ViResiST: its contribution to our knowledge

of the relationship between antimicrobial use and resistance

Dominique L. Monnet

About antibiotics...

• ”As soon as we use it, we loose it”

• ”The more we use it, the more we loose it”

Antimicrobial resistance

ANTIMICROBIAL RESISTANCE

4 - Cross-transmission

3 - Selection

DoseDuration

New antimicrobials(promotion)

1 - Concern

2 - Broad-spectrumempiric therapy

The Antimicrobial Resistance Spiral

2010

Genetic Diversity and Adaptation

Tautavel (France), approx. 450,000 years ago

Adapted from: Geberding JL, CDC/NCID/HIP, 1999. Picture from: URL: http://www.culture.fr/culture/arcnat/tautavel/en/homme-fr.htm

approx. 15,000 generations humansapprox. 1010 generations of 109 E. coli

Illustration: Prittie EJ. Philadeplphia, PA: JC Winston, 1930.

Antimicrobial resistance

ANTIMICROBIAL RESISTANCE

4 - Cross-transmission

3 - Selection

DoseDuration

New antimicrobials(promotion)

1 - Concern

2 - Broad-spectrumempiric therapy

The Antimicrobial Resistance Spiral

?

Study designs for the relationship between

antimicrobial use and resistance

Source: Malhotra-Kumar S, et al. Lancet 2007;369:482-490.

Pharyngeal Carriage of Macrolide-Resistant Streptococci Following Exposure to Azithromycin and Clarithromycin

0 20 40 60 800.00

0.05

0.10

0.15

0.20

No fluoroquinolone

Fluoroquinone exposed

Source: Harbarth S, et al. Clin Infect Dis 2001;33:1462-1468.

Days

Pro

babi

lity

ofre

sist

ance

Cumulative Hazard Estimates for Emergence of Fluoroquinolone Resistance

Following Fluoroquinolone Exposure

0

10

20

30

40

50

0 50 100 150 200 250

Total Fluoroquinolone Use(Daily Doses per 1,000 patient-days)

% C

ipro

floxa

cin-

Res

ista

ntPs

eudo

mon

asae

rugi

nosa

(%)

Fluoroquinolone Use and Ciprofloxacin-ResistantP. aeruginosa, SCOPE-MMIT Hospitals, 1999-2000

Source: Polk RE, et al. 41st ICAAC, Chicago (IL), 2001, late-breaker abstr. UL-1.

y = 0.0832x + 18.461R2 = 0.29p = 0.01

Retrospective Information to Guide Empiric Prescription of Antimicrobials

Source: Snyder JW, Beam L. University of Louisville Hospital, Louisville (Kentucky), 1994.

Before ViResiST…

Bzzzz...

ViResiSTUpdated from: López-Lozano JM, et al. Int J Antimicrob Agents 2000;14:21-30.

0

5

10

15

20

25

Jan-9

1

Jul-9

1

Jan-9

2

Jul-9

2

Jan-9

3

Jul-9

3

Jan-9

4

Jul-9

4

Jan-9

5

Jul-9

5

Jan-9

6

Jul-9

6

Jan-9

7

Jul-9

7

Jan-9

8

Jul-9

8

0

5

10

15

20

25

30

% Im

ipen

em-r

esis

tant

/inte

rmed

iate

Pse

udom

onas

aeru

gino

sa

5-Month Moving Average Percent Imipenem- Resistant/Intermediate P. aeruginosa and Hospital

Imipenem Use, Hospital Vega Baja, Spain, 1991-2002

Hos

pita

l im

ipen

emus

e(D

DD

/1,0

00 p

atie

nt-d

ays)

Average delay = 1 month1 DDD/1,000 pat-days +0.40 %R

Applications of ViResiST in other hospitals

0

10

20

30

40

Jan-99

Jan-00

Jan-01

Jan-02

Jan-03

Jan-04

Car

bape

nem

use

(D

DD

/100

pt-d

ays)

0

0.1

0.2

0.3

0.4

0.5

Imip

enem

-res

ista

nt

P.ae

rugi

nosa

(%)

Univ. Hospital, Ulm (D)Lepper et al. AAC 2002;46:2920-5.

Univ. Hospital, Antwerp (B)Goossens H, et al. Unpublished data.

Univ. Hospital, Utah (USA)Samore MH, et al. Unpublished data.

Centre Hosp. Mulhouse (F)Aujoulat O, Delarbre JM. ViResiST.

Averagedelay

= 0-1 month

Averagedelay

= 0-2 months

Averagedelay

= 0-1 month

Averagedelay

= n.a.

%Carbapenem-Resistant Pseudomonas aeruginosa and Carbapenem Use in 4 Hospitals, 1996-2003

0

10

20

30

40

Jan-97

Jan-98

Jan-99

Jan-00

Jan-01

Jan-02

Car

bape

nem

use

(D

DD

/100

pt-d

ays)

0

1

2

3

4

5

Carb

apen

em-re

sist

ant

P.a

erug

inos

a(%

)

0

10

20

30

40

Jan-96

Jan-97

Jan-98

Jan-99

Jan-00

Jan-01

Car

bape

nem

use

(D

DD

/100

pt-d

ays)

0

0.5

1

1.5

2

Carb

apen

em-re

sist

ant

P.a

erug

inos

a(%

)

Explaining variable

for monthly %MRSA

Lag (months)

Estimated

coefficient

%MRSA

1

0.420

Macrolide use

1,2,3

0.165

Third-generation

cephalosporin use

4,5,6,7

0.290

Fluoroquinolone use

4,5

0.255

Constant

-

- 36.7

R2=0.902

Source: Monnet DL, et al. Emerg Infect Dis 2004;10:1432-1441.

%MRSA and Monthly Use of Macrolides, Third-Generation Cephalosporins and Fluoroquinolones,

Aberdeen Royal Infirmary, 01/1996-12/2001

Multivariate time series models to explain hospital MRSA

Source: Vernaz N, et al. JAC 2008;62:601-607; Aldeyab MA, et al. JAC 2008;62:593-600.

University of Geneva Hospitals, 2000-2006

Antrim Area Hospital, Northern Ireland, 2000-2004

What did ViResiST achieve?

Confirmation of the relationship between antimicrobial use and resistance with new methodology using routine laboratory and pharmacy data

Collection of longitudinal, electronic data from several hospitals in Europe

Confirm the models with data from these European hospitals (generalisation)

Acceptance of the methodology

Transition from research to routine practice

Use models in real time to guide prescriptions in order to beat resistance before it increases

B... B... B... B...

With ViResiST!

Beat the Bug Before it Bites

18 noviembre 2010

http://antibiotic.ecdc.europa.eu