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Transfer of resistant bacteria from animals to humans – relation to antibiotic use as growth promoters and therapeutics Niels Frimodt-Møller Professor, MD, DMSc. Dept. for Microbiological  Surveillance and Research Statens Serum Institut Copenhagen Denmark
Antibiotic resistance:  Clinical consequence   * P < 0.05 1,29 (1,04 – 1,59)* S.pneumoniae : PenR vs PenS Tleyjeh et al. CID 2006;42:778-97 2,52  (1,9 - 3,4)* Enterococcus : VR vs VS DiazGranados et al.  CID 2005;41:327-33 4,41 (1,03 – 18,81)* E. coli : FQ-R vs FQ-S   Lautenbach et al.   CID 2005;41:923-9   1,93 (1,54 – 2,42)* S.aureus : MR vs MS   Cosgrove et al. CID 2003;36:53-59 Odds Ratio (95% CI) for mortality
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Enterococcus faecium :  Vancomycin resistant (VRE) ~  vanA  gene, located on transposon, transferable via plasmid ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Enterococcus faecium :  Vancomycin resistant (VRE) ~  vanA  gene, located on transposon, transferable via plasmid ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Isolation from a patient of a vancomycin resistant  S. aureus  containing the  vanA  element from  E. faecalis  present in same wound   Flannagan et al. AAC  2003 ; 47:3954–9.
Growth promoters select for resistance in animals and transfer of resistance (or resistant bacteria) from food production animal to humans ?  e.g. vancomycin resistant E. faecium (VRE) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Correlation between use of Avoparcin as growth promoter and prevalence of Vancomycin-Resistant  E. faecium  (VRE) Aarestrup, F. M.  1995. Occurrence of glycopeptide resistance among  E.faecium  isolates from conventional and ecological poultry farms. Microb.Drug Resist.  1: 255–257. 2 32 ,[object Object],[object Object],32 40 + avoparcin in  feed No. of flocks  with VRE No. of flocks investigated Poultry farms
Transfer of VRE from animal to humans:  Scientific evidence Same type VRE in poultry and farmer Simonsen et al. Microb Drug Resist. 1998; 4: 313-8. Same VRE in poultry before and after slaughter Aarestrup et al. APMIS 1998; 106:606–22 VRE in food .  Wegener et al. Int J Food  Microbiol 1997; 35:57–66.  Robredo Int J Food Microbiol.  2000; 54: 197-204. VRE carriers in countries, where avoparcin used,  but not else Ieven [abstract LB-8, 41st ICAAC, 2001.  Klare et al. Microb Drug Resist. 1999; 5: 45-52.  Klare et al. Microb Drug Resist. 1995;1: 265-72. Same type VRE in pigs and patients   Jensen et al. AAC 1999; 43:724–5;  Hammerum et al. JAC 2004; 53:547–9.
Results of ban of growth promoters Avoparcin and Virginiamycin in Denmark
Fecal carrier rates of Vancomycin Resistant  E. faecium  (VRE) in non-hospitalised humans 12/100  11/40  6/100  13/400  1/670  3/169  2/6023 % pos with VRE Ban of Avoparcin Van den Bogard et al., JAC 2000, 46: 146 Van den Auwera et al. JID 1996, 173:  Klare et al. Microb Drug Resist. 1999;5:45-52.  Gambarotto et al. J Clin Microbiol. 2000; 38: 620–624.  Torell et al. J Clin Microbiol .  1999; 37: 3509–3513  Kolar et al.J Med Microbiol. 2005; 54: 965-7.  .   S F D NL D Cz D
Significant decrease of VRE infections and colonization rates in patients at hospital admission after AGP ban Colonization at admission Infections in hospitals W. Witte, personal comm. M. Leven et.al. ICAAC 2001 Germany Belgium N=335  N=353 % vanA % vanA
Growth promoters select for resistance in animals and transfer of resistance (or resistant bacteria) from food production animal to humans ?  e.g. vancomycin resistant E. faecium (VRE) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Use of Streptogramin Growth Promoters in Poultry and Isolation of Streptogramin-Resistant Enterococcus faecium  from Humans Kieke et al. The Journal of Infectious Diseases 2006; 194:1200–8 Minnesota, Wiscosin, USA
[object Object]
Campylobacter infection:  Clinical consequences ,[object Object]
Campylobacter, erythromycin-resistance and relative mortality ,[object Object],[object Object],[object Object],Helms et al. JID 2005;  Molbak et al. 2002
Macrolide use and - resistance in  Campylobacter coli  from pigs
[object Object]
Antibiotic resistant Salmonella:  Clinical importance ,[object Object],[object Object]
Salmonella:  Antibiotic resistance associated with antibiotic use ? ,[object Object],[object Object],[object Object]
No. of  human  Salmonella,   Campylobacter and Yersinia cases in Denmark 1980-2009
[object Object]
E. coli:  Intestinal commensal, causing diarrhoea or extraintestinal  infections such as urinary tract infection (UTI) Lautenbach et al. CID 2005;41:923-9 Manges et al, NEJM 2001, 345: 1007;    Burman et al., Am J Med 2003, 115: 358;      Johnson et al. Lancet 2002; 359:2249;    Phillips et al. Lancet 1988, 331: 1038;      Olesen et al. SJID 1994, 26: 406;    Pitout et al. JCM 2005; 43: 2844 ,[object Object],[object Object],[object Object]
E. coli: UTI ,[object Object],[object Object],[object Object],[object Object],[object Object],Trobos et al. JAC, 2009
Conclusion:  Transfer of resistance animal > human:   Enterococci, Salmonella, Campylobacter and  E. coli : ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Why was VRE more prevalent in US hospitals than in Europe ? Vancomycin usage in USA vs. Europe Klare et al. IJFM 2003
EARSS 2008
Staphylococcus aureus (Sa) : MRSA epidemiology Spa types in 2008 1 % of  SA bacteraemias ~

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Transfer of resistant bacteria from animals to humans

  • 1. Transfer of resistant bacteria from animals to humans – relation to antibiotic use as growth promoters and therapeutics Niels Frimodt-Møller Professor, MD, DMSc. Dept. for Microbiological Surveillance and Research Statens Serum Institut Copenhagen Denmark
  • 2. Antibiotic resistance: Clinical consequence * P < 0.05 1,29 (1,04 – 1,59)* S.pneumoniae : PenR vs PenS Tleyjeh et al. CID 2006;42:778-97 2,52 (1,9 - 3,4)* Enterococcus : VR vs VS DiazGranados et al. CID 2005;41:327-33 4,41 (1,03 – 18,81)* E. coli : FQ-R vs FQ-S Lautenbach et al. CID 2005;41:923-9 1,93 (1,54 – 2,42)* S.aureus : MR vs MS Cosgrove et al. CID 2003;36:53-59 Odds Ratio (95% CI) for mortality
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  • 8. Transfer of VRE from animal to humans: Scientific evidence Same type VRE in poultry and farmer Simonsen et al. Microb Drug Resist. 1998; 4: 313-8. Same VRE in poultry before and after slaughter Aarestrup et al. APMIS 1998; 106:606–22 VRE in food . Wegener et al. Int J Food Microbiol 1997; 35:57–66. Robredo Int J Food Microbiol. 2000; 54: 197-204. VRE carriers in countries, where avoparcin used, but not else Ieven [abstract LB-8, 41st ICAAC, 2001. Klare et al. Microb Drug Resist. 1999; 5: 45-52. Klare et al. Microb Drug Resist. 1995;1: 265-72. Same type VRE in pigs and patients Jensen et al. AAC 1999; 43:724–5; Hammerum et al. JAC 2004; 53:547–9.
  • 9. Results of ban of growth promoters Avoparcin and Virginiamycin in Denmark
  • 10. Fecal carrier rates of Vancomycin Resistant E. faecium (VRE) in non-hospitalised humans 12/100 11/40 6/100 13/400 1/670 3/169 2/6023 % pos with VRE Ban of Avoparcin Van den Bogard et al., JAC 2000, 46: 146 Van den Auwera et al. JID 1996, 173: Klare et al. Microb Drug Resist. 1999;5:45-52. Gambarotto et al. J Clin Microbiol. 2000; 38: 620–624. Torell et al. J Clin Microbiol . 1999; 37: 3509–3513 Kolar et al.J Med Microbiol. 2005; 54: 965-7. . S F D NL D Cz D
  • 11. Significant decrease of VRE infections and colonization rates in patients at hospital admission after AGP ban Colonization at admission Infections in hospitals W. Witte, personal comm. M. Leven et.al. ICAAC 2001 Germany Belgium N=335 N=353 % vanA % vanA
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  • 13. Use of Streptogramin Growth Promoters in Poultry and Isolation of Streptogramin-Resistant Enterococcus faecium from Humans Kieke et al. The Journal of Infectious Diseases 2006; 194:1200–8 Minnesota, Wiscosin, USA
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  • 17. Macrolide use and - resistance in Campylobacter coli from pigs
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  • 21. No. of human Salmonella, Campylobacter and Yersinia cases in Denmark 1980-2009
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  • 27. Why was VRE more prevalent in US hospitals than in Europe ? Vancomycin usage in USA vs. Europe Klare et al. IJFM 2003
  • 29. Staphylococcus aureus (Sa) : MRSA epidemiology Spa types in 2008 1 % of SA bacteraemias ~