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

hans.joern.kolmos@ouh.regionsyddanmark.dk

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

End of antibiotics - the ultimate consequenceEnd of antibiotics - the ultimate consequence

Measures against multidrug resistanceMeasures against multidrug resistance

1. Stop selection Antibiotic restriction

2. Stop transmission Hygiene Food animal management

3. Develop new drugs antibiotics helper compounds to

antibiotics