

then be transferred into the community. Our findings illustrate that adverse effects are

aggravated by self-medication when unnecessary drugs, such as chloramphenicol, tetracycline,

and aminoglycosides, are taken. Other problems related to self-medication include drug

interactions, masked diagnoses, and superinfection.

Our results are comparable to those of other studies such as the Eurobarometer study

(14,19,27). A study on antimicrobial drug storage among Spanish households showed that 42%

of Spanish households had drugs at home, including those currently used (14). This finding is

comparable to the prevalence of drugs stored (50%) in our study. In Malta, a higher prevalence

(19%) of self-medication was found (19) than in our study, perhaps because the study included

self-medication in the previous 2 years, while our study included the previous 12 months.

Furthermore, the pattern of the prescribed use of drugs in different regions of Europe in our

study is similar to that found in the study by Goossens et al., which was based on information

from national databases (4).

A strength of our study is that we used the same methods and comparable samples in

all countries, which facilitated an overview of the European situation. The low response rate in

some countries is a limitation of our study, however. Although we calculated the prevalence

rates adjusted for non-response, they are based on the assumption that respondents who

replied after the reminder most resemble non-respondents.

As with all self-reported data, results of this survey have the potential for recall bias,

underreporting, or overreporting. We attached the list of the most commonly used

antimicrobial drugs in each country to the questionnaires to reduce recall problems. To

Chapter 2

28

discourage underreporting of self-medication, the questions about drug use were formulated

in a neutral way in which the source of the drug could be chosen from 6 predefined sources or

“other source.” Substantial variation in the prevalence rates of antimicrobial drug self-

medication among the European regions suggests that cultural (37) and socioeconomic factors

play a role, as do disparities in health care systems such as reimbursement policies, access to

health care, and drug dispensing policies. Another factor is the acquisition of antimicrobial

drugs from pharmacies without prescription, which occurred most frequently in eastern

European countries. Although over-the-counter sale of antimicrobial drugs is illegal in all

participating countries, there is clearly a need to enforce the law in some countries.

Antimicrobial drug self-medication is a cause for concern in Europe. Even the lowest

prevalence, 1 person per 1,000 respondents, implies that 10,000 persons in a population of

10,000,000 are self-medicating annually. Our study indicates a high prevalence of self-

medication in countries that reported high resistance levels (southern and eastern countries).

Even in the countries with low actual self-medication, substantial intended self-medication

and drug storage occurs. Efforts to reduce inappropriate use of antimicrobial drugs should

include the issue of self-medication and should involve prescribers, pharmacists, and the

general public. The number of tablets dispensed in pharmacies should be limited, and patients

should be instructed to discard their leftover drugs. Large-scale public campaigns, such as

those recently launched in the United States, Canada, Belgium, and Australia (38), should

include detailed instructions and emphasize the potential risks of using antimicrobial drugs

without medical guidance.

AcknowledgementsAcknowledgementsAcknowledgementsAcknowledgements

This study was funded by a grant from DG/Sanco of the European Commission

(SPC2002333), the European Commission Public Health Directorate DG SANCO, and the

participating institutions.

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22. Sample size for population proportion. Available from

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31. Keeter S, Miller C, Kohut A et al. Consequences of reducing nonresponse in a national telephone

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Is self-medication with antibiotics in Europe driven

by prescribed use?

Larissa Grigoryan, Johannes G M Burgerhof,

Flora M Haaijer-Ruskamp, John E Degener, Reginald Deschepper,

Dominique L Monnet, Antonella Di Matteo, Elizabeth A Scicluna,

Ana- Claudia Bara, Cecilia Stålsby Lundborg, Joan Birkin, on behalf of the SAR group

Journal of Antimicrobial Chemotherapy, 2007;59(1): 152-156

Chapter 3

34

Abstract Abstract Abstract Abstract

BackgroundBackgroundBackgroundBackground:::: Self-medication with antibiotics may increase the risk of inappropriate use and

the selection of resistant bacteria. One of the triggers for using self-medication may be past

experience with antibiotics prescribed by health professionals. We examined the association

between prescribed use and self-medication with antibiotics.

MethodsMethodsMethodsMethods:::: A population survey was conducted in 19 European countries, covering 15 548

respondents. Multinomial logistic regression analysis was used to study the relationship

between prescribed use and self-medication for all symptoms/diseases and for upper

respiratory tract infections (URTIs).

ResultsResultsResultsResults:::: The association between prescribed use and self-medication was modified by source of

self-medication, region in Europe and education. This association was consistently stronger for

self-medication from leftovers than from other sources, primarily directly from a pharmacy. It

was stronger also for respondents from Northern/Western Europe than respondents from

Eastern Europe and Southern Europe and those with low education. Prescribed use for URTIs

(minor ailments such as throat symptom, influenza, etc.) increased the likelihood of self-

medication with leftover antibiotics for these symptoms/diseases in all European regions.

ConclusionsConclusionsConclusionsConclusions:::: Our study shows consistent associations between prescribed use and self-

medication with antibiotics from leftovers, but has not been able to support the hypothesis

that self-medication from other sources than leftovers is triggered by earlier prescribed use.

Preventing leftovers may be one effective way of preventing self-medication. This can be

achieved by ensuring that the amount dispensed corresponds to the amount prescribed, by

educating patients and by making doctors aware that prescribing for minor ailments may

increase the risk of self-medication for such ailments.

Is self-medication with antibiotics in Europe driven by prescribed use?

35


Self-medication with antibiotics may lead to a wrong choice of antibiotics, use of

insufficient dosages or unnecessary therapy. This inappropriate use increases the risk of

selection of resistant bacteria (1) and may contribute to antibiotic resistance (2). Previous

studies have shown that self-medication with antibiotics occurs in the United States and

Europe, in particular for colds and upper respiratory tract symptoms (3,4). The rates of

antibiotic prescribing for upper respiratory tract infections (URTIs) remain at high levels (5),

although the majority of these illnesses have a viral cause. This may imply that one of the

triggers for using self-medication by people can be a past experience with prescribed use of

antibiotics.

A study in Spain found that the main reason for using self-medication was a previous

medical prescription of the same medication (6). This is likely to be true for antibiotics as they

were one of the commonly used pharmacological groups in this study (6). Moreover, several

studies suggested that unrealistic patient expectations regarding the need for antibiotics may

be generated by previous inappropriate prescribing by the physician (3,5,7). Information about

the relationship between prescribed antibiotic use and self-medication with antibiotics can be

helpful in designing interventions to prevent self-medication. To date, no study has explored

this relationship. We investigated whether prescribed use triggers self-medication with

antibiotics in European countries.


A cross-sectional survey was conducted simultaneously in 19 European countries.

Countries participating in two European networks of surveillance systems [European

Surveillance of Antimicrobial Consumption (8) and European Antimicrobial Resistance

Surveillance System (9)] were invited to participate in this study. The following countries

agreed to participate: Austria, The Netherlands, Sweden, the UK, Ireland, Denmark, Italy, Malta,

Luxembourg, Belgium, Spain, Israel, Romania, Czech Republic, Slovakia, Lithuania, Slovenia,

Croatia and Poland. The design of the study, the characteristics of the respondents in each

country and the prevalence rates of self-medication and prescribed use in each country have

been published elsewhere (4). A multistage sampling design was used for sample selection in

each participating country. Within each country, a region with average prescribed antibiotic

consumption was chosen and in each chosen region a middle-size city and rural area were

selected. Questionnaires were mailed to adults randomly selected in the identified cities and

rural areas.

Chapter 3

36

Questions included the respondent’s use of antibiotics during the past 12 months, name

of the medicine, source, symptom or disease, coded with ICPC (10) and demographic

characteristics. Symptoms and diseases included in this study were self-reported. When the

reported symptom overlapped with a disease (i.e. cough and bronchitis) only the disease was

included. Only antibacterials for systemic use, ATC class J01 (11) were included in the analyses.

Respondents were classified as self-medicating if they reported that they had taken any

antibiotic in the previous 12 months without a prescription from a physician, dentist or a nurse

and as prescribed users if antibiotics had been prescribed in the same time period.

In this study, we studied the relationship between prescribed use and self-medication

in general (for all symptoms/diseases). We also studied the relationship between prescribed

use and self-medication for URTIs. URTIs were classified as cough, sneezing/nasal congestion,

throat symptom, sinus symptom, sinusitis, upper respiratory infection, acute tonsillitis,

influenza and strep throat). These minor ailments are very common in the general population

(12,13). Each adult experiences at least two colds per year (12,13). We may therefore assume that

all respondents had experienced at least one of these in the previous 12 months.

Statistical analyses

Multinomial logistic regression analysis was used to study the relationship between

prescribed use of antibiotics and self-medication with antibiotics in general (for all

symptoms/diseases) and for URTIs. All 15 548 respondents were included in each regression

analysis. In the multinomial logistic regression for antibiotic use in general, we considered

three groups as follows: (i) respondents who used leftover antibiotics for self-medication; (ii)

respondents who used self-medication with antibiotics obtained directly from a pharmacy or

other source; and (iii) as a reference group respondents who did not self-medicate. We

examined separately self-medication with leftover antibiotics and self-medication with

antibiotics obtained from other sources as a stronger relation must be expected between

prescribed use and self-medication with leftovers. In the multinomial logistic regression for

URTIs, the reference group consisted of the people who did not self-medicate for URTIs,

including respondents who did not self-medicate and those who used self-medication for other

symptoms.

The models were adjusted for the factors associated with self-medication use (region in

Europe, education, age and presence of a chronic disease) based on earlier results (4). Countries

were grouped together in regions (Northern/Western Europe, Southern Europe and Eastern

Europe) based on combination of different criteria as described elsewhere (4). Education was

categorized into low (incomplete primary education, completed primary education and lower

vocational or general education) and high (intermediate or higher vocational or general

education, college or university). In order to identify effect modifiers we tested for each model

possible statistical interactions between prescribed use and other determinants of self-


37

medication (14). We tested interactions between prescribed use and determinants found to be

significant and set the significance at P < 0.01 for interaction terms. Data were analysed using

SPSS (version 12) for Windows (SPSS, Inc., Chicago, IL, USA).


Of the 15 548 respondents who completed the questionnaires, 206 had used both

prescribed antibiotics and self-medication (Figure 1). Of these 206 respondents, 95 (46%) used

leftover antibiotics for self-medication and 111 (54%) used antibiotics obtained directly from a

pharmacy or other source. In both subgroups many respondents used prescribed antibiotics

and self-medication for the same symptoms/diseases or used the same antibiotic for both

(Figure 1).

Figure 1. Flow chart describing antibiotic use in the last 12 months by the respondents Figure 1. Flow chart describing antibiotic use in the last 12 months by the respondents Figure 1. Flow chart describing antibiotic use in the last 12 months by the respondents Figure 1. Flow chart describing antibiotic use in the last 12 months by the respondents

279 only used self-medication

with antibiotics (of whom 78 used

leftovers and 201 directly from a

pharmacy or other source*)

206 used both

prescribed antibiotics

and self-medication

3653 only used prescribed

antibiotics only

15548 completed the questionnaires 11410 did not use antibiotics

95 self-medications with

leftover antibiotics from a

previous prescription

111 self-medications

directly from a pharmacy

or other* source

71 for the same

symptom/disease†

69 with the same

antibiotic‡

59 for the same

symptom/disease†

44 with the same

antibiotic‡

* including antibiotics obtained from relatives/friends, directly from a pharmacy/store from abroad or the

Internet

† prescribed use and self-medication for the same symptom/disease

‡ the same antibiotic for prescribed use and self-medication

Chapter 3

38

URTIs were the most common reasons for self-medication in all three European regions

(44% of all respondents who used self-medication in Northern/Western Europe, 56% in

Southern Europe and 41% in Eastern Europe). The second most common reasons were teeth or

gum symptoms in Southern (16%) and Eastern (19%) Europe and cystitis/urinary infection in

Northern/Western Europe (13%).

The use of prescribed antibiotics was associated with self-medication with antibiotics

in the previous 12 months. The unadjusted odds ratio (OR) was 3.6 (95% CI 2.6–4.8) for self-

medication with leftover antibiotics and 1.6 (95% CI 1.3–2.0) for self-medication from other

sources. The first group in the multinomial logistic regression included 173 respondents who

used leftover antibiotics for self-medication (including 95 who had been prescribed antibiotics

and 78 who had not). The second group included 312 respondents who used self-medication

with antibiotics obtained directly from a pharmacy or other source (including 111 who had been

prescribed antibiotics and 201 who had not). The reference group is comprised of those who did

not self-medicate (including 3653 who had been prescribed antibiotics and 11 410 who had not).

Significant statistical interactions were found between prescribed use of antibiotics

and region in Europe and prescribed use and education (P < 0.001 for both interaction terms).

Based on these interactions in the multinomial logistic model, we calculated the ORs within

each region of Europe for both self-medication with leftovers and self-medication from other

sources (Table 1). As expected, the relationship between prescribed use and self-medication

with leftover antibiotics was stronger than with self-medication from other sources; however,

this was only significant in Northern/Western and Eastern regions (Table 1). In Southern Europe

we saw the same tendency, but the associations were not significant. Educational level was the

second effect modifier. Prescribed use was a stronger determinant of self-medication in the

lower educated respondents than in the higher educated respondents. The relationship

between prescribed use and self-medication from sources other than leftovers was significant

only in Northern/Western Europe, again with a stronger association among respondents with

lower education.

For URTIs, a significant association was found between prescribed use and self-

medication with leftover antibiotics. The unadjusted OR was 7.2 (95% CI 4.6–11.1) for self-

medication with leftover antibiotics and 1.7 (1.1–2.8) for self-medication from other sources. The

first group in the multinomial logistic regression included 84 respondents who used self-

medication for URTIs with leftover antibiotics (including 35 who had been prescribed an

antibiotic for URTIs and 49 who had not). The second group included 129 respondents who

used self-medication with antibiotics obtained directly from a pharmacy or other source

(including 19 who had been prescribed an antibiotic for URTIs and 110 who had not). The

reference group includes those who did not self-medicate for URTIs (including 15063 who did

not self-medicate and 272 who used self-medication for other symptoms/diseases).

Table 1.

Table 1.

Table 1.

Table 1. The effect of prescribed use on

The effect of prescribed use on

The effect of prescribed use on

The effect of prescribed use on self

self

self

self- ---m

edication in subgroups of regions in Europe and educational level

medication in subgroups of regions in Europe and educational level



* Northern/W

estern Europe includes Sweden, D

enmark, The Netherlands, Austria, Belgium, Luxembourg, U

nited Kingdom and Ireland; Southern Europe includes

Malta, Italy, Spain and Israel; and Eastern Europe includes Czech Republic, Slovenia, Croatia, Poland, Slovakia, Romania and Lithuania

† adjusted for presence of chronic diseases and age

‡ Low education was defined as incomplete primary education, completed primary education, and lower vocational or general education

Ad

juste

d

OR

† (

95

% C

I)

Within

Nort

hern

/ W

este

rn E

uro

pe

* W

ithin

South

ern

Euro

pe

Within

Ea

ste

rn E

uro

pe

Self-m

ed

ication

Am

ong r

esp

ond

ents

w

ith low

edu

cation

‡

Am

on

g

respo

nd

ents

w

ith

hig

h

edu

cation

Am

ong

respo

nd

en

ts

with low

ed

uca

tion

Am

ong

respo

nd

ents

w

ith h

igh e

du

catio

n

Am

ong

resp

ond

en

ts

with low

ed

uca

tion

*

Am

ong

re

sp

ond

ents

w

ith h

igh

e

du

catio

n

W

ith lefto

ver

antib

iotics

15.7

4 (

6.1

3-4

0.4

2)

8.6

0 (

3.6

8-2

0.1

2)

2.1

9 (

0.9

5-5

.06)

1.2

0 (

0.5

9-2

.43)

3.2

6 (

1.6

8-6

.32)

1.7

8 (

1.0

7-2

.97)

With a

ntibio

tics o

bta

ined

dir

ectly

from

pharm

acy o

r oth

er

so

urc

e

4.0

3 (

1.8

1-

8.9

6)

2.2

1 (

1.0

4-

4.7

0)

1.9

4 (

0.8

7-4

.30

) 1.0

6 (

0.5

0-2

.23)

1.5

5 (

0.9

8-2

.45)

0.8

5 (

0.6

0-1

.20)

39


Chapter 3

40

A significant interaction was found between prescribed use and region in Europe (P <

0.001). In Northern/Western Europe, respondents who had used prescribed antibiotics for

URTIs had a 37.45 (95% CI 9.89–141.75) higher odds of self-medication for URTIs. The effects

were smaller in Southern Europe (OR 3.64, 95% CI 1.60–8.25) and Eastern Europe (3.64, 1.96–

6.74). These associations were not significant for self-medication from sources other than

leftovers (1.96, 0.45–8.67 in Northern/Western Europe, 1.58, 0.51–4.87 in Southern Europe and

1.06, 0.59–1.93 in Eastern Europe). No interaction was found between prescribed use and

education for URTIs.


To our knowledge, this is the first study exploring the relationship between prescribed

antibiotic use and self-medication with antibiotics. The association between prescribed use

and self-medication in general implies that antibiotics prescribed for one symptom/disease

may be used both as self-medication for (repeated) episodes of the same symptom/disease

and for another symptom/disease. The association for URTIs implies that prescribed use for

URTIs increases the probability of self-medication for URTIs.

Our results indicate an association between prescribed use and self-medication with

antibiotics in general from a leftover source in Northern/Western and Eastern Europe. In both

regions the effect of prescribed use was larger in lower educated respondents. One could

hypothesize that respondents with low education are less aware about the consequences of

repeating prescriptions of the doctors for the same symptom/disease or for another

symptom/disease. This effect of education disappeared when looking at the relation between

prescribed use and self-medication for URTIs. The effect of prescribed use on self-medication

for URTIs with leftover antibiotics in all European regions was the same for both educational

levels. For self-medication from sources other than leftovers the associations did not reach

statistical significance. This might be due to a lack of statistical power to detect a smaller

effect.

A limitation of our study is the low response rate in some of the countries. However,

the results were similar after exclusion of countries with response rates below 40% (data not

shown). Therefore, we believe that the bias resulting from non-response did not result in an

overestimation of the relationships reported in this study. A second limitation is that no data

were available about actual occurrence of URTIs. However, evidence indicates that practically

everybody experiences such symptoms/diseases more than once a year (12,13). Therefore, we

based our analysis on the assumption that all respondents have had at least one URTI in the

previous year.

Our findings indicate that preventing leftovers from prescribed courses may be one

effective way of preventing self-medication with antibiotics. This can be done by technical


41

measures, such as promoting the dispensing of the exact numbers of tablets or by educating

patients. In addition, doctors should be aware that prescribing for minor ailments may also

increase the risk of self-medication for such ailments. The effect to be expected may be the

strongest in Northern/Western Europe, but in that part of Europe self-medication is low,

implying that the absolute effect would be limited. In Eastern European countries, though self-

medication with antibiotics obtained directly from pharmacies is the most common, the

absolute expected effect may be more pronounced, since self-medication from leftovers occurs

frequently (4). In Southern Europe, the relevance of prescribed use seems to be limited to using

leftovers for self-medication for URTIs. This may imply that the respondents from Southern

Europe are more ‘cautious’ and tend to repeat prescriptions of the doctors only for URTIs. In

Northern/Western and Eastern Europe respondents may repeat prescriptions of the doctors

not only for URTIs but also for other symptoms/diseases or use self-medication for a different

symptom/disease. However, in both cases there is reason for concern. URTIs are usually not an

appropriate indication for the use of antibiotics, so in these cases antibiotics should not be

used either prescribed or as self-medication. The use of leftover antibiotics for a variety of

indications without professional advice is just as inappropriate. In both cases action should be

undertaken to prevent the use of leftovers.

Besides leftovers, self-medication from other sources should be prevented. In the

future, the problem of self-medication with antibiotics might be aggravated also because of

increased accessibility of the Internet as a source of buying antibiotics without a prescription.

Strengthening pharmacy regulations and educating the public may prevent self-

medication directly from the pharmacy or from other sources.

In conclusion, our study shows consistent associations between prescribed use and self-

medication from leftovers, but has not been able to support the hypothesis that self-

medication from other sources than leftovers is triggered by earlier prescribed use.


We are grateful to Reli Mechtler (Austria), Arjana Tambic- Andrasevic (Croatia),

Retnosari Andrajati (Czech Republic), Robert Cunney (Ireland), Hana Edelstein (Israel), Rolanda

Valinteliene (Lithuania), Alaa Alkerwi (Luxembourg), Pawel Grzesiowski (Poland), Thomas Tesar

(Slovakia), Milan Cizman (Slovenia) and Jose Campos (Spain) for participation in the design of

the study and data collection. The study was funded by the European Commission Public

Health Directorate DG SANCO. In addition, funding was also provided from funds of the

participating institutions. The researchers of this study have been independent of funding

source.

Chapter 3

42

Transparency declarationsTransparency declarationsTransparency declarationsTransparency declarations

None to declare.

ReferReferReferRefereeeencesncesncesnces



Agents Chemother 1998; 42:521-527.


risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998; 279:365-

370.

3. Richman PB, Garra G, Eskin B, Nashed AH, Cody R. Oral antibiotic use without consulting a

physician: a survey of ED patients. Am J Emerg Med 2001; 19:57-60.

4. Grigoryan L, Haaijer-Ruskamp FM, Burgerhof JGM et al. Self-medication with antimicrobial drugs

in Europe. Emerg Infects Dis 2006; 12:452-459.

5. Belongia EA, Schwartz B. Strategies for promoting judicious use of antibiotics by doctors and

patients. BMJ 1998; 317317317317:668-671.

6. Moral Serrano S, Aguaron Joven E, Adan Gil FM et al. Do the patients medicate themselves

correctly? Aten Primaria 1994; 13131313:242-246.

7. Hong JS, Philbrick JT, Schorling JB. Treatment of upper respiratory infections: do patients really

want antibiotics? Am J Med 1999; 107107107107:511-515.

8. European Surveillance of Antimicrobial Consumption. Available at URL:

http://www.ua.ac.be/esac (Accessed 24 July, 2006).

9. European Antimicrobial Resistance Surveillance System. Available at URL:

http://www.earss.rivm.nl (Accessed 24 July, 2006).

10. World Organization of Family Doctors (WONCA) International Classification Committee.

International Classification of Primary Care ICPC-2. New York: Oxford University Press; 1998.

11. WHO Collaborating Centre for Drug Statistics Methodology. ATC index with DDDs 2002. Oslo,

Norway: WHO Collaborating Centre for Drug Statistics Methodology; 2002.


43

12. Heikkinen T, Jarvinen A. The common cold. Lancet 2003; 361361361361:51-59.

13. Garibaldi RA. Epidemiology of community-acquired respiratory tract infections in adults.

Incidence, etiology, and impact. Am J Med 1985; 78787878:32-37.

14. Douglas DG, Altman JM. Practical statistics for medical research. London, Chapman and Hall, 1991.

Determinants of self-medication with antibiotics in

Europe: the impact of beliefs, country wealth and

health care system

Larissa Grigoryan, Johannes G M Burgerhof, John E Degener,

Reginald Deschepper, Cecilia Stålsby Lundborg, Dominique L Monnet,

Elizabeth A Scicluna, Joan Birkin, and Flora M Haaijer-Ruskamp, on behalf of the SAR consortium

Submitted

Chapter 4

46

Abstract Abstract Abstract Abstract

We studied the impact of predisposing (attitudes, beliefs and knowledge) and enabling

factors (country wealth and health care system factors) on self-medication with antibiotics in

Europe. In total, 1101 respondents were interviewed in 11 countries. A multilevel analysis with

two levels (country and respondent) was performed. Among the predisposing factors, positive

attitudes towards appropriateness of self-medication with antibiotics for bronchitis and

incorrect beliefs about antibiotics for minor ailments were related to higher likelihood of self-

medication. Among the enabling factors at country level, country wealth (higher GDP) and

dispensing the exact number of tablets in the pharmacies were independently associated with

lower likelihood of self-medication. At individual level, perceived availability of antibiotics

without a prescription was related to increased probability of self-medication. Interventions

aimed at preventing self-medication with antibiotics should include public education, stricter

control over the laws influencing sale of antibiotics and dispensing the exact number of tablets

of prescribed antibiotics in pharmacies.

Determinants of self-medication with antibiotics in Europe: the impact of beliefs, country wealth and

health care system

47


Self-medication with antibiotics occurs among the population in Europe, in

particular in Southern and Eastern countries (1,2). Several studies in the United States (US) have

also shown considerable self-medication with antibiotics obtained from leftovers from

previous courses, at a local pharmacy or outside the country (3-6). The most common reasons

for self-medication were colds and upper respiratory tract symptoms (1,4) which are self-

limiting and mostly caused by viruses. This inappropriate use may contribute to antibiotic

resistance (7) which is reaching alarming levels in Southern and Eastern Europe (8).

Most health behaviours are determined by multiple factors and interventions that

address several key factors are likely to be the most successful (9,10). The PRECEDE model of

behaviour change (11) is a standardized theoretical framework that has been used to design

successful, large-scale health interventions (12,13). According to the PRECEDE model, health

behaviour is influenced by predisposing factors (characteristics that lead to or motivate

behaviour such as knowledge and beliefs), enabling factors (characteristics that facilitate or are

needed to perform the particular behaviour, such as resources in the environment) and

reinforcing factors (rewards and punishments received from others).

The determinants of self-medication with antibiotics in low-income countries include

over-the-counter sale of antibiotics (14), the cost of medical consultation, low satisfaction with

medical practitioners (15), and misconceptions regarding the efficacy of antibiotics (16). Studies

in the US showed that recent immigrants from Latin American countries, where antibiotics are

available over- the-counter, had the greatest expectations for antibiotics for upper respiratory

infections (3,17). The cultural beliefs and a lack of health insurance were other possible

determinants of self-medication with antibiotics for these immigrants (3). In Europe,

differences in attitudes to antibiotic use have been described (18), but little is known about

their effect on self-medication. In the present study we examined the impact of predisposing

(attitudes, beliefs and knowledge) and enabling factors (country wealth and the health care

system factors) on self-medication with antibiotics in Europe.


Face to face structured interviews were conducted in 12 countries. Countries were

selected to represent Northern/Western (Austria, The Netherlands, Sweden, United Kingdom

and Belgium), Southern (Italy, Malta, Israel and Spain) and Eastern (Czech Republic, Lithuania

and Croatia) European regions. Because of data collection problems, Spain was excluded from

the analyses. Data were collected between October 2003 and May 2004, after approval of the

appropriate institutional review boards. This study is a follow-up from a European survey

Chapter 4

48

estimating prevalence of both self-medication and prescribed use of antibiotics (1). In this

previous survey we used a multistage sampling design. Within each country, a region with

average prescribed antibiotic consumption was chosen and in each chosen region a middle-

sized city and rural area were selected. Questionnaires were mailed to 1000-3000 randomly

selected adults in each country, who were equally distributed in urban and rural areas. The

characteristics of the respondents in each country and the prevalence rates of self-medication

and prescribed use in each country are described elsewhere (1).

This follow-up study was limited to respondents in 12 countries willing to be

interviewed. We aimed to recruit at least 100 respondents in each country, 50 users of self-

medication and 50 non-users, both equally distributed in urban and rural areas. If the number

of self-medication users willing to be interviewed was less than 50 in a country, non-users of

self-medication were added to achieve 100 respondents. In Lithuania, the number of non-users

willing to be interviewed did not reach 50, therefore, self-medication users were added.

Respondents who failed to identify antibiotics correctly (for example confusing antibiotics with

painkillers) were excluded from the study.

The questionnaire for interviews was developed in English, translated into national

languages, and back translated to English to ensure consistency. Pre-testing of the questions

took place in each country. Interviewers from all countries were trained in a collaborative

workshop. The first two interviews with respondents were “training interviews” and were

immediately followed by an in-depth discussion between the trainer and the interviewer.

These first two interviews were excluded from the analysis.

In this study, we have included individual characteristics of the interviewees as well as

characteristics of the country of residence. Predisposing factors included individual data on

attitudes, beliefs and knowledge concerning antibiotic use and self-medication (table 1).

Enabling factors included both individual and country data. Individual data comprised

perceived availability of antibiotics without a prescription, and reimbursement of prescribed

antibiotics. Country data included the Gross Domestic Product (GDP) per capita and dispensing

regulations. Attitudes, beliefs and knowledge concerning antibiotic use and self-medication

were assessed with items measured on a Likert scale, partly derived from other studies

(6,19,20). Items were grouped in scales and the mean scores were computed for each scale,

after reversing those items that were worded in opposite direction (i.e. “antibiotics can kill

bacteria”). Higher scores for each scale represented more inappropriate attitudes, beliefs or

knowledge.

Dimensionality of the data was assessed by factor analysis which revealed four scales,

consistent with the conceptual basis. Items were included in a factor (scale) when the factor-

loading was > 0.40. The first scale assessed attitudes towards appropriateness of self-

medication with antibiotics for bronchitis (table 1). Bronchitis was chosen because antibiotics

might be indicated for treatment (21) and it is considered as a serious illness by lay people (22).


health care system

49

The other scales addressed beliefs about antibiotics for minor ailments (table 1), attitudes

towards situational use of antibiotics and knowledge about the effectiveness of antibiotics on

bacteria and viruses. As shown in table 1, all four scales showed satisfactory reliability

(Cronbach’s alpha and mean inter-item correlation). The respondents’ knowledge about health

dangers associated with taking antibiotics was assessed with an open-ended question, “Are

you aware of any dangers to your health or the health of other people associated with taking

antibiotics?” derived from another study (6). We classified the answers into two categories:

knowledge of antibiotic resistance and knowledge of adverse effects of antibiotics (including

allergies/reactions, antibiotics may kill “friendly”/good flora, diarrhoea, vomiting etc.).

Table 1. Scales of attitudes, beliefs and Table 1. Scales of attitudes, beliefs and Table 1. Scales of attitudes, beliefs and Table 1. Scales of attitudes, beliefs and knowledge, including the underlying itemsknowledge, including the underlying itemsknowledge, including the underlying itemsknowledge, including the underlying items

I. Inappropriate attitudes towards appropriateness of self-medication with antibiotics for bronchitis (α=0.9)||

Items included:* Just imagine you have bronchitis. How appropriate is it in your view to get antibiotics without a prescription?

-…Over the weekend in a normal situation -…Over the weekend with an important event coming up -…On holiday abroad -…You have no time to go to the doctor -…When it is difficult to contact the doctor -…When the doctor has no time to see you immediately -…When a consultation with a doctor is too expensive -…When you have a good experience with taking this antibiotic -…When your doctor always prescribes you this antibiotic -…When the pharmacist advises you which antibiotic to take II. Incorrect beliefs about antibiotics for minor ailments (α=0.7)|| Items included† When one has a sore throat, one should take antibiotics to prevent getting a more serious illness When one gets a cold antibiotics help to get better more quickly By the time you yourself are sick enough to visit a doctor with a bad cold, you usually expect a prescription for antibiotics You usually know if you yourself need an antibiotic for a sore throat before seeing a doctor Most of your friends/relatives think people should take an antibiotic for a cold III. Inappropriate Attitudes towards situational use of antibiotics (0.6)¶ Item included† The use of antibiotics when you are sick in order to remain active (work, family, study) is appropriate The use of antibiotics when you are sick for helping to get through an important event (exam, funeral, wedding) is appropriate IV. Incorrect knowledge about the effectiveness of antibiotics on bacteria and viruses (0.3)¶ Item included‡

Antibiotics can kill bacteria§ Antibiotics can kill viruses

* Measured on a 5 point scale (1=”completely inappropriate” and 5=”completely appropriate”)

† Measured on a 5 point scale (1=”strongly disagree” and 5=”strongly agree”)

‡ Measured on a 4 point scale (1=”strongly disagree” and 4=”strongly agree”)

§ For this item coding was reversed (1=“strongly agree” and 4=”strongly disagree”)

|| Cronbach alpha

¶ mean inter-item correlation (mean inter-item correlation is presented because the scale contains only

2 items)

Chapter 4

50

Perceived availability of antibiotics from pharmacies without a prescription was

assessed by the question, “Could you tell me if it is possible for you to get an antibiotic directly

from the pharmacy without prescription?” The responses for this item were “yes, easily”, “yes,

sometimes”, “no” and “do not know”. We asked about perceived availability of antibiotics

directly from pharmacy because illegal acquisition of antibiotics without prescription from

pharmacies occurs frequently in some countries (1).

For the question about the reimbursement of antibiotics we classified the answers in

three categories “full reimbursement”, “patient co-payment” and “no reimbursement”.

Reimbursement was measured at the individual level, because within a country different

reimbursement schemes are available for individuals.

Respondents were asked whether they had ever taken an antibiotic without a

prescription. They were classified as users of self-medication if they reported that they had ever

taken any antibiotic without a prescription from a physician, dentist or a nurse. Self-medication

included use of antibiotics obtained directly from pharmacy, leftovers from treatment courses

prescribed earlier, obtained from relatives or friends or other sources.

Sociodemographic information included age, educational level and presence of a

chronic disease. Education was categorized as low (incomplete primary education, completed

primary education and lower vocational or general education) or high (intermediate or higher

vocational or general education, college or university).

Data on GDP per capita were retrieved from the 2004 World Health Organization’s core

health indicators (23) and information on regulations regarding the dispensing of exact

numbers of tablets or per package size was provided by country co-investigators of this study

(table 2).

Statistical analysisStatistical analysisStatistical analysisStatistical analysis

Chi-square tests were used to compare users and non-users of self-medication for

differences in categorical variables (sex, education, presence of a chronic disease, location,

predisposing and enabling factors) and a t-test was used for differences in age. SPSS (version

12) for Windows (SPSS, Inc, Chicago, IL) was used. Variables that were statistically significantly

different between users and non-users of self-medication (p<0.05) were considered for

inclusion into the multilevel regression analyses. Due to data’s hierarchical nature multilevel

logistic regression analysis was applied. In the present analysis, the levels were: respondents

(level 1) and countries (level 2). Multilevel analysis allows to split total variance of self-

medication and to attribute it to each level. We used the partitioning of the variance based on

the threshold representation as suggested by Snijders and Bosker (24). The analysis was

performed in three steps. Firstly, an “intercept-only model” was created, which included only


health care system

51

countries (level 2) and did not include any explanatory variables. This model revealed each

level’s contribution to variation. Secondly, explanatory variables on the individual level which

where significantly different between users and non-users of self-medication were included.

Finally, variables at country level were added. The contribution of each determinant in

the multilevel analysis was expressed as odds ratio (OR) and a 95% confidence interval (CI).

Interaction terms were examined for the significant determinants. MLwiN version 2.00 was

used to test multilevel logistic regression models.

Table 2. Country characteristics (n=11)Table 2. Country characteristics (n=11)Table 2. Country characteristics (n=11)Table 2. Country characteristics (n=11)

* Data retrieved from the 2004 World Health Organization’s core health indicators

† PPP$, Purchase Power Parity dollar or “international dollar”. This is a common currency unit that takes

into account differences in the relative purchasing power of various currencies.


In total 1101 respondents were interviewed. Eleven respondents who failed to identify

what was an antibiotic were excluded from the analyses. The mean response rate of the

countries was 89%. Table 3 summarizes the difference between users and non-users of self-

medication in demographic characteristics, predisposing and enabling factors. General

characteristics (age, sex, education, presence of a chronic disease and location) were not

Country Dispensing regulations for prescribed antibiotics in pharmacies

Per capita GDP* in PPP$ †

Czech Republic Exact number of tablets 18,598

Israel Exact number of tablets 22,731

The Netherlands Exact number of tablets 31,143

United Kingdom Exact number of tablets 31,308

Croatia Per package size 11,406

Lithuania Per package size 12,572

Malta Per package size 18,308

Italy Per package size 27,952

Sweden Per package size 30,336 Belgium Per package size 31,481

Austria Per package size 31,648

Chapter 4

52

significantly different between users and non-users of self-medication (table 3). Users of self-

medication had significantly more inappropriate attitudes towards self-medication with

antibiotics for bronchitis than non-users (21% versus 7%). The same trend was observed for

beliefs about antibiotics for minor ailments and attitudes towards situational use of antibiotics

(table 3). Incorrect knowledge about the effectiveness of antibiotics on bacteria and viruses

was slightly higher among non-users of self-medication, though the difference was not

statistically significant. Non-awareness about antibiotic resistance was significantly higher

among users of self-medication. By contrast, non-awareness about adverse effects was

significantly higher among non-users of self-medication.

As shown in table 3, significant differences between users and non-users of self-

medication were also observed with respect to enabling factors i.e. perceived availability of

antibiotics directly from pharmacies and reimbursement of prescribed antibiotics. Users of self-

medication were more likely to perceive that antibiotics are available directly from pharmacies

without prescription. Users of self-medication were less likely to receive complete

reimbursement for prescribed antibiotics and more likely to get no reimbursement at all.

As shown in table 4, “the intercept only” model showed that variation on country level

contributed considerably to the model (18%) though most variation was explained by the

individual characteristics of respondents (82%). The total variance explained by the second

model including factors at the individual level was 32%. The residual variance at the country

level decreased (7%), indicating that a part of the differences between countries had been

explained by the information on the individual level. After adding variables at the country level,

the proportion of total variance explained by the third model was 38%. The between-country

residual variance was 2% and the residual variance at the individual level was 60%.

Determinants of self-m

edication with antibiotics in Europe: the im

pact of beliefs, country wealth and health care system

Table 3. Re

Table 3. Re

Table 3. Re

Table 3. Respondent characteristics according to use of self

spondent characteristics according to use of self

spondent characteristics according to use of self

spondent characteristics according to use of self- ---m

edication (n=1090)

medication (n=1090)

medication (n=1090)

medication (n=1090)

* Percentage of respondents who answ

ered to at least 75%

of the item

s in the dim

ension incorrectly

† p values refer to chi-square tests for nominal variables and t-test for age

Va

riab

les

Users

of

se

lf-m

ed

ica

tion

(n=

25

1)

Non-u

sers

of

se

lf-

med

ication

p v

alu

e†

Gen

era

l ch

ara

cte

risti

cs

Mean

ag

e (

ye

ars

± S

D)

49 ±

15

49±

15

0.7

4

Fem

ale

(%

) 5

5

55

0.9

6

Low

edu

cation

(%

) 2

6

29

0.4

1

Pre

sen

ce o

f a

chro

nic

dis

ea

se

(%

) 2

6

21

0.0

7

Urb

an

lo

cation

(%

) 5

3

50

0.3

4

Pre

dis

po

sin

g f

acto

rs

Ina

ppro

pri

ate

attitud

es t

ow

ard

s s

elf-m

ed

ica

tio

n w

ith

an

tib

iotics f

or

bro

nchitis

(%

)*

21

7

<0.0

01

Incorr

ect

be

liefs

abo

ut a

ntibio

tics f

or

min

or

ailm

ents

(%

)*

21

7

<0.0

01

Inap

pro

pri

ate

att

itud

es t

ow

ard

s s

itua

tio

na

l u

se

of

an

tib

iotics (

%)*

2

4

12

<0.0

01

Incorr

ect kn

ow

ledg

e a

bou

t th

e e

ffe

ctive

ne

ss o

f antibio

tics o

n b

acte

ria

an

d v

iru

se

s (

%)*

1

5

17

0.4

4

Non-a

wa

ren

ess a

bo

ut

an

tib

iotic r

esis

tan

ce

(%

) 6

0

47

<0.0

01

No

n-a

ware

ne

ss a

bou

t ad

ve

rse

eff

ects

of

an

tib

iotics (

%)

4

1

50

0.0

1

En

ab

lin

g f

ac

tors

Pe

rceiv

ed p

ossib

ility

of

obta

inin

g a

ntib

iotics d

ire

ctly

from

pha

rmacie

s

No (

%)

38

64

Ye

s e

asily

(%

) 2

3

7

Ye

s s

om

etim

es (

%)

33

14

Do n

ot kn

ow

(%

) 6

15

<0.0

01

R

eim

burs

em

en

t of

pre

scrib

ed a

ntibio

tics

No r

eim

burs

em

ent

(%)

38

21

Patien

t co

-pa

yme

nt (%

) 4

6

53

Com

ple

te r

eim

burs

em

en

t (%

) 1

6

26

<0.0

01

53

Chapter 4

54

Table 4. Variance partition (%) in the Table 4. Variance partition (%) in the Table 4. Variance partition (%) in the Table 4. Variance partition (%) in the multilevel analysis* multilevel analysis* multilevel analysis* multilevel analysis*

Empty model

(intercept-only model)

Model including variables at the individual level‡

Model including individual and country level variables§

Variance explained 0 32 38 Residual variance at the country level (n=11)

18 7 2

Residual variance at the individual level (n=916†)

82 61 60

* * * * based on the threshold representation as suggested by Snijders and Bosker (24) † total number is lower because respondents with missing values were excluded ‡ including variables which were significantly different between users and non-users of self-medication in the univariate analyses § including also dispensing regulations for prescribed antibiotics in pharmacies and per capita GDP

The results of the multilevel logistic regression analysis including those variables that

were significantly different between users and non-users of self-medication in the univariate

analyses are presented in table 5. Among the five predisposing factors, only two were

statistically significant in the final multilevel logistic regression. As expected, respondents who

had more inappropriate attitudes towards self-medication with antibiotics for bronchitis had

higher likelihood of actual self-medication (OR 2.13, 95% CI 1.70-2.66). Having incorrect beliefs

about antibiotics for minor ailments was also independently associated with higher likelihood

of self-medication. Inappropriate attitudes towards situational use of antibiotics and non-

awareness about antibiotic resistance and adverse effects of antibiotics were not associated

with use of self-medication anymore in the multilevel analysis.

Among the four enabling factors, three were significant determinants of self-

medication (table 5). Country wealth (higher GDP per capita) was related to a lower likelihood

of self-medication. Dispensing the exact number of antibiotics was associated with a

decreased risk of self-medication (OR 0.51, 0.27-0.98). Respondents who perceived antibiotics

as easily or sometimes available directly from pharmacies, had a higher risk of self-medication

whereas those who answered “do not know” had a lower risk compared to respondents

perceiving that antibiotics are not available (table 5). Reimbursement of prescribed antibiotics

was not independently associated with use of self-medication in the multilevel regression

analysis. No statistical interaction was found between the determinants of self-medication in

the multilevel logistic regression analysis.


health care system

55

Table 5Table 5Table 5Table 5. Multilevel model of the relationship between predisposing and enabling factors and use of self Multilevel model of the relationship between predisposing and enabling factors and use of self Multilevel model of the relationship between predisposing and enabling factors and use of self Multilevel model of the relationship between predisposing and enabling factors and use of self----

medicationmedicationmedicationmedication

* Mean score computed for each dimension; higher score indicates more inappropriate attitudes and

more incorrect beliefs

Determinants Actual self-medication Odds Ratio (95%CI)

Predisposing factors At individual level: Inappropriate attitudes towards self-medication with antibiotics for bronchitis *

2.13 (1.70-2.66)

Incorrect beliefs about antibiotics for minor ailments * 1.76 (1.32-2.34) Inappropriate attitudes towards situational use of antibiotics* 0.89 (0.72-1.09) Non-awareness about antibiotic resistance 0.94 (0.62-1.42) Non-awareness about adverse effects 0.84 (0.57-1.24)

Enabling factors At country level: Per capita Gross Domestic Product (GDP) 0.95 (0.92-0.99) Dispensing exact number of tablets in pharmacies

No Yes

Referent

0.51 (0.27-0.98) At individual level: Perceived possibility of obtaining antibiotics directly from pharmacy

No Yes, easily

Yes sometimes Don’t know

Referent 2.51 (1.40-4.48) 2.06 (1.28-3.32) 0.36 (0.16-0.79)

Reimbursement of prescribed antibiotics No reimbursement Patient co-payment

Complete reimbursement

Referent

1.22 (0.68-2.17) 0.81 (0.42-1.57)

Chapter 4

56


To our knowledge, the present study is the first one that includes an analysis of

predisposing and enabling factors to evaluate determinants of self-medication with antibiotics

in Europe. Positive attitude towards appropriateness of self-medication with antibiotics and

incorrect beliefs about antibiotics for minor ailments, i.e. sore throat and common cold, were

predisposing factors for use of self-medication. The perceived availability of antibiotics from

pharmacies without a prescription was the main enabling factor at the individual level. Other

enabling factors included country characteristics, i.e. country wealth (GDP per capita) and

dispensing regulations for prescribed antibiotics in pharmacies. Country wealth and dispensing

exact number of prescribed tablets in pharmacies were independently associated with lower

self-medication. Dispensing antibiotics per package size can produce leftovers which, in a

previous study, have been shown to substantially contribute to self-medication, with 36 % of

those who self-medicated using leftovers (25).

In general, determinants of self-medication must be sought primarily at the level of

the individual and much less as a characteristic of a country, though the latter may be relevant

as well. In the present study, we were able to explain almost all variance at the country level

with the included determinants. However, the 60% residual variance at the individual level

indicates that much remains to be explained. It is not clear why the wealth of a nation is an

important determinant of self-medication with antibiotics. One might hypothesize that wealth

could indicate a more structured health care system, with adequate accessibility to health care.

Attitudes towards situational use of antibiotics, awareness about antibiotic resistance and

adverse effects, and reimbursement of prescribed antibiotics were associated with self-

medication in the univariate analyses, but became non-significant in the multilevel analysis.

This might be because of the correlations between these factors and the determinants of self-

medication that remained significant in the multilevel model. In particular, awareness about

antibiotic resistance was correlated with beliefs about antibiotics for minor ailments and

awareness about adverse effects was correlated with the attitude towards self-medication

with antibiotics. Attitude towards situational use of antibiotics was correlated with both these

determinants. Reimbursement of prescribed antibiotics was correlated with the perceived

availability of antibiotics directly from pharmacies.

Our findings are consistent with the results of other studies, indicating that availability

of antibiotics without prescription and misconceptions about the efficacy of antibiotics

influence self-medication with antibiotics (3,14-16). Studies in low-income countries showed

that the cost of medical consultation and low satisfaction with medical practitioners were also

related to self-medication with antibiotics (15). In our study, the scale measuring the attitude

towards appropriateness of self-medication with antibiotics consisted to a large extent of

items indicating practical barriers for consulting a doctor, such as time constraints and


health care system

57

expense, as appropriate reasons for self-medication. Despite the fact that we do not know to

what extent such difficulties in accessing health care actually exist in the countries included in

this study, this attitude was clearly relevant as a determinant of self-medication. Further

research in actual accessibility may clarify the issue further. Satisfaction with medical

practitioners may also influence use of self-medication. The effect of satisfaction with medical

practitioners on the appropriate use of antibiotics for mild respiratory tract infections was

investigated in another European study (26). Low patient satisfaction was correlated with less

compliant behavior, whereas involving the patient more fully in the management of their

illness was related to a lower probability of antibiotic misuse. Satisfaction with medical

practitioners may also influence use of self-medication. Another area where additional studies

are needed is the relevance of reinforcing factors for use of self-medication, which were not

included in this study. Attitudes and behavior of health personnel may reinforce use of self-

medication with antibiotics. In our earlier study we found that previous prescribed use of

antibiotics for upper respiratory tract infections (URTIs) increased the likelihood of self-

medication with leftover antibiotics from previous courses for these symptoms/diseases

although URTIs are usually not an appropriate indication for the use of antibiotics (25).

Additional information on individual-level factors, such as doctor-patient relationship, patient

satisfaction and perceived accessibility to health care will increase our understanding of

determinants of self-medication with antibiotics in Europe.

A limitation of our study is its reliance on self-reported data about self-medication with

antibiotics. Another limitation is that our population sample may not be representative of the

general population in the studied countries. Nevertheless, our findings have implications for

understanding the relative importance of various determinants for use of self-medication, the

need for additional information and the needed interventions to prevent self-medication with

antibiotics.

Our results suggest that interventions aimed at reducing and preventing self-

medication with antibiotics in Europe should focus on both predisposing and enabling factors.

Public education aimed at predisposing factors should emphasize the potential risks of using

self-medication and the inappropriateness of antibiotic therapy for URTIs. Education will be

effective only when coupled with strategies aimed at modifying enabling factors. One of the

important, potentially modifiable enabling factors facilitating self-medication is absence of

enforcement of the laws regulating the sale of antibiotics. Over–the-counter sale of antibiotics

is illegal in all participating countries and enforcing the law would prevent self-medication.

Dispensing regulation is another enabling factor. To prevent self-medication with antibiotics,

prescribed antibiotics should not be dispensed according to package size. Dispensing exact

number of antibiotic tablets in pharmacies as implemented in the United Kingdom, The

Netherlands, The Czech Republic and Israel, as well as in the United States, could be promoted

in other countries.

Chapter 4

58

In conclusion, our study identified several determinants of self-medication with

antibiotics, both at individual and country level. Interventions aimed at preventing self-

medication with antibiotics should be directed primarily at diminishing the availability of

antibiotics without a prescription, at facilitating the dispensation of the exact numbers of

antibiotic tablets, and at educating the general public to reduce misconceptions about the use

of antibiotics for minor ailments.

Ethics approvalEthics approvalEthics approvalEthics approval

Ethics or data committee approval for the survey was required in six countries

(Belgium, United Kingdom, Malta, Czech Republic, Croatia, and Lithuania) and was obtained

from the local ethics or data committees of these countries.

FundingFundingFundingFunding

The study was funded by the European Commission Public Health Directorate DG

SANCO. In addition, funding was also provided from funds of the participating institutions. The

researchers of this study have been independent of funding source.

The SARThe SARThe SARThe SAR----consortium consortium consortium consortium

Antonella Di Matteo (Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy);

Arjana Tambic-Andrasevic (University Hospital for Infectious Diseases, Zagreb, Croatia);

Retnosari Andrajati (Faculty of Pharmacy, Charles University, Prague, Czech Republic); Hana

Edelstein (Ha'Emek Medical Center, Afula, Israel); Rolanda Valinteliene (Institute of Hygiene,

Vilnius, Lithuania); Reli Mechtler (University of Linz, Linz, Austria); Luc Deliens (Vrije Universiteit

Brussel, Brussels, Belgium); and Greta Van der Kelen (Vrije Universiteit Brussel, Brussels,

Belgium)


health care system

59


1. Grigoryan L, Haaijer-Ruskamp FM, Burgerhof JGM, et al. Self-medication with antimicrobial

drugs in Europe. Emerg Infect Dis. 2006 Mar;12(3):452-9.

2. Mitsi G, Jelastopulu E, Basiaris H, Skoutelis A, Gogos C. Patterns of antibiotic use among adults

and parents in the community: a questionnaire-based survey in a Greek urban population. Int J

Antimicrob Agents 2005 May;25(5):439-43.

3. Mainous AG, III, Cheng AY, Garr RC, Tilley BC, Everett CJ, McKee MD. Nonprescribed antimicrobial

drugs in Latino community, South Carolina. Emerg Infect Dis 2005 Jun;11(6):883-8.

4. Richman PB, Garra G, Eskin B, Nashed AH, Cody R. Oral antibiotic use without consulting a

physician: a survey of ED patients. Am J Emerg Med 2001 Jan;19(1):57-60.


infections in a diverse community. J Fam Pract 1999 Dec;48(12):993-6.

6. Vanden Eng J, Marcus R, Hadler JL, et al. Consumer attitudes and use of antibiotics. Emerg Infect

Dis 2003 Sep;9(9):1128-35.

7. Guillemot D, Carbon C, Balkau B, et al. Low dosage and long treatment duration of beta-lactam:

risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998 Mar

4;279(5):365-70.

8. Mayor S. Antibiotic resistance is highest in south and east Europe. BMJ 2005 Feb

19;330(7488):383-b.

9. Oxman AD, Thomson MA, Davis DA, Haynes RB. No magic bullets: a systematic review of 102

trials of interventions to improve professional practice. CMAJ 1995 Nov 15;153(10):1423-31.

10. Mullen PD, Hersey JC, Iverson DC. Health behavior models compared. Soc Sci Med

1987;24(11):973-81.

11. Green LW, Kreuter MW. Health Promotion Planning: An Educational and Environmental

Approach. 2nd ed. Mountain View, CA: Mayfield Publishing Co. 1991.

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attitudes, knowledge, and self-efficacy regarding cholesterol screening and management. Am J

Prev Med 1993 Mar;9(2):101-6.

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follow-up care among persons at risk for hypertension. Am J Prev Med 1988 Nov;4(6):331-5.

Chapter 4

14. Lansang MA, Lucas-Aquino R, Tupasi TE, et al. Purchase of antibiotics without prescription in

Manila, the Philippines. Inappropriate choices and doses. J Clin Epidemiol 1990;43(1):61-7.

15. Saradamma RD, Higginbotham N, Nichter M. Social factors influencing the acquisition of

antibiotics without prescription in Kerala State, south India. Soc Sci Med 2000 Mar;50(6):891-

903.

16. Radyowijati A, Haak H. Improving antibiotic use in low-income countries: an overview of

evidence on determinants. Soc Sci Med 2003 Aug;57(4):733-44.

17. Corbett KK, Gonzales R, Leeman-Castillo BA, Flores E, Maselli J, Kafadar K. Appropriate antibiotic

use: variation in knowledge and awareness by Hispanic ethnicity and language. Prev Med 2005

Feb;40(2):162-9.

18. Pechere JC. Patients' interviews and misuse of antibiotics. Clin Infect Dis 2001 Sep 15;33 Suppl

3:S170-S173.

19. Belongia EA, Naimi TS, Gale CM, Besser RE. Antibiotic Use and Upper Respiratory Infections: A

Survey of Knowledge, Attitudes, and Experience in Wisconsin and Minnesota. Prev Med 2002

Mar;34(3):346-52.

20. Collett CA, Pappas DE, Evans BA, Hayden GF. Parental knowledge about common respiratory

infections and antibiotic therapy in children. Southern Med J. 1999 Oct;92(10):971-6.

21. Wong DM, Blumberg DA, Lowe LG. Guidelines for the use of antibiotics in acute upper

respiratory tract infections. Am Fam Physician 2006 Sep 15;74(6):956-66.


attitudes and utilisation of antibiotics in a Belgian and a Dutch city. Patient Educ Couns.

2002;48(2):161-9.

23. GDP per capita, Core Health Indicators, World Health Organization.Available form

http://www3.who.int/whosis/country/compare.cfm.last accessed december 11, 2006.

24. Snijders T, Bosker R. An introduction to basic and advanced multilevel modelling. London. Sage

publications. 1999.

25. Grigoryan L, Burgerhof JG, Haaijer-Ruskamp FM et al. Is self-medication with antibiotics in

Europe driven by prescribed use? J Antimicrob Chemother. 2007;59(1):152-156.

26. Pechere JC, Cenedese C, Muller O, et al. Attitudinal classification of patients receiving antibiotic

treatment for mild respiratory tract infections. Int J Antimicrob Agents 2002 Dec;20(6):399-406.

60

Attitudes, beliefs and knowledge concerning

antibiotic use and self-medication: a comparative

European study

Larissa Grigoryan, Johannes G M Burgerhof, John E Degener,

Reginald Deschepper, Cecilia Stålsby Lundborg, Dominique L Monnet,

Elizabeth A Scicluna, Joan Birkin, and Flora M Haaijer-Ruskamp, on behalf of the SAR consortium

Submitted

Chapter 5

62

SummarySummarySummarySummary

Purpose.Purpose.Purpose.Purpose. Although the relevance of cultural factors for antibiotic use has been recognized, few

studies exist in Europe. We compared public attitudes, beliefs and knowledge concerning

antibiotic use and self-medication between 11 European countries.

MethodsMethodsMethodsMethods. In total, 1101 respondents were interviewed on their attitudes towards

appropriateness of self-medication with antibiotics and situational use of antibiotics, beliefs

about antibiotics for minor ailments, knowledge about the effectiveness of antibiotics on

viruses and bacteria and awareness about antibiotic resistance. To deal with the possible

confounding effect of both use of self-medication and education we performed stratified

analyses, i.e. separate analyses for users and non-users of self-medication, and for respondents

with high and low education. The differences between countries were considered relevant

when regression coefficients were significant in all stratum-specific analyses.

Results.Results.Results.Results. Respondents from the UK, Malta, Italy, Czech Republic, Croatia, Israel and Lithuania

had significantly less appropriate attitudes, beliefs or knowledge for at least one of the

dimensions compared with Swedish respondents. The Dutch, Austrian and Belgian

respondents did not differ from Swedish for any dimension.

Conclusions.Conclusions.Conclusions.Conclusions. The most pronounced differences were for awareness about resistance, followed

by attitudes towards situational use of antibiotics. Awareness about antibiotic resistance was

the lowest in countries with higher prevalence of resistance.

Attitudes , beliefs and knowledge concerning antibiotic use and self-medication: a comparative

European study

63


Large variations in outpatient antibiotic use between countries have been reported

(1,2). It has been suggested that cultural determinants may have an impact on differences in

outpatient antibiotic use in the United States (US) and Germany (3,4) resulting in different

resistance prevalences in respiratory pathogens on a national level. Different opinions and

traditions regarding how to treat infectious conditions in different countries have been

described (5). Studies in the US reported ethnic and cultural differences in levels of public

knowledge and attitudes concerning antibiotic use and awareness of antibiotic resistance (6-

8). A first Pan-European study in five EC countries and Turkey conducted in 1993 (9) and

extended to other continents (10) suggested that patients’ attitudes to antibiotic use varied

according to their country of residence. In particular, the proportion of patients definitely

expecting to receive antibiotics for respiratory tract infections was highest in Turkey, France

and Spain among European countries. However, this survey did not test if differences were

statistically significant between countries. Moreover, no attention was given to attitudes

towards self-medication with antibiotics, which varies widely between countries (11),

awareness about antibiotic resistance and knowledge about effectiveness of antibiotics on

bacteria and viruses.

Understanding cultural differences in the public’s attitudes, beliefs and knowledge is a pre-

requisite to develop effective educational interventions. The aim of this study was to explore

attitudes, beliefs and knowledge concerning antibiotic use and self-medication and compare

them between countries.

Subjects and methodsSubjects and methodsSubjects and methodsSubjects and methods

Subjects

Face to face structured interviews were conducted in 12 countries. Countries were

selected to represent Northern/Western (Austria, The Netherlands, Sweden, United Kingdom

and Belgium), Southern (Italy, Malta, Israel and Spain) and Eastern (Czech Republic, Lithuania

and Croatia) European regions. Because of data collection problems, Spain was excluded from

the analyses. Data were collected between October 2003 and May 2004, after approval of the

appropriate institutional review boards. This study is a follow-up from a European survey

estimating prevalence of both self-medication and prescribed use of antibiotics. In this

previous survey we used a multistage sampling design. Within each country, a region with

average prescribed antibiotic consumption was chosen and in each chosen region a middle-

sized city and rural area were selected. Questionnaires were mailed to 1000-3000 randomly

selected adults in each country, who were equally distributed in urban and rural areas. The

Chapter 5

64

characteristics of the respondents in each country and the prevalence rates of self-medication

and prescribed use in each country are described elsewhere (11).

This follow-up study was limited to respondents in 12 countries willing to be

interviewed. We aimed to recruit at least 100 respondents in each country, 50 users of self-

medication and 50 non-users, both equally distributed in urban and rural areas. If the number

of self-medication users willing to be interviewed was less than 50 in a country, non-users of

self-medication were added to achieve 100 respondents. In Lithuania, the number of non-users

willing to be interviewed did not reach 50, therefore, self-medication users were added.

Respondents who failed to identify antibiotics correctly (for example confusing antibiotics with

painkillers) were excluded from the study.

Survey instrument

We developed an English structured interview, translated it into national languages,

and back translated it to English to ensure consistency. Pre-testing of the questions took place

in each country. Interviewers from all countries were trained in a collaborative workshop. The

first two interviews with respondents were “training interviews” and were immediately

followed by an in depth discussion between the trainer and the interviewer. These first two

interviews were excluded from the analysis.

The questions included attitudes towards antibiotic use and self-medication with

antibiotics, beliefs about antibiotics for minor ailments, knowledge about the effectiveness of

antibiotics on bacteria and viruses and awareness of any health dangers associated with taking

antibiotics. Each of these domains was assessed with a series of items, partly derived from

other studies (8,12,13). The instrument contained 5-point Likert scale statements (table 1) and

one open ended question.

Respondents’ knowledge about health dangers associated with taking antibiotics was

assessed with an open-ended question, “Are you aware of any health dangers to your health or

the health of other people associated with taking antibiotics?” derived from another study (12).

We classified the answers into two categories: knowledge of antibiotic resistance and

knowledge of adverse effects of antibiotics (including allergies/reactions, antibiotics may kill

“friendly”/good flora, diarrhoea, vomiting etc.).

Sociodemographic information included age, sex, educational level, presence of a

chronic disease, and place of residence (rural or urban). Education was categorized as low

(incomplete primary education, completed primary education and lower vocational or general

education) or high (intermediate or higher vocational or general education, college or

university).


European study

65

Respondents were asked whether they had ever taken an antibiotic without a

prescription. They were classified as users of self-medication if they reported that they had ever

taken any antibiotic without a prescription from a physician, dentist or a nurse.

Construction of scales measuring attitudes and beliefs

An exploratory factor analysis was performed to demonstrate the dimensionality of the

data. The selection of the number of components to be rotated was based on the “eigenvalue

greater 1” criterion. We set a cut-off value of 0.40 for factor loadings as inclusion criterion in a

factor. After Varimax rotation factor analyses revealed four underlying constructs, which were

consistent with the conceptual basis for the scales (table 1). Reliability of each subset of items

was computed using Cronbach’s alpha and mean inter-item correlation. As described in table 1,

all four scales showed satisfactory reliability. The first scale was attitudes towards

appropriateness of self-medication with antibiotics for bronchitis (table 1). Bronchitis was

chosen because antibiotics might be indicated for treatment (14) and it is considered as a

serious illness by lay people (15). The other scales were beliefs about antibiotics for minor

ailments (table 1), attitudes towards situational use of antibiotics and knowledge about the

effectiveness of antibiotics on bacteria and viruses. The mean scores were computed for each

scale, after reversing those items that were worded in opposite direction (i.e. “antibiotics can

kill bacteria”). Higher scores for each scale represented less appropriate attitudes, beliefs or

knowledge.

Data analysesData analysesData analysesData analyses

To analyse the differences between countries, regression analyses were used with the

outcome variable being each of the dimensions of attitudes, beliefs and knowledge. Multiple

linear regression analysis was used for continuous variables (attitudes towards

appropriateness of self-medication with antibiotics for bronchitis, beliefs about minor

ailments, attitudes towards situational use of antibiotics and knowledge about the

effectiveness of antibiotics on bacteria and viruses) and logistic regression for binary variables

(knowledge of antibiotic resistance and adverse effects of antibiotics).

The number of users and non-users of self-medication as well as those with low and high

education willing to be interviewed differed between countries. To deal with the possible

confounding effect of both use of self-medication and education, we performed stratified

analyses, i.e. studying the differences between the countries separately for users and non-users

of self-medication, and for participants with high and low education. The differences between

countries were considered relevant when regression coefficients were significant in all

stratum-specific analyses.

Chapter 5

66

Table 1. Exploratory factor analysis




F

acto

r lo

adin

g

Item

†

1

2

3

4

Just

imagin

e y

ou h

ave b

ronchitis

. H

ow

appro

priate

is it in

your

vie

w t

o g

et

antibio

tics w

ithout

a p

rescription

?

…O

ver

the w

eeke

nd in a

norm

al situatio

n

0.7

…O

ver

the w

eeke

nd w

ith a

n im

port

ant

event

co

min

g u

p

0.8

…O

n h

olid

ay a

bro

ad

0.6

…Y

ou h

ave n

o t

ime to g

o t

o t

he d

octo

r 0.8

…W

hen it is

difficult t

o c

onta

ct

the d

octo

r 0.9

…W

hen the d

octo

r has n

o tim

e t

o s

ee y

ou im

media

tely

0.8

…W

hen a

consultation w

ith a

docto

r is

to

o e

xp

ensiv

e

0.7

…W

hen y

ou h

ave a

good e

xperie

nce w

ith t

akin

g t

his

antibio

tic

0.4

…W

hen y

our

docto

r alw

ays p

rescribes y

ou this

antibio

tic

0.4

When the p

harm

acis

t advis

es y

ou w

hic

h a

ntibio

tic to take

0.5

When o

ne h

as a

sore

thro

at,

one s

hould

take a

ntibio

tics t

o p

revent g

ett

ing a

more

serio

us illn

ess

0.6

W

hen o

ne g

ets

a c

old

antibio

tics h

elp

to g

et

bett

er

more

quic

kly

0.7

B

y t

he tim

e y

ou y

ours

elf a

re s

ick e

no

ug

h t

o v

isit a

docto

r w

ith a

bad c

old

, you u

sually

exp

ect

a p

rescri

ption f

or

antibio

tics

0.5

You u

sually

kn

ow

if yo

u y

ours

elf n

eed a

n a

ntibio

tic f

or

a s

ore

thro

at

befo

re s

eein

g a

docto

r

0.4

M

ost of

yo

ur

frie

nds/r

ela

tives t

hin

k p

eople

should

take a

n a

ntibio

tic f

or

a c

old

0.5

T

he u

se o

f a

ntibio

tics w

he

n y

ou a

re s

ick in o

rder

to r

em

ain

active (

work

, fa

mily

, stu

dy)

is a

ppro

pri

ate

0.7

The u

se o

f a

ntibio

tics w

he

n y

ou a

re s

ick f

or

help

ing to g

et

thro

ugh a

n im

port

ant

eve

nt

(exa

m, fu

nera

l, w

eddin

g)

is

appro

priate

0.7

Antibio

tics c

an k

ill b

acte

ria*

0.5

A

ntibio

tics c

an k

ill v

iruses

0.6

Cro

nbach a

lph

a

α=

0.9

α

=0.7

α

=0.8

α

=0.4

M

ea

n inte

r-item

corr

ela

tio

n

0.5

0.3

0.6

0.3

Notes: Only loadings with an absolute value >0.40 are shown in the table. Factor 1, attitudes towards appropriateness of self-medication with antibiotics for

bronchitis (1=”completely inappropriate” and 5=”completely appropriate”); factor 2, beliefs about antibiotics for minor ailments (1=”strongly disagree”-

5=”strongly agree”); factor 3, attitudes towards situational use of antibiotics(1=”strongly disagree”-5=”strongly agree”); factor 4, knowledge about the

effectiveness of antibiotics on bacteria and viruses (1=”strongly disagree” and 4=”strongly agree”)

* For this item coding was reversed (1=“strongly agree” and 4=”strongly disagree”)

†Three statements were not included because of low loadings on all factors


European study

67

The effects of other possible confounding variables (presence of a chronic disease,

gender, age, and place of residence) were considered in all analyses. Sweden was used as a

reference country in all analyses as it has the lowest prevalence of total antibiotic use i.e.

prescribed use and self-medication (11). Data were analysed using SPSS (version 12) for

Windows (SPSS, Inc, Chicago, IL).

Results Results Results Results

In total 1101 respondents were interviewed. The mean response rate of the countries was

89%. General characteristics of the respondents in each country are shown in table 2. The

number of users of self-medication differed between the countries because of the variation in

both prevalence of self-medication and willingness to be interviewed between the countries

(table 2). In comparison to the respondents in the previous survey (11), interviewees in the

follow-up study more often had a high education, but were similar with regard to age, sex,

presence of a chronic disease, and place of residence (urban/rural). Eleven respondents who

failed to identify what was an antibiotic were excluded from the analyses.

There was a wide variation in the percentage of respondents who answered incorrectly to

at least 75% of the items for each dimension between the countries (table 3). In most of the

countries this percentage was low. High percentages were obtained in Lithuania and Malta for

three dimensions. In the UK high percentage was found regarding the attitudes towards

appropriateness of self-medication with antibiotics for bronchitis.

More inadequate knowledge was reported about the effectiveness of antibiotics on

viruses (on average, 54% of the respondents answered incorrectly) than on bacteria (22%

answered incorrectly, data not shown). Overall, non-awareness of antibiotic resistance was

high (approximately half of the respondents) with a wide variation between countries, from

87% in Malta to 29% in Belgium. Non-awareness of adverse effects of antibiotics was also high

(48%) with less variation between countries (table 3).

Chapter 5

68

Table 2. General characteristics of interviewees in each participating European country




* Low education was defined as incomplete primary education, completed primary education, and lower vocational or general education

† Including any of the following diseases: asthma, chronic bronchitis, emphysema, HIV, cystic fibrosis, diabetes, endocarditis, tuberculosis, prostatitis, chronic


Coun

try

Respon

se

ra

te (

%)

No.

respo

nd

en

ts

inte

rvie

we

d

No.

users

of

self-

me

dic

atio

n

Mean

ag

e

(years

± S

D)

Fem

ale

(%

)

Lo

w e

du

cation

le

vel*

(%

)

Pre

sen

ce o

f a

ch

ron

ic

dis

ea

se

s†(%

)

Urb

an

location

(%)

Nort

he

rn a

nd

we

ste

rn

Th

e N

eth

erl

and

s

92

116

3

43±

11

69

10

16

48

Sw

eden

9

4

103

13

50±

18

56

36

15

58

Au

str

ia

88

101

19

47±

13

55

50

13

60

Belg

ium

9

2

99

1

8

43±

15

65

20

13

45

United K

ingd

om

5

7

95

1

5

50±9

54

30

16

50

Sou

thern

M

alta

9

2

99

2

9

48±

15

57

61

32

51

Isra

el

100

100

17

51±

14

65

5

22

36

Italy

100

80

1

7

45±

15

59

39

33

51

Ea

ste

rn

Cze

ch R

ep

ublic

7

7

100

21

50±

13

30

29

25

50

Cro

atia

8

7

96

3

6

54±

15

47

1

26

58

Lith

uan

ia

97

101

63

58±

17

42

32

34

52

Attitudes , beliefs and knowledge concerning antibiotic use and self-medication: a comparative European study

69

Table 3. Percentage of interviewees who



Table 3. Percentage of interviewees who had inappropriate attitu

had inappropriate attitu

had inappropriate attitu

had inappropriate attitudes, beliefs and knowledge concerning antibiotic use, self

des, beliefs and knowledge concerning antibiotic use, self

des, beliefs and knowledge concerning antibiotic use, self

des, beliefs and knowledge concerning antibiotic use, self- ---medication and antibiotic

medication and antibiotic



resistance by country




* Percentage of respondents who answered “completely appropriate” or “appropriate” to at least 75% of the items for attitudes towards appropriateness of

self-medication with antibiotics for bronchitis; “strongly agree” or “agree” to at least 75% of the items for beliefs about antibiotics for minor ailments,

attitudes towards situational use of antibiotics; and “strongly disagree” or “disagree” to “antibiotics can kill bacteria” and “strongly agree” or “agree” for

“antibiotics can kill viruses”.

Perc

en

tag

e o

f in

terv

iew

ee

s w

ho a

nsw

ere

d to a

t le

ast

75%

of

the ite

ms in t

he

dim

en

sio

n incorr

ectly*

P

erc

enta

ge o

f in

terv

iew

ees w

ho

a

nsw

ere

d in

corr

ectly

Coun

try

Attitud

es t

ow

ard

s

appro

pri

ate

ne

ss o

f se

lf-m

edic

atio

n w

ith

antibio

tics fo

r bro

nchitis

Be

liefs

abo

ut

antibio

tics f

or

min

or

ailm

en

ts

Att

itud

es t

ow

ard

s

situ

atio

nal use o

f antibio

tics

Know

ledg

e a

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12

16

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om

33

5

22

15

3

2

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2

60

32

48

8

7

31

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el

5

3

16

10

4

7

65

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ly

3

0

8

9

6

9

55

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ch R

ep

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lic

11

5

4

22

4

0

36

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atia

9

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25

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35

2

3

26

13

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50

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ll 10

1

0

14

16

5

0

48

Chapter 5

70

Country of residence was associated with each dimension of attitudes, beliefs and knowledge

when adjusting for use of self-medication, education, presence of a chronic disease, sex, age,

and place of residence (tables 4 and 5). Differences significant in all stratum-specific analysis

were found for the UK, Malta, Italy, Czech Republic, Croatia, Israel and Lithuania. Respondents

from these countries were consistently significantly different compared with respondents from

Sweden for at least one of the dimensions (tables 4 and 5). The Dutch, Austrian and Belgian

respondents were not significantly different from Swedish for any of the dimensions.

Lithuanian interviewees responded differently on the most dimensions from Swedish, with

more positive attitudes towards both self-medication and situational use of antibiotics,

stronger beliefs in antibiotics for minor ailments and less knowledge about both antibiotics

and antibiotic resistance. Similar significant differences were noted in Malta with the

exception of attitudes towards appropriateness of self-medication for bronchitis. In particular,

beliefs in antibiotics for minor ailments were very strong in Malta (table 4). Italian

interviewees had more positive attitudes towards situational use of antibiotics and less

knowledge of both antibiotics and antibiotic resistance. More positive attitudes towards self-

medication and situational use of antibiotics and lower knowledge of antibiotic resistance

were noted in Croatia. Interviewees in the UK, Czech Republic and Israel differed only for one

dimension from Sweden, indicating more positive attitudes towards self-medication in the UK

and Czech Republic and lower knowledge of antibiotic resistance in Israel. No country was

significantly different from Sweden concerning awareness about adverse effects of antibiotics

(data not shown).

Attitudes , beliefs and knowledge concerning antibiotic use and self-medication: a comparative European study

71

Table 4. Results of multiple regression analyses relating respondent characteristic to attitudes, beliefs and knowledge




Notes: β =regression coefficient; CI=95% confidence interval;

Higher coefficients indicate more positive attitudes towards self-medication and situational use of antibiotics; stronger beliefs in antibiotics for

minor ailments; and less knowledge about the effectiveness of antibiotics on bacteria and viruses.

• not significant

� not significant in all stratum specific analyses (by education and by self-medication)

* adjusted for place of residence (rural/urban)

† adjusted for sex

Presence of a chronic disease and age were not significant in any of the analyses

Pre

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0.5

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(0.3

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0.3

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(0.2

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(-

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) -0

.25

(-

0.3

5;

-0.1

5)

Chapter 5

72

Table 5. Logistic regression analysis of awareness about antibiotic resistanceTable 5. Logistic regression analysis of awareness about antibiotic resistanceTable 5. Logistic regression analysis of awareness about antibiotic resistanceTable 5. Logistic regression analysis of awareness about antibiotic resistance

Notes: lower OR indicates poor awareness about antibiotic resistance. The Netherlands, Austria, UK,

Belgium and Czech Republic were not significantly different from Sweden in the stratified analyses

Use of self-medication, sex and age were not significant

* adjusted for presence of a chronic disease and place of residence (rural/urban)

Discuss Discuss Discuss Discussionionionion

Our survey results showed significant differences in levels of public attitudes, beliefs and

knowledge concerning antibiotic use, self-medication and antibiotic resistance in Europe.

Respondents from all participating southern and eastern countries had less appropriate

attitudes, beliefs or knowledge compared with Swedish respondents at least for one of the

dimensions. With the exception of the UK, respondents from northern and western countries

did not differ from respondents in Sweden for any of the dimensions. British respondents had

more positive attitudes towards self-medication with antibiotics for bronchitis. This finding is

in line with the results of a survey conducted in the UK showing that respondents had great

expectations for antibiotics for the symptoms of acute lower respiratory tract illness. In

particular, 72% of previously well adults consulting with these symptoms wanted a

prescription for antibiotics from their general practitioner (16). Other countries demonstrating

more positive attitudes towards self-medication for bronchitis were Lithuania and Czech

Republic.

Evidence indicates that patients may influence antibiotic prescribing through overt

requests for antibiotics or non-overt pressure (17-20). We found that respondents in southern

and eastern countries had stronger beliefs about the need for antibiotics for minor ailments,

more positive attitudes towards use of antibiotics in different situations and less accurate

knowledge about the effectiveness of antibiotics in killing bacteria and viruses. Higher levels of

misconceptions in southern and eastern countries may in some part explain the high levels of

Predictors OR* 95% Confidence intervals

Country Sweden reference

Israel 0.40 (0.21;0.75) Italy 0.21 (0.11; 0.43)

Malta 0.10 (0.05; 0.22) Croatia 0.32 (0.17; 0.60)

Lithuania 0.09 (0.04; 0.18) Education

Low education referent High education 2.44 (1.71; 3.46 )


European study

73

antibiotic use seen in these countries (11). The most pronounced differences between countries

were for awareness about antibiotic resistance, followed by attitudes towards situational use

of antibiotics. In general, there was no consistency between all dimensions, i.e. higher score on

one dimension did not lead to higher scores for the other dimensions.

The respondents from northern and western countries were similar in their beliefs about

antibiotics for minor ailments. A study comparing patients’ views on respiratory tract

symptoms and antibiotics in The Netherlands, UK and Belgium also found that the respondents

in these three countries were similar in their perception of effectiveness of antibiotics to

prevent these symptoms from deteriorating and to speed recovery (21).

Overall, only half of the respondents in our survey were aware about antibiotic resistance.

This awareness was the lowest in countries with higher prevalence of resistance. Our average

results for Europe are comparable to the US data from 1998-1999, reporting that 48% of the

respondents being aware of health dangers associated with taking antibiotics of whom 58%

were aware of antibiotic resistance (12). Other US data have shown much higher levels of such

awareness (73% in Colorado), but this could be due to a difference in methodology in the latter

study that used a closed-response statement instead of an open question (6).

Differences in implementing drug regulations that affect the availability of antibiotics in

different countries can play an important role in misconceptions about antibiotics (7). In the

US, recent immigrants from Mexico, where antibiotics are available over the counter, had the

greatest expectations for antibiotics for upper respiratory infections and the least

understanding of the problem of inappropriate use and antibiotic resistance (6). Our study

indicates high levels of misconceptions concerning antibiotic use and resistance in southern

and eastern European countries where acquisition of antibiotics from pharmacies without

prescription occurs frequently (11), despite the fact that this is against the law. In addition to

these regulatory aspects, other differences in health care systems such as drug prices and

reimbursement policies may also influence the attitudes of the public towards antibiotic use

and self-medication.

The results of our study are limited by small sample size in each country. The selection of

the samples was non-random and the samples of the countries differed in the proportion of

both users of self-medication and respondents with high education. To deal with possible

confounding effects of both self-medication use and education, we used a conservative

approach considering as relevant only those differences which were significant in all stratum-

specific analyses. As a consequence, we might have underestimated differences between

countries.

Our results indicate that, while the inappropriate attitudes and knowledge in the other

domains are clustered in a few countries, lack of awareness of antibiotic resistance and adverse

effects is a problem in all the participating European countries. This is an indication that most

people in these countries still do not realize enough that excessive use of antibiotics is

Chapter 5

74

associated with serious risks affecting individuals as well as the ecosystem as a whole (22).

Continuous efforts are needed to reduce these misconceptions. Strategies to improve the

situation however, will have to be country-specific in view of the different problems identified

in this study. Such attitude shifts have occurred before for example in public’s beliefs about

tobacco use and saturated fat consumption (22). Public-education campaigns have been

shown to be effective in changing attitudes and knowledge about antibiotic use and resistance

as well (18, 23). This will require concerted action of the medical world in collaboration with

patient organisations and policy makers with a long-term view. Our study indicates that the

need for public-education campaigns is strong in countries reporting high resistance levels i.e.

southern and eastern European countries.

One single campaign, however, may not be enough for changing the attitudes of the general

public. A national campaign targeting both the general public and health professionals was

undertaken in Malta in 2002-2003 (24). However, despite the efforts of this campaign we

found high levels of misconceptions concerning antibiotic use in Malta in our study. This

campaign was done only once using posters, brochures and sporadic media slots to inform the

public. More intensive (such as involving the mass media or other multi-faceted approaches)

and focused strategies should be used, which have been found to be effective (18). In contrast

to Malta, a national Swedish project named STRAMA (25) has been continuously implementing

activities in multidisciplinary groups including prescribers, pharmacists and general public

since 1995. Although not proved, it is believed that STRAMA through its activities has had a

positive effect on increasing the knowledge in Sweden regarding antibiotic use and resistance.

Repeated national campaigns were also conducted in Belgium (26). In our study awareness

about antibiotic resistance was the highest in Belgium, which might be related to these

campaigns.

In conclusion, our study showed clear cultural differences in levels of public attitudes, beliefs

and knowledge concerning antibiotic use, self-medication and antibiotic resistance in 11

European countries. The levels of misconceptions contributing to inappropriate use were the

highest in southern and eastern countries, indicating a strong need for public education

campaigns in these countries. Awareness about antibiotic resistance was the lowest in

countries reporting high prevalence of resistance.

Key pointsKey pointsKey pointsKey points

We found cultural differences in public attitudes, beliefs and knowledge concerning

antibiotic use, self-medication and antibiotic resistance in 11 European countries.

The levels of misconceptions contributing to inappropriate use were the highest in southern

and eastern countries, indicating a strong need for public education campaigns in these


European study

75

countries. Awareness about antibiotic resistance was the lowest in countries reporting high

prevalence of antibiotic resistance.

Ethics approvalEthics approvalEthics approvalEthics approval

Ethics or data committee approval for the survey was required in six countries (Belgium,

United Kingdom, Malta, Czech Republic, Croatia, and Lithuania) and was obtained from the

local ethics or data committees of these countries.

The SARThe SARThe SARThe SAR----consortiumconsortiumconsortiumconsortium

Antonella Di Matteo (Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy); Arjana

Tambic-Andrasevic (University Hospital for Infectious Diseases, Zagreb, Croatia); Retnosari

Andrajati (Faculty of Pharmacy, Charles University, Prague, Czech Republic); Hana Edelstein

(Ha'Emek Medical Center, Afula, Israel); Rolanda Valinteliene (Institute of Hygiene, Vilnius,

Lithuania); Reli Mechtler (University of Linz, Linz, Austria); Luc Deliens (Vrije Universiteit

Brussel, Brussels, Belgium); and Greta Van der Kelen (Vrije Universiteit Brussel, Brussels,

Belgium).


This study was funded by a grant from DG/Sanco of the European Commission (SPC2002333),

the European Commission Public Health Directorate DG SANCO, and the participating

institutions.

Conflict of interest statementConflict of interest statementConflict of interest statementConflict of interest statement

None to declare.

Chapter 5

76


1 . Goossens H, Ferech M, Vander Stichele R, Elseviers M. Outpatient antibiotic use in Europe and

association with resistance: a cross-national database study. Lancet. 2005;365(9459):579-587.


pneumoniae and Streptococcus pyogenes. Emerg Infect Dis. 2004;10(3):514-517.

3. Harbarth S, Albrich W, Goldmann DA, Huebner J. Control of multiply resistant cocci: do

international comparisons help? Lancet Infect Dis. 2001;1(4):251-261.

4. Harbarth S, Albrich W, Brun-Buisson C. Outpatient antibiotic use and prevalence of antibiotic-

resistant pneumococci in France and Germany: a sociocultural perspective. Emerg Infect Dis.

2002;8(12):1460-1467.

5. Llor C, Bjerrum L. Background for different use of antibiotics in different countries. Clin Infect

Dis. 2005;40(2):333.

6. Corbett KK, Gonzales R, Leeman-Castillo BA, Flores E, Maselli J, Kafadar K. Appropriate antibiotic

use: variation in knowledge and awareness by Hispanic ethnicity and language. Prev Med.

2005;40(2):162-169.

7. Cummings KC, Rosenberg J, Vugia DJ. Beliefs about appropriate antibacterial therapy, California.

Emerg Infect Dis. 2005;11(7):1138-1141.

8. Belongia EA, Naimi TS, Gale CM, Besser RE. Antibiotic Use and Upper Respiratory Infections: A

Survey of Knowledge, Attitudes, and Experience in Wisconsin and Minnesota. Preventive

Medicine. 2002;34(3):346-352.


antibiotics. Journal of International Medical Research. 1996;24(3):229.

10. Pechere JC. Patients' interviews and misuse of antibiotics. Clin Infect Dis. 2001;33 Suppl 3:S170-

S173.


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11. Grigoryan L, Haaijer-Ruskamp FM, Burgerhof JGM et al. Self-medication with antimicrobial drugs

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13 Collett CA, Pappas DE, Evans BA, Hayden GF. Parental knowledge about common respiratory

infections and antibiotic therapy in children. Southern Medical Journal. 1999;92(10):971-976.

14. Wong DM, Blumberg DA, Lowe LG. Guidelines for the use of antibiotics in acute upper

respiratory tract infections. Am Fam Physician. 2006;74(6):956-966.


attitudes and utilisation of antibiotics in a Belgian and a Dutch city. Patient Education and

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antibiotic management of acute lower respiratory tract illness in general practice: questionnaire

study. BMJ. 1997;315(7117):1211-1214.

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respiratory infections and the ways patients pressure physicians for a prescription. J Fam Pract.

2001;50(10):853-858.

18. Finch RG, Metlay JP, Davey PG, Baker LJ. Educational interventions to improve antibiotic use in

the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium,

2002. Lancet Infect Dis. 2004;4(1):44-53.

19. Davey P, Pagliari C, Hayes A. The patient's role in the spread and control of bacterial resistance to

antibiotics. Clin Microbiol Infect. 2002;;;;8 Suppl 2:43-68.


population. Int. J. Antimicrob. Agents 2002;20(4):253-257.

21. van Duijn H, Kuyvenhoven M, Jones RT, Butler C, Coenen S, Van Royen P. Patients' views on

respiratory tract symptoms and antibiotics. Br J Gen Pract. 2003;53(491):491-492.

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22. Avorn J, Solomon DH. Cultural and economic factors that (mis)shape antibiotic use: the

nonpharmacologic basis of therapeutics. Ann Intern Med. 2000;133(2):128-135.

23. Madle G, Kostkova P, Mani-Saada J, Weinberg J, Williams P. Changing public attitudes to

antibiotic prescribing: can the internet help? Inform Prim Care. 2004;12(1):19-26.

24. National antibiotic campaign in Malta. Available from

http://www.slh.gov.mt/icunit/icuantibiotic.asp, last accessed December 20, 2006.

25. The Swedish Strategic Programme for the Rational Use of Antimicrobial Agents (STRAMA).

Available from http:// www.strama.se, last accessed December 20, 2006.

26. Bauraind I, Goossens H, and Hendrickx E, et al. Two years of national public campaigns to

promote apporpiate use of antibiotics in the community in Belgium [Abstract A-1362]. In

Abstracts of the 43 rd Annual Interscience Conference on Antimicrobial Agents and

Chemotherapy; Chicago, IL; 2003 Sept 14-17. Washington, DC: American Society for Microbiology,

2003:26. 2003.

Are cultural dimensions relevant for explaining

cross-national differences in antibiotic use in

Europe?

Reginald Deschepper, Larissa Grigoryan,

Cecilia Stålsby Lundborg, Geert Hofstede, Joachim Cohen, Greta van der Kelen,

Luc Deliens, and Flora M Haaijer-Ruskamp on behalf of the SAR consortium

Submitted

Chapter 6

80

AbstractAbstractAbstractAbstract

Objectives:Objectives:Objectives:Objectives: To explore whether differences between national cultures as described in

Hofstede’s model of cultural dimensions (Power Distance, Individualism, Masculinity and

Uncertainty Avoidance) are associated with cross-national differences in use of antibiotics

(prescribed and non-prescribed).

Methods:Methods:Methods:Methods: A survey on reported use of systemic antimicrobial drugs in the last 12 months (SAR-

study) was conducted in 19 European countries. Country-level data from this survey were

correlated to country-specific scores of cultural dimensions obtained from Hofstede. Results

were verified by doing the same for data from 3 other studies on antibiotic use.

Results: Results: Results: Results: The SAR-study resulted in a response rate higher than 20% in 17 countries for which

scores on the cultural dimensions were also available. The three other studies provided data on

antibiotic use for 27 European countries in total, for which scores of cultural dimensions were

also available. Significant positive correlations were found between Power Distance and

prescribed (0.59) and non-prescribed (0.54) use of antibiotics. Data from the other 3 studies

gave similar results. Uncertainty Avoidance was not significantly correlated with the data on

antibiotic use from the SAR-study but was significantly positively correlated to the antibiotic

use as reported in the three other studies. Individualism was significantly negatively correlated

with self-medication (-0.41), but not with prescribed antibiotics. No significant correlations

between Masculinity and antibiotic use were found.

ConclusionsConclusionsConclusionsConclusions: Of the dimensions of national culture, in particular Power Distance seems to be

associated with antibiotics use. Campaigns aimed at more rational antibiotics use thus require

good understanding of national culture.

Are cultural dimensions relevant for explaining cross-national differences in antibiotic use in Europe?

81


Antibiotics are important and widely used medicines (1,2). There is, however, a growing

concern that the use and especially the unnecessary use of these medicines leads to resistance,

avoidable costs and adverse reactions (1-3). Hence, a more prudent use of antibiotics has been

advocated (4).

There are considerable cross-national differences in public attitudes towards antibiotics

use (5) as well as in actual use of prescribed antibiotics (2,6,7) and self-medications with

antibiotics (8). These cross-national differences in use of antibiotics can only partially be

explained by epidemiological differences and differences in health care structure. Cultural

factors also are known to play an important role in illness behaviour and consumption of

antibiotics (9). Most cross-cultural comparisons are about factors directly related to illness

behaviour (e.g. labelling and presumed causes of illnesses). Few studies have explored the

broader and general cultural characteristics of a country that at first sight are not directly

related to illness behaviour (10). One of the difficulties in many studies is that the concept of

culture is often used as a general concept for all inexplicable cross-national differences. It is

also hard to operationalise the concept of culture into quantifiable measures that can be used

in comparative studies.

A possible solution is the use of cultural dimensions. These dimensions are aspects from

which a culture can be compared with other cultures. They provide a relatively general

framework for analysis that can be easily applied because it reduces the complexities of culture

and its interactions into quantifiable dimensions (11-13). Based on surveys in more than 50

countries, Hofstede initially found 4 cultural dimensions on which countries can be scored: (i)

Power Distance, (ii) Individualism, (iii) Masculinity and (iv) Uncertainty Avoidance. Power

Distance refers to the degree of hierarchy in a country, it has been defined by Hofstede as the

extent to which the less powerful members of organizations and institutions accept and

expect that power is distributed unequally. Individualism refers to the prevalence of the

interests of an individual versus the group. This dimension is defined as the degree to which

individuals are integrated into groups. Masculinity, as opposed to femininity, refers to a culture

in which the emotional roles between the genders are clearly separated; masculine cultures are

for instance very assertive and competitive. Uncertainty Avoidance deals with a society's

tolerance for uncertainty and ambiguity; this cultural dimension indicates to what extent a

culture programs its members to feel either uncomfortable or comfortable in novel, unknown

or surprising situations. Later, a fifth dimensions (Long Term versus Short Term Orientation)

was found, based on Asian studies. While the influence of cultural dimensions on illness

behaviour and use of medicines has been suggested in previous studies (14,15), very few studies

have actually linked the scores on cultural dimensions with diseases and illness behaviour (16)

Chapter 6

82

and, to our knowledge, no study did this with regard to use of antibiotics. The aim of this study

is to explore whether cultural dimensions, are associated with cross-national differences in the

prescribed use of antibiotics and self-medication with antibiotics.

MaterialsMaterialsMaterialsMaterials and methodsand methodsand methodsand methods

Data on prescribed use of antibiotics and self-medication were obtained from a survey in

2003 on reported use of systemic antimicrobial drugs in the last year in 19 European countries

(SAR: Self-medication with antibiotics and Resistance in Europe). A multistage sampling design

was used in each participating country. Within each country, a region with average prescribed

antibiotic consumption was chosen, based on available national data on use of medicines. In

each region an urban (with a population 75,000- 350,000) and a rural area (population 5,000-

10,000) were selected. Persons > 18 years of age were randomly selected from population

registries in the selected regions. The questionnaire was developed specifically for this survey

in English, translated into national languages, and back-translated for consistency. The

questionnaire is available in English from the corresponding author. More information is

provided elsewhere (8). Respondents were classified as self-medicating if they reported that

they had taken any antimicrobial drugs in the previous 12 months without a prescription from a

physician, dentist, or nurse and as prescribed users if antimicrobial drugs had been prescribed.

For all countries in the SAR-study with a response rate higher than 20%, prevalence of reported

self-medication and prescribed use of antibiotics in the previous 12 months per 1000

population were estimated (8). To verify whether the findings based on our data were

consistent with results based on other studies and other European countries, we also made use

of country-data on outpatient antibiotic use published by the European Surveillance on

Antimicrobial Consumption (2), on reported use of antibiotics in the last year published by

Eurobarometer (7), and on outpatients antibiotics sales using IMS data (6). In contrast to the

data of the SAR-study, these other studies could not differentiate between prescribed

antibiotics and self-medication with antibiotics.

Data on cultural dimensions were obtained from Hofstede (13). We only used the 4 initial

dimensions because data about the fifth dimension (Long Term Orientation) were only

available for a limited number of countries. Scores on these dimensions, called indexes,

indicate the relative positions of countries with regard to each other. For an initial set of 40

countries they were derived from carefully matched samples of employees in different national

subsidiaries of the same multinational corporation (17). These relative positions turned out to

be remarkably stable over time; they were replicated in a number of successive studies by

different researchers using a variety of other matched samples of respondents (for an overview

see Hofstede, 2001). Later additions used a simplified questionnaire, the Values Survey Module

1994 (18). It consists of 20 content questions and 6 demographic questions. The most recently


83

published lists contain index values on the first four dimensions for 74 countries and regions

(13). Spearman’s correlation coefficient rho was used to calculate correlations between country-

aggregated use of antibiotics and country-specific scores of cultural dimensions.

ResResResResultsultsultsults

There were 17 countries from the SAR-study (including 14,877 respondents) for which we

had information on reported self-medication with antibiotics, prescribed use of antibiotics in

the last 12 months and the scores on Hofstede’s cultural dimensions (table 1). Via the ESAC-

study (24 countries), the Eurobarometer study (15 countries) and the study by Cars et al (15

countries) we disposed over similar data for in total 27 European countries (2,6,7).

Significant positive correlations were found for Power Distance Index with prescribed use

of antibiotics (0.59) and self-medication (0.54). Comparison with data available from other

studies and other countries demonstrated significant correlations in the same directions (table

2). The Individualism Index is significantly negatively correlated with self-medication of

antibiotics (-0.41). Moderate but non-significant correlations were found for prescribed use in

the SAR-study and antibiotic use as reported in the other 3 studies. The Masculinity Index

correlates moderately but non-significantly with self-medication (0.31) and prescribed use

(0.42). This is consistent with the correlations based on the other studies. The finding of a

positive correlation of Uncertainty Avoidance Index with self-medication (0.43) and prescribed

use (0.32) is consistent with those of the other data sets. The correlations based on data of the

SAR-study are however not significant, which they are for the data based on the other studies.

The differences between correlation coefficients for prescribed use and self-medication are

very small with regard to Power Distance and Individualism. For Masculinity and Uncertainty

Avoidance they are somewhat higher.

Table 1. Self

Table 1. Self

Table 1. Self

Table 1. Self- ---medication, prescribed use of antibiotics in the past 12 m

medication, prescribed use of antibiotics in the past 12 m

medication, prescribed use of antibiotics in the past 12 m

medication, prescribed use of antibiotics in the past 12 months (prevalence rate per 1000 respondents) and indexes of four cultural

onths (prevalence rate per 1000 respondents) and indexes of four cultural



dimensions.

dimensions.

dimensions.

dimensions.

Note: PDI (Power Distance Index); ID

V (Individualism

index); MAS (M

asculinity); U

AI (Uncertainty avoidance index)

Countr

y

Response R

ate

(%)

No.

Respon

dents

Self-m

edic

ation

with a

ntib

iotics

Pre

scribed

use

of

antib

iotics

PD

I ID

V

MA

S

UA

I

The N

eth

erl

ands

55

1634

1

152

38

80

14

53

Sw

ed

en

69

704

4

135

31

71

5

29

Denm

ark

63

1881

7

172

18

74

16

23

Luxem

bourg

50

675

9

288

40

60

50

70

Belg

ium

(F

landers

)

54

1734

9

222

61

78

43

97

Malta

54

541

56

422

56

59

47

96

Czech.

Rep

. 59

1169

7

253

57

58

57

74

Slo

vakia

55

546

42

569

104

52

110

51

Rom

ania

43

430

198

307

90

30

42

90

Austr

ia

28

442

9

159

11

55

79

70

United K

ingd

om

23

675

12

221

35

89

66

35

Irela

nd

26

793

14

353

28

70

68

35

Italy

21

213

62

512

50

76

70

75

Slo

ve

nia

38

1143

17

293

71

27

19

88

Cro

atia

31

615

31

439

73

33

40

80

Pola

nd

32

935

33

199

68

60

64

93

Lith

uan

ia

25

747

210

275

42

60

19

65

Chapter 6

84


85

Table 2. Correlations between use of antibiotics and cultural dimensionTable 2. Correlations between use of antibiotics and cultural dimensionTable 2. Correlations between use of antibiotics and cultural dimensionTable 2. Correlations between use of antibiotics and cultural dimensionssss

** Correlation is significant at the 0.01 level (2-tailed).

* Correlation is significant at the 0.05 level (2-tailed).


Power distance is positively correlated with self-medication and prescribed use of

antibiotics in all the data sets. Uncertainty Avoidance, at first sight, does not seem to be

relevant but significant positive correlations were found with antibiotic use as reported in

other previous studies (partially based on other European countries). The findings for the

Individualism and Masculinity are not conclusive, since not all data point out to significant

correlations.

Power Distance

In countries with a high Power Distance inequality is expected and preferred.

Subordinates will expect their superior to tell them what to do. In countries with a low Power

Distance, to the contrast, people in less powerful positions will feel less dependent of more

powerful people. They are expected to take initiatives and there is a preference for

consultation. This may have implications for collaboration between doctors and other health

care providers, such as pharmacists and nurses, as well as in the doctor-patient

communication. An example of the former, is the collaboration between physicians and

pharmacists. In countries with high Power Distance, hierarchic differences will be more

manifested and doctors will have a more pronounced (therapeutic) autonomy, in other

countries doctors feel more part of a team. In the Netherlands (a country with a low Power

Power

Distance

Individualism Masculinity Uncertainty

Avoidance

SAR data

Self-medication

Prescribed use

Other data sets

0.54*

0.59*

-0.41*

-0.45

0.31

0.42

0.43

0.32

ESAC (N=24) 0.59** -0.29 0.22 0.59**

Eurobarometer (N=15) 0.62* -0.30 0.31 0.58*

Cars et al. (N=15) 0.78** -0.38 0.16 0.78**

Chapter 6

86

Distance and one of the lowest use of antibiotics) Pharmacotherapy Counselling Groups, in

which GPs and local community pharmacists regularly meet to exchange information about

drug therapy, has been the spearhead of a successful policy for more rational use of antibiotics

and other medicines (10,19,20). Power Distance will also affect the doctor patient- relationship,

besides the relations between professionals. In countries with a high Power Distance patients

look up to their doctor. They expect great expertise of them and feel little need for being

involved in the decision-making. Asking “what do you think yourself of taking an antibiotic?”

would embarrass the ‘modal’ patient. Either so, a physician acknowledging that he is not sure

whether it is a viral or bacterial infection and hence says: “well, let us wait and see” will, in such

a cultural context, not inspire much confidence. Prescribing antibiotics has strong symbolic

connotations and it can be seen as a sign of power and expertise. Hence, antibiotics not only

have a pharmaceutical but also a communicative aspect. The clinician-patient encounter has

been described as ‘one of the most important battlegrounds’ in the struggle with the microbe

(21). Countries with low Power Distance, to the contrast, show a preference for shared decision-

making in which the patient discloses his concerns and point of view, e.g. with regard to pros

and cons of antibiotics. It is true that patients often put pressure on the physician to prescribe

antibiotics but doctors often overestimate patients demand (22). Taking the time to talk about

patients concerns and to make patient expectations explicit has been promoted as a good

strategy to attain a more rational use of antibiotics (23-26). The finding that Power Distance is

relevant with regard to use of antibiotics is in line with other studies (24) that indicate that

doctor-patient relationship and dissatisfaction with the doctor is an important determinant of

antibiotic misuse. Of four types of patients (involved, deferent, ignored and critical types), the

Involved, i.e. patients which ensure they are part of the decision-making process and seeing

themselves as equal to the doctor, have views on and use of antibiotics most in line with the

medical views. Therefore, changing the patient to the more involved type is suggested as a

strategy to limit the use of antibiotics. However this might be more difficult in countries with

high Power Distance.

Uncertainty Avoidance

Uncertainty Avoidance deals with a society's tolerance for uncertainty and ambiguity.

Typically, people in such societies can accept known risks but they try to avoid unclear situation

and want to have control over things. If applied to medical situations, patients and physicians

will have an aversion to diagnostic uncertainty and will prefer a clear labelling of diseases.

However, many symptoms, such as coughing, sore throat, mild fever, etc. are difficult to label

and remarkable cross-cultural variations have been found (14,27). Based on a clinical

examination of the patient, it is often impossible to determine whether the problem is caused

by a (self-limiting) viral infection or a bacterial infection, in which cases antibiotics might be


87

warranted (28). Hence, it is usually good practice to ‘wait and see’. However, there is always a

small risk of a dangerous infection. If doctor and patient are not willing to accept risks, they

rather start using antibiotics immediately, likely with a preference to the newest and strongest

broad spectrum antibiotics. When the Uncertainty Avoidance is high, rather than returning

home with the message that ‘the doctor does not know’ neither what disease they have, nor

how to cure it, they accept the known risks of using antibiotics. In the latter case, patients feel

confident that they have a disease with a clear cause that is under control. The above attitude

of avoiding any risk is known as defensive medicine and leads to unnecessary high medical

consumption (29).

Prescribed use versus self-medication

We found little differences between the effects of cultural dimensions on prescribed use

versus self-medication of antibiotics. This suggests that in countries with high incidence of

self-medication with antibiotics, the prescription of antibiotics is also high and that self-

medication and prescribing are practices affected by the same cultural dimensions. This adds

evidence to the hypothesis that notwithstanding the physician is formally the only person to

decide whether or not antibiotics should be used, the final decision is the result of a complex

interaction between patient and physicians in a particular cultural context. There is no

indication in our data that behaviour with regard to use of antibiotics of physicians is less

dependent of the local cultural context than that of the lay people (the patients).

Our study had some limitations. First, the response rate for the SAR data was low in some

countries. We therefore repeated the analysis, limited to countries with response rates of

>40%. We also plotted the results and checked for the effect of possible outliers. These

verifications corroborated our results. Second, culture is certainly a much richer phenomenon

than the presented reduction into 5 dimensions and Hofstede has been criticized for trying ‘to

measure the immeasurable’ (30,31). However, equivalents of Hofstede’s cultural dimensions

were found by several other authors and the cultural dimensions were validated in multiple

other studies (12). An advantage of the use of cultural dimensions is that they enable

quantitative analysis of cultural aspects in relation to other relevant issues such as the use of

antibiotics (11). This is not possible using thicker descriptions of cultures, i.e. anthropological

descriptions based on qualitative data.

In summary, our study indicates that Power Distance is a cultural aspect associated with

antibiotic use, suggesting that the culturally-specific way people deal with authority is an

important factor in explaining cross-national differences in antibiotic use. Uncertainty

Avoidance can lead to defensive medicine which might result in unnecessary use of antibiotics.

Further cross-national comparative research is needed to better understand the correlations

between the cultural dimensions and the use of antibiotics and the reasons for this so that our

Chapter 6

88

hypothetical explanations can be corroborated or falsified. These findings and the deduced

explanations suggest that countries are likely to react differently on campaigns aiming at a

more rational use of antibiotics. It should be taken into account that cultural dimensions can

be obstacles or facilitators which, by their nature, are hard to change (26,32). The

understanding of the effect of cultural dimensions might explain why campaigns are less

successful in some countries than in others (21, 26, 33-35). A better understanding of cultural

dimensions can be used to anticipate reactions to a campaign in a particular country. For

example, our results suggest that in countries with low Power Distance, campaigns for more

appropriate use of antibiotics should involve both professionals and the general public, while

in countries with high Power Distance campaigns to improve antibiotic use should focus

primarily at the physicians.


The overall study was funded by the European Commission Public Health Directorate DG

SANCO (SPC2002333). In addition, funding was also provided from funds of the participating

institutions. The researchers of this study have been independent of funding source.

The SARThe SARThe SARThe SAR----consoconsoconsoconsortium rtium rtium rtium

Antonella Di Matteo (Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy);

Arjana Tambic-Andrasevic (University Hospital for Infectious Diseases, Zagreb, Croatia);

Retnosari Andrajati (Faculty of Pharmacy, Charles University, Prague, Czech Republic); Hana

Edelstein (Ha'Emek Medical Center, Afula, Israel); Rolanda Valinteliene (Institute of Hygiene,

Vilnius, Lithuania); Reli Mechtler (University of Linz, Linz, Austria).

Transparency Transparency Transparency Transparency ddddeclarationeclarationeclarationeclaration

None to declare.


89


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General discussion

Chapter 7

94

General discussionGeneral discussionGeneral discussionGeneral discussion

This thesis addresses the problem of self-medication with antibiotics in Europe. It is

well recognised that unnecessary and inappropriate use of antibiotics is the major determinant

of antibiotic resistance. Most studies have focused on prescribed use and little attention has

been given to self-medication. We estimated the prevalence of self-medication with antibiotics

in 19 European countries and explored its determinants. Because cultural factors play an

important role in the consumption of antibiotics we also studied the influence of cultural

differences on international differences in antibiotic consumption in Europe.

The studies in this thesis were based on two European surveys. The first one was a

postal survey including 1000-3000 randomly selected persons in each of the 19 participating

countries. The second follow-up survey was face-to-face interviews limited to respondents in 12

countries willing to be interviewed.

In this general discussion, an overview of the main findings in this thesis will be given.

In addition, some methodological issues will be discussed. Finally, implications for the

strategies to prevent inappropriate use of antibiotics and recommendations for future research

will be given.

Main findingsMain findingsMain findingsMain findings

Self-medication with antibiotics in Europe

Self-medication with systemic antibiotics occurred in each of the 19 participating

countries. The prevalence of actual self-medication varied widely, with the highest rates in

eastern and southern countries, and the lowest in northern and western. A throat symptom

(e.g. inflamed, red or sore throat), teeth or gum symptoms and bronchitis were the most

common reasons for self-medicating. In general, respondents’ self-diagnosed disorders were

self-limiting and antibiotics would not have been indicated. In eastern countries, the major

source of self-medication was the pharmacy without prescription, followed by leftover

antibiotics from previous prescribed courses. By contrast, in southern, northern, and western

countries use of leftover antibiotics was more prevalent, followed by antibiotics obtained

directly from the pharmacy. The rates of at-risk self-medication (those who indicated the

intention to self-medicate or store antibiotics at home) also tended to be higher in southern

and eastern Europe than in northern and western Europe. Intended self-medication with

antibiotics had a much higher prevalence than actual self-medication, indicating that

population at-risk is much larger than those who have actually self-medicated in the previous

12 months. Persons who were more prone to self-medicate with antibiotics were younger

persons, more educated and had chronic diseases.

General discussion

95

The relationship between prescribed use of antibiotics and self-medication

In chapter 3 the relationship between prescribed use and self-medication was studied.

The association between prescribed use and self-medication in general implies that antibiotics

prescribed for one symptom/disease may be used both as self-medication for (repeated)

episodes of the same symptom/disease and for another symptom/disease. The association for

URTIs implies that prescribed use for URTIs increases the probability of self-medication for

URTIs. We found an association between prescribed use and self-medication with antibiotics in

general from a leftover source in Northern/Western and Eastern Europe. In both regions the

effect of prescribed use was larger in lower educated respondents. One could hypothesize that

respondents with low education are less aware about the consequences of repeating

prescriptions of the doctors for the same symptom/disease or for another symptom/disease.

This effect of education disappeared when looking at the relation between prescribed use and

self-medication for URTIs. The effect of prescribed use on self-medication for URTIs with

leftover antibiotics in all European regions was the same for both educational levels. For self-

medication from sources other than leftovers the associations did not reach statistical

significance. This might be due to a lack of statistical power to detect a smaller effect.

Determinants of self-medication with antibiotics in Europe

Using the PRECEDE model of behaviour change we examined the impact of

predisposing and enabling factors on self-medication with antibiotic in Europe in chapter 4. We

considered both country and individual level factors. Predisposing factors included in the

analyses were attitudes, beliefs and knowledge concerning antibiotic use and self-medication.

Enabling factors were country wealth and health care system factors. Positive attitude towards

appropriateness of self-medication with antibiotics and incorrect beliefs about antibiotics for

minor ailments, i.e. sore throat and common cold, were predisposing factors for use of self-

medication. The perceived availability of antibiotics from pharmacies without a prescription

was the main enabling factor at the individual level. Other enabling factors included country

characteristics, i.e. country wealth (GDP per capita) and dispensing regulations for prescribed

antibiotics in pharmacies. Country wealth and dispensing exact number of prescribed tablets in

pharmacies were independently associated with lower self-medication.

Cultural differences between countries influencing antibiotic use in Europe

We compared public attitudes, beliefs and knowledge concerning antibiotic use and

self-medication between 11 European countries in chapter 5. Respondents were interviewed on

their attitudes towards appropriateness of self-medication with antibiotics and situational use

of antibiotics, beliefs about antibiotics for minor ailments, i.e. sore throat and common cold,

Chapter 7

96

knowledge about the effectiveness of antibiotics on viruses and bacteria and awareness about

antibiotic resistance and adverse effects of antibiotics. Respondents from all participating

southern (Malta, Israel and Italy) and eastern (Czech Republic, Croatia and Lithuania) countries

had less appropriate attitudes, beliefs or knowledge compared with Swedish respondents at

least for one of the dimensions. With the exception of the UK, respondents from northern and

western countries did not differ from respondents in Sweden for any of the dimensions.

Awareness about antibiotic resistance was the lowest in countries reporting high prevalence of

antibiotic resistance.

Cultural dimensions and antibiotic use

In Chapter 6, data on both prescribed use of antibiotics and self-medication were

correlated with country-specific scores on cultural dimensions (1). Results were verified by

correlating the data on antibiotic use from three other studies (2-4) and scores on cultural

dimensions. Power distance index (PDI) was positively correlated with both prescribed use and

self-medication in all the datasets. This suggests that the culturally-specific way people deal

with authority is an important factor in explaining cross-national differences in antibiotic use.

In countries with a high PDI, hierarchic differences will be more manifested and doctors will

have a more pronounced (therapeutic) autonomy, while in countries with a low PDI doctors

feel more part of a team. Power distance will also affect the doctor-patient relationship,

besides the relations between professionals. In countries with a high PDI patients feel little

need for being involved in the decision-making and a physician acknowledging that he is not

sure whether it is a viral or bacterial infection will in such a cultural context not inspire

confidence. Therefore, antibiotics not only have a pharmaceutical but also a communicative

aspect in this culture. We did not find consistent significant correlations between antibiotic use

in all four datasets and other cultural dimensions (IDV, MAS and UAI).

Methodological considerationsMethodological considerationsMethodological considerationsMethodological considerations

The prevalence of self-medication with antibiotics from various sources among the

population can be investigated in a survey only. It is possible to estimate over-the-counter use

by subtracting the difference between sales and reimbursement data. However, the data on

self-medication with antibiotics from leftovers from previous prescribed courses or obtained

from relatives or friends are not registered in any database. Therefore, we chose a

comprehensive approach i.e. the population survey. Low response rates are a continuing

problem for surveys and may lead to biased estimates of prevalence rates. Low response rates

were observed in several countries in our postal survey. To deal with this problem we

calculated the prevalence rates adjusted for non-response based on the assumption that

General discussion

97

respondents who replied after the reminder most resemble non-respondents. It might be that

this assumption is not strictly true. However, we included the data from countries with low

response rates because in most of theses countries (except Spain) no other information is

available about self-medication. Moreover, low response rate is a general problem of surveys in

these countries (5;6) and if we want to obtain information about these countries we will

always face the problem of non-response. In addition, debate is growing that low response is

less problematic in affecting survey estimates than previously assumed (7). Nevertheless, the

prevalence rates of self-medication in countries with low response rates should be considered

as a rough estimate and interpreted as an indication that the problem exists.

As with all self-reported data, results of this survey have the potential for recall bias,

underreporting, or overreporting. We attached the list of the most commonly used antibiotics

in each country to the questionnaires to reduce recall problems. To discourage underreporting

of self-medication, the questions about antibiotic use were formulated in a neutral way in

which the source of the drug could be chosen from 6 predefined sources or “other sources”.

In our second follow-up survey we conducted face-to-face interviews with the

respondents of the postal survey. We recruited a limited number of respondents in each

country. The samples were not selected randomly and therefore may not be representative of

the general population in the studied countries. They differed in the proportion of both users of

self-medication and respondents with high education. To compare public attitudes, beliefs and

knowledge concerning antibiotic use and self-medication with antibiotics between the

countries we had to take into account these differences between the samples. We performed

stratified analyses, i.e. separate analysis for users and non-users of self-medication, and for

respondents with high and low education. We used a conservative approach considering as

relevant only those differences which were significant in all stratum-specific analyses. As a

consequence, we might have underestimated differences between countries.

A lesson learnt from our international survey is that the choice of data collection

technique depends on the country. Different data collection techniques (postal self-

administered questionnaires or interviewer administered etc.) are appropriate in different

countries. For example, in Romania a higher response rate can be expected when

questionnaires are administered by the interviewer because many respondents in rural areas

have difficulties in understanding some questions. In other countries interviews at home are

not accepted by people and may lead to low response rates. Therefore, before choosing a data

collection technique in a particular country it is important to conduct a pilot study.

Chapter 7

98

ImplicationsImplicationsImplicationsImplications

Self-medication with systemic antibiotics occurred in all 19 countries that participated

in our survey. Antibiotics obtained directly from pharmacies and leftovers from previous

prescribed courses were the main sources of self-medication. In Eastern and Southern

European countries self-medication obtained directly from pharmacies was the highest though

over the counter sale is illegal in these countries. Investigation of the reasons for such

permissive policy is very important. The number of pharmacies per inhabitant may be related

to over-the-counter sale of antibiotics. For example the number of pharmacies is 10 times

greater in Spain than in Denmark (8), which may lead to a higher level of competition between

pharmacies in Spain. This may trigger pharmacists to sell antibiotics without prescription. Our

multilevel analysis revealed that perceived possibility of obtaining antibiotics directly from

pharmacies was one of the determinants of self-medication. Enforcing pharmacy regulations is

an effective way of combating self-medication. This will be possible when the advantages of

obeying to the laws will outweigh the advantages of disobeying in these countries. The

European Commission and the World Health Organization can have an important role in

drawing the attention of the governments of these countries to this issue.

Leftovers from previous prescribed courses was another common source of self-

medication in Europe. Antibiotics could be left over because extra tablets were dispensed or

because of patient non-compliance. Dispensing antibiotics per package size was an important,

potentially modifiable enabling factor facilitating self-medication in our study. Dispensing

exact number of antibiotic tablets in pharmacies as implemented in the UK, The Netherlands,

The Czech Republic and Israel, as well as in the United States, could be promoted in other

countries.

Actions to prevent self-medication with leftovers should also include physician

education. Doctors should be aware that prescribing for minor respiratory tract infections may

increase the risk of self-medication for such ailments. It is well known that not all upper and

lower respiratory tract infections need antimicrobial therapy (9), because many of these

illnesses are of viral origin and self-limiting. Promising results for changing the practice in

managing community-acquired lower respiratory tract infections (LRTIs) are expected from

GRACE (Genomics to Combat Resistance against Antibiotics in Community-acquired LRTI in

Europe), a recently launched new scientific network. LRTIs account for a major part of the

community burden of antibiotic use and contribute dramatically to the rising prevalence of

resistance. In particular, GRACE aims to provide doctors with algorithms that can help to

distinguish viral from bacterial infections and discern patients with community acquired LRTI

at risk for complications from patients with self-limiting diseases with low risk for poor

outcome (10).

General discussion

99

Another issue in combating inappropriate antibiotic use includes widespread

misconceptions about antibiotic use among the general public in southern and eastern

countries. Continuous and intensive efforts (such as involving the mass media) are needed to

reduce these misconceptions. A better understanding of cultural dimensions can be used to

anticipate reactions to a campaign in a particular country. For example, in countries with lower

Power Distance, campaigns for more appropriate use of antibiotics should involve both

professionals and the general public, while in countries with high Power Distance campaigns to

improve antibiotic use should focus primarily at the physicians.

Future researchFuture researchFuture researchFuture research

We were able to explain almost all variance at the country level in our multilevel

analysis. However, much remains to be explained at the individual level. Further research

should be focused on other determinants of self-medication such as accessibility to health care,

patient satisfaction and doctor-patient relationship. Another area of research should focus on

assessing the effectiveness of different interventions, as described in the previous section,

aiming to prevent self-medication.

ConclusionsConclusionsConclusionsConclusions

Self-medication with systemic antibiotics is a reason for concern in Europe. A high

prevalence of self-medication was observed in southern and eastern countries reporting high

prevalence of antibiotic resistance. It is extremely difficult to demonstrate a proven causal link

between self-medication with antibiotics and resistance because of the large number of

confounding factors which are not possible to control. However, self-medication usually

involves frequent intake of antibiotics in small doses which definitely contributes to the

resistance (11). The European agenda addressing inappropriate use of antibiotics should be

expanded to address the issue of self-medication. An integral approach involving policy

makers, pharmacists, prescribers, and general public is needed. Because resistant

microorganisms do not recognize geographical borders the problem acquires a global

importance. In the words of Lao Tzu, “the biggest problem in the world could have been solved

when it was small."

Chapter 7

100


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association with resistance: a cross-national database study. Lancet 2005 February

12;365(9459):579-87.

3. Cars O, Molstad S, Melander A. Variation in antibiotic use in the European Union. The Lancet

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4. The health of adults in the European Union. Available from

//europa.eu.int/comm/public_opinion/archives/ebs/ebs_183.7_en.pdf , last accessed February 11,

2007. Special Eurobarometer 183-7/wqve 58.2- European Opinion Research Group, December

2003.

5. O'Neill TW, Marsden D, Matthis C et al. Survey response rates: national and regional differences

in a European multicentre study of vertebral osteoporosis. J Epidemiol Community Health 1995

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6. Community Trade Mark Survey 2002, Final report, Office for Harmonisation in the Internal

Market (OHIM).

7. Keeter S, Miller C, Kohut A et al. Consequences of reducing nonresponse in a national telephone

survey. Public Opin Q 2000;64(2):125-48.

8. Llor C, Bjerrum L. Background for different use of antibiotics in different countries. Clin Infect Dis

2005 January 15;40(2):333.

9. Revised SWAB guidelines for antimicrobial therapy of Community-acquired pneumonia, Dutch

Working Party on Antibiotic Policy (SWAB), April. Available from

http://www.swab.nl/swab/swabcms.nsf/, last accessed February 11, 2007.

10. Genomics to Combat resistance against Antibiotics in Community-acquired LRTI in Europe

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risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998 March

4;279(5):365-70.

SummarySummarySummarySummary

Summary

102

At the beginning of 21 century antimicrobial resistance has developed against every class of

antimicrobial drugs and has become a rapidly increasing global problem, with widely varying

prevalences among countries. An important international issue is to avoid further increase in

resistance by reducing unnecessary and inappropriate use of antibiotics. Most studies in

Europe have focused on prescribed use of antibiotics. However, consumption of antibiotics may

also include self-medication, i.e. using antibiotics obtained without prescription, leftover

antibiotics from treatment courses prescribed earlier, antibiotics obtained from relatives,

friends or other sources. Use of antibiotics without medical guidance may lead to a wrong

choice of antibiotics, use of insufficient dosages or unnecessary treatment. Such inappropriate

use increases the risk of selection of resistant bacteria and may contribute to antibiotic

resistance.

This thesis describes the prevalence of self-medication with antibiotics in 19 European

countries and determinants of self-medication with a focus on 1) prescribed use of antibiotics,

2) predisposing and enabling factors. In addition, differences in attitudes, beliefs and

knowledge concerning antibiotic use and self-medication between countries and the influence

of cultural dimensions on antibiotic use in Europe are studied.

In chapter 2 In chapter 2 In chapter 2 In chapter 2 we present the results of the postal survey estimating the prevalence of self-

medication with antibiotics and prescribed use in the previous 12 months among the general

population of 19 European countries (Austria, The Netherlands, Sweden, United Kingdom,

Ireland, Denmark, Italy, Malta, Luxembourg, Belgium, Spain, Israel, Romania, Czech Republic,

Slovakia, Lithuania, Slovenia, Croatia and Poland). A multistage sampling design was used for

sample selections in each country. Within each country, a region with average prescribed

antibiotic consumption was chosen. In those countries where this information was not

available, a region was selected that was representative of the country’s population in terms of

age and sex. In each region, a city (75000-750000 inhabitants) and a rural area (5000-10000)

were selected. By using population registries, including lists of persons in the identified cities

and rural areas, persons >18 years of age were selected by simple random sampling. Self-

administered questionnaires were mailed between March and July 2003, and reminders with a

new questionnaire attached were sent 2-4 weeks later. A total of 15548 respondents completed

the questionnaires. The mean response rate of the countries was 40%. Self-medication with

systemic antibiotics occurred in each of the participating countries. The prevalence of actual

self-medication in the previous 12 months varied from 1 (The Netherlands) to 210 (Lithuania)

per 1000. The highest rates were observed in eastern countries (in particular Lithuania and

Romania), followed by southern countries (Malta, Spain and Italy). The lowest rates were found

in northern and western countries (The Netherlands and Sweden). The most common reasons

of self-medication were throat symptoms (e.g. red or sore throat). The main medication

sources were pharmacies and leftovers from previous prescriptions. The rates of at risk self-

medication (those who indicated the intention to self-medicate or store antibiotics at home)

Summary

103

also tended to be higher in southern and eastern Europe than in northern and western Europe.

Younger age, higher education and presence of a chronic disease were associated with higher

rates of self-medication.

IIIIn Chapter 3n Chapter 3n Chapter 3n Chapter 3 we studied the relationship between prescribed use of antibiotics and self-

medication to gain insight into determinants of self-medication. We used multinomial logistic

regression analyses to study the association between previous prescribed use and self-

medication for all symptoms/diseases and for upper respiratory tract infections (URTIs). We

examined separately self-medication with leftover antibiotics and self-medication with

antibiotics obtained from other sources as a stronger relation must be expected between

prescribed use and self-medication with leftovers. The association between prescribed use and

self-medication was modified by source of self-medication, region in Europe and education.

This association was consistently stronger for self-medication with leftovers than from other

sources, primarily directly from a pharmacy. It was stronger also for respondents from

Northern/Western Europe than respondents from Eastern and Southern Europe and those

with low education. For URTIs, a significant association was found between prescribed use and

self-medication with leftover antibiotics. A significant interaction was found between

prescribed use and region in Europe (P<0.001). In Northern/Western Europe, respondents who

had used prescribed antibiotics for URTIs had a 37.45 (95% CI 9.89-141.75) higher odds of self-

medication for URTIs. The effects were smaller in Southern Europe (OR 3.64, 1.60-8.25) and

Eastern Europe (3.64, 1.96-6.74). These associations were not significant for self-medication

from sources other than leftovers (1.96, 0.45–8.67 in Northern/Western Europe, 1.58, 0.51–4.87

in Southern Europe and 1.06, 0.59–1.93 in Eastern Europe). We showed consistent associations

between prescribed use and self-medication with leftover antibiotics, but were not able to

support the hypothesis that self-medication from other sources than leftovers is triggered by

earlier prescribed use. The association between prescribed use and self-medication in general

implies that antibiotics prescribed for one symptom/disease may be used both as self-

medication for (repeated) episodes of the same symptom/disease and for another

symptom/disease. The association for URTIs implies that prescribed use for URTIs increases the

probability of self-medication for URTIs. In both cases there is reason for concern. URTIs are

usually not an appropriate indication for the use of antibiotics, so in these cases antibiotics

should not be used either prescribed or as self-medication. The use of leftovers for a variety of

indications without professional advice is just as inappropriate. In both cases action should be

undertaken to prevent the use of leftovers.

Continuing with our investigation of determinants of self-medication, in Chapter 4, in Chapter 4, in Chapter 4, in Chapter 4 we studied

the impact of predisposing and enabling factors on self-medication with antibiotics in Europe

using the PRECEDE model of behaviour change. According to the PRECEDE theoretical model,

health behaviour is influenced by predisposing factors (characteristics that lead to or motivate

behaviour such as knowledge and beliefs), enabling factors (characteristics that facilitate or

Summary

104

are needed to perform the particular behaviour, such as resources in the environment ) and

reinforcing factors (rewards and punishments received from others). We conducted a follow-

up study with the respondents of our previous survey willing to be interviewed. In total, 1101

respondents in 11 countries representing Northern/Western (Austria, The Netherlands,

Sweden, United Kindom and Belgium), Southern (Italy, Malta and Israel) and Eastern (Czech

Republic, Lithuania and Croatia) European regions were interviewed. We aimed to recruit at

least 100 respondents in each country, 50 users of self-medication and 50 non-users, both

equally distributed in urban and rural areas. If the number of self-medication users willing to

be interviewed was less than 50 in a country, non-users of self-medication were added to

achieve 100 respondents. In Lithuania, the number of non-users willing to be interviewed did

not reach 50, therefore, self-medication users were added. A multilevel analysis with two levels

(country and respondent) was performed. Among the five predisposing factors, only two were

statistically significant in the final multilevel logistic regression analysis. As expected,

respondents who had more inappropriate attitudes towards self-medication with antibiotics

for bronchitis had a higher likelihood of actual self-medication (OR 2.13, 1.70-2.66). Having

incorrect beliefs about antibiotics for minor ailments was also independently associated with

higher likelihood of self-medication (1.76, 1.32-2.34). Inappropriate attitudes towards situational

use of antibiotics and non-awareness about antibiotic resistance and adverse effects of

antibiotics were not associated with use of self-medication in the final model. Among the four

enabling factors, three were significant determinants of self-medication. Country wealth

(higher GDP per capita) was related to a lower likelihood of self-medication. Dispensing the

exact number of antibiotics was associated with a decreased risk of self-medication (0.51, 0.27-

0.98). Respondents who perceived antibiotics as easily or sometimes available directly from

pharmacies, had a higher risk of self-medication whereas those who answered “do not know”

had a lower risk compared to respondents perceiving that antibiotics are not available.

Reimbursement of prescribed antibiotics was not independently associated with use of self-

medication in the multilevel regression analysis. We conclude that interventions aimed at

preventing self-medication with antibiotics should include public education, stricter control

over the laws influencing sale of antibiotics and dispensing exact number of tablets of

prescribed antibiotics in pharmacies.

In chapterchapterchapterchapterssss 5 5 5 5 and 6 and 6 and 6 and 6 we move beyond use of self-medication and study the influence of cultural

factors on antibiotic use in general in Europe. In chapter 5In chapter 5In chapter 5In chapter 5 we compare public attitudes, beliefs

and knowledge concerning antibiotic use in general and self-medication between 11 European

countries. We used data from our follow-up study where 1101 respondents were interviewed

on their attitudes towards appropriateness of self-medication with antibiotics and situational

use of antibiotics, beliefs about antibiotics for minor ailments, knowledge about the

effectiveness of antibiotics on viruses and bacteria and awareness about antibiotic resistance

and adverse effects of antibiotics. Each of these domains was assessed with a series of items,

Summary

105

partly derived from other studies. An exploratory factor analysis revealed four underlying

constructs consistent with the conceptual basis for the scales. The first scale was attitudes

towards appropriateness of self-medication with antibiotics for bronchitis. The other scales

were beliefs about antibiotics for minor ailments, attitudes towards situational use of

antibiotics and knowledge about the effectiveness of antibiotics on bacteria and viruses.

To analyse the differences between countries, regression analyses were used with the outcome

variable being each of dimensions of attitudes, beliefs and knowledge. Multiple linear

regression analysis was used for continuous variables (the four aforementioned scales) and

logistic regression for binary variables (knowledge of antibiotic resistance and adverse effects

of antibiotics). The number of users and non-users of self-medication as well as those with low

and high education willing to be interviewed differed between countries. To deal with the

possible confounding effect of both use of self-medication and education, we performed

stratified analyses, i.e. studying the differences between the countries separately for users and

non-users of self-medication, and for respondents with high and low education. The

differences between countries were considered relevant when regression coefficients were

significant in all stratum-specific analyses. The effects of other possible confounding variables

(presence of a chronic disease, sex, age and place of residence) were considered in all analyses.

Differences significant in all stratum-specific analysis were found for the UK, Malta, Italy, Czech

Republic, Croatia, Israel and Lithuania. Respondents from these countries had less appropriate

attitudes, beliefs or knowledge compared with Swedish respondents at least for one of the

dimensions. The Dutch, Austrian and Belgian respondents were not significantly different from

Swedish for any of the dimensions. The most pronounced differences were for awareness

about resistance followed by attitudes towards situational use of antibiotics. Awareness about

antibiotic resistance was the lowest in countries with higher prevalence of resistance.

In Chapter 6Chapter 6Chapter 6Chapter 6 we investigate whether broad and general cultural characteristics of countries

are correlated with cross-national differences in use of antibiotics. Country-specific scores on

cultural dimensions obtained from Hofstede are correlated with country-level data on

antibiotic use. Cultural dimensions included Power Distance, Individualism, Masculinity and

Uncertainty Avoidance. We used data on antibiotic use from our postal survey and verified

results by using data from three other studies on antibiotic use. Spearman’s correlation

coefficient rho was used to calculate correlations between country-aggregated use of

antibiotics and country-specific scores of cultural dimensions. Power distance index (PDI) was

positively correlated with both prescribed use and self-medication in all datasets. This suggests

that the culturally-specific way people deal with authority is an important factor in explaining

cross-national differences in antibiotic use. In countries with a high PDI, hierarchic differences

will be more manifested and doctors will have a more pronounced (therapeutic) autonomy,

while in countries with a low PDI doctors feel more part of a team. Power distance will also

affect doctor-patient relationship. In countries with a high PDI patients feel little need for

Summary

106

being involved in the decision-making and a physician acknowledging that he is not sure

whether it is a viral or bacterial infection will in such a cultural context not inspire confidence.

Therefore, antibiotics not only have a pharmaceutical but also a communicative aspect in this

culture. We did not find consistent significant correlations between antibiotic use in all four

datasets and other cultural dimensions (Individualism, Masculinity and Uncertainty

Avoidance).

Finally, in chapter 7chapter 7chapter 7chapter 7 we discuss the main implications from all the studies presented in this

thesis for the strategies to prevent unnecessary and inappropriate use of antibiotics. We

conclude that self-medication with systemic antibiotics is a reason for concern in Europe. A

high prevalence of self-medication was observed in southern and eastern countries reporting

high prevalence of antibiotic resistance. Antibiotics obtained directly from pharmacies was

one of the main sources of self-medication in these countries. Moreover, perceived possibility

of obtaining antibiotics directly from pharmacies was one of the determinants of self-

medication. Investigation of the reasons for such permissive policy is very important. The

European Commission and the World Health Organization can have an important role in

drawing the attention of the governments of these countries to this issue. Leftovers from

previous prescribed courses was another common source of self-medication in Europe.

Dispensing antibiotics per package size was an important potentially modifiable enabling

factor facilitating self-medication. Dispensing exact number of tablets in pharmacies as

implemented in the UK, The Netherlands, The Czech Republic and Israel, as well as in the

United States, could be promoted in other countries. Actions to prevent self-medication with

leftovers should also include physician education. Doctors should be aware that prescribing for

minor respiratory tract infections may increase the risk of self-medication for such ailments.

Another issue in combating inappropriate antibiotic use includes widespread misconceptions

about antibiotic use among the general public of southern and eastern countries. Continuous

and intensive efforts (such as involving the mass media) are needed to reduce these

misconceptions. A better understanding of cultural dimensions can be used to anticipate

reactions to a campaign in a particular country.

In conclusion, self-medication with antibiotics occurs in all European countries that

participated in this study. The European agenda addressing inappropriate use of antibiotics

should be expanded to address the issue of self-medication. An integral approach involving

policy makers, pharmacists, prescribers and general public is needed using both educational

and regulatory measures.

SamenvattingSamenvattingSamenvattingSamenvatting

Samenvatting

108

Antimicrobiële resistentie heeft zich vanaf het begin van de introductie van antimicrobiële

middelen en tot op heden tegen elke nieuwe klasse antimicrobiële middelen ontwikkeld. Het

is een snel stijgend globaal probleem geworden, met sterk wisselende prevalenties in

verschillende Europese landen. Een belangrijke internationaal aandachtspunt is het voorkomen

van verdere ontwikkeling van resistentie door het verminderen van onnodig en onjuist

antibioticagebruik. De meeste studies in Europa hebben zich geconcentreerd op het

voorgeschreven antibioticagebruik. Antibioticagebruik kan ook zelfmedicatie omvatten, d.w.z.

antibioticagebruik zonder doktersvoorschrift door het gebruik van ‘restanten’ van antibiotica

uit eerdere niet afgemaakte antibioticakuren of antibioticagebruik verkregen van familie,

vrienden of andere bronnen. Antibioticagebruik zonder medische begeleiding kan tot een

verkeerde keus, een ontoereikende dosering, ongewilde bijwerkingen of onnodige behandeling

met antibiotica leiden. Dergelijk onjuist gebruik kan door verhoging van de selectiedruk een

bijdrage leveren aan de kans op resistentie.

Dit proefschrift beschrijft de prevalentie van zelfmedicatie met antibiotica in 19 Europese

landen en determinanten van zelfmedicatie met een nadruk op 1) voorgeschreven

antibioticagebruik, 2) predisposing (predisponerende) factoren (kennis, opvattingen en

waarden) en enabling (faciliterende) factoren (vaardigheden, reguleringen, toegankelijkheid

van voorzieningen). Bovendien worden de verschillen in houding, opvatting en kennis

betreffende antibioticagebruik en zelfmedicatie tussen landen en de invloed van culturele

aspecten op antibioticagebruik in Europa bestudeerd.

In hoofdstuk 2hoofdstuk 2hoofdstuk 2hoofdstuk 2 presenteren we de resultaten van een schriftelijk vragenlijstonderzoek naar het

vaststellen van de prevalentie van zelfmedicatie met antibiotica en voorgeschreven

antibioticagebruik in de afgelopen twaalf maanden in de algemene bevolking van 19 Europese

landen (Oostenrijk, Nederland, Zweden, Verenigd Koninkrijk, Ierland, Denemarken, Italië,

Malta, Luxemburg, België, Spanje, Israël, Roemenië, Tsjechië, Slowakije, Litouwen, Slovenië,

Kroatië en Polen). Een getrapte steekproefopzet werd gebruikt voor steekproefselecties in elk

land. Binnen elk land werd een gebied met een gemiddelde antibioticaconsumptie gekozen. In

die landen waar deze informatie niet beschikbaar was, werd een gebied geselecteerd dat

representatief was voor de bevolking van het land in termen van leeftijd en geslacht. In elk

gebied werd een stad (75000-750000 inwoners) en een plattelandsgebied (5000-10000

inwoners) geselecteerd. Bevolkingsregistraties werden gebruikt om lijsten met personen van 18

jaar en ouder in de geselecteerde steden en de plattelandsgebieden te genereren. Uit deze

lijsten werden steekproefsgewijs personen geselecteerd die in de periode van maart tot juli

2003 een vragenlijst kregen toegestuurd. Twee tot vier weken later werd een herinneringsbrief

met een nieuwe vragenlijst verzonden. In totaal deden 15548 ondervraagden mee aan het

vragenlijstonderzoek. De gemiddelde respons over alle deelnemende landen was 40%.

Zelfmedicatie met systemische antibiotica kwam voor in alle deelnemende landen. De

prevalentie van zelfmedicatie in de afgelopen twaalf maanden varieerde van 1 (Nederland) tot

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109

aan 210 (Litouwen) per 1000 personen. De hoogste cijfers werden waargenomen in oostelijke

landen (in het bijzonder Litouwen en Roemenië), gevolgd door de zuidelijke landen (Malta,

Spanje en Italië). De laagste cijfers werden gevonden in noordelijke en westelijke landen

(Nederland en Zweden). De meest voorkomende redenen van zelfmedicatie waren

keelproblemen (bijvoorbeeld keelpijn). De belangrijkste bronnen waren apotheken en

restanten van eerdere kuren. Het risico van zelfmedicatie (personen die te kennen geven op

eigen initiatief antibiotica te nemen of thuis antibiotica op voorraad te hebben) neigde ook

hoger te zijn in zuidelijk en oostelijk Europa dan in noordelijk en westelijk Europa. Jongere

leeftijd, hoger opleidingsniveau en de aanwezigheid van een chronische ziekte waren

geassocieerd met hogere kans op zelfmedicatie.

Om inzicht te krijgen in determinanten van zelfmedicatie bestudeerden we in hoofdstuk 3hoofdstuk 3hoofdstuk 3hoofdstuk 3 het

verband tussen voorgeschreven antibioticagebruik en zelfmedicatie. We gebruikten

multinomiale logistische regressieanalyse om de associatie tussen voorgeschreven

antibioticagebruik en zelfmedicatie voor alle symptomen/ziekten alsmede voor bovenste

luchtweginfecties apart te bestuderen. We onderzochten afzonderlijk zelfmedicatie met

restanten van antibiotica uit eerdere niet afgemaakte antibioticakuren en zelfmedicatie met

antibiotica die uit andere bronnen werd verkregen, aangezien een sterkere relatie tussen

voorgeschreven antibioticagebruik en zelfmedicatie met restanten van antibiotica werd

verwacht. De associatie tussen voorgeschreven antibioticagebruik en zelfmedicatie veranderde

na correctie voor bron van zelfmedicatie, gebied in Europa en opleidingsniveau. Deze

associaties waren steeds sterker voor zelfmedicatie met restanten van antibiotica dan voor

zelfmedicatie uit andere bronnen, voornamelijk antibiotica direct verkregen bij de apotheek.

Deze associaties waren ook sterker voor ondervraagden uit noordelijk en westelijk Europa dan

voor ondervraagden uit oostelijk en zuidelijk Europa en ondervraagden met een laag

opleidingsniveau. Voor bovenste luchtweginfecties werd een significante associatie gevonden

tussen voorgeschreven antibioticagebruik en zelfmedicatie met restanten van antibiotica. Een

significante interactie werd gevonden tussen voorgeschreven antibioticagebruik en gebied in

Europa (p<0.001). Ondervraagden in noordelijk/westelijk Europa die voorgeschreven

antibiotica voor bovenste luchtweginfecties hadden gebruikt, hadden een 37 maal hogere kans

(95% betrouwbaarheidsinterval 10-142) op zelfmedicatie voor bovenste luchtweginfecties. Het

effect was kleiner in zuidelijk Europa (odds ratio [OR] 3.64, 1.60-8.25) en oostelijk Europa (OR

3.64, 1.96-6.74). Deze associaties waren niet significant voor zelfmedicatie uit bronnen anders

dan restanten van antibiotica (OR 1.96, 0.45-8.67 in noordelijk/westelijk Europa, OR 1.58, 0.51-

4.87 in zuidelijk Europa en OR 1.06, 0.59-1.93 in oostelijk Europa). We toonden consistente

associaties aan tussen voorgeschreven antibioticagebruik en zelfmedicatie met restanten van

antibiotica, maar konden niet de hypothese onderbouwen dat zelfmedicatie uit andere

bronnen dan restanten van antibiotica wordt teweeggebracht door eerder voorgeschreven

antibioticagebruik. De associatie tussen voorgeschreven antibioticagebruik en zelfmedicatie

Samenvatting

110

impliceert dat de antibiotica die voor één symptoom/ziekte wordt voorgeschreven in het

algemeen zowel als zelfmedicatie voor (herhaalde) episoden van hetzelfde symptoom/ziekte

als voor een ander symptoom/ziekte kunnen worden gebruikt. De associatie voor bovenste

luchtweginfecties impliceert dat het voorgeschreven antibioticagebruik voor bovenste

luchtweginfecties de kans op zelfmedicatie voor bovenste luchtweginfecties verhoogt. In beide

gevallen is er reden voor zorg. Bovenste luchtweginfecties zijn gewoonlijk geen indicatie voor

antibiotica. Dit betekent dat antibiotica in deze gevallen in het algemeen niet moet worden

voorgeschreven noch moet worden gebruikt als zelfmedicatie. Het gebruik van restanten van

antibiotica voor een verscheidenheid van indicaties zonder professioneel advies is ook

verkeerd. In beide gevallen zou de actie moeten worden ondernomen om het gebruik van

restanten van antibiotica uit eerdere niet afgemaakte antibioticakuren te verhinderen.

In hoofdstuk hoofdstuk hoofdstuk hoofdstuk 4444 gaan we nader in op het vaststellen van determinanten van zelfmedicatie en

bestuderen we het effect van predisposing en enabling factoren op zelfmedicatie met

antibiotica in Europa met behulp van het PRECEDE model van gedragsverandering. Volgens het

PRECEDE model wordt het gezondheidsgedrag beïnvloed door predisposing factoren

(kenmerken die leiden tot gedrag of gedrag motiveren zoals kennis en opvattingen), enabling

factoren (kenmerken die nodig zijn om bepaald gedrag uit te voeren, zoals omgevingsfactoren)

en reinforcing factoren (beloningen en straffen van anderen). We deden een vervolgstudie

onder de ondervraagden uit ons vragenlijstonderzoek die bereid waren om te worden

geïnterviewd. In totaal werden 1101 ondervraagden geïnterviewd in landen in

noordelijk/westelijk (Oostenrijk, Nederland, Zweden, Verenigde Koninkrijk en België), zuidelijk

(Italië, Malta en Israël) en oostelijk Europa (Tsjechië, Litouwen en Kroatië). We probeerden

minstens 100 ondervraagden in elk land te werven, 50 gebruikers van zelfmedicatie en 50 niet-

gebruikers, waaronder evenveel ondervraagden uit stedelijke en plattelandsgebieden. Als het

aantal zelfmedicatie gebruikers dat bereid gevonden werd om te worden geïnterviewd minder

dan 50 ondervraagden was, werden de niet-gebruikers van zelfmedicatie toegevoegd om 100

geïnterviewden per land te bereiken. In Litouwen vonden we minder dan 50 niet-gebruikers

van zelfmedicatie bereid om te worden geïnterviewd en daarom werden meer gebruikers van

zelfmedicatie toegevoegd. Een multilevel analyse met twee niveaus (land en ondervraagde)

werd uitgevoerd. Onder de vijf predisposing factoren waren slechts twee statistisch significant

in het uiteindelijke logistische multilevel regressiemodel. Zoals verwacht hadden de

ondervraagden met een verkeerde houding ten opzichte van zelfmedicatie met antibiotica

voor bronchitis een hogere kans op zelfmedicatie (OR 2.13, 1.70-2.66). Het hebben van onjuiste

opvattingen over antibiotica voor zelflimiterende aandoeningen was ook geassocieerd met

hogere kans op zelfmedicatie (1.76, 1.32-2.34). In het uiteindelijke regressiemodel bleken een

verkeerde houding ten opzichte van antibioticagebruik in specifieke gevallen, het niet bewust

zijn van antimicrobiële resistentie en de bijwerkingen van antibiotica niet geassocieerd te zijn

met gebruik van zelfmedicatie. Onder de vier enabling factoren, waren drie significante

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determinanten van zelfmedicatie. Rijkdom van het land (hoger bruto binnenlands product per

hoofd van de bevolking) was geassocieerd met een lagere kans op zelfmedicatie. Het

verstrekken van een nauwkeurig aantal antibiotica tabletten was ook geassocieerd met een

lagere kans op zelfmedicatie (OR 0.51, 0.27-0.98). Ondervraagden die aangaven gemakkelijk

aan antibiotica te kunnen komen, waaronder het verkrijgen van antibiotica in de apotheek

zonder recept, hadden een hogere kans op zelfmedicatie. Ondervraagden die aangaven niet te

weten of zij aan antibiotica konden komen, hadden een lager risico op zelfmedicatie in

vergelijking met ondervraagden die aangaven dat antibiotica niet beschikbaar waren. In het

multilevel regressiemodel was vergoeding van voorgeschreven antibiotica niet onafhankelijk

geassocieerd met gebruik van zelfmedicatie. We concluderen dat interventies gericht op het

verhinderen van zelfmedicatie met antibiotica moeten bestaan uit openbare voorlichting,

striktere controle over de wetgevingdie de verkoop van antibiotica beïnvloedt en het

verstrekken van het exacte aantal voorgeschreven tabletten antibiotica in apotheken.

In hoofdstukken 5 en 6hoofdstukken 5 en 6hoofdstukken 5 en 6hoofdstukken 5 en 6 bestuderen we de invloed van culturele factoren op antibioticagebruik

in Europa. In hoofdstuk 5hoofdstuk 5hoofdstuk 5hoofdstuk 5 vergelijken we algemene houdingen, opvattingen en kennis

betreffende voorgeschreven antibioticagebruik en zelfmedicatie tussen 11 Europese landen. We

gebruikten gegevens van onze vervolgstudie waarin 1101 ondervraagden werden geïnterviewd

over 1) hun houdingen ten opzichte van geschiktheid van zelfmedicatie met antibiotica en

antibioticagebruik in specifieke situaties, 2) over hun opvattingen betreffende antibiotica voor

zelflimiterende aandoeningen, 3) over kennis van het al of niet werkzaam zijn van antibiotica

tegen bacteriën en virussen, en 4) over hun bewustzijn van antimicrobiële resistentie en

bijwerkingen van antibiotica. Elk van deze domeinen werd gemeten met een reeks stellingen,

die gedeeltelijk uit andere studies werden afgeleid. Een oriënterende factoranalyse leverde vier

onderliggende concepten op die overeenkwamen met de conceptuele basis voor de schalen. De

eerste schaal was houdingen ten opzichte van de geschiktheid van zelfmedicatie met

antibiotica voor bronchitis. De andere schalen waren opvattingen over antibiotica voor

zelflimiterende aandoeningen, houdingen ten opzichte van antibioticagebruik in specifieke

situaties en kennis over het al of niet werkzaam zijn van antibiotica tegen bacteriën en

virussen.

Om de verschillen tussen landen te analyseren, werden regressieanalyses gebruikt met als

afhankelijke variabele elk van de dimensies van houdingen, opvattingen en kennis. Multipele

lineaire regressieanalyse werd gebruikt voor continue variabelen (de vier eerdergenoemde

schalen) en logistische regressie voor binaire variabelen (kennis van antimicrobiële resistentie

en bijwerkingen van antibiotica). Het aantal gebruikers en niet-gebruikers van zelfmedicatie

evenals het aantal personen met een laag en hoog opleidingsniveau dat bereid was om

geïnterviewd te worden, verschilde tussen de landen. Om rekening te houden met het

mogelijke verstorende effect van zowel het aantal gebruikers van zelfmedicatie als het

opleidingsniveau, voerden we gestratificeerde analyses uit, d.w.z. het afzonderlijk bestuderen

Samenvatting

112

van de verschillen tussen de landen voor gebruikers en niet-gebruikers van zelfmedicatie, en

voor ondervraagden met een hoog en laag opleidingsniveau. De verschillen tussen landen

werden als relevant beschouwd wanneer de regressiecoëfficiënten in alle gestratificeerde

analyses significant waren. Voor het verstorende effect van andere potentiële confounders

(aanwezigheid van een chronische ziekte, geslacht, leeftijd en woonplaats) werd gecorrigeerd

in alle analyses. Significante verschillen in alle gestratificeerde analyses werden gevonden voor

het Verenigd Koninkrijk, Malta, Italië, Tsjechië, Kroatië, Israël en Litouwen. De ondervraagden

van deze landen hadden verkeerde houdingen, opvattingen of kennis in vergelijking met de

Zweedse ondervraagden op tenminste één van de dimensies. De Nederlandse, Oostenrijkse en

Belgische ondervraagden waren niet beduidend verschillend van de Zweedse ondervraagden

op deze dimensies. De meest uitgesproken verschillen werden gevonden voor kennis van

resistentie gevolgd door houdingen ten opzichte van antibioticagebruik in specifieke situaties.

Het bewustzijn over antimicrobiële resistentie was het laagst in landen met een hoge

prevalentie van resistentie.

In hoofdstuk 6hoofdstuk 6hoofdstuk 6hoofdstuk 6 onderzoeken we of de brede en algemene culturele kenmerken van landen

gecorreleerd zijn met verschillen in antibioticagebruik. De landspecifieke scores op culturele

dimensies volgens Hofstede zijn gecorreleerd met gegevens over antibioticagebruik. De

culturele dimensies omvatten machtsafstand, individualisme / collectivisme, masculiniteit /

femininiteit en onzekerheidsvermijding. We gebruikten gegevens over antibioticagebruik uit

ons vragenlijstonderzoek en verifieerden de resultaten door gegevens te gebruiken uit drie

andere studies over antibioticagebruik. Spearman’s correlatiecoëfficiënt werd gebruikt om

correlaties tussen antibioticagebruik per land en landspecifieke scores van culturele dimensies

te berekenen. De machtafstandsindex was positief gecorreleerd met zowel voorgeschreven

antibioticagebruik als zelfmedicatie in alle datasets. Dit suggereert dat de cultuurspecifieke

manier waarop mensen omgaan met gezag een belangrijke factor is in het verklaren van

verschillen in antibioticagebruik tussen landen. In landen met een hoge machtafstandsindex

zullen de hiërarchische verschillen zich meer manifesteren en zullen artsen een meer

uitgesproken (therapeutische) autonomie hebben, terwijl in landen met een lage

machtafstandsindex artsen zich meer deel van een team zullen voelen. De machtsafstand zal

ook de arts-patiënt verhouding beïnvloeden. In landen met een hoge machtafstandsindex

voelen patiënten weinig behoefte om in de besluitvorming te worden betrokken en een arts

die erkent dat hij niet zeker is of het een virale of bacteriële besmetting betreft zal in een

dergelijke culturele context geen vertrouwen wekken. Daarom hebben antibiotica niet alleen

een farmaceutisch maar ook een communicatief aspect in deze cultuur. We vonden geen

consistente significante correlaties tussen antibioticagebruik in alle vier datasets en andere

culturele dimensies (individualisme, masculiniteit en onzekerheidsvermijding).

Tenslotte bespreken we in hoofdstuk 7hoofdstuk 7hoofdstuk 7hoofdstuk 7 de belangrijkste implicaties van alle onderzoeken in dit

proefschrift over de strategieën om onnodig en onjuist antibioticagebruik tegen te gaan. We

Samenvatting

113

concluderen dat zelfmedicatie met antibiotica voor systemisch gebruik in Europa een reden tot

zorg is. Een hoge prevalentie van zelfmedicatie werd in zuidelijke en oostelijke landen

waargenomen, landen die tevens een hoge prevalentie van antimicrobiële resistentie melden.

De antibiotica die direct uit de apotheek worden verkregen waren één van de belangrijkste

bronnen van zelfmedicatie in deze landen. Wanneer ondervraagden denken dat antibiotica

direct bij de apotheek verkregen kunnen worden, wordt de kans op zelfmedicatie groter.

Onderzoek naar de redenen voor dergelijk tolerant beleid is zeer belangrijk. De Europese

Commissie en de Wereldgezondheidsorganisatie kunnen een belangrijke rol spelen in het

vestigen van de aandacht van de overheden van deze landen op deze kwestie.

De restanten van eerdere voorgeschreven kuren waren een andere belangrijke bron van

zelfmedicatie in Europa. Het afleveren van antibiotica per doosje was een belangrijke enabling

factor die zelfmedicatie vergemakkelijkt. Het verstrekken van het exacte aantal benodigde

tabletten zoals dat wordt gedaan in apotheken in het Verenigd Koninkrijk, Nederland, Tsjechië

en Israël, evenals in de Verenigde Staten, zou in andere landen kunnen worden bevorderd.

Activiteiten om zelfmedicatie met restanten te verhinderen zouden ook onderwijs aan artsen

moeten omvatten. Artsen zouden zich ervan bewust moeten zijn dat het voorschrijven van

antibiotica voor zelflimiterende aandoeningen, zoals bovenste luchtweginfecties en bronchitis

het risico van zelfmedicatie voor dergelijke kwalen kan verhogen. Een ander aandachtspunt is

de bestrijding van misvattingen over antibioticagebruik onder het grote publiek van zuidelijke

en oostelijke landen. Ononderbroken en intensieve inspanningen (zoals het erbij betrekken van

de massamedia) zijn nodig om deze misvattingen te verminderen. Een beter inzicht in culturele

dimensies kan worden gebruikt om te anticiperen op reacties op een campagne in een bepaald

land. Concluderend kan gezegd worden dat zelfmedicatie met antibiotica voorkomt in alle

Europese landen die onderdeel waren van deze studie. De Europese agenda waarop het onjuist

antibioticagebruik staat, zal uitgebreid moeten worden met het probleem van zelfmedicatie

met antibiotica. Een integrale benadering is nodig waarbij zowel beleidsmakers, apothekers,

voorschrijvers en de bevolking worden betrokken en waarbij gebruik gemaakt wordt van zowel

onderwijs als regelgevende maatregelen.

Acknowledgements

116

I would like to thank the many people whose various contributions over the past four and a half

years have made the writing of this thesis possible. One of the most exciting parts of this project

has been working with an international team of co-investigators.

Firstly, I would like to thank my first promotor, Prof. Flora Haaijer-Ruskamp. Dear Flora, thank you

for the time and efforts you have spent guiding, advising and motivating me over the past four

and a half years. Your ideas, insight and connections made it possible to realize this project. I am

also very grateful to you for your encouragement in my difficult times. I admire your interest in

different cultures and it was extremely nice for me to hear that your trip to Armenia was among

the five top holidays that you ever had. I want to thank also Prof. John Degener, my second

promotor. John, it was always a pleasure to work with you and to learn from you. Thank you for

our always interesting discussions and your constructive feedback. I extend my special gratitude

to Johannes Burgerhof for his professionalism, dedication, assistance, big contribution and

admirable patience! Dear Hans, I could not have made it without you. Thanks a lot for everything.

The realization of this project was only possible through efforts and input of our co-investigators

from other European countries. I would like to thank each of you for your input, time, patience and

sincere support. I am very grateful to Dominique Monnet. Dear Dominique, your strong interest in

our research and valuable suggestions improved greatly the quality of the studies. Our phone and

e-mail discussions and meetings at the conferences were always inspiring. I also thank you for

your belief in me and willingness to help with my future career. I express my special gratitude to

Reginald Deschepper, Luc Delians, Greta van der Kelen and Joachim Cohen. Thanks for your big

contribution, efforts and support. Many thanks go to Cecilia Stålsby Lundborg. Dear Cecilia, thank

you for your committed efforts to help me. I have always admired your ability to work on so many

projects in different parts of the world and your always on-time feedback to my articles and

questions. I want to thank Reli Mechtler, Arjana Tambic-Andrasevic, Retnosari Andrajati, Robert

Cunney, Antonella Di Matteo, Hana Edelstein, Rolanda Valinteliene, Alaa Alkerwi, Elizabeth

Scicluna, Pawel Grzesiowski, Ana-Claudia Bara, Thomas Tesar, Milan Cisman, Jose Campos and

Joan Birkin for their continuous sincere support, valuable suggestions, dedication, big contribution

and patiently answering my many questions. It was a great pleasure to work with you and I thank

you all for your good collaboration!

I am very grateful to Monique Elseviers for her contribution and willingness to help to set up the

“SAR” project. Many thanks go to Eric Van Sonderen and Willem Lok from the Northern Center for

Healthcare Research (NCH) for their contribution to the “SAR” project. Many thanks also go to the

colleagues from the Social Pharmacy and Pharmacoepidemiology for their valuable input during

the dRUGS meetings. I want to thank also the entire department of Medical Microbiology for our

interesting discussions and their valuable comments.

Acknowledgements

117

I would like to thank the members of the reading committee, Prof. dr. H. Grundmann, Prof. dr.

M.J.M. Bonten and Prof. dr. T.J.M. Verheij for assessing this thesis. My special thanks go to Prof.

Marc Bonten who gave me the opportunity after completing the “SAR “ project to continue with

the “MOSAR” project.

I am very grateful to my former colleagues from the Department of Clinical Pharmacology. Many

thanks go to Jacoba and Heidrun. It was a very nice and extremely quiet experience to be sharing

an office with both of you. Dear Jacoba, thanks for the nice time spent both in- and outside the

office, your help with research problems and your support in difficult times. Special thanks for

translating my summary into Dutch. Dear Heidrun, thanks for sharing your knowledge and your

continuous support. I am grateful to Petra Denig. Petra, I have very much appreciated your

comments and input whenever they were needed, thanks a lot. Many thanks go to Ruth, Peter,

Jasperien, Amany, Daniela, Frank, Anuschka and Jaco for all their support and chats and laughs on

so many occasions. Dear Jasperien, thank you for standing beside me on this special day. Frank,

thanks a lot for helping with the cover. Many thanks go to Wessel Sloof and Adriaan van Doorn for

solving my computer problems and sincere support. I am grateful to Ellen, Ardy and Alexandra for

their willingness to help in all occasions. Dear Ellen, thanks for your help and nice time spent

outside the office.

I would like to thank my friends in Groningen. Dear Lena and Simon, thanks a lot for your

friendship, all your support and incredible trust in me. Dear Berty and Ruben, thanks for so many

nice moments and helping me feel at home in Groningen. I would like to thank Jean-Pierre

Macquart for the nice time spent together. Special thanks also go to Tom Breur who gave me

important tips to work with my data and helped me to solve many problems with my database.

Many thanks go to Liana and Sascha for the very nice time spent together. Dear Liana, my best

friend, former colleague and paranymph, I can’t begin to tell you how much your friendship and

support means to me. You have been always there for me whether we lived in the same city or far

away and shared all the ups and downs both in Armenia and The Netherlands. Thanks a lot for

being such a great friend.

I would like to thank my lecturers from the American University of Armenia and Erasmus Medical

Center Rotterdam who taught me how to do good research.

Many thanks go to the respondents of the “SAR” project for completing the questionnaires and

participating in the interviews without whom this thesis would not have been possible.

Finally, I would like to thank my parents, my brother and my sister-in-law for their love, support

and encouragement of everything I do.

About the authorAbout the authorAbout the authorAbout the author

About the author

120

Larissa Grigoryan was born on 2 November 1976 in Yerevan, Armenia. She passed her secondary

school exams at the “Russian secondary school# 83 after V. Tereshkova” in Yerevan, Armenia in

1993. She was admitted to the Yerevan State Medical University and obtained her medical

degree in 1999. In 2000, she completed her residency in Epidemiology at the Armenian

National Institute of Health. Afterwards, she entered the Master Program in Public Health at

the American University of Armenia, affiliated with Johns Hopkins Bloomberg School of Public

Health (supervisors: Prof. Haroutune Armenian and Dr. George Jakab). During these years she

worked at the Centre for Health Services Research of the American University of Armenia. In

July 2001 she moved to Rotterdam to follow a Master Programme In Epidemiology at the

Netherlands Institute for Health Sciences (Erasmus University). Here she studied the relation

between statin use and dementia using the Rotterdam Study database (supervisors: Dr.

Monique Breteler and Prof. dr. Bruno Stricker).

In July 2002, she started the project described in this thesis at the Department of Clinical

Pharmacology of the University Medical Center Groningen (supervisors Prof. dr. Flora Haaijer-

Ruskamp and Prof. dr. John Degener). She was a member of the Evidence Based Medicine

research group of the Northern Center for Healthcare Research (NCH).

Currently she is working as a post-doc on the European project “Mastering hospital

Antimicrobial Resistance and its spread into the Community” at the Julius Center for Health

Sciences and Primary Care, University Medical Center Utrecht.

List of pList of pList of pList of publicationsublicationsublicationsublications

List of publications

122

1. Grigoryan L Grigoryan L Grigoryan L Grigoryan L , Haaijer-Ruskamp FM, Burgerhof JGM et al. Self-medication with

antimicrobial drugs in Europe. Emerging Infectious Diseases 2006; 12: 452-9.

2. Grigoryan L Grigoryan L Grigoryan L Grigoryan L , Burgerhof JGM, Haaijer-Ruskamp FM, Degener JE et al. Is self-medication

with antibiotics in Europe driven by prescribed use? Journal of Antimicrobial

Chemotherapy; 2007; 59(1):152-156

3. Grigoryan LGrigoryan LGrigoryan LGrigoryan L, Burgerhof JGM, Degener JE, et al. Attitudes, beliefs and knowledge

concerning antibiotic use and self-medication: a comparative European study. Submitted

4. Grigoryan LGrigoryan LGrigoryan LGrigoryan L, Burgerhof JGM, et al. Determinants of self-medication with antibiotics in

Europe: the impact of beliefs, country wealth and health care system. Submitted

5. Deschepper R, Grigoryan LGrigoryan LGrigoryan LGrigoryan L, et al. Are cultural dimensions relevant for cross-national

differences in antibiotic use? Submitted

6. Muscat M, Monnet DL, Klemmensen T, Grigoryan LGrigoryan LGrigoryan LGrigoryan L, Jensen MH, Andersen M, Haaijer-

Ruskamp FM. Patterns of antibiotic use in the community in Denmark. Scand J Infect Dis.

2006; 38: 597-603

7. Raz R, Edelstein H, Grigoryan LGrigoryan LGrigoryan LGrigoryan L, Haaijer-Ruskamp FM. Self-medication with antibiotics by

a population in northern Israel. Israel Medical Association Journal 2005; 7777: 722-5.

8. Berzanskyte A, Valinteliene R, Haaijer-Ruskamp FM, Gurevicius and Grigoryan L. Grigoryan L. Grigoryan L. Grigoryan L. Self-

medication with antibiotics in Lithuania. . . . International Journal of Occupational Medicine

and Environmental Health. 2006;19(4):246-53

NorthernNorthernNorthernNorthern Center for Healthcare Research (NCH) Center for Healthcare Research (NCH) Center for Healthcare Research (NCH) Center for Healthcare Research (NCH) and and and and

previous dissertationsprevious dissertationsprevious dissertationsprevious dissertations

Northern Center for Healthcare Research (NCH) and previous dissertations

124

This thesis is published within the research program Evidence Based Medicine in PracticeEvidence Based Medicine in PracticeEvidence Based Medicine in PracticeEvidence Based Medicine in Practice of the

Northern Center for Healthcare Research. More information regarding the institute and its

research can be obtained from our internet site: www.med.rug.nl/nch.

Previous dissertations from the program Evidence Based MedicineEvidence Based MedicineEvidence Based MedicineEvidence Based Medicine in Practice in Practice in Practice in Practice:

Sturm HBSturm HBSturm HBSturm HB (2007) Influencing physician prescribing in an international context: the role

of systems, policies and patients.

Supervisors: prof dr FM Haaijer-Ruskamp, prof dr WH van Gilst

Greving JGreving JGreving JGreving J (2007) Trends in cardiovascular drug prescribing in Dutch general practice:

role of patient and physician related characteristics.

Supervisors: prof dr FM Haaijer-Ruskamp, prof dr D de Zeeuw

Co-supervisor: dr P Denig

Dobre DDobre DDobre DDobre D (2006) Treatment of heart failure and patient outcomes in real life.

Supervisors: prof dr FM Haaijer-Ruskamp, prof dr R Sanderman,

prof dr DJ van Veldhuisen

Co-supervisors: dr AV Ranchor, dr MLJ de Jongste

Houweling STHouweling STHouweling STHouweling ST (2005) Taakdelegatie in de eerste en tweedelijns diabeteszorg;

resultaten van de DISCOURSE studies.

Supervisor: prof dr B Meyboom-de Jong

Co-supervisor: dr HJ Bilo

Mol PGMMol PGMMol PGMMol PGM (2005) The quest for optimal antimicrobial therapy.

Supervisors: prof dr FM Haaijer-Ruskamp, prof dr ROB Gans, prof dr JE Degener

Bergman GJDBergman GJDBergman GJDBergman GJD (2005) Manipulative therapy for shoulder complaints in general practice.

Supervisors: prof dr B Meyboom-de Jong, prof dr K Postema

Co-supervisors: dr JS Winters, dr GJMG van der Heijden

Baarveld FBaarveld FBaarveld FBaarveld F (2004) Sportgerelateerde problemen in de huisartspraktijk.


Co-supervisors: dr J Schuling, dr GC van Enst

UbinkUbinkUbinkUbink----Veltmaat LJVeltmaat LJVeltmaat LJVeltmaat LJ (2004) Type 2 diabetes mellitus in a dutch region; epedemiology and

shared care.


Co-supervisor: dr HJG Bilo

Kasje WNKasje WNKasje WNKasje WN (2004) Implementing joint treatment guidelines to improve prescribing in

general practice.

Supervisors: prof dr FM Haaijer-Ruskamp, prof dr PA de Graeff

Co-supervisor: dr P Denig

university of groningen self-medication with antibiotics

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