1. The complex and diverse
epidemiologies of ESBLs and
carbapenemases in the UK
Neil Woodford
HPA – ARMRL - Colindale

2. E. coli, 2010 (Ears-Net)
3GC-I/R Carba-I/R
• In the UK:
• c. 30,000 cases E. coli bacteraemia p.a.
• c. 6.5 % CTX and/or CAZ resistance = c. 2000 cases p.a

3. The UK’s CTX-M problem
• ~1500 CTX-M-producing E. coli analysed
- 91% contain alleles encoding group 1 enzymes (mainly CTX-M-15)
• massive clonal spread
- 8.5% contain alleles encoding group 9 enzymes
• diverse strains, some intra-centre strain spread
- 8 isolates contain an allele encoding group 2 enzymes
- 1 isolate contains an allele encoding a group 8 enzyme

4. Which E. coli clones cause
bacteraemia (and UTI)?
ST Bacteraemia 2001 Bacteraemia 2010 UTIs
(n=152) (n=116) (n=300)*
73 20.5% 21.2% 16.6%
95 7.9% 11.0% 6.3%
131 3.3% 13.6% 12.3%
12 5.3% 7.6% 0.7%
127 4.6% 5.9% 3.6%
69 4.0% 5.1% 9.0%
Other 54.4% 35.6% 51.5%
(58 STs) (30 STs) (97 STs)
• 83 STs identified in 2001 + 2010
• Less diversity in 2010; major types increase from 45.6% to 64.4%
• ST131 - most significant increase
* Gibreel et al. JAC 2012; 67: 346-56

5. ST131 and spread of CTX-M-15-
producing E. coli in the UK
Strains B, C, D, E
+ others
ST131
Strain A

6. Prolonged faecal carriage of
ST131 variants: UK strains A & D
• Potential for persistence in community settings
• 50% colonized for up to 1 month
• 30% colonized between 1 - 12 months
Warren et al., CMI 2008, 14 (suppl. 1), 124-33

7. Multi-resistance plasmids help to
spread CTX-M -15 ESBL
Antibiotic
Genes Mechanism
classes
aac6’-Ib-cr
Aminoglycosides Modify drug
aadA5
blaCTX-M-15
β-lactams blaOXA-1 Destroy drug
blaTEM-1
Chloramphenicol catB4 Modify drug
Macrolides mph(A) Efflux
Fluoroquinolones aac6’-Ib-cr Modify drug
Sulfonamides sulI By-pass
Trimethoprim dhfrXVII By-pass
Tetracycline tet(A) Efflux Woodford, Carattoli et al. AAC

8. The biogeography / ecology of
resistance is complex
Success of the gene
• Good promoter
• Mobilizing agent (IS)
• Successful plasmid
carrier
Success of the clone or strain
• Prevalence
• Virulence potential
• Locally, nationally or
internationally
• Often poorly understood
Stokes & Gillings, FEMS Microbiol Rev, 2011