What’s happening now ?
Epidemiology of (carbapenem)
resistance
Neil Woodford
HPA – AMRHAI - Colindale
The resistance ratchet keeps
turning
Pathogen
Established problems
Emerging threats
E. faecium
VRE, HLGR, Amp-R
Lin-R, Dap-R, Tig-R
S. aureus
MRSA (ha/ca)
Van-R, Lin-R, Dap-R
Klebsiella
ESBLs
Carbapenemases, Col-R
Acinetobacter
MDR, Carbapenemases
Tig-R, Col-R
Pseudomonas
MDR, except Col
Carbapenemases, Col-R
Enterobacter
AmpC, ESBLs
Carba-R, Carbapenemases
E. coli
Cip-R, ESBLs
Carbapenemases
• 5 of 7 ESKAPEEs are Gram-negative
• Increasing reliance on carbapenems
• Rising incidence of carbapenem resistance
• The resistance issue for the next 5-10 years
% Resistant
E. coli from blood & CSF in the UK
- a recent fall in resistance
Hospital antibiotic sales (kg)
IMS data
25000
20000
15000
Carbapenems
Oxyimino cephs
Amox clav
Piptaz
Fluoroquinolones
10000
5000
0
199819992000200120022003200420052006200720082009
•  use of pip/taz, co-amoxiclav (& carbapenems)
• new selective pressures ..., but what consequences ?
Carbapenem non-susceptibility,
2011 (Ears-Net)
E. coli
K. pneumoniae
• <1.5% non-susceptibility in E. coli as judged by surveys
• 3 countries reported >5% non-susceptibility in K. pneumoniae
http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/database.aspx
...a worsening picture
70.8%
29.6%
http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/graph_report.aspx
Canton et al, CMI 2012
Carbapenemase-producing
Enterobacteriaceae in the UK
(n = 1802)
Imported & ‘home grown’
Early cases often imported
Klebsiella spp. 79%; E. coli 12%, Enterobacter spp., 7%; others 2%
AMRHAI, Unpublished data
More labs are isolating ‘CPE’
in the UK
133 labs referred at least one isolate, 2003-2012
AMRHAI, Unpublished data
Regional distribution of ‘CPE’ referrals, 2003-2012
KPC
NDM
OXA-48
VIM
AMRHAI, Unpublished data
Why isn’t ‘ST258’ K. pneumoniae
a bigger problem in the UK?
• The dominant KPC +ve lineage internationally
•
•
•
•
7
Several related STs
Endemic in many parts of US, most of Greece
Caused a nationwide outbreak in Israel
Rapid, nationwide spread in Italy
• First detected in UK in 2007
1
2
• Ongoing NIHR study (non-NW isolates)
1
3
1
2
3
0
1
4
3
•
•
•
•
65/108 tested = ‘ST258 complex’
42/82 ‘MLST-ed’ isolates are classic ST258
8/82 are its SLV, ST512
≥1 isolate in most UK regions, …but over 6 years
• Why not (yet) a major problem in the UK ?
Findlay et al., Unpublished data
Highly-related IncFII plasmids are spreading
KPC in NW England
3 SNPs
2 SNPs
2 SNPs
1 SNPs
pKpQIL-D1
3 SNPs
pKpQIL-D2
1 SNPs
Doumith et al., Unpublished data
Non-fermenters with metallocarbapenemases in the UK
(n = 393)
Number
P. aeruginosa
Acinetobacter
Pseudomonas spp.
AMRHAI, Unpublished data
More labs are isolating MBL
+ve non-fermenters in the UK
VIM +ve Pseudomonas,
2003-2012
98 labs referred at least one isolate, 2000-2012
AMRHAI, Unpublished data
VNTR analysis of MBLproducing P. aeruginosa
• 6 groups account for 85%
(251/297) of MBL- positive
isolates
ST235
58 isolates,
28 labs
• 25 ‘types’ in remaining
15%
ST233
35 isolates,
16 labs
ST773
21 isolates,
12 labs
ST654
31 isolates,
13 labs
ST111
90 isolates,
28 labs
• do widely occurring
strains represent true
spread or just prevalence ?
• horizontal spread of MBL
genes
ST357
16 isolates,
8 labs
Wright et al., Unpublished data
Advice on treatment when
multi-resistance is the norm
Metallo-enzyme Producers
(IMP, NDM or VIM)
≥90%
HPR, 2011; 5: issue 24 (17/06/11; Woodford & Livermore)
Activity of colistin in vitro,
carbapenemase +ve vs. -ve
80
60
E. coli 1-2% Col-R
40
+
-
20
0
% isolates
0.125
0.25
0.5
1
2
4
8
16
32
80
60
Klebsiella 5-6% Col-R
40
+
-
20
0
0.125
0.25
0.5
1
2
4
8
16
32
80
Enterobacter 5-6% Col-R
60
40
+
20
-
0
0.125
0.25
0.5
1
2
4
8
16
32
MIC, mg/L
AMRHAI, Unpublished data
Containing multi-resistant
bacteria: the critical triangle
Multi-disciplinary approach
to limit risk and impact
Outbreaks
contained
Effective IPC
• microbiology
• surveillance
• infection prevention and
control
• diagnostics
• drug development
• diagnostic / reference /
R&D / industrial
partnerships
Containing multi-resistant
bacteria: the critical triangle
Multi-disciplinary approach
to limit risk and impact
Outbreaks
contained
Effective IPC
• microbiology
• surveillance
• infection prevention and
control
• diagnostics
• drug development
• diagnostic / reference /
R&D / industrial
partnerships
‘Resistance’ threatens the UK
and the NHS every day
Colonized residents
or visitors
Non-human
reservoirs: foodstuffs
(domestic or imported)
Non-human
reservoirs: animals
and environment
Hospital treatment or
travel overseas
Inter-hospital
transfers (UK)
Victims from
conflict zones
• Multiple risks to be assessed to minimize damage
• Requires the detail to be understood
• Continuous education of NHS staff at all levels
Multi-pronged attack on
resistance
• Better intelligence (improved global surveillance initiatives)
• Identify global hot spots / high risk patients
• Inform damage limitation strategies...
• Faster and more accurate diagnostics
• Better infection prevention and control (public health)
• More effective therapies (individuals)
• Now...rational antibiotic use (right drug, right time, right regimen)
• Future...a pipeline of new agents to overcome current problems
Training Opportunities
21st March - Carbapenem resistance: how should we
respond? (MIC Centre, Euston)
20th May – “A Crash Course on Carbapenem Resistance”
(Colindale; pilot ½-day course for Greater London)