Infect Dis Clin N Am 17 (2003) 615–634
Intracellular pharmacodynamics of antibiotics
Stéphane Carryn, Hugues Chanteux, Cristina Seral, Marie-Paule
Mingeot-Leclercq, Françoise Van Bambeke, Paul M. Tulkens,
Unité de Pharmacologie Cellulaire et Moléculaire,
Université Catholique de Louvain, UCL 73.70 Avenue E. Mounier
73, Brussels B-1200, Belgium
Abstract:
Treatment of intracellular bacterial infection remains both a medical
and
economic challenge. Pathogens thriving or maintaining themselves in
cells, or simply taking transient refuge therein, are indeed shielded
from many of the humoral and cellular means of defense. They also seem
more or less protected against many antibiotics. This explains why
intracellular bacteria not only are harmful for the host cells but may
also constitute a reservoir for recurrence and reinfection. Because
antibiotics poorly act on intracellular bacteria, selection of
resistant mutants may also be fostered. All these considerations stress
the importance of understanding (1) whether and to what extent
antibiotics may or may not act against intracellular bacteria, (2)
which are the pharmacokinetic and pharmacodynamic parameters governing
their activity, and (3) how chemotherapy can be improved on that basis.
This article examines these issues starting from basic knowledge about
the disposition of bacteria and antibiotics in cells and moving to an
of these concepts to rationalize the various but quite often
contradictory
experimental observations concerning intracellular activity.
integration