ViResiST: its contribution to our knowledge of the relationship between antimicrobial use and resistance Dominique L. Monnet
May 29, 2015
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