Transcript HPA Presentation 2

National and International Spread
of Antimicrobial Resistance:
Clones and Genes
Professor Alan Johnson,
Health Protection Services - HPA
Antimicrobial Resistance
• Streptococcus
pneumoniae
• Staphylococcus aureus
• Escherichia coli
Global Spread of Multi-Resistant Clone of
Streptococcus pneumoniae (Spain23F-1)
Cleveland
Finland
France
BM4200
1978 ?
Spain
South Korea
Tennessee
Taiwan
Hong Kong
Philippines
Thailand
Mexico
Colombia
Malaysia
Singapore
Brazil
Chile
Uruguay
Argentina
South
Africa
Munoz et al . J Infect Dis 1991; 164:302-06
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/
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
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
Erythromycin Resistance in Invasive
Pneumococci, England and Wales
40%
PCV-7
35%
30%
Resistance (%)
2mo to <2yrs
25%
20%
15%
10%
Older patients
5%
0%
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Year
Henderson K et al. J Antimicrob Chemother 2010; 65: 369-70.
Bacteraemia Due to MRSA,
England & Wales
50
% MRSA
40
30
20
10
0
92
93
94
95
96
97
Year
98
99
00
01
02
Hospitals in England & Wales Sending
EMRSA-15/16 to Reference Laboratory
Correlation of MRSA and Use of Macrolides,
Cephalosporins and Fluoroquinolones
Monnet DL et al. EID 2004; 10:1432-41.
Spread of EMRSA-15/16
• Ciprofloxacin is excreted in sweat
• Disruption of normal skin microflora?
• Colonization of skin by ciprofloxacin-resistant MRSA?
Distribution of MRSA
Spa Types in Europe
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)
PFGE Profile of CTX-M-producing E. coli
• 5 related strains
• Serotype O25:H4
• MLST 131
• Other isolates diverse
Woodford N et al.J Antimicrob Chemother 2004; 54: 735-43
Spread of E. coli Strain A
• CTX-M-15
• Serotype O25:H4
• Sequence type 131
• Global spread
International Spread of E. coli
025:H4 ST131 with CTX-M-15
PFGE Profile of CTX-M-producing E. coli
• 5 related strains
• Serotype O25:H4
• MLST 131
• Other isolates diverse
Woodford N et al.J Antimicrob Chemother 2004; 54: 735-43
Bacterial Plasmids
Conjugating bacteria
Spread of AMR
• Vancomycin-resistant enterococci
• Klebsiella pneumoniae
• Acinetobacter baumanii
• MDR TB
• Cephalosporin-resistant gonococci
• Carbapenemase-producing Gram-negative bacteria
What We Do and Don’t 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)?