Transcript Link:Presentation of Laurent Gutmann

Resistance to antibiotics :
Preserving a precious resource
Laurent Gutmann
Hopital Européen Georges Pompidou
1) The main question: Why do we have to preserve the
antibiotics
1) Infections are still present and will not disappear !
In the community
-Pneumonia:
-Meningitis :
-Urinary tract infections:
-Gastrointestinal infections:
-Cutaneous :
Streptococcus pneumoniae…
Tuberculosis XDR
Meningococcus, S;pneumoniae
Escherichia coli…..
Salmonella….
Staphylococcus aureus ….
In the hospital
-In the intensive care units and after complex surgery
-Nosocomial infections : intubation for assisted lung ventilation;
intravenous and urinary catheters ; immunodepression
Enterobacteriaceae, Pseudomonas , S.aureus
2) Antibiotics are widely Used in the community and the
hospital (≈ 50/50) : 600 Tons in human in france.
How do we prescribe antibiotics
Regular prescriptions: although should be done according
to the best recommendations'
Over the counter especially in low developed countries
A major problem : no control whatever is the antibiotic
old !, recent! , quantities!
Are human the only consumers ??
-Animals (more than in humans)
-Agriculture
2) What are the consequences of the “intensive”
usage of antibiotics
This knowing that we cannot stop using antibiotics
-We need to cure infections in humans
-This can also be true for animals
This is the dilemma
Use !! ↔ Preserve !!
AB exerts a strong selection pressure on the bacteria
1) Mutations
Selection of resistant bacteria
Gut..
2) Acquisition of genetic
material harboring
resistance mechanisms
- Multiresitance
AB
Enterobacteriaceae
Pseudomonas
CARBAPENEMS
b-LACTAMS
+
Inhibitor of b-lactamases
3e g CEPHALOSPORINES
CARBAPENEMASES
CEPHALOSPORINASE
+ efflux
1e and 2e CEPHALOSPORINE
PENICILLINS
TEM/SHV variant
Hospital
BLSE
BLSE
CTXM
Community
PENICILLINASE and TEM/SHV
1950-1984
1984-2006
2000-2008
At the present time there is no antibiotic
for which resistance has not appeared
After a certain number “of tons of usage”
This included the most recent :
Carbapenems, oxazolidinone,
fluoroquinolones
Bacteria which become a problem in human
Gram positive
Gram negative
Community
Community
-S. aureus CAMRSA
-S.pneumoniae (5-30%)
-Enterobacteriacae (4-20%)
-H. influenzae
-Gonococcus
Hospital
Hospital
-S. aureus MRSA (5-30%)
-E. faecalis and faecium
-Enterobacteriaceae (5-50%)
-Pseudomonas ; -Acinetobacter
(50% in ICU in the US)
3) Dissemination a major threat
The resistance is amplified by the dissemination
Of genes between bacteria in different reservoir
And by the inter-human transmission and others types
of transmission
This is true in the hospital in the community
and from one to the other
including the intercontinental travelling
Since we can harbor these resistant bugs on
the skin and in the gut
Hand transmission !!!!!!
Pool of antibiotic resistance genes
Farm:animal
Food: meat
Humans
Environmental
Soil, Dust, Wastes, Sewages
Wild life
(Birds, Rodents, Insects….)
Fruits,Vegetab
les…. Food
Humans
Some examples of species and resistance
which have and which are disseminating
being a real problem for the humans
NDM-1 and KPC among the most dangerous
carbapenemases present in the Multiresistant
strains of E.coli ,and or Klebsiella pneumoniae
KPC
Deshpande et al SENTRY 2007
EARSS 2007
Staphylococcus aureus Methi R: always present
And now in the community
Conclusions
The selective pressure is such that there always will be new
resistance toward new molecules
However to combat the existing resistances we need
new antibiotics
-Search for novel drugs is needed
Against known targets
Search for novel targets is needed but difficult!!!
-Chemistry is the essential tool: New or modified molecules
-Structural biology is becoming an essential tool for drug design
Good Usage of antibiotics which is a fundamental issue to slow
down the appearance of new resistances
 We need Good Practices to decrease the dissemination of the
existing resistant bacteria
SARM chez les animaux
Methicillin resistant Staphylococcus aureus: , pigs and pets
.Am Assoc Swine Vet 2008 P15-20
Resistance to Streptococcus pneumoniae
Plan antibiotiques1
PCV72
55 200 souches étudiées
60
52
53
48
48
43
38
36
38
35
32
30
32
31
2009
40
25
17
20
20
4
5
1988
0,5 0,7
1
1986
10
1987
12
1984
7
A major problem in meningitis
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
1991
1990
1989
0
1985
% de PSDP
43
2008
50
Multiresistance
linked to integrons
D’costa et al science 2006