1. Antimicrobial Resistance: from Global to Local
11th October 2011
Antimicrobial Resistance: from Global to Local
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 and Enterobacter sp.: infections are on the rise and a new beta-lactamase, NDM-1, is causing alarm
Neisseria gonorrheae 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 and Enterobacter sp.: infections are on the rise and a new beta-lactamase, NDM-1, is causing alarm
Neisseria gonorrheae 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 (eg cefotaxime)
Associated resistance to many other classes of antibiotics
Not identified until late 1980s
TEM/SHV/CTX-M

8. E. coli resistance to Cefotaxime rates from HPA

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

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

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

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

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

16. Odds ratio for revisiting GP within next 30 days:
1.47 (95% CI = ) if R to any antibiotic
1.49 (95% CI = ) for ampicillin resistance
2.48 (95% CI = ) for trimethoprim resistance.
British Journal of General Practice; 2006; 56: 686–692

25. “~30% antimicrobial use inappropriate”

26. “~30% antimicrobial use inappropriate”

27. Good practice promoted via Antimicrobial Stewardship Forum

29. Good practice promoted via Antimicrobial Stewardship Forum

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

39. 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

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DIM-1 – Poirel and Nordmann (unpublished data)
TMB-1 – El Salabi, Toleman and Walsh (unpublished data)

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

42. Carbapenemase +ve Enterobacteria referred to ARMRL, 2003-May 2011
HPR June 17th 2001

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

44. 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)

45. 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