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


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