Download Lemaire-ISAP-Post-IC..

Activity of Carbapenems
against intracellular
MRSA
S. Lemaire, F. Van Bambeke, M.-P. Mingeot-Leclercq,
Y. Glupczynski and P.M. Tulkens
Unité de Pharmacologie cellulaire et moléculaire,
Université Catholique de Louvain, Brussels, Belgium
Introduction

Recurrent and persistent infections
A) Intracellular reservoir
Macrophages :
Adherence
Internalisation
Intracellular
survival

Recurrent and persistent infections
B) Resistance acquisition
Denis et al. (http://www.healt.fgov.be/antibiotics)
How to treat intracellular MRSA ?
-lactams
Oxacillin
MIC (mg/L)
MSSA (ATCC 25923) MRSA (ATCC 33591)
pH 7.4
0.25
pH 5.5
0.06
pH 7.4
256
pH 5.5
0.25
Phagolys.
Weinrick et al., JB, 2004
Aim of the study


To compare the activity of -lactams (OXA,
CEF, MEM, ETP and FAR) in pH-adjusted
broth (7.4 or 5.5)
To examine the intracellular activity of lactams in a model of THP-1 macrophages
towards MSSA and MRSA
Results

Activity in broth
-lactams
antibiotics
MIC (mg/L)
MSSA (ATCC 25923)
MRSA (ATCC 33591)
pH 7.4
0.25
pH 5.5
0.06
pH 7.4
256
pH 5.5
0.25
2
1
256
4
0.125
0.06
16
0.125
Ertapenem
0.125
0.06
32
0.06
Faropenem
0.06
0.03
128
0.03
Oxacillin
Cefepime
Meropenem
MRSA becomes as sensitive to -lactams as MSSA
in acidic milieu
Results

Extracellular and intracellular activity of meropenem
Results

Intracellular activity
Results

Do MRSA remain MRSA at acidic milieu ?
Yes !
•
Expression of mecA gene (SQ-RT-PCR) 
•
PBP2a detection (Latex agglutination assay,
Oxoid test) 
Conclusion

Acidic pH does not affect MRSA phenotype
(mecA, PBP2a) but restores carbapenems
activity towards MRSA

Carbapenems are as active against intracellular
MRSA than MSSA, probably due to the acidic
environment of the infected compartment
Thanks for your attention !
Acknowledgments

F.A.C.M Unit
 Prof.
P.M. Tulkens, F. Van Bambeke,
M.-P. Mingeot-Leclercq
 « Intracellular » team

F.R.I.A.
Dr. Y. Glupczynski
 Dr. Y. Jossin

Food
poisoning
Septicemia,
Bacteriemia
S. aureus
Urinary tract
infections
Endocarditis
(Sinha and Herrmann, 2005)
Post-operatory
infections
Respiratory
infections
Osteomyelitis
(Ellington et al., 2003),
Complicated
skin infections
(Clement et al., 2005)
(Von Eiff, 2001)
,