Dose-activity relationships in chemotherapy.

The in vitro antibacterial effects of subinhibitory and suprainhibitory concentrations of a number of beta-lactam antibiotics and aminoglycosides on microbial growth are presented. The type and extent of the subinhibitory activity of a drug can be well defined by means of growth curves obtained with different subinhibitory concentrations; from these values one can deduce and define the minimal active concentration (MAC) as the concentration at which morphological alterations or inhibition of growth of the bacteria can be seen. The effect of suprainhibitory concentrations can be evaluated by studying the kinetics of the bactericidal activity of a drug. Different types of bactericidal dose-activity relationships can be observed; in many cases a minimal optimal concentration (MOC) can be defined as the lowest concentration of a drug which causes no further appreciable enhancement of efficacy on increasing the concentration. Usually chemotherapy is carried out at subinhibitory drug levels--with decreasing and increasing concentrations--and at present it would appear difficult to assess these constant changes in an in vitro test. Bacteriologists should thus take into account the clinicians' demands for more precise bacteriological data on antibacterial agents.