National and International Spread of Antimicrobial Resistance: Clones and Genes

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National and International Spread of
Antimicrobial Resistance Clones and Genes
Professor Alan Johnson, Health Protection
Services - HPA
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Antimicrobial Resistance

• Streptococcus pneumoniae
• Staphylococcus aureus
• Escherichia coli

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Global Spread of Multi-Resistant Clone of
Streptococcus pneumoniae (Spain23F-1)
Finland
France BM4200 1978 ?
Cleveland
Spain
South Korea
Tennessee
Taiwan
Mexico
Hong Kong
Philippines
Thailand
Colombia
Malaysia
Singapore
Brazil
Chile
South Africa
Uruguay
Argentina
Munoz et al . J Infect Dis 1991 164302-06
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Pneumococcal Molecular Epidemiology Network
Clone Serotype Resistance pattern
Spain23F-1 23F PEN, CHL, TET
Spain6B-2 6B PEN, CHL, TET
Spain9V-3 9V PEN
Tennessee23F-4 23F CTX, ERY
Spain14-5 14 PEN, CHL, TET
Hungary19A-6 19A PEN, ERY, CLIN, CHL, TET
S. Africa19A-7 19A PEN
S. Africa6B-8 6B PEN
England14-9 14 ERY
SCR14-10 14 PEN, ERY, CLIN, CHL, TET
PMEN, Pneumococcal Molecular Epidemiology
Network http//www.sph.emory.edu/PMEN/
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Pneumococcal Bacteraemia in a British District
General Hospital, Jan 2000-Mar 2001

• 56 cases of pneumococcal bacteraemia
• 18 isolates (32) were antibiotic-resistant
• Three isolates of Spain9V-3 clone (pen-R)
• 14 isolates of England14-9 clone (ery-R)
• One isolate of Spain6B-2 clone (multi-R)

Birtles A et al. J Med Microbiol 2004 53
1241-1246
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Pneumococcal vaccines

• Pneumococci comprise 90 serotypes
• Polysaccharide capsule is a virulence
  determinant (inhibits phagocytosis)
• Capsule antigens form basis for vaccines
• 7-valent conjugate vaccine (2006)
• 13-valent conjugate vaccine

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Erythromycin Resistance in Invasive Pneumococci,
England and Wales
PCV-7
2mo to lt2yrs
Older patients
Henderson K et al. J Antimicrob Chemother 2010
65 369-70.
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Bacteraemia Due to MRSA, England Wales
MRSA
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Hospitals in England Wales Sending EMRSA-15/16
to Reference Laboratory
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Correlation of MRSA and Use of Macrolides,
Cephalosporins and Fluoroquinolones
Monnet DL et al. EID 2004 101432-41.
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Spread of EMRSA-15/16

• Ciprofloxacin is excreted in sweat
• Disruption of normal skin microflora?
• Colonization of skin by ciprofloxacin-resistant
  MRSA?

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Distribution of MRSA Spa Types in Europe
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Epidemiology of Cephalosporin Resistance in UK is
Changing

• 1980-90s
• Nosocomial (e.g. ICUs)
• Commonly Klebsiella spp.
• TEM/SHV ESBLs
• Since 2003
• Commonly E. coli
• CTX-M type ESBLs
• UTIs in elderly patients in the community
  (difficult to determine if community or HCAI)

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PFGE Profile of CTX-M-producing E. coli

• 5 related strains
• Serotype O25H4
• MLST 131

• Other isolates diverse

Woodford N et al.J Antimicrob Chemother 2004 54
735-43
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Spread of E. coli Strain A

• CTX-M-15
• Serotype O25H4
• Sequence type 131
• Global spread

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International Spread of E. coli 025H4 ST131 with
CTX-M-15
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PFGE Profile of CTX-M-producing E. coli

• 5 related strains
• Serotype O25H4
• MLST 131

• Other isolates diverse

Woodford N et al.J Antimicrob Chemother 2004 54
735-43
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Bacterial Plasmids
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Conjugating bacteria
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Spread of AMR

• Vancomycin-resistant enterococci
• Klebsiella pneumoniae
• Acinetobacter baumanii
• MDR TB
• Cephalosporin-resistant gonococci
• Carbapenemase-producing Gram-negative bacteria

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What We Do and Dont Know

• Antibiotic resistance involves both strain and
  gene spread
• Why are some strains epidemic and others not?
• How do we prevent strain spread
  (local/national/international)?
• Can we prevent plasmid spread?
• How important is plasmid spread in the gut?
• Epidemiology of resistance in commensal
  bacteria?
• Interventions (e.g. rapid tests antibiotic
  stewardship)?

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