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

The resistance ratchet keeps turning PathogenEstablished problemsEmerging threats E. faeciumVRE, HLGR, Amp-RLin-R, Dap-R, Tig-R S. aureusMRSA (ha/ca)Van-R, Lin-R, Dap-R KlebsiellaESBLsCarbapenemases, Col-R AcinetobacterMDR, CarbapenemasesTig-R, Col-R PseudomonasMDR, except ColCarbapenemases, Col-R EnterobacterAmpC, ESBLsCarba-R, Carbapenemases E. coliCip-R, ESBLsCarbapenemases 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 % Resistant

Hospital antibiotic sales (kg) IMS data  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

...a worsening picture Canton et al, CMI % 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Carbapenemase-producing Enterobacteriaceae in the UK (n = 1802) AMRHAI, Unpublished data Early cases often imported Imported & ‘home grown’ Klebsiella spp. 79%; E. coli 12%, Enterobacter spp., 7%; others 2%

AMRHAI, Unpublished data More labs are isolating ‘CPE’ in the UK 133 labs referred at least one isolate,

Regional distribution of ‘CPE’ referrals, KPCNDM VIM OXA-48 AMRHAI, Unpublished data No denominators.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

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 ? Findlay et al., Unpublished data

2 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3 SNPs 1 SNPs pKpQIL-D1 pKpQIL-D2 1 SNPs Highly-related IncFII plasmids are spreading KPC in NW England Doumith et al., Unpublished data

Non-fermenters with metallo- carbapenemases in the UK (n = 393) AMRHAI, Unpublished data

More labs are isolating MBL +ve non-fermenters in the UK AMRHAI, Unpublished data 98 labs referred at least one isolate, VIM +ve Pseudomonas,

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 ST isolates, 28 labs ST isolates, 28 labs ST isolates, 16 labs ST isolates, 13 labs ST isolates, 12 labs ST 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 % isolates 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 or travel 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 21 st March - Carbapenem resistance: how should we respond? (MIC Centre, Euston) 20 th May – “A Crash Course on Carbapenem Resistance” (Colindale; pilot ½-day course for Greater London)