Presentation given during Cost AMiCI meeting in Tallinn Nov 2017 by Irja Lutsar MD, PhD Professor of Medical Microbiology University of Tartu

1. 22‐Jan‐18
1
Use of antibiotics in health care and
problems with AMR in Estonia:
comparison with Europe
Irja Lutsar MD, PhD
Professor of Medical Microbiology
University of Tartu
16. November 2017
Antibiotic resistance is a global
problem

2. 22‐Jan‐18
2
The history of Neisseria gonorrhoeae
antimicrobial resistance
Nature Reviews Microbiology 12, 223–229 (2014)
Chest 2000;118:146-155
Initial adequate AB therapy & mortality
of sepsis

3. 22‐Jan‐18
3
Resitant bacteria without antibiotic
Resistant bacteria have no advantages, their adaptation is worse and they are
destroyed by antagonism of susceptible microbes
Resistentsetel bakteritel pole paljunemises eelist ning nad surutakse maha tundlike
bakterite poolt
Resistant bacteria with ineffective antibiotics
If antibiotics are in environment resistant bacteria have strong advantage (selection),
they will survive and susceptible bacteria will die
Ebapiisava antibiootikumi kontsentratsiooni korral resistentsetel mikroobidel tekib
kasvueelis kuna tundlikud bakterid hävitatakse

4. 22‐Jan‐18
4
Proportion of resistant G‐negatives in adults
(EARS‐Net) and children (ARPEC)
0
10
20
30
40
50
60
70
80
% of resistantstrains
EARS‐Net ARPEC
E.coli K.pneumoniae P.aeruginosa
*p < 0.05Pediatr Infect Dis J. 2015 Jul;34(7):734‐41
Proportion of resistant G‐positives in
adults (EARS‐Net) and children (ARPEC)
0
5
10
15
20
25
30
35
MRSA PNSP *Macrolide
NSSP
VRE
% of resistantstrains
EARS‐Net
ARPEC
Pediatr Infect Dis J. 2015 Jul;34(7):734‐41 *p < 0.05

5. 22‐Jan‐18
5
Relevant hospital acquired microbes
G-positive Resistance
in Estonia
G-negative Resistance in Estonia
MRSA 4% Klebsiella spp. 22% MDR
21% AG-R
24% 3rd gen Ceph-R
MRSA  VRSA None E.coli 47% Amp.
11% 3rd gen Ceph-R
15% FQ-R
VRE Extremely
rare
P.aeruginosa 6% AG-R
12% Carb-R
0% FQ-R
0% MDR
Acinetobacter
baumanii
2% of bloodstream
isolates
EARS- Net 2015
Methicillin resistant
Staphylococcus aureus (MRSA)
Eesti 4%
2007 2015
Eesti 9%
MRSA rate is stable in Europe

6. 22‐Jan‐18
6
(ESBL) Klebsiella pneumoniae resistant to 3rd
generation cephalosporins
Estonia 24%
2007 2015
Estonia 3%
Resistence of Gram‐negative microorganisms i in rise
K.pneumoniae resistance to 3rd
gen cephalosporins (%)
Estonia, Latvia, Finland
0
10
20
30
40
50
60
70
Estonia Finland
Latvia Linear (Estonia)
EARS-Net 2012
0
5
10
15
20
25
30
35
40
45
Eesti Soome Läti

7. 22‐Jan‐18
7
P.aeruginosa karbapeneem-
resistentsus (%)
EARS-Net 2012
0
10
20
30
40
50
60
70
Eesti Soome Läti
Eesti, Soome, Läti
0
5
10
15
20
25
30
35
40
45
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
Estonia Finland Latvia
MRSA in Estonia, Latvia,
Finland
0
5
10
15
20
25
Estonia Finland Latvia
EARS-Net 2012

8. 22‐Jan‐18
8
Antibiotic consumption is related
to antibiotic resistance
Total outpatient antibiotic use in 26
European countries in 2002
Lancet 2005; 365: 579-587

9. 22‐Jan‐18
9
Penicillins use and prevalence of PNS
- S. pneumoniae
Lancet 2005; 365: 579-587
EST
Consumption of antibiotics for systemic
use in the community in EU, in 2016
2002
Netherlands
Estonia
Austria
Latvia
Germany

10. 22‐Jan‐18
10
Consumption of antibiotics for systemic
use in the hospitals in EU, in 2016
2002
Netherlands
Norway
Portugal
Bulgaria
*Consumption of carbapenems in Estonia is
increasing, in 2016 greater than EU average
*Consumption of polymyxins in increasing
Overuse of antibiotics is not
the only reason of antibiotic
resistance

11. 22‐Jan‐18
11
Resistance patterns – P. aeruginosa
Aminoglycoside resistance Fluoroquinolone resistance
Prevalence of aminoglycoside resistance:
26.7%, 95%CI: 16.1‐39.7%
Prevalence of fluoroquinolone resistance :
28.3%, 95%CI 17.5‐41.4%
Prevalence of aminoglycoside resistance in
EARS‐Net: 17.7%
Prevalence of fluoroquinolone resistance in
EARS‐Net: 22.5%
4 North South
Full
dataset
Resistant 0 1 16 17
Susceptible 2 16 27 43
0
5
10
15
20
25
30
35
40
45
50
Number of isolates
4 North South
Full
dataset
Resistant 0 3 13 16
Susceptible 22 14 30 44
0
5
10
15
20
25
30
35
40
45
50
Number of isolates
P.aeruginosa carbapenem resistance and
antibiotic consumption in hospitals
P.aeruginosa resistance
0
20
40
60
80
Eesti Soome Läti
Antibiotic consumption in
hospitals in 2011
EARS-Net 2012

12. 22‐Jan‐18
12
Cumulative percentage of patients with CRGNO in
rectal swab
Meropenem vs SOC
0
5
10
15
20
baseline EOT FU visit
% of ptwithresistantstrains
meroepenem SOC
Meropenem yes vs no
0
5
10
15
20
baseline 72h EOT FU visit
meropenem+ meropenem‐
CRGNO – carbapenem resistant Gram‐negative organisms
Nature 2013; 499: 394–396

13. 22‐Jan‐18
13
Endemic spread of Serratia infection
in neonatal units of TUC
Adamson et al. BMC Infect Dis. 2012; 12: 281
K. pneumoniae kolonisatsioon: ALFP
143 isolaati 48 haigelt
aug 2006 märts 2007 dets 2007
Osakond A
Osakond B
A1
R
H
G F
K
M
N
A
J
T
*
**
* *
*
Puhang I 14 aug-9 märts
23 pt
Puhang II 21 mai-8 nov
6 pt
ALFP – amplified fragment length polymorphism Parm et al. 2012

14. 22‐Jan‐18
14
Future directions
Antibiotic resistance vs new
antibiotics

15. 22‐Jan‐18
15
Antibiotic pipeline 2009
Antibiotics approved in EU in 21 century
46%
27%
27%
Gram positive
Gram negative
Both
Aztreonam lysin
Ceftaroline fosamil
Daptomycin
Doripenem
monohydrate
Ertapenem sodium
Fidaxomicin
Linezolid
Moxifloxacin
Retapumilin
Telithromycin
Tigecyclin
International Journal of Antimicrobial Agents 42 (2013) 99– 118

16. 22‐Jan‐18
16
Conclusions
• Compared to other EU countries Estonia has relatively low
antibiotic resistance rates
– MRSA stable
– ESBL K.pneumoniae is increasing
• Compared in other countries Estonia has low antibiotic
consumption in ambulatory setting but medium level in
hospital settings
– Use of broad spectrum is increasing
• Changes in antibiotic prescription rates are very slow
• There is limited number of new and more effective
antibiotics emerging
• AB resistance is combination of antibiotic policy and
controlling the spread of resistant strains