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What’s happening now ? Epidemiology of (carbapenem) resistance

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

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What’s happening now ? Epidemiology of (carbapenem) resistance

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  1. What’s happening now ? Epidemiology of (carbapenem) resistance Neil Woodford HPA – AMRHAI - Colindale

  2. The resistance ratchet keeps turning • 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

  3. E. coli from blood & CSF in the UK - a recent fall in resistance % Resistant

  4. Hospital antibiotic sales (kg)IMS data • use of pip/taz, co-amoxiclav (& carbapenems) • new selective pressures ..., but what consequences ?

  5. 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

  6. ...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

  7. 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& ‘home grown’ Early cases often imported Klebsiella spp. 79%; E. coli 12%, Enterobacter spp., 7%; others 2% AMRHAI, Unpublished data

  8. More labs are isolating ‘CPE’ in the UK 133 labs referred at least one isolate, 2003-2012 AMRHAI, Unpublished data

  9. Regional distribution of ‘CPE’ referrals, 2003-2012 KPC NDM No denominators. Not mandatory = no true sense of ascertainment. Need national surveillance. OXA-48 VIM AMRHAI, Unpublished data

  10. Why isn’t ‘ST258’ K. pneumoniae a bigger problem in the UK? • 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 ? 7 1 2 1 3 1 2 3 0 4 3 1 Findlay et al., Unpublished data

  11. 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

  12. Non-fermenters with metallo-carbapenemases in the UK (n = 393) AMRHAI, Unpublished data

  13. More labs are isolating MBL +ve non-fermenters in the UK VIM +vePseudomonas, 2003-2012 98 labs referred at least one isolate, 2000-2012 AMRHAI, Unpublished data

  14. VNTR analysis of MBL-producing P. aeruginosa • 6 groupsaccount 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 ST235 58 isolates, 28 labs ST233 35 isolates, 16 labs ST773 21 isolates, 12 labs ST111 90 isolates, 28 labs ST654 31 isolates, 13 labs ST357 16 isolates, 8 labs Wright et al., Unpublished data

  15. 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)

  16. Activity of colistin in vitro, carbapenemase +vevs. -ve E. coli 1-2% Col-R Klebsiella 5-6% Col-R % isolates Enterobacter 5-6% Col-R MIC, mg/L AMRHAI, Unpublished data

  17. 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 treatment Outbreaks contained Effective IPC

  18. 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 treatment Outbreaks contained Effective IPC

  19. ‘Resistance’ threatens the UK and the NHS every day Colonized residents or visitors Hospital treatment or travel overseas Non-human reservoirs: foodstuffs (domestic or imported) Inter-hospital transfers (UK) Victims from conflict zones Non-human reservoirs: animals and environment • Multiple risks to be assessed to minimize damage • Requires the detail to be understood • Continuous education of NHS staff at all levels

  20. 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

  21. 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)

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