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What’s happening now ? Epidemiology of (carbapenem) resistance. Neil Woodford HPA – AMRHAI - Colindale. The resistance ratchet keeps turning. 5 of 7 ESKAPEEs are Gram-negative Increasing reliance on carbapenems Rising incidence of carbapenem resistance - PowerPoint PPT Presentation
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What’s happening now ? Epidemiology of (carbapenem) resistance
Neil WoodfordHPA – AMRHAI - Colindale
The resistance ratchet keeps turning
Pathogen Established problems Emerging threatsE. 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, CarbapenemasesE. 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
E. coli from blood & CSF in the UK- a recent fall in resistance
% R
esis
tant
Hospital antibiotic sales (kg)IMS data
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 20090
5000
10000
15000
20000
25000CarbapenemsOxyimino cephsAmox clavPiptazFluoroquinolones
• use of pip/taz, co-amoxiclav (& carbapenems)• new selective pressures ..., but what consequences ?
Carbapenem non-susceptibility, 2011 (Ears-Net)
K. pneumoniae• <1.5% non-susceptibility in E. coli as judged by surveys• 3 countries reported >5% non-susceptibility in K. pneumoniae
E. coli
http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/database.aspx
...a worsening picture
Canton et al, CMI 2012
http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/graph_report.aspx
29.6%
70.8%
Carbapenemase-producing Enterobacteriaceae in the UK (n = 1802)
AMRHAI, Unpublished data
Early cases often imported
Imported & ‘home grown’
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AMRHAI, Unpublished data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
Regional distribution of ‘CPE’ referrals, 2003-2012KPC NDM
VIMOXA-48
AMRHAI, Unpublished data
No denominators.
Not mandatory = no tru
e sense of ascertainment.
Need national surveillance.
Why isn’t ‘ST258’ K. pneumoniae a bigger problem in the UK?
13
1
7
2
3
1
4
2
31
0
• The dominant KPC +ve lineage internationally• 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
• Ongoing NIHR study (non-NW isolates)• 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
2 SNPs
2 SNPs
3 SNPs
3 SNPs
1 SNPs
pKpQIL-D1
pKpQIL-D2
1 SNPs
Highly-related IncFII plasmids are spreading KPC in NW England
Doumith et al., Unpublished data
Non-fermenters with metallo-carbapenemases in the UK (n = 393)
AMRHAI, Unpublished data
Number
P. aeruginosaAcinetobacterPseudomonas spp.
More labs are isolating MBL +ve non-fermenters in the UK
AMRHAI, Unpublished data
98 labs referred at least one isolate, 2000-2012
VIM +ve Pseudomonas, 2003-2012
VNTR analysis of MBL-producing P. aeruginosa
• 6 groups account for 85% (251/297) of MBL- positive isolates
• 25 ‘types’ in remaining 15%
• do widely occurring strains represent true spread or just prevalence ?
• horizontal spread of MBL genes
Wright et al., Unpublished data
ST11190 isolates,
28 labs
ST23558 isolates,
28 labs
ST23335 isolates,
16 labs
ST65431 isolates,
13 labs
ST77321 isolates,
12 labs
ST35716 isolates,
8 labs
Advice on treatment when multi-resistance is the norm
HPR, 2011; 5: issue 24 (17/06/11; Woodford & Livermore)
Metallo-enzyme Producers (IMP, NDM or VIM)
≥90%
Activity of colistin in vitro, carbapenemase +ve vs. -ve
0.125 0.25 0.5 1 2 4 8 16 320
20
40
60
80
+-
0.125 0.25 0.5 1 2 4 8 16 320
20
40
60
80
+-
0.125 0.25 0.5 1 2 4 8 16 320
20
40
60
80
+-
% is
olat
es
AMRHAI, Unpublished data
E. coli 1-2% Col-R
Klebsiella 5-6% Col-R
Enterobacter 5-6% Col-R
MIC, mg/L
Containing multi-resistant bacteria: the critical triangle
Multi-disciplinary approach to limit risk and impact
• microbiology • surveillance • infection prevention and
control• diagnostics • drug development• diagnostic / reference /
R&D / industrial partnerships
Rapid Detection
Effective IPC
Effective treatment
Outbreaks contained
Containing multi-resistant bacteria: the critical triangle
Multi-disciplinary approach to limit risk and impact
• microbiology • surveillance • infection prevention and
control• diagnostics • drug development• diagnostic / reference /
R&D / industrial partnerships
Rapid Detection
Effective IPC
Outbreaks contained
Effective treatment
‘Resistance’ threatens the UK and the NHS every day
Colonized residents or visitors
Non-human reservoirs: animals
and environment
Victims from conflict zones
Hospital treatment ortravel overseas
• Multiple risks to be assessed to minimize damage• Requires the detail to be understood
• Continuous education of NHS staff at all levels
Inter-hospital transfers (UK)
Non-human reservoirs: foodstuffs (domestic or imported)
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)