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STATENS SERUM INSTITUT Antimicrobial Resistance and Usage Patterns in Europe: Focus on Dutch-Belgian Differences and Complementarity & Lessons for the Future Dominique L. Monnet Antimicrobial Resistance Surveillance Unit, Dept. of Antimicrobial Resistance & Hospital Hygiene, Statens Serum Institut, Copenhagen, Denmark
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Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

Jul 03, 2018

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Page 1: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Antimicrobial Resistanceand Usage Patterns in Europe:Focus on Dutch-Belgian Differences and

Complementarity & Lessons for the Future

Dominique L. Monnet

Antimicrobial Resistance Surveillance Unit, Dept. of Antimicrobial Resistance & Hospital Hygiene,

Statens Serum Institut, Copenhagen, Denmark

Page 2: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

MRSA in Europe, 1990-1991

Source: Voss A, et al. Eur J Clin Microbiol Infect Dis 1994;13:50-55.

< 1%1-2%5.5%

20-29%30-35%

Page 3: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: EARSS. Available from: URL: http://www.earss.rivm.nl/

< 3% 3-9%

10-29%> 30%

Methicillin-Resistant Staphylococcusaureus (MRSA) from Blood, 2001

Page 4: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Ticarcillin-Resistant Pseudomonasaeruginosa in Europe (ICU NIs only), 1992

Source: EPIC Study (Régnier B. Pathol Biol 1996;44:113-23).

no data 0% 15-25% 50-65% 80%

Page 5: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUTThe World According to… Human BacterialPathogens and Their Habitat

H

S. pneumoniae

H. influenzae

Pseudomonas aeruginosaAcinetobacter baumannii

S. aureus

le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ;-).

Food

An

imal

sH

uman

sH

uman

s

Salm.

Camp.

E. coli

E. coli

MRSA

S. aureus

Page 6: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

< 3% 3-9%

10-29%> 30%

Source: EARSS. Available from: URL: http://www.earss.rivm.nl/ (Accessed: 31/7/2002)

Penicillin-Non Susceptible Streptococcuspneumoniae (PNSP) from Sterile Sites

20022001

Page 7: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

< 3% 3-9%

10-29%> 30%

Erythromycin-Resistant Streptococcus pneumoniae from Sterile Body Sites

2002

Source: EARSS. Available from: URL: http://www.earss.rivm.nl/ (Accessed: 31/7/2002)

2001

Page 8: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUTErythromycin-Resistant Streptococcuspneumoniae from Community-Acquired

Respiratrory Tract Infections, 1998

Sources: Alexander Project, FINRES, STRAMA and DANMAP.

no data 0-5% 5.1-10% 10.1-30% >30%

Page 9: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

• Lower use of macrolides (less exposed, shorter duration)• Lower use of other antimicrobials• Better compliance (dose, intervals)

• Vaccination• Breast feeding

• Age (extremes)• Respiratory and other diseases

• Pre-school facilities• Long-term care?• Better living conditions• Socio-economic status• Climate?• Less travel• Different clones

Different population?Better protectionagainst disease?

Less cross- transmission?Lower Percentage of

Erythromycin-R S. pneumoniaein Community-Acquired RTIs

More rational utilization of antimicrobials?

Page 10: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: Cars O, et al. Lancet 2001; 357: 1851-3.

Page 11: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Is It Relevant to Examine OverallAntibiotic Consumption? (1)

! Overall antibiotic consumption (no. DDD) is relatedto no. antibiotic prescriptions and no. personsexposed to antibiotics

! It only accounts for some aspects of antibioticmisuse, e.g. prescribed when not indicated, durationtoo long, but cannot account for errors in dosing orlow compliance

! Nevertheless, if the antibiotic course prescribed isnot completed, then it is probably used at anotheroccasion

Page 12: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Is It Relevant to Examine OverallAntibiotic Consumption? (2)

! Antibiotics have an effect not only on the patientswho are treated but also an effect on other patientsand the environment

! Relationship between antibiotic use and resistanceis an ecological problem!

! There is room for improvement considering theextent of variations both in the amount and thepattern of use among European countries

Page 13: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0

20

40

60

0 2 4 6 8C o nsu m ption of m acrolides an d lin cosam id es

in p rim ary h ealth care in 1997 (D D D /1,000 in h .-d ays)

Eryth

romycin-resistant

S. pneumoniae in 1998 (%)

Sources: Alexander Project, FINRES, STRAMA, DANMAP, and Cars O, et al. Lancet 2001; 357: 1851-3.

Erythromycin-Resistant Streptococcuspneumoniae and Macrolide Consumptionin EU Member States, 1997-1998

Page 14: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

NS<0.114Tetracyclines (J01A)

<0.0010.8214 Macrolides and lincosamides (J01F)

0.040.3214Fluoroquinolones (J01MA, Ln tr.)

0.0030.5514Cephalosporins (J01DA)

0.0050.49 (-)14Beta-lactamase sensitive penicil. (J01CE, Ln tr.)

NS0.1414Other antibacterials (from ATC group J01)

NS<0.114Trimethoprim (J01EA, Ln tr.)

NS<0.1 (-)14Beta-lactamase resistant penicillins(J01CF)

<0.0010.7414Extended spectrum penicillins (J01CA , Ln tr.)

PR2 No. EU

countriesIndependent variable (ATC group)

%Erythromycin-R S. pneumoniae (Logodds transf.)

and Antimicrobial Consumption in Europe

Source for resistance data: Alexander Project.Source for antimicrobial consumption data: Cars O, et al. Lancet 2001; 357: 1851-3.

Page 15: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0

20

40

60

80

100

120

UKFran

ceBelg

iumTurke

y

Italy

Morocco

ColumbiaSpain

Thailan

d

Saved partof coursefor futureuse (%)

Claimed tofinishcourse (%)

Source: Pechère J-C. Clin Infect Dis 2001; 33 (Suppl 3): S170-S173.

Patients’ Interviews andMisuse of Antibiotics, 1993-

Page 16: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0.030.3314Persons living in households with children (%)

NS<0.112Households lacking at least one of three basicamenities, i.e. bath, toilet or hot water (%, Ln transf.)

0.050.2914Persons in overcrowded households (%, Ln transf.)

0.060.2714Nights spent in EU countries with high %Ery-R S.p.(per 1,000 inh.-days, incl. domestic, Ln transf.)

0.060.3212Persons living below the ”poverty line” (%, Ln tr.)

NS0.12(-)14

Population whose daily caring activities prevent themfrom undertaking the same amount of paid work (%)

0.060.3910Preschool children taking up offers of preschoolservices (%)

PR2 No. EU

countriesIndependent variable

Sources: Danish National Institute of Social Research, EC Eurostat, and European Travel Commission (ETC) Tourism Statistics.

%Erythromycin-R S. pneumoniae (Logodds transf.) andFactors That Might Facilitate Cross-Transmission

Page 17: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0.010.47 (-)13Infants breastfed at 3 months of age (%, Ln tr.)

NS0.1214Daily cigarette smokers (%)

NS0.2213Households that cannot afford to keep homeadequately warm (%, Ln transf.)

NS<0.114Distributed doses of pneumococcal vaccine (per10,000 inhabitants, 1996, Ln transf.)

0.050.29 (-)14Persons with at least 3 hours of physicalactivity (leisure) in a typical week (%)

NS<0.1 (-)14Population whose age is <= 4 years (%)

NS0.1314Population whose age is >65 years (%)

PR2No. EUcountries

Independent variable

Sources: U.S. Bureau of the Census, EC Eurostat, WHO Regional Office for Europe, and Fedson DS. Clin Infect Dis 1998;26:1117-23.

%Erythromycin-R S. pneumoniae (Logodds transf.)and Susceptibility to/Protection against Disease

Page 18: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0.011-13.100-1.619Infants breastfed at 3 months of age (%, Ln tr.)

0.0126.7960.840Macrolides and lincosamides (J01F)

PtββββIndependent variable

Multiple Linear Regression Models for Predictionof %Erythromycin-R S. pneumoniae (Logodds transf.):Preliminary Results

R2=0.959

<0.0017.3290.904Macrolides and lincosamides (J01F)

<0.001-12.398-(Constant)

PtββββIndependent variable

R2=0.817

Page 19: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT Factor Analysis (PCA) of %ERSP (Logodds transf.) and Other Variables: Preliminary Results (1)

0.8790.342Persons living in households with children (%)

0.1590.784Fluoroquinolones (J01MA, Ln transf.)

0.4890.781 Macrolides and lincosamides (J01F)

0.9540.189Persons in overcrowded households (%, Ln transf.)

210.4100.779%Erythromycin-R S. pneumoniae (Logodds tr.)

-0.303-0.750Persons with at least 3 hours of physical activity(leisure) in a typical week (%)

-0.090-0.755Infants breastfed at 3 months of age (%, Ln transf.)

-0.428-0.795Beta-lactamase sensitive penicil. (J01CE, Ln trsf.)

0.5740.755Extended spectrum penicillins (J01CA , Ln transf.)

0.5020.702Cephalosporins (J01DA)

ComponentVariable

Page 20: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

ln(sup1_room)

rysp))

Factor Analysis (PCA) of %ERSP (Logodds transf.) and Other Variables: Preliminary Results (2)

Page 21: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: EARSS, May 2000. Available from: URL: http://www.earss.rivm.nl/

Penicillin-Non Susceptible Streptococcuspneumoniae (PNSP) from Sterile Sites, 2000

%PNSP

no data <3 3-9 10-29 >30

Page 22: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: Bronzwaer SLAM, et al. Emerg Infect Dis 2002; 8: 278-282.

Penicillin-Non Susceptible S. pneumoniaefrom Sterile Sites (1998-99, log odds transf.) &Consumption of Beta-Lactams (1997) in the EU

Page 23: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

NS<0.114Tetracyclines (J01A)

<0.0010.7114 Macrolides and lincosamides (J01F)

0.060.2614Fluoroquinolones (J01MA, Ln tr.)

<0.0010.7414Cephalosporins (J01DA)

0.040.31 (-)14Beta-lactamase sensitive penicil. (J01CE, Ln tr.)

NS0.1814Other antibacterials (from ATC group J01)

NS<0.114Trimethoprim (J01EA, Ln tr.)

NS<0.1 (-)14Beta-lactamase resistant penicillins(J01CF)

<0.0010.6614Extended spectrum penicillins (J01CA , Ln tr.)

PR2 No. EU

countriesIndependent variable (ATC group)

%PNSP (Logodds transf.) and AntimicrobialConsumption in Europe

Source for resistance data: EARSS.Source for antimicrobial consumption data: Cars O, et al. Lancet 2001; 357: 1851-3.

Page 24: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Multiple Linear Regression Model for Predictionof %PNSP (Logodds transf.): Preliminary Results

<0.0015.8390.860Cephalosporins (J01DA)

<0.001-10.386-(Constant)

PtββββIndependent variable

R2=0.740

Page 25: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUTNalidixic Acid-Resistant Escherichia coli from

Community-Acquired Uncomplicated UTIsin Women, ECO-SENS Project, 1999-2000

Source: Kahlmeter G. Clin Microbiol Infect 2001;7(Suppl 1): 86.

no data <3% 3.1-6% 6.1-10% >10%

Page 26: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

NS0.1114Tetracyclines (J01A)

0.030.3514 Macrolides and lincosamides (J01F)

0.0050.4914Fluoroquinolones (J01MA, Ln tr.)

NS0.2014Cephalosporins (J01DA)

0.0010.64 (-)14Beta-lactamase sensitive penicil. (J01CE, Ln tr.)

NS0.1514Other antibacterials (from ATC group J01)

NS<0.1 (-)14Trimethoprim (J01EA, Ln tr.)

NS<0.1 (-)14Beta-lactamase resistant penicillins(J01CF)

0.040.3114Extended spectrum penicillins (J01CA , Ln tr.)

PR2 No. EU

countriesIndependent variable (ATC group)

Source for resistance data: Kahlmeter G, et al. ECO.SENS.Source for antimicrobial consumption data: Cars O, et al. Lancet 2001; 357: 1851-3.

%Nalidixic Acid-Resistant E. coli (Logodds transf.)

and Antimicrobial Consumption in Europe

Page 27: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

GP or specialist

Patient

Pharmacist

Over-the-counterdispensation of antimicrobials

Prescription ofantimicrobials

Infection /Microorganism

Pathways of Antimicrobial Usein Primary Health Care

Page 28: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

GP or specialist

Patient

Pharmacist

Over-the-counterdispensation of antimicrobials

Prescription ofantimicrobials

Infection /Microorganism

Pathways of Antimicrobial Usein Primary Health Care (1)

Page 29: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Different Susceptibility to/ProtectionAgainst Infectious Diseases or Incidence ofCommunity-Acquired Infectious Diseases?

! Demography! Incidence of certain diseases, e.g. diabetes, cancer! Living conditions: overcrowding, day care, hygiene! Protecting factors: breastfeeding, vaccinations

! Incidence of community-acquired infections:bacterial RTIs, influenza-like illness

! Prevalence of resistance among community-acquired bacteria

Page 30: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

323 Pop. cannot afford to keep home adequately warm(%)

111217 Pop.below ”poverty line” (%)9310 Pop. in overcrowded homes (%)

868997 Urban population (%, WHO)

151417 Pop. > 65 year old (%)

666 Pop. 0-4 year old (%)

1

464

15.7

Netherlands

37 Pop. without at least one of bath, toilet or hot water (%)

125336 Pop. density (inhab./km2)

5.310.2 Population (million inhab.)

Denmark Belgium

Source: U.S. Bureau of the Census, WHO HFA database & EC Eurostat.

Characteristics of the Populationof 3 EU Member States, 1996-1999 (1)

Page 31: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

No repororadic/LoRegional0

10

20

30

40

50

DDD

/1,0

00 in

h.-d

ays

Influenza-Like Illness Activity and OverallConsumption of Systemic Antibacterials (ATC J01)in Primary Health Care, EU Member States, 1997

Influenza-Like Illness Activity, 1997Source: FluNet. Available from:

http://oms2.b3e.jussieu.fr/flunet/activity.html

No activity Sporadic Regional // No report / Local Widespread

50

40 30

20 10

0C

onsu

mpt

ion

of a

ntib

acte

rials

fo

r sys

tem

ic u

se A

TC J

01 (D

DD

per

1,0

00 in

h-da

ys)

Page 32: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Overall Consumption of Systemic Antibacterials(ATC J01) in Primary Health Care andBreastfeeding, EU Member States, 1985-1997

Breastfeeding & Respiratory Illness During Childhood

Wilson AC, et al. BMJ 1998;316:21-25.

0

10

20

30

40

50

0 20 40 60 80 100

Infants breastfed at 3 m onths(% , 1985-1997, U K : at 4 m ths)

Consumption of antibacterials

for sys

temic use A

TC J01

(DDD per 1,000 in

h-days

, 1997)

R2=0.28 P=0.05

Source: Health For All database, WHO.

See also:

Page 33: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

113150 Distrib. doses pneumococcal vaccine (no./10,000 inhab., 1996)

556065 Persons living in households with children (%)

525730 Pop. with at least 3 hours of physical activity (leisure) in typical week (%)

1,4487041,319 Respiratory diseases (no./100,000)

804795 Preschool children taking up offers of preschool services (%)

41

34

Netherlands

7031 Infants breastfed at 3 months (%)

3831 Daily smokers (%)

Denmark Belgium

Source: WHO Health For All database & EC Eurostat.

Characteristics of the Populationof 3 EU Member States, 1996-1999 (2)

Page 34: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUTLabelling of Disease and Attitude TowardsUpper Respiratory Tract Infections

"A cold"

"Bronchitis"

"Flu"

Unlabelled (e.g., coughing,runny nose)Other (e.g., "sinusitis","angina")

Consulting a doctor

Self-medication

Nursing one's illness

Flanders Netherlands

Source: Deschepper R, et al. Pat. Educ. Counsel. 2002;48:161-169.

Page 35: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

213 Bacteriological tests (%)

52

6886140

Netherlands (n=62 pts)

80 No test, prescribed antibiotics (%)

1005

6021

Prescribed antibiotics (%) - penicillin V (%) - amoxicillin (%) - macrolide (%)

Belgium (n=44 pts)

Source: Touw-Otten FWMM & Staehr Johansen K. Family Pract. 1992;9:255-262.

Prescription of Antimicrobialsand Bacteriological Testing forAcute Tonsillitis, 1989-1990

Page 36: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Patient

Pharmacist

Over-the-counterdispensation of antimicrobials

Prescription ofantimicrobials

Infection /Microorganism

Pathways of Antimicrobial Usein Primary Health Care (2)

GP or specialist

Page 37: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

! Cultural differences: perceived severity of illness! Social issues: pressure to be back at work/day care! Economical issues: income vs. price! Education and information: information campaigns! Health care system and regulation: cost of GP

consultation, price of antimicrobials after reimbursement,direct access to specialists(?)

! Promotion: direct-to-consumer advertising

Factors that Influence Prescription (1):Related to the Patient

Page 38: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Factors that Influence Prescription (2):Related to the GP or the Specialist

! Cultural differences: willingness to help! Education and information: information campaigns,

guidelines, drug compendia, registered indications for aspecific antibiotic, promotional material provided byrepresentatives

! Health care system and regulation: type of healthcaresystem, rostering of patients, GP remuneration, workinghours, point-of-care diagnostic tests, economical incentives,fear of litigation

! Pharmaceutical industry and promotion: competitionamong pharmaceutical companies, intensity of promotionalactivity to GPs/specialists

Page 39: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: Deschepper R, et al. Pat. Educ. Counsel. 2002;48:161-169.

Attitude Towards Upper Respiratory TractInfections, by Region and Religion

2544886717

Use of antibiotics during the past 5 years - none/low (%)

0440050 - strong believer (%)251163330

Belief in antibiotics - sceptic (%)

0

0

88

Protestant,

NL (n=8)

44

56

0

Non- churchg., FL (n=9)

0083 Fear of complications (%)

0

33

Catholic,

NL (n=3)

050 - high/very high (%)

750 Healing power of body (%)

Non- churchg., NL (n=4)

Catholic,

FL (n=6)

Page 40: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Majority protestant Majority catholics0

10

20

30

40

50

DD

D/1

,000

inh.

-day

s

What About Cultural Differencesin the European Union?

WELL…, INSTEAD OFALWAYS POINTING AT

CULTURAL DIFFERENCES TOEXCUSE OUR LACK OF ACTION

OR PREVIOUS MISTAKES, MAY BE…WE COULD LEARN FROM (OTHER)DIFFERENCES AMONG COUNTRIES

OR REGIONS AND IDENTIFY AREAS FOR IMPROVEMENT!

P=0.001

Con

sum

ptio

n of

ant

ibac

teria

ls

for s

yste

mic

use

ATC

J01

(DD

D p

er 1

,000

inh-

days

)

50

40

30

20

10

0

Majority Majorityprotestants catholics

Page 41: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: Coenen S, et al. Lancet 2001;358:1272; Thiadens HA, et al. Lancet 2001;358:1272-3; Audit Project Odense, 2001 report.

Antimicrobial Prescribing Attitudesof GPs Can Be Modified ThroughPeer-Review/Education!

! Netherlands: peer-review groups (incl. collaboratingpharmacist), mandatory clinical audits every 2 or 4 weeks(pharmacist reviews prescriptions)

! Belgium: no such peer-review groups! Denmark: Audit Project Odense (APO), voluntary audits

and reviews, originally for Danish counties, now expandingin other European countries

Page 42: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: Beauraind I, et al. Personal communication. http://www.antibiotiques.org/

! Expect antibiotic for ’flu’: 49% resp. (before) vs. 30% (after)! Expect antibiotic for sore throat: 32% (before) vs. 18% (after)! Less antibiotic to avoid resistance: 64% (before) vs. 75% (after)! Antibiotics must be protected: 13% (before) vs. 25% (after)! Total antibiotic sales decreased

by approx. 10%

Impact of a Public Campaign for a More RationalUse of Antibiotics in Belgium, 11/2000-03/2001

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STATENS SERUM INSTITUT

Dimensions 30x21x7 cm 30x21x5 cm 17x11x2.5 cm Weight 3.1 kg 1.8 kg 380 g Main classif. by company by disease+alph. by disease Financing pharm. industry pharm. industry med. assoc. Guidelines no no yes (27 pages)

Characteristics of Spanish vs. Danish Compendia

Page 44: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

NoNo

YesYes

Capitation/Fee

48

Netherlands

Max./yearMax./year

No50 – 100%

Partially15 – 25%

Patient pays for: - consultations - antibiotics

YesYesNo Referral to specialistsYesYesNo Rostering of patients

Salary/FeeFeeFee Remuneration GPs

5664153 GP/100,000 inh.

Sweden Denmark Belgium

Source: Hendrickx E, et al. 41st ICAAC, Chicago (IL), 16-19/12/2001, #401.

Characteristics of Primary HealthCare Systems in Four EU MemberStates, 1997

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STATENS SERUM INSTITUT

Salary/capitation Fee-for-service0

10

20

30

40

50

DD

D/1

,000

inh.

-day

s

Rostering No rostering0

10

20

30

40

50

DD

D/1

,000

inh.

-day

s

Overall Consumption of Systemic Antibacterials(ATC J01) in Primary Health Care, Fee-for-Serviceand Rostering of Patients by GPs, EU, 1997

Sources: Cars O, et al. Lancet 2001; 357: 1851-3, and ”Highlights on Health”, WHO/EURO.

Salary or Fee-for- capitation service

Rostering No rosteringof patients of patients

50

40 30

20 10

0

Con

sum

ptio

n of

ant

ibac

teria

ls

for s

yste

mic

use

ATC

J01

(DD

D p

er 1

,000

inh-

days

) P < 0.001NS

Con

sum

ptio

n of

ant

ibac

teria

ls

for s

yste

mic

use

ATC

J01

(DD

D p

er 1

,000

inh-

days

)

50

40 30

20 10

0

Page 46: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

Source: Johansen HL, Danish Medicines Agency, and Elsberg C, Statens Serum Inst., 2000.

Monthly Tetracycline Prescription Rate andTetracycline Resistance in S. aureus BloodIsolates, Denmark, 01/1994-12/1999

0

1

2

3

4

5

1994

1995

1996

1997

1998

1999

0

2

4

6

8 Change in subsidization: from 50 to 0% (01/1996)

Te

trac

yclin

e U

se (

# pr

escr

iptio

ns p

er 1

,000

inha

bita

nts)

Te

trac

yclin

e -R

S. a

ureu

s B

lood

Isol

ates

(%, 5

-mon

th m

ovin

g av

erag

e)

Page 47: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0

2

4

6

0 0.5 1 1.5

A verage cost of 1 D D D of oral tetracycline after reim bursem ent

(P P P U S $, 1998)

Consumption of tetracyc

lines

for sys

temic use A

TC J01A

(DDD per 1,000 in

h-days

, 1997)

0

1

2

3

4

5

0 2 4 6

A verage cost of 1 D D D of oral fluoroquinolone after reim bursem ent

(P P P U S $, 1998)

Consu

mptio

n of flu

oroquinolones

for sy

stemic use ATC J01M

A (DDD per 1,000

inh-day

s, 1

997)

Sources: Sources: Cars O, et al. Lancet 2001; 357: 1851-3, and EudraMat, April 1998.

Cost After Reimbursement and Consumption ofTetracyclines and Fluoroquinolones in PrimaryHealth Care, EU Member States, 1997

[ ]

[ ]

[ ][ ]

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STATENS SERUM INSTITUT

0

2

4

6

8

0 10 20 30 40 50

O ral fluoroquinolone product nam es (N o., incl. brands and generics, 1998)

Ex-factory price

of 1 D

DD of oral

fluoroquinolone (P

PP U

S$, 199

8)

Source: EudraMat, April 1998.

Ex-Factory Price and Number of Brands ofTetracyclines and Fluoroquinolones on Market,EU Member States, 1998

0

1

2

3

4

0 20 40 60 80

O ral tetracycline product nam es (N o., incl. brands and generics, 1998)

Ex-factory price of 1 D

DD of oral

tetracyc

line (PPP US$, 1998)

Page 49: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0

2

4

6

0 20 40 60 80

O ral tetracycline product nam es (N o., incl. brands and generics, 1998)

Consu

mptio

n of tetrac

yclin

esfor sy

stemic use ATC J01A

(DDD per 1,000

inh-day

s, 1

997)

0

1

2

3

4

5

0 10 20 30 40 50

O ral fluoroquinolone product nam es (N o., incl. brands and generics)

Consumption of fluoro

quinolones

for sys

temic use A

TC J01MA

(DDD per 1,000 in

h-days

, 1997)

Sources: Sources: Cars O, et al. Lancet 2001; 357: 1851-3, and EudraMat, April 1998.

Overall Consumption of Fluoroquinolones (ATCJ01MA) in Primary Health Care, Companies andBrands of Antibiotics, EU Member States, 1997

( )

R2=0.36 P=0.05

( )

( )

( )

NS

( )

Page 50: Antimicrobial Resistance and Usage Patterns in Europe Symposium/Monnet Domin… · le MONDe de la Résistance Intrinsèque et Acquise aux ANtibiotiques ... Sources: Alexander Project,

STATENS SERUM INSTITUT

0

10

20

30

40

50

0 40 80 120

C om panies m arketing antibiotics(N o.)

Consumption of antibacterials

for sys

temic use A

TCJ01

(DDD per 1,000 in

h-days

)

0

10

20

30

40

50

0 100 200 300

O ral antibiotic product nam es(N o., incl. brands and generics)

Consumption of antibacterials

for sys

temic use A

TCJ01

(DDD per 1,000 in

h-days

)

( )

( )

( )

R2=0.52 P=0.008

( )

R2=0.42 P=0.01

Sources: Sources: Cars O, et al. Lancet 2001; 357: 1851-3, and EudraMat, April 1998.

Overall Consumption of Systemic Antibacterials(ATC J01) in Primary Health Care, Companies andBrands of Antibiotics, EU Member States, 1997

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STATENS SERUM INSTITUT

GP or specialist

Patient

Pharmacist

Over-the-counterdispensation of antimicrobials

Prescription ofantimicrobials

Infection /Microorganism

Pathways of Antimicrobial Usein Primary Health Care (3)

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STATENS SERUM INSTITUT

Over-The-Counter (OTC) Dispensation of Antimicrobials in Europe! Anecdotal evidence from colleagues…! Spain: 42% of 1,000 households reported having

antimicrobial packages at home. Only 2/3 of thesepackages were the result of a physician’s prescriptionOrero A, et al. Med Clin (Barc) 1997; 109: 782-785.

! Greece: 69% and 86% of pharmacists offeredantibiotics when presented with a high-fever and alow-fever rhinosinusitis scenario, respectivelyContopoulos-Ioannidis DG, et al. Clin Infect Dis 2001; 33: 76-82.

! EC-funded project ”Self-medication with Antibiotics”started on 1st October, 2002

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STATENS SERUM INSTITUT

0

5

10

15

20

E I

FIN

A

UK

S

DK

IRL

Consumption of medicines

without prescription

(% in

terviewed, 1996)

0

10

20

30

40

50

0 5 10 15 20 25

C onsum ption of m edicinesw ithout prescription (% int., 1996)

Consumption of antibacterials

for sys

temic use A

TC J01

(DDD per 1,000 in

h-days

, 1997)

Sources: Eurobarometer 44.3, European Commission; Cars O, et al. Lancet 2001; 357: 1851-3.

Overall Consumption of Systemic Antibacterials(ATC J01) in Primary Health Care and Consumptionof Medicines Without Prescription, EU, 1996-1997

R2=0.37 P=0.02

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STATENS SERUM INSTITUT

0

5

1 0

1 5

2 0

2 5

0 5 ,0 0 0 1 0 ,0 0 0 1 5 ,0 0 0 2 0 ,0 0 0N o. inhabitants per public pharm acy

(1997)

Consumption of medicines

without prescription (% pop., 1996)

0

0.1

0.2

0.3

0.4

0.5

0 5,000 10,000 15,000 20,000

N o. inhabitants per public pharm acy(1997)

Annual revenues fro

m sales

of pharm

aceuticals per public

pharm

acy (M

illion PPP US$, 1997)

Sources: Eurobarometer 44.3, European Commission in Key Data on Health 2000, Eurostat;and GIRP and IMS Health.

Consumption of Medicines Without Prescription, No.Inhabitants per Pharmacy, and Annual Revenues fromSales of Pharmaceuticals per Pharmacy, EU, 1996-1997

R2=0.59 P=0.001

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STATENS SERUM INSTITUT

Conclusions! Food for thought…! A ”substantial” part of the observed differences in

resistance are certainly due to different levels andpatterns antimicrobial use

! Better understand determinants of antimicrobial use inEurope and generate hypotheses for interventions

! Study the possible adverse effects of restrictive andconservative antimicrobial use!

! Some missing data should soon be provided byEuropean collaborative projects, e.g. ESAC (primaryhealth care and hospitals), ARPAC (mainly hospitals),SAR (self-medication with antibiotics)