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 (Spain 23F -1) Tennessee Cleveland Mexico Colombia Brazil Argentina Uruguay Chile South Africa Singapore Malaysia Thailand Philippines Hong Kong Taiwan South Korea Spain France BM ? Finland Munoz et al. J Infect Dis 1991; 164:302-06

Pneumococcal Molecular Epidemiology Network CloneSerotypeResistance pattern Spain 23F -123FPEN, CHL, TET Spain 6B -26BPEN, CHL, TET Spain 9V -39VPEN Tennessee 23F -423FCTX, ERY Spain PEN, CHL, TET Hungary 19A -619APEN, ERY, CLIN, CHL, TET S. Africa 19A -719APEN S. Africa 6B -86BPEN England ERY SCR PEN, ERY, CLIN, CHL, TET PMEN, Pneumococcal Molecular Epidemiology Network:

Pneumococcal Bacteraemia in a British District General Hospital, Jan 2000-Mar cases of pneumococcal bacteraemia 18 isolates (32%) were antibiotic-resistant Three isolates of Spain 9V -3 clone (pen-R) 14 isolates of England clone (ery-R) One isolate of Spain 6B -2 clone (multi-R) Birtles A et al. J Med Microbiol 2004; 53:

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 PCV-7 2mo to <2yrs Older patients Henderson K et al. J Antimicrob Chemother 2010; 65:

Bacteraemia Due to MRSA, England & Wales % MRSA

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:

Ciprofloxacin is excreted in sweat Disruption of normal skin microflora? Colonization of skin by ciprofloxacin-resistant MRSA? Spread of EMRSA-15/16

Distribution of MRSA Spa Types in Europe

Epidemiology of Cephalosporin Resistance in UK is Changing… s: 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 Woodford N et al.J Antimicrob Chemother 2004; 54: Other isolates diverse

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 Woodford N et al.J Antimicrob Chemother 2004; 54: Other isolates diverse

Bacterial Plasmids

Conjugating bacteria

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

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)? What We Do and Don’t Know