The role of an AMR reference laboratory

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The role of an AMR reference laboratory Professor Neil Woodford Antimicrobial Resistance & Healthcare Associated Infections (AMRHAI) Reference Unit Crown copyright

Primary purpose: regional AMR threats to healthcare 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 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 2 CARPHA Workshop, 9th December 2014 Crown Copyright

What tests should an AMR reference laboratory offer? What the customer wants ( are you sure about this?) Expert advice about their needs / how this may differ from their wishes What do resources allow? Regular review of its services Demands Needs 3 CARPHA Workshop, 9th December 2014 Crown Copyright

What tests should an AMR reference laboratory offer? What the customer wants ( are you sure about this?) Expert advice about their needs / how this may differ from their wishes What do resources allow? Regular review of its services Customers don t need / want Customers need / want Ref Lab doesn t offer Negotiate / Review* Ref Lab offers Satisfies wider need* * Reference Laboratory must be objective, not defensive 4 CARPHA Workshop, 9th December 2014 Crown Copyright

What tests should an AMR reference laboratory offer? Susceptibility testing for confirmation of exceptional resistances Infer resistance mechanisms from antibiograms Investigation of priority resistance mechanisms Strain typing to aid outbreak investigation Treatment advice; infection prevention & control advice +/- Research +/- Evaluations of new drugs / diagnostics 5 CARPHA Workshop, 9th December 2014 Crown Copyright

My Unit s goals Setting England s (the UK s) Resistance and HCAI Problems into National and Global Context Better understanding of (resistant) bacterial clones distribution (global, national, regional) contribution resistance plays to success Coordinated surveillance of mechanisms global, regional and national Identify geographic hot spots and high risk patients early, targeted IPC interventions 6 CARPHA Workshop, 9th December 2014 Crown Copyright

AMRHAI s Research Agenda Setting England s (the UK s) Resistance and HCAI Problems into National and Global Context Outbreak strains Resistance elements Population biology, ecology and biogeography Transmission pathways Reasons for success Better diagnostics, therapies and rational interventions 7 CARPHA Workshop, 9th December 2014 Crown Copyright

Our commonest AMR-related questions Can you confirm resistance to drug X? We got different AST results with two methods. Which is right? Why is this isolate resistant to drug X? Are these isolates the same / different - is there evidence for transmission? What can I treat the patient with? increasingly, does resistance in these different strains / species / genera represent plasmid spread? 8 CARPHA Workshop, 9th December 2014 Crown Copyright

International Consensus: AMR is a critical public health threat 9 CARPHA Workshop, 9th December 2014 Crown Copyright

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 The resistance issue for the next 5-10 years 10 CARPHA Workshop, 9th December 2014 Crown Copyright

Raising awareness of resistance: the AMRHAI Newsletter Twice a year Short, chatty pieces (coffee break reading) Service updates Wider science Sent electronically to our entire customer database Links to PubMed entries for all of our publications in previous 6 months 11 CARPHA Workshop, 9th December 2014 Crown Copyright

Reference labs must work with surveillance scientists Pathogen % carbapenem resistance 2008 2009 2010 2011 2012 2013 E. coli 0.08 0.09 0.11 0.18 0.25 0.22 K. pneumoniae 0.7 0.4 0.6 1.2 1.1 1.6 Should provide specialist microbiology that seeks to explain trends Should be at the centre of a national / regional laboratory network Should benefit from a spider s web effect Should monitor new and emerging AMR issues, long before they register in surveillance programmes 12 CARPHA Workshop, 9th December 2014 Crown Copyright Courtesy, Prof Alan Johnson

Frequency CPE in the UK, 2000-2013 1200 Imported & home grown 1000 800 600 400 200 Early cases often imported 0 IMP VIM KPC OXA-48 NDM IMI KPC + VIM NDM + OXA-48 Klebsiella spp. 79%; E. coli 12%, Enterobacter spp., 7%; others 2% 13 CARPHA Workshop, 9th December 2014 Crown Copyright AMRHAI, Unpublished data

Raising awareness of resistance: Resistance Alerts Dec 05 - Carbapenemresistant Enterobacteriaceae Jan 09 - Carbapenemaseproducing Enterobacteriaceae in the UK: multi-faceted emergence Jul 09 - NDM (New Delhi Metallo-) -lactamase: repeated importation from Indian subcontinent 14 CARPHA Workshop, 9th December 2014 Crown Copyright

National & international capacity building Without lab testing we re blind to (the extent of) AMR problems Improve lab access; aim for a reference lab in every country / region Each serving as the hub of a national network Each acting as a spoke in an international network Performing essential techniques, proficient to international standards Sharing data / experience 15 Tokyo, 10th November 2014 Crown Copyright

Goals for the future Better capture of patient-level metadata, linked with lab data Outbreaks contained Effective IPC Routine deployment of WGS for typing and resistance analysis evaluate accuracy of resistance / susceptibility prediction discover novel mechanisms Robust (sensitive and specific) rapid diagnostics New treatment options 16 CARPHA Workshop, 9th December 2014 Crown Copyright