Multidrug resistant organisms: What are we up against?

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Multidrug resistant organisms What are we up
against?

• Hans Jørn Kolmos MD DMSc
• Professor, consultant
• Department of Clinical Microbiology
• Odense University Hopsital
• hans.joern.kolmos_at_ouh.regionsyddanmark.dk

Progress in Studies in the Reversal of Drug
Resistance SDU 4 June 2012
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AntibioticsMiracle drugs, it started out so
well, but .
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The antibiotic crisisaccelerating resistance
little new drug development
Clatworthy. Nature Biochem Biol 2007 3 541-8
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Multi-drug resistant bacteria a rough overview
Clostridium difficile Corynebactera
Staph aureus (MRSA) Pneumococci Enterococci
MDR- XDR-TB
Gonococci
E. Coli (ESBL) Klebsiella (ESBLCPE) Salmonella Ps
eudomonas Acinetobacter Stenotrophomonas Helicobac
ter plus many others
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MRSA in Europe 2009
http//www.salute.gov.it/imgs/C_17_pubblicazioni_1
404_allegato.pdf
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ESBL producing E. coli Klebsiella pneumoniae
http//www.salute.gov.it/imgs/C_17_pubblicazioni_1
404_allegato.pdf
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Beyond ESBL carbapenem resistance - the
ultimate horror scenario
Resistance to
ESBL producing Enterobacteriaceae Penicillins Cephalosporins
Carbapenem resistant Enterobacteriaceae (VIM,NDM-1, KPC-2,oxa-48) Penicillins Cephalosporins Carbapenems others
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The ecology of resistanceSelection and
transmission
Selection with antibiotics
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ESBL The steps from contamination to infection
Many
Some
Few
Patient with invasive infection
Breach of natural barriers (surgery,
catheters, chemotherapy etc)
Selection of ESBL (high conc)
Destruction of normal intestinal flora by
antibiotics
Intestinal colonization (low conc)
Acquisition of ESBL by human contact food
Healthy individual
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Bugs fighting backAntibiotic resistance
mechanisms
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A direct relationship between antibiotic
consumption and antibiotic resistance
Bronzwaer et al. Emerg Infect Dis 2002 8 278-82
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Coupling of resistance on plasmids or gene
cassettesthe genetic background for co-selection
Rcopper
Rzinc
Rtetra
Rampi
Virulence factors
Rceph
Rgenta
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Co-selection with tetracyclinesa driving force
behind MRSA ESBL in food animals
MRSA, ESBL
Tetracycline resistance
ESBL E. coli (broilers pigs) 89-97
MRSA CC398 (pigs) 95
Costa et al. Vet Microbiol 2009 138 339-44 Ho
et al. JAC 2011 66 765-8 DANMAP 2008
DANMAP 2010
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Why worry?

• MDRO are dangerous
• More difficult to treat
• May be more virulent
• Increase mortality
• Increase morbidity
• Resource-intensive
• More expensive antibiotics
• Increase length of hospitalization
• Increase demand for isolation-facilities
• Derived problems
• Drug toxicity
• Poorer quality of care due to single room
  isolation

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End of antibiotics - the ultimate consequence
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Measures against multidrug resistance

• Stop selection
• Antibiotic restriction
• Stop transmission
• Hygiene
• Food animal management
• Develop new drugs
• antibiotics
• helper compounds to antibiotics