Relevance of antibiotic tissue penetration in treating respiratory tract infections.
The majority of bacterial respiratory tract infections are caused by streptococci, Haemophilus spp. and Moraxella catarrhalis. These pathogens are located extracellularly. In logical consequence, the bactericidal action of the antimicrobial is required in these loci. To define the reasonable dosing regimen for effective eradication without creating unnecessary toxic potential we need to know (1) the distribution principles and kinetics, and (2) the correct correlation between concentration profiles in extracellular fluid (ECF) and blood. According to the permeability of the vascular capillaries unbound drug concentrations in plasma and ECF are in a dynamic equilibrium. Thus, for the beta-lactam antibiotics therapeutic efficacy is predictable by maintaining the free drug concentration above the bacterial minimum inhibitory concentration. Tissue homogenate data can only be useful if correctly interpreted by correcting for the partitioning between the tissue components.
Kneer
J
J
Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy*; D002199:Capillary Permeability; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism
D000900:Anti-Bacterial Agents