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Multidrug resistant organismsMultidrug resistant organisms: : WWhat are we up against?hat are we up against?
Hans Jørn Kolmos MD DMSc
Professor, consultant
Department of Clinical Microbiology
Odense University Hopsital
Progress in Studies in the Reversal of Drug ResistanceSDU 4 June 2012
Antibiotics:Antibiotics:Miracle drugs, it started out so well, but ….Miracle drugs, it started out so well, but ….
The antibiotic crisis:The antibiotic crisis:accelerating resistance & little new drug developmentaccelerating resistance & little new drug development
Clatworthy. Nature Biochem Biol 2007; 3: 541-8Clatworthy. Nature Biochem Biol 2007; 3: 541-8
Staph aureus (MRSA)
Pneumococci
Enterococci
Gonococci
Clostridium difficile
Corynebactera
E. Coli (ESBL)Klebsiella (ESBL+CPE)SalmonellaPseudomonasAcinetobacterStenotrophomonasHelicobacter…plus many others
Multi-drug resistant bacteria: a rough overviewMulti-drug resistant bacteria: a rough overview
MDR- & XDR-TB
http://www.salute.gov.it/imgs/C_17_pubblicazioni_1404_allegato.pdf
MRSA in Europe 2009MRSA in Europe 2009
ESBL producing ESBL producing E. coliE. coli & & Klebsiella pneumoniae Klebsiella pneumoniae
http://www.salute.gov.it/imgs/C_17_pubblicazioni_1404_allegato.pdf
Beyond ESBL: carbapenem resistanceBeyond ESBL: carbapenem resistance - the ultimate horror scenario- the ultimate horror scenario
Resistance to
ESBL producing Enterobacteriaceae
Penicillins
Cephalosporins
Carbapenem resistant Enterobacteriaceae(VIM,NDM-1, KPC-2,oxa-48)(VIM,NDM-1, KPC-2,oxa-48)
Penicillins
Cephalosporins
Carbapenems
+ others
The ecology of resistance:The ecology of resistance:Selection and transmissionSelection and transmission
Selection with antibioticsSelection with antibioticsSelection with antibioticsSelection with antibiotics
ESBL: The steps from contamination to ESBL: The steps from contamination to infectioninfection
Healthy individual
Intestinal Intestinal colonization colonization (low conc)(low conc)
Acquisition of ESBL by human contact & food
Selection Selection of ESBL of ESBL (high conc)(high conc)
Destruction of normal intestinal flora by antibiotics
Breach of natural barriers (surgery, catheters, chemotherapy etc)
Patient with invasive infection
ManyMany SomeSome Few Few
Bugs fighting back:Bugs fighting back:Antibiotic resistance mechanismsAntibiotic resistance mechanisms
A direct relationship between A direct relationship between antibiotic consumption and antibiotic resistanceantibiotic consumption and antibiotic resistance
Bronzwaer et al. Emerg Infect Dis 2002; 8: 278-82
Coupling of resistance on plasmids or gene cassettes:Coupling of resistance on plasmids or gene cassettes:the genetic background for co-selectionthe genetic background for co-selection
RRtetratetra
RRampiampi
RRcephceph
RRgentagenta
RRcoppercopper
RRzinczinc
VirulenceVirulence factorsfactors
Co-selection with tetracyclines:Co-selection with tetracyclines:a driving force behind MRSA & ESBL in food a driving force behind MRSA & ESBL in food
animalsanimals
DANMAP 2010
ESBL E. coli (broilers & pigs)
89-97 %
MRSA CC398
(pigs)
95 %
Costa et al. Vet Microbiol 2009; 138: 339-44Ho et al. JAC 2011; 66: 765-8DANMAP 2008
Tetracycline resistanceTetracycline resistanceMRSA, ESBLMRSA, ESBL
Why worry?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