Patterns ofPatterns of Antibiotic UseAntibiotic Use

In European HospitalsIn European Hospitals

Fiona M. MacKenzieFiona M. MacKenzie

Aberdeen Royal Infirmary, Aberdeen Royal Infirmary, ScotlandScotland

““Development of Strategies Development of Strategies for Control and Prevention for Control and Prevention of Antibiotic Resistance in of Antibiotic Resistance in

European HospitalsEuropean Hospitals””

Policies associated with Policies associated with low antibiotic use low antibiotic use

low antibiotic resistance rates low antibiotic resistance rates low rates of transmissible pathogenslow rates of transmissible pathogens

ARPAC

ARPAC: Antibiotic Use dataARPAC: Antibiotic Use data

Annual, aggregated hospital data (2001)Annual, aggregated hospital data (2001)

Unit = Defined Daily Dose /100 bedUnit = Defined Daily Dose /100 bed--daysdays

DDD = assumed average maintenance dose per day for a drug for its main indication in a 70kg adult

DDDs assigned by WHO collaborative Centre for Drug Statistics

Methodology (Norway)

Anatomical Therapeutic Chemical (ATC) classification

J01 subclass; “antibacterials for systemic use”

Monnet DL. ABC Calc - Antibiotic consumption calculator[Microsoft® Excel application]. Version 3.0

Copenhagen (Denmark): Statens Serum Institut 2005ABC Calc

OROR

Number of hospitals Number of hospitals supplying antibiotic use datasupplying antibiotic use data

North North n = 19n = 19

South South + Israel + Israel

+ Turkey + Turkey n = 27n = 27

West West n = 52n = 52 Central Central

/Eastern + /Eastern + Baltic States Baltic States

n = 34n = 34

SouthSouth--East East n = 8n = 8

TotalTotalAntibiotic ConsumptionAntibiotic Consumption

Antibiotic use data: Distribution (n = 140) Antibiotic use data: Distribution (n = 140) 20012001Fr

eque

ncy

Antibiotic use (DDDs / 100 bed-days)

Median = 50 (37,67) Minimum = 5 Maximum = 121

West

54 France

61

26

13

18

32

23

15

10 117

1 1 10

5

10

15

20

25

30

35

10 20 30 40 50 60 70 80 90 100 110 120 130

Antibiotic UseAntibiotic UseJ01 Median values (J01 Median values (DDDsDDDs/100 BD)/100 BD)

North North n = 19n = 19

South South + Israel + Israel

+ Turkey + Turkey n = 27n = 27

West West n = 52n = 52 Central Central

/Eastern + /Eastern + Baltic States Baltic States

n = 34n = 34

SouthSouth--East East n = 8n = 8

3131

4242

4848

5454

7575

NorthNorth

n=19

WestWest

n=52

SouthSouth

n=28

SouthSouth--EastEast

n=8

Central/ EastCentral/ East

n=33

DD

D/1

00 b

edD

DD

/100

bed

-- day

sda

ysMedian total antibiotic use: 2001

By Geographical Region, n = 140

3131 4242 4848 5454 7575MediansMedians

p < 0.001p < 0.001

0

20

40

60

80

100

120

140

Central-East South-East North West South

Antibiotic Consumption:Antibiotic Consumption:

The major classesThe major classes

0 5 10 15 20

J01A Tetracyclines

J01B Amphenicols

J01C β-lactams, Penicillins

J01D Other β-lactams

J01E Sulfonamides & Trimethoprim

J01F Macrolides, Lincosamides, Streptogramins

J01G Aminoglycosides

J01M Quinolones

J01X Other antibacterials

DDDs /100 bed-days, Median values (n = 140)

n = 140

Median use of penicillin class (J01 C)

p < 0.001p < 0.001By Geographical Region, n = 140

99 1313 2323 2222 2121Median Median valuesvalues

DD

D/1

00 b

edD

DD

/100

bed

-- day

sda

ys

NorthNorth

n=19

WestWest

n=52

SouthSouth

n=28

SouthSouth--EastEast

n=8

Central/ EastCentral/ East

n=33

0

10

20

30

40

50

60

Central-East South-East North West South

Comb. of pen + BLI

BL inhibitors

BL-resistant

BL-susceptible

Extended spectrum

J01C subJ01C sub--classes classes –– as proportion of total J01 C useas proportion of total J01 C use

Median use of Median use of J01 C J01 C

DDD/100 BDDDD/100 BD

PenicillinsPenicillins

North West SouthSouth-EastCentral/ East

99 1313 2222 2222 2222

0

5

10

15

20

25

c-east s-east north west south

Median use of non-penicillin beta lactams (J01 D)D

DD

/100

bed

DD

D/1

00 b

ed-- d

ays

days

p < 0.001p < 0.001By Geographical Region, n = 140

88 1010 88 1212 1616

Median valuesMedian values

NorthNorth

n=19

WestWest

n=52

SouthSouth

n=28

SouthSouth--EastEast

n=8

Central/ EastCentral/ East

n=33

0

5

10

15

20

25

30

35

Central-East South-East North West South

Carbapenems

Monobactams

4GC

3GC

2GC

1GC

Carbapenems

Monobactams

4GC

3GC

2GC

1GC

J01 D subJ01 D sub--classes classes –– as proportion of total J01 D useas proportion of total J01 D useMedian use of Median use of

J01 D J01 D DDD/100 BDDDD/100 BD

NonNon--penicillin Bpenicillin B--lactamslactams

North West SouthSouth-EastCentral/ East

88 1010 88 1212 1616

0

2

4

6

8

10

12

c/east s-east north west south

Antibiotic Consumption:Antibiotic Consumption:

Individual antibioticsIndividual antibiotics

Spearman Rank Correlation Coefficients

r = 0.431

P<0.01

Relationship between number of individual antibiotics used and total antibiotic use

DD

D/1

00 b

edD

DD

/100

bed

-- day

sda

ys

Number of antibiotics on Number of antibiotics on ““formularyformulary””

0

20

40

60

80

100

120

140

0 20 40 60 80 100

Top - 5 antibiotics used

All hospitals, n = 140All hospitals, n = 140

Amox + BLI O

Amox + BLI P

Ciprofloxacin O

Cefuroxime P

Amoxicillin O

1

2

3

4

5

WEST, n = 52WEST, n = 52

Amox + BLI P

Amox + BLI O

Ciprofloxacin O

Cefuroxime P

Amoxicillin O

1

2

3

4

5

Sulfa - Trim O 1%

Ciprofloxacin P 2%

Ciprofloxacin O 2%

Top - 10 antibiotics used (Median values. % of total use)(Median values. % of total use)

Amox + BLI O 27%

Amoxicillin O 16%

Ofloxacin O 5%

Amoxicillin P 5%

Amox + BLI P 4%

Ceftriaxone P 3%

Pristinamycin O 2%

1

2

3

4

5

6

7

8

9

10

FranceFrance

67 agents used

Top-10 = 67% of total use

RecommendationsHospitals

Agree universal unit

Local surveillance of antibiotic use

Feedback to prescribers

Investigate fluctuations & relationship with resistance

Clinical pharmacy services to support prescribing

RecommendationsNational / European Health Authorities

National programmes to monitoring antibiotic use.

Implementation of a national surveillance system for collation, feedback and benchmarking of antibiotic consumption data in hospitals.

Integrate with National programmes co-ordinatingantibiotic resistance, antibiotic stewardship, policy and practice.

Education.

Acknowledgements Acknowledgements

ARPAC participating hospitalsARPAC participating hospitals

ARPAC Steering GroupARPAC Steering Group

BenjaminBenjamin PellePelle

European CommissionEuropean Commission

ESCMID (ESGAP)ESCMID (ESGAP)

www.www.abdnabdn.ac..ac.ukuk//arpacarpac

Antibiotic ConsumptionAntibiotic Consumption

andand

Antibiotic resistanceAntibiotic resistance

Antibiotic Use versus MRSA PrevalenceOverviewOverview

All antibiotics (J01)All antibiotics (J01)J01 less glycopeptidesJ01 less glycopeptidesCephalosporinsCephalosporins33rdrd GCGC

FluoroquinolonesFluoroquinolonesMacrolidesMacrolidesAminoglycosidesAminoglycosides

MRSAMRSA

Correlations

Scatterplots (antibiotic use versus Alert organism prevalence)

Correlation coefficients

Regression Modelling

Linear regression modelling

Adjustment for case mix and geographical variation

Total antibiotic user = 0.262p = 0.003

Relationship between MRSA prevalence and antibiotic use Spearman Rank Correlation Coefficients

Antibiotic use (DDDs / 100 occupied bed days

% M

RS

A A

ll pa

tien t

s

Total antibiotic use less glycopeptides

r = 0.258p = 0.003

3rd generation cephalosporinsr = 0.387p < 0.001

01020304050607080

0 20 40 60 80 100 120 140

01020304050607080

0 20 40 60 80 100 120 140

01020304050607080

0 2 4 6 8 10 12 14 16

ARPAC European hospitals (n=263)ARPAC European hospitals (n=263)

140140 ARPAC hospitals submitted useable ARPAC hospitals submitted useable antibiotic consumption dataantibiotic consumption data

Project ICARE Project ICARE n=45n=45(Intensive Care Antimicrobial Resistance Epidemiology)(Intensive Care Antimicrobial Resistance Epidemiology)

CDC / NNIS system CDC / NNIS system n=68n=68(National(National NosocomialNosocomial Infections Surveillance)Infections Surveillance)

SCOPE SCOPE n=37n=37(Surveillance and Control of Pathogens of (Surveillance and Control of Pathogens of Epidemiological Importance)Epidemiological Importance)

Exploration of variation in Antibiotic UseExploration of variation in Antibiotic Use

Geographical regionExpenditure on health as % of GDPEU status

Hospital sizeTeaching status

ICU sizeICU beds as proportion of total

Number of paediatric bedsPaediatric beds as proportion of total

Number of long stay bedsLong stay beds as proportion of totalC

ase

mix

indi

cato

rs

Antibiotic use data: Distribution (n = 140) Antibiotic use data: Distribution (n = 140) 20052005Fr

eque

ncy

Antibiotic use (DDDs / 100 bed-days)

Median = 50 (37,67) Minimum = 5 Maximum = 121

26

13

18

32

23

15

10 117

1 1 10

5

10

15

20

25

30

35

10 20 30 40 50 60 70 80 90 100 110 120 130

Usage of antibiotics ranked 1Usage of antibiotics ranked 1--10, 10, expressed as % of total usageexpressed as % of total usage

(n = 140)(n = 140)

%MedianMedian 20%20% 32%32% 41%41% 49%49% 55%55% 75%75%

0102030405060708090

100

Top 1 Top 2 Top 3 Top 4 Top 5 Top 10

Top - 5 antibiotics used

Gentamicin P

Amox + BLI O

Ciprofloxacin O

Amox + BLI P

Ampicillin P

1

2

3

4

5

Central / Eastern Europe, Central / Eastern Europe, n = 34n = 34

Gentamicin P

Ciprofloxacin O

Amox + BLI O

Ampicillin P

Sulfa + Trim O

1

2

3

4

5

South East Europe, South East Europe, n = 8n = 8

Top - 5 antibiotics used

Penicillin V O

Cefuroxime P

Penicillin G P

Ciprofloxacin O

Amoxicillin O

1

2

3

4

5

Northern Europe, Northern Europe, n = 19n = 19

Amox + BLI O

Amox + BLI P

Ciprofloxacin O

Ceftriaxone P

Cefuroxime O

1

2

3

4

5

Southern Europe, Southern Europe, n = 26n = 26

North West SouthSouth-EastCentral/ East

Kruskal Wallis Test, p = 0.001

MedianMedian 52524444 484836364646

European differences in numbers of European differences in numbers of antibiotics prescribed (formulary)antibiotics prescribed (formulary)

0

10

20

30

40

50

60

70

80

90

C-East S_East North West South