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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
Antimicrobial Resistance: from Global to Local

11th October 2011

Robin A Howe

Antimicrobial use in Primary Care

amr a major challenge
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
amr a major challenge1
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
a global epidemic of esbls 2001 2009
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
development and spread of antimicrobial resistance is multifactorial
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
slide12

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
slide16

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

project to develop all wales guidance for infection management and antimicrobial usage
Project to develop all-Wales guidance for infection management and antimicrobial usage
carbapenemases metallo beta lactamases
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

slide40

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)

slide41

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)

carbapenemases in wales
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)
conclusions
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