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Antimicrobial Resistance: from Global to Local

Antimicrobial Resistance: from Global to Local. 11 th October 2011. Robin A Howe. World Health Day 2011. AMR: a major challenge. Tuberculosis (TB): 440,000 new multidrug resistance (MDR) TB cases annually; extensively drug resistance (XDR) TB cases reported in 64 countries so far

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Antimicrobial Resistance: from Global to Local

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  1. Antimicrobial Resistance: from Global to Local 11th October 2011 Robin A Howe Antimicrobial use in Primary Care

  2. World Health Day 2011

  3. AMR: a major challenge • Tuberculosis (TB): 440,000 new multidrug resistance (MDR) TB cases annually; extensively drug resistance (XDR) TB cases reported in 64 countries so far • Malaria: Emergence of Artemisin resistance linked to ongoing use of monotherapies • HIV: With expanded use of antiretrovirals (ARVs), resistance is a concern • Methicillin-resistant Staphylococcus aureus: lethal infections in hospital settings becoming increasingly frequent • Multi-drug resistant E.coli, K.pneumoniae andEnterobactersp.: infections are on the rise and a new beta-lactamase, NDM-1, is causing alarm • Neisseriagonorrheae and Shigella: becoming increasingly resistant to drugs

  4. AMR: a major challenge • Tuberculosis (TB): 440,000 new multidrug resistance (MDR) TB cases annually; extensively drug resistance (XDR) TB cases reported in 64 countries so far • Malaria: Emergence of Artemisin resistance linked to ongoing use of monotherapies • HIV: With expanded use of antiretrovirals (ARVs), resistance is a concern • Methicillin-resistant Staphylococcus aureus: lethal infections in hospital settings becoming increasingly frequent • Multi-drug resistant E.coli, K.pneumoniae andEnterobactersp.: infections are on the rise and a new beta-lactamase, NDM-1, is causing alarm • Neisseriagonorrheae and Shigella: becoming increasingly resistant to drugs

  5. A global epidemic of “ESBLs” 2001 - 2009 • Extended spectrum beta-lactamases • Seen in coliforms (eg E. coli) • Confer resistance to 3rd generation cephalosporins (egcefotaxime) • Associated resistance to many other classes of antibiotics • Not identified until late 1980s • TEM/SHV/CTX-M

  6. E. coli resistance to Cefotaxime rates from HPA

  7. ECDC/EMEA JOINT TECHNICAL REPORT (2009). The bacterial challenge: time to react

  8. ECDC/EMEA JOINT TECHNICAL REPORT (2009). The bacterial challenge: time to react

  9. Development and spread of Antimicrobial Resistance is Multifactorial • Globalisation • Bacterial factors • Strain virulence • Genetic linkage of resistance with resistance • Genetic linkage of resistance with other resistance • Genetic mobility of resistance genes • Antibiotic use • Evolutionary pressure • (effective treatment reduces disease burden) • Infection control • Community – sanitation etc • Hospital • Immunisation

  10. Sub-lethal concentrations of Ciprofloxacin induce the SOS response • Ciprofloxacin • recA:GFP fusion • Amikacin tetracycline • A. Couce and Jesus Blazquez 2009 FEMS Microbiol Rev 531-538

  11. All-Wales antimicrobial resistance rates for coliforms from community urines(2005-10)

  12. Odds ratio for revisiting GP within next 30 days: • 1.47 (95% CI = 1.10 - 1.95) if R to any antibiotic • 1.49 (95% CI = 1.11 - 2.00) for ampicillin resistance • 2.48 (95% CI = 1.70 - 3.59) for trimethoprim resistance. British Journal of General Practice; 2006; 56: 686–692

  13. “~30% antimicrobial use inappropriate”

  14. “~30% antimicrobial use inappropriate”

  15. Good practice promoted via Antimicrobial Stewardship Forum

  16. Good practice promoted via Antimicrobial Stewardship Forum

  17. Project to develop all-Wales guidance for infection management and antimicrobial usage

  18. Carbapenemases/ metallo-beta-lactamases • Carbapenems (imipenem, meropenem) are v.broad spectrum agents • (Gram positive, Gram negative, aerobes, anaerobes) • Carbapenemases • breakdown carbapenems (and all beta-lactams) conferring resistance • associated with resistance to many (all) alternative agents Antimicrobial Resistance & Usage

  19. IMP VIM SPM-1 GIM-1 AIM-1 SIM-1 NDM-1 DIM-1 TMB-1 KHM-1 Location of Mobile MBL- Containing Organisms DIM-1 – Poirel and Nordmann (unpublished data) TMB-1 – El Salabi, Toleman and Walsh (unpublished data)

  20. IMP VIM SPM-1 GIM-1 AIM-1 SIM-1 NDM-1 DIM-1 TMB-1 KHM-1 Location of Mobile MBL- Containing Organisms DIM-1 – Poirel and Nordmann (unpublished data) TMB-1 – El Salabi, Toleman and Walsh (unpublished data)

  21. Carbapenemase +veEnterobacteria referred to ARMRL, 2003-May 2011 HPR June 17th 2001

  22. Kumarasamy et al (2010) TLID (online Aug 11 2010)

  23. Carbapenemases in Wales • 2008: • VIM-2 in P. aeruginosa from 2 patients (Cardiff) • GES in 1 isolate of A. baumanii (Newport) • 2009: • VIM-2 in P. aeruginosa (Newport) • 2010: • VIM-1 in K. pneumoniae from 2 patients (Wrexham) • VIM-1 in 1 isolate K. Pneumoniae (Rhyl) • 2011: • OXA-48 in 1 isolate of K. pneumoniae (Swansea) • NDM in multiple isolates of A. baumanii (Swansea) • NDM in 1 isolate of E. cloacae from (Newport) • VIM-2 in 1 isolate of P. aeruginosa (Abergavenny)

  24. Conclusions • Antimicrobial resistance is a global public health issue • Development and spread of resistance is multifactorial • Global resistance will become a local issue • Local “good practice” can influence spread (and treat patients optimally) • Post-Antimicrobial age is getting closer

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