The in vivo significance of tissue concentration

Abstract

The minimal inhibitory concentrations (MIC) of most bacteriostatic antibiotic drugs is only slightly lower than the maximally effective concentration, whereas that of many bactericidal antibiotics is much lower. Moreover, the effect of β-lactam antibiotics in vitro is time-dependent, and concentrations in vivo, especially of bactericidal antibiotics, fluctuate widely because of rapid elimination. For these reasons it is incorrect to regard MIC values as equal to minimal effective concentrations in vivo. In infected tissues neither micro-organisms nor antibiotics are evenly distributed. Therefore, total tissue contents give a false impression of the aqueous concentrations at the site of infection. Direct determination of the concentration in extracellular fluid is a laborious procedure; the concentration in the lymph probably gives a good indication indirectly. The most important application of tissue-content determination is for the study of the accessibility of a tissue for an antibiotic drug, the data being interpreted in relation to the plasma concentration.